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Michele Reilly is a scientist, an artist, and a systems thinker whose work resists easy classification. She trained in architecture and art at Cooper Union, where she began building intelligent machines and quickly became fascinated by the logic behind them. That curiosity drew her into mathematics, cryptography, macroeconomics, and eventually quantum physics. Her path has been shaped less by credentials than by the depth of her questions.
At MIT, where she teaches in the Department of Mechanical Engineering, Michele works at the intersection of computation and the structure of spacetime. She explores how information flows through the universe, drawing from Claude Shannon’s foundational theories and extending them into the quantum realm. Her research is ambitious, but it is rooted in careful thinking. She is not interested in speculation for its own sake. She wants to know what can be built, what can be measured, and what will last.
In 2016, she co-founded Turing, a quantum technology startup focused on building portable quantum memories and tools for long-distance quantum communication. She works closely with physicist Seth Lloyd on designing the scalable, robust systems needed to move quantum computing from theory into practice. The work is intricate and deliberate, building slowly toward a future that she sees as both beautiful and unfamiliar.
Michele is also a storyteller. Her science fiction series Steeplechase has received awards at Cannes and other international festivals. It reflects her belief that narrative and science are not separate pursuits, but parallel ways of exploring the unknown. In her teaching, she brings these strands together, guiding students through exercises that combine quantum theory, creative writing, and world-building. One of her courses, supported by MIT’s Center for Art, Science and Technology, invites students to imagine speculative futures grounded in scientific inquiry.
On her arm is a tattoo of Alan Turing. It is not ornamental. It is a quiet tribute to a thinker whose life and work continue to shape her own. Turing’s dedication to truth, structure, and the ethical weight of technology is a constant presence in her thinking. She carries it with her, quite literally.
The portrait above was made at The Interval at the Long Now Foundation in San Francisco. Michele is seated beside a polished table that reflects her image. Behind her stands the Orrery, a planetary model designed to keep time for ten thousand years. The setting reflects the spirit of her work. She is grounded in the present but always thinking forward, asking how we might live in ways that honor complexity, care, and continuity. She does not speak often about legacy. She speaks about attention, about precision, and about the discipline of staying with difficult questions until they begin to yield something real.
Robert A. Gillam
CEO and Chief Investment Officer, McKinley Capital Management, LLC
Michael Metcalfe
Senior Managing Director, Head of Multi Asset Strategy, State Street Global Markets
Roxanne Davies
Advisory Board Member, Miras Investments LLC; CEO, Parly Singapore Pte Ltd
Alireza Zaimi
Executive Director and Head of Corporate Finance, Public Investment Fund of Saudi Arabia
It's been a year since I've done one of these. I am currently going to school part-time, and I will be going full time in the summer. My bag is a Manhattan Portage Dana's messenger bag, which is small enough to not get annoying, but large enough to hold everything. Contents include: 1. A cheap bluetooth keyboard from Amazon, 2. a Microsoft wireless mouse for when I bring my laptop to my programming class, 3. a currently obsolete tablet stand, 4. a recently-acquired 1st gen iPad Mini, 5. a Thirty-One wallet, 6. my macroeconomics notebook, 7. a cocoon grid- it organizer, and 8. my rarely used Star Trek planner.
Westerners have a tendency for self praise. Indeed thought, which has been shown not to be will (Libet, 2009; Nisbett and Wilson, 1977) may be a stream of self comforting, justifications (Haidt, 2001), or even a negotiation" (Rochat, 2009) or sexual self-stimulation (Derrida, 1976) that we whisper and of which we are ashamed (Quran 50:16).
Whispering in the mind is similar to Keynesian macroeconomic stimulation of the fiscal kind. Westerners tell themselves that "I can do it," "I'll will win" and motivate themselve to do just that. They feed themselves empty simbols, that otherwise have exchange value, to get a postive feedback loop going. Central banks print money, symbols that otherwise have exchange value, to get an economic positive feedback loop going. Both work in the short term but may become an addictive maelstrom of self-stimulation in the longer term.
With regard to the mental self-stimulation it has been shown that the the Japanese probably do not do it, at least nearly so much (Kim, 2002; Heine et al., 1999). Japanese sports persons refrain from self praise even when they win. This is not to say that there is not a Japanese equivalent to self-praise. The sports person picture above in the Yamaguchi Newspaper indulged in Psychological Keynsianism Japanese style. Before the final of his rock climbing event he brought forth an imagine in his mind of himself, winning the event in the spotlight in front of the massive crowd. This image helped propell him to his win, with unconstrained enthusiam (nobi nobi 伸び伸び).
One possible advantage of the Japanese style of self-stimulation is that it may not require comparison (Yuki, 2003).
Linguistic signs always exist and have meaning in distinction to other signs (De Saussure, 2011; Maruyama et al., 1993, p19). "I will win" implies someone will loose. "I am great" implies, if "great" is to have any meaning, that someone else is not great. Unless there is to be rampant inflation some nefarious technique of maintaing the myth of 'everyone is better than average' must be brought into play. This is often achieved for instance by the negative evaluation of outgroups (Said, 1979; Tajfel and Turner, 2004). British people can be all "great", because orientals are all "savages". British people could all be rich because they took wealth from the rest of the world.
The Japanese are even better than Americans at maintaining a myth that everyone is better than average (Hamamura, Heine, & Takemoto, 2007). Their technique of just imagining the beauty, however, does not necessarily require downward comparison. In the case of the sportsperson above it is true he imagined himself winning but the important thing was that he was in the spotlight. Downwards comparison was not present nor necessary. Indeed conversely it may be the case that Japanese psychological Keynsianism can feed off positivity, such that Japanese like to imagine, and photograph, themselves alongside the triumph and beauty of others. Japanese tourists, armed with selfie-sticks are masters at 'basking in reflected glory' (Cialdini et al., 1976).
Japanese economic self-stimulation has generally taken the form of public works projects to construct roads, and various "boxy" (hakomono) infrastructure. Such public works were generally funded by loans. Perhaps Japanese sports person can only pump themselves up with images of victory if they accept that there will be a payback time (perhaps at the moment of victory, when the spotlight is not all that enjoyable after all).
Recently, both on the psychological and economic front however the current prime minister of Japan is encouging the Japanese to praise themselves (Abe, 2006), and resorted to symbolic, fiscal stimulation of the Japanese economy. The Bank of Japan is printing yen and purchasing Japanese government bonds. The Prime Minister also espouses an increase in Japanese millitary strength. It seems to me that simbolic self-stimulation, without inflation, and violence go hand in hand. I think that this physical recreation of the Western mind in the global pollitical economy is the 'unveiling' that we need to avoid.
Bibliography
Abe, S. (2006). Utsukushii kuni e [Towards a beautiful country]. Tokyo: Bungei Shunju.
Cialdini, Robert B., et al. "Basking in reflected glory: Three (football) field studies." Journal of personality and social psychology 34.3 (1976): 366.
Derrida, J. (1976). Of grammatology, trans. G. Spivak. Baltimore: Johns Hopkins University.
De Saussure, F. (2011). Course in General Linguistics [1916]. New York, NY: Columbia University Press.
Haidt, J. (2001). The emotional dog and its rational tail: a social intuitionist approach to moral judgment. Psychological review, 108(4), 814.
Hamamura, T., Heine, S. J., & Takemoto, T. R. (2007). Why the better-than-average effect is a worse-than-average measure of self-enhancement: An investigation of conflicting findings from studies of East Asian self-evaluations. Motivation and Emotion, 31(4), 247-259.
Heine, Steven J., Darrin R. Lehman, Hazel Rose Markus, and Shinobu Kitayama. "Is there a universal need for positive self-regard?." Psychological review 106, no. 4 (1999): 766.
Kim, H. S. (2002). We talk, therefore we think? A cultural analysis of the effect of talking on thinking. Journal of personality and social psychology, 83(4), 828.
Libet, B. (2009). Mind time: The temporal factor in consciousness. Harvard University Press.
Maruyama, M. et al. 丸山圭三郎, 行人柄谷, 健二立川, 秀岸田, & 芳郎竹内. (1993). 文化記号学の可能性 (増補完全). 夏目書房.
Nisbett, Richard E., and Timothy D. Wilson. "Telling more than we can know: Verbal reports on mental processes." Psychological review 84.3 (1977): 231.
Rochat, P. (2009). Others in mind: Social origins of self-consciousness. Cambridge University Press.
Said, E. W. (1979). Orientalism. Vintage.
Tajfel, H., & Turner, J. C. (2004). The Social Identity Theory of Intergroup Behavior.
Yuki, M. (2003). Intergroup comparison versus intragroup relationships: A cross-cultural examination of social identity theory in North American and East Asian cultural contexts. Social Psychology Quarterly, 166–183. Retrieved from www.jstor.org/stable/pdfplus/1519846.pdf
Image: Deliberately blurred photo of an article in the Yamaguchi Newspaper from October 2016.
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En el actual marco macroeconómico
Encaminándonos hacia la profecía deflacionista
Y teniendo en cuenta nuestros EBITDA,
Que queramos o no tienen algo de complementarios,
Con la natural desconfianza en las subprimes
(¿ cuantas tenemos bajo la alfombra?)
Y aún más en la collaterizaled debt obligations
(¿ cuantas se nos colaron debajo de la puerta?)
Y eso sin mencionar las credit default swaps
(¿ cuantas se te aparecen cuando no puedes dormir?),
Y antes de degradarnos a AA ó A
O Dios no lo quiera BBB ó BB,
Y dado que la extinción de nuestras obligaciones
Nos costaría 8 besos/año por amores temporales
O 20 besos/año por despidos emocionales
Por causas empresariales
O 45 besos/año por amores indefinidos
Creo que deberíamos unir definitivamente
nuestros risk defaults
Yendo a una joint venture articulada,
Quizás en forma de OPA si no amorosa
Al menos nada hostil…
In the current macroeconomic framework
Prophecy heading toward deflation
And given our EBITDA
We want or do not have some complementary
With the natural distrust of subprime
(How many have under the carpet?)
And even more in debt obligations collaterizaled
(How many we slipped under the door?)
Not to mention the credit default swaps
(How many you are when you can not sleep?)
And before downgrading to AA or A
Or God forbid BBB or BB,
And since the extinction of our obligations
8 kisses would cost / year for temporary love
O 20 kisses / emotional year for layoffs
For business reasons
O 45 kisses / year indefinite love
I think we should definitely join
our Risk defaults
Going to an articulated joint venture,
Perhaps as if not loving OPA
At least nothing hostile ...
They wrote in the old days that it is sweet and fitting to die for one's country. But in modern war, there is nothing sweet nor fitting in your dying. You will die like a dog for no good reason.
- Ernest Hemmingway
On December 10th, Mauricio Macri will mark two years as President of Argentina. A great deal has changed since his surprising electoral victory in 2015. Macri has presided over an improved macroeconomic situation and has set out an ambitious reform agenda aimed at boosting competitiveness and growth. Following a recession in 2016, Argentina is expected to grow at 3 percent this year.
There have, however, been considerable costs associated with the economic policy shift, which made Macri’s Cambiemos coalition’s defeat of a divided Peronist Party in October’s mid-term elections all the more striking.
Can we expect the Macri Administration to achieve its reform agenda in the next two years? What are the likely obstacles and how does the government plan to deal with them? Will the formerly dominant Peronist Party be able to reorganize after suffering two consecutive defeats? What is the likely role of former President (and now Senator) Cristina Kirchner?
To discuss the Macri administration so far, as well as the challenges ahead in the next two years, the Dialogue is pleased to welcome Carlos Pagni, one of Argentina’s best informed and most influential political journalists and commentators.
On December 10th, Mauricio Macri will mark two years as President of Argentina. A great deal has changed since his surprising electoral victory in 2015. Macri has presided over an improved macroeconomic situation and has set out an ambitious reform agenda aimed at boosting competitiveness and growth. Following a recession in 2016, Argentina is expected to grow at 3 percent this year.
There have, however, been considerable costs associated with the economic policy shift, which made Macri’s Cambiemos coalition’s defeat of a divided Peronist Party in October’s mid-term elections all the more striking.
Can we expect the Macri Administration to achieve its reform agenda in the next two years? What are the likely obstacles and how does the government plan to deal with them? Will the formerly dominant Peronist Party be able to reorganize after suffering two consecutive defeats? What is the likely role of former President (and now Senator) Cristina Kirchner?
To discuss the Macri administration so far, as well as the challenges ahead in the next two years, the Dialogue is pleased to welcome Carlos Pagni, one of Argentina’s best informed and most influential political journalists and commentators.
March 30, 2023 - NIGER. World Bank Group President David Malpass delivers his 2023 Spring Meetings Positioning Speech at the Mahatma Gandhi International Convention Center in Niamey, Niger. During his speech, President Malpass discussed challenges facing development policy, including the need for macroeconomic stability, the importance of private capital to international integration, and the increasing need to support global public goods. President Malpass emphasized the role of education in supporting growth and creating pathways out of fragility and extremism, which are both critical for Africa’s Sahel Region. The event was hosted by the Abdou Moumouni University of Niamey. Photo: World Bank / Torie Smith
PHOTO ID: 033023-Niger-DM-02728
The winter 2016 meeting was hosted by the Volatility Institute at New York University's Stern School of Business. This meeting featured sessions on the role of the housing market in the macroeconomy, the impact of big data and machine learning on macroeconomic research, and the potential of innovation contests to push macroeconomic modeling into new and exciting territory.
Recently, many economies have come under sharp foreign exchange pressures, reflecting large commodity price declines, volatile external financing conditions, and country-specific factors. This seminar will invite central bank officials from emerging and frontier markets to discuss their recent experiences in dealing with these pressures, including the role of exchange rate flexibility and constraints imposed by the overall macroeconomic policy frameworks and balance sheets.
Portrait of Dr. Hanan Morsy, Director of Macroeconomic Policy, Forecasting and Research Department of African Development Bank while addressing during African Economic Conference (AEC) 2019 - Plenary Session 2 - Institutions and Policies for Job Creation, Skills Acquisition and Capacity Building of African Youth (AFDB) on December 02, 2019, in Sharm el-Sheikh, Egypt.
Natural history of universe history // // // human history, world history --- Research Overview
Chronology of World History (Natural universe, the earth, the human world, life) // New geological new astronomical - chronological universe
Historical records and research according to the World, World History, the history of world civilization, chronicle world events, as well as natural history, earth history, history of the universe, geological history, biological history and the like.
World History books have a lot of authority, the United States, Britain, Russia, Europe, middle country have similar universal history masterpiece. Scroll a few million words, it is worth intensive reading. Shanfanjiujian this article, a brief description of some of the problems, as superficial academic exchanges.
Chronology of World History
About 300,400 million years ago: humans appeared on earth.
About 200,300 --1 million years ago: Palaeolithic humans. Chipped stone popular, has been the use of fire
Collection industry, descent and family matriarchal commune produced.
BC 3 - 1 million years ago: the primitive religion appears.
About 12,000 BC - 4000 BC: Stone Age humans. Invention and using a bow, fine stone widely used hunting industry.
From about 8000 BC - Former 2000: mankind has entered the Neolithic Age. Popular burnishing stone, there have been primitive agriculture and animal husbandry
. Matriarchal commune prosperity.
6000 BC: Asia Minor appeared linen and wool fabrics.
Circa 6000 - 1000 BC: ancient Mesopotamia, Asia Minor, Greece, Rome, Persia, India and other places were primitive and ancient religions
Teach prevalent.
BC 4000 - 3000 BC: Ancient Egypt, Southwest Asia, Southern Europe, Central Europe and China and other places have started to use copper ore.
3500 BC - 3100 years ago: in ancient Mesopotamia Uruk period. It appears pottery wheel pottery and ziggurat building, creating a cuneiform. Gouy
And national (Nome) is formed. It appeared hieroglyphics.
3500 BC - 3000 BC: Ancient Mesopotamia residents began to use wheeled transport. The ancient Egyptians used in agriculture plow, harrow
And fertilization.
3100 years ago: the rulers of ancient Egypt conquered Lower Egypt Menes, the initial formation of national unity. Egypt started the Early Dynastic Period.
3000 BC: Ancient Mesopotamia Sumerian city-state area appeared slavery.
3000 BC: Ancient Egyptian appear paddle and sail boats. The ancient Egyptians used bronze mirrors. Ancient Indians invented the stamp characters.
Before 2686 - before 2181: the Egyptian Old Kingdom. Complete national unity, large-scale construction of the pyramid.
Before the 27th century: the heroic epic of ancient Mesopotamia Sumerian era of the "Epic of Gilgamesh" is formed.
26th century BC: the famous ancient Egyptian Sphinx completed.
Europe appears knitting machine.
Chronology of World History "World History, World History." Long and complicated history of the world, some historical facts will inevitably have questions or inaccurate too, need to continue to identify and correct them later modified to restore the original appearance of history.
About 300,400 million years ago: humans appeared on earth.
About 200,300 --1 million years ago: Palaeolithic humans. Chipped stone popular, it has been the use of fire, late extensive use of bone, horn device. Hunting.
Collection industry, descent and family matriarchal commune produced.
About 170 million years ago: Yuanmou Yuanmou Chinese people living in this area, has been able to manufacture and use of stone tools.
{[(See World History, encyclopedias Stavros reason Oceanus: "Global History" McNeil "Rise of the West - the history of the human community" and "World History", as well as W · H.. McNeil's "World History" (1967), Stavrianos "global History" and so on.}
1
BC 3 - 1 million years ago: the primitive religion appears.
About 12,000 BC - 4000 BC: Stone Age humans. Invention and using a bow, fine stone widely used hunting industry.
From about 8000 BC - Former 2000: mankind has entered the Neolithic Age. Burnishing stone popular, there have been primitive agriculture and animal husbandry.
. Matriarchal commune prosperity.
6000 BC: Asia Minor appeared linen and wool fabrics.
Circa 6000 - 1000 BC: ancient Mesopotamia, Asia Minor, Greece, Rome, Persia, India and other places were primitive and ancient religions
Teach prevalent.
Circa 5000: Start with a cold forging method and processing of natural copper southwest Asia and Central Asia. Ancient Egypt has been used and other arms balance scale, the most known
Weighing early.
From about 5000 BC - Former 4000: In ancient Egypt, the sun and moon appear as regular calendar.
BC 4000 - 3000 BC: Ancient Egypt, Southwest Asia, Southern Europe, Central Europe and China and other places have started to use copper ore.
3760 years ago: the first year of the ancient Jewish calendar.
3500 BC - 3100 years ago: in ancient Mesopotamia Uruk period. It appears pottery wheel pottery and ziggurat building, creating a cuneiform. Gouy
And national (Nome) is formed. It appeared hieroglyphics.
3500 BC - 3000 BC: Ancient Mesopotamia residents began to use wheeled transport. The ancient Egyptians used in agriculture plow, harrow
And fertilization.
{5ooo BC before}
Before 2686 - before 2181: the Egyptian Old Kingdom. Complete national unity, large-scale construction of the pyramid.
26th century BC: the famous ancient Egyptian Sphinx completed.
2,500 years ago: the ancient Sumerian Medicine found that mineral water has healing properties, the ancient Sumerians used oil lamps, learn to bake bread and brew beer
liqueur. Europe appears knitting machine.
Circa 2500 - 1500 BC: Xiyaguya said period
Before the 25th century - before the 23 century: in Ancient Babylonians invention of pottery carved on the map.
Before 2378 - before 2371: the ancient Sumerian king of Lagash Urukagina reign,
Before 2371 - before 2154: the ancient Mesopotamian Akkadian Kingdom.
From about 2300 BC - Former 1750: Ancient Indian Harappa culture period.
Before 2181 - before 2040: First Intermediate Period of Ancient Egypt.
Before 2017 - before 1595: the era of ancient Mesopotamia Ancient Babylon
Before 2000: - Aegean Mycenaean civilization appears. Ancient Egypt appear library, mummification.
Before 1900-- before 1600: the ancient Greek text appears linear, bronze widely used.
Walsh (William H.Walsh, 1913-1986), British philosopher>
Before 1792 - before 1750: Ancient Mesopotamia Ancient Babylon 6th generation reign of King Hammurabi, will be "Code of Hammurabi"
Before 1786 - before 1567: the Second Intermediate Period of ancient Egypt. Hyksos invasion of Egypt ruled over a hundred years.
Before the 18th century: ancient Babylon occurred farmers almanac, including irrigation, cultivation and harvesting, as the earliest known farmers almanac.
Before 1567 - before 1085: New Kingdom of ancient Egypt.
The ancient Babylonians created a well-developed mathematics and astronomy. Horses start for vehicle transport. UK Salisbury and Wiltshire areas built
Build Stonehenge. Ancient Egyptians used mercury.
About 14 centuries ago: Chinese Pan Geng moved to Yin from Om generate Oracle.
The first 14 - Former 12th century: the ancient Hittite Empire in West Asia.
The mid-14th century BC - 11th century ago: the ancient Xiyaguya said Empire.
About 13 centuries ago: Chinese Shang bronzes heyday. Late Shang Si Mu Wu Ding is the largest remaining bronze.
Former 11-- 9th century BC: the ancient Greek Homeric.
1000 BC - Former 600 years: The ancient Indian Vedic period. Aryan state formation, Brahmanism spread.
10th century - 612 years ago: the ancient Assyrian West New Empire. Iron appeared and widely used.
Top 10 - Top 5 Century: Ancient Indian earliest philosophical writings, Brahmanism classic "Upanishads" formation.
841 years ago
9 century ago: the ancient Greek Sparta state formation.
8th century: the ancient Greek epic "Iliad", "Odyssey" is formed, transfer to Homer. Pergamum invented parchment people in the Middle East.
Ancient Greek first Olympic Games held in Olympia.
BC 700 - 600 years ago: the ancient Phoenicians with suet and mountain ash into soap.
Before 8 - 6th century BC: the Roman monarchy era.
Before 626 BC - 539 years: the ancient Mesopotamia the Neo-Babylonian Kingdom.
Before 624 BC - 547 years: the ancient Greek philosopher Thales alive, the creation of Miletus school.
Before 610 BC - 546 years: the ancient Greek philosopher Anaximander alive.
About 7 centuries ago: the Babylonians found eclipses recurring Saros.
Before 604 BC - 561 years: the ancient Mesopotamia the Neo-Babylonian king Nebuchadnezzar II reign, the construction of the Hanging Gardens, destroy the Jewish state.
594 years ago: the ancient Greek Athenian Solon implement political and economic reform, issued the "Code of Attica."
From about 580 BC - 500 years ago: the ancient Greek mathematician and philosopher Pythagoras was alive, the creation of the Pythagoreans.
About 563 years ago - 483 years ago: Sakyamuni, founder of Buddhism alive.
Before 558 BC - 330 years: the ancient Persian Empire and West Asia.
551 BC - 479 BC: Confucius alive, the creation of the Confucian school of thought, the first private school, presided over the compilation of ancient culture finishing. Existing "The Analects
"
.
About the first 500-- 449 years ago: Persian War.
Before 485 BC - 425 years: the ancient Greek historian Herodotus alive.
Before 469 BC - 399 years: the ancient Greek philosopher Socrates alive.
Before about 460 BC - 401 years: the ancient Greek historian Thucydides alive, author of "History of the Peloponnesian War."
About the first 460-- 370 years ago: the ancient Greek philosopher Democritus alive.
432 years ago: the ancient Greek Parthenon, built by the sculptor Phidias decorative design.
Former 431-- 404 years ago: the occurrence of the Peloponnesian War. World military history.
Before 427 BC - 348 years / 347 years ago: the ancient Greek philosopher Plato alive.
Before 334 BC - 324 years: the Macedonian king Alexander the Great led his army conquests of Persia, Central Asia and India, travel thousands of miles, the world's ancient history
The famous military expedition. .
Before 330 BC - 275 years: the ancient Greek mathematician Euclid alive, the "Geometry."
323 BC - 187 years ago: the ancient Indian kingdom of Magadha Mauryan period.
4th century BC - AD 3,4 century: the ancient Indian epic "Mahabharata" is formed.
Before 287 BC - 212 years: the ancient Greek mathematician and physicist Archimedes alive.
About 280 years ago: the ancient port city of Alexandria, Egypt built the Pharos lighthouse, one of the seven wonders of the ancient world.
About 269 years ago - 232 years ago: the ancient Indian kingdom of Magadha Mauryan king Ashoka reign of the Mauryan entered its peak phase.
7 years ago or four years ago: According to legend, the founder of the birth of Jesus Christ.
1st century: Greek sculptor Ndiaye Sandra Ross, Nuoduoluosi, 波利佐罗斯 three carved marble statue of "Laocoon."
1st century AD the Roman Empire began
395 years of Christianity
476 years of the Roman Empire split
Early 7th century Frankish kingdom established
622 years of the rise of Islam
676 Japanese Taika Reforms begin
8 mid-century Silla unified the Korean Peninsula most
In the early 9th century Arab empire become
843 formed the Kingdom of the English.
Charlie is not the 12th century division of the empire, France, Germany, and Italy produce prototype
Japan entered the 14-16 century during the reign of the Shogunate
1453 Renaissance in Europe
1453 Byzantine Empire
1492 Dias voyage along the southern coast of Africa
1497--1498, Columbus reached America / Columbus discovered the New World
1519-1522 Voyage Vasco da Gama India
1640 Magellan sailed round the world fleet
1688 English bourgeois revolution began
1760s British coup, the new bourgeoisie and the establishment of the rule of Guizhou
1775--1783 British industrial revolution began
July 4, 1776 North American War of Independence
North American Continental Congress issued a "Declaration of Independence", the United States declared independence
Power 1785 Watt improved the steam engine is made to start a textile machine used / technological revolution, industrial
1848--1849 European revolution
1861 Russian serfdom reform
1861 --1865 US Civil War
Japan's Meiji Restoration began in 1868
Finalize the unification of Italy in 1870
1871 completed the unification of Germany, the German Empire was established
1939.9 Second World War broke out
1
1943.12.1, the United States, Britain issued the Cairo Declaration <>
The United Nations established 1945.10
The former Soviet Union.
1993 establishing the European Union
World History events
Create ancient Egyptian civilization
Old Babylonian kingdom
"Code of Hammurabi" development
Trojan War
Solon
Darius Battle
Battle of Marathon
The birth of Ancient Greek Philosophy / human history, cultural heritage, European civilization
/
Olympic Games / World Sports Events
[Many major events in world history, important people, it is difficult to accurately include all of them. There are various versions of the General History of the World, it is difficult consensus.]
Rise and Fall of the Roman Empire
Establishment and spread of Christianity
"Justinian Code" handed down
Germanic peoples migration
Founding and demise of the Mayan civilization
Collisions of European civilization
The collapse of the Byzantine Empire
The rise of the Ottoman Empire
Hundred Years War
Renaissance
Shakespeare Drama Creation
Opening of new routes
The European Reformation
Copernicus presented heliocentric
Newton discovered gravity
English bourgeois revolution
Faraday invention motor
Enlightenment
Reform of Peter I / Russia
The first industrial revolution
American Revolutionary
The French Revolution
The rise and fall of Napoleon
Latin American War of Independence
1848 European Revolution
Darwin's Theory of Evolution
the Meiji Reform
The establishment of the first international
second industrial revolution
Telephone and radio technology invention
Wright brothers and the birth of the aircraft
Birth car
Krstic invention Train
World War I
Establishment of an international coalition
Einstein theory of relativity
Second World War
The former Soviet Union / the end of the Cold War.
The establishment of the United Nations
New Changes in the third technological revolution the international political and economic new pattern of new trends
Modern society / world economy and world politics / World Military / World Culture / World Religion / World Population, etc.
Globalization - new opportunities, new challenges, new world and evolution
Man on the moon / cosmic revolution, the revolutionary planet, the planet began to society
{{ "The Outline of History" (English) Hz with Joe Wells.
"The Outline of History: Biological and concise history of mankind" (English) Hz with Joe Wells.
"History of Western civilization," [US] · E · Robert Lerner waited. This is a very influential book in North America, three co-historian. The former Soviet Academy of Sciences Editor: World History
"World history of civilization," [US] Philip Lee Ralph waited. 4 co-historian.
"World history of civilization," the Weierdulan. An amazing work. }}
Appears cloning / modern biological technology
Create ancient Egyptian civilization
Old Babylonian kingdom
Trojan War
Solon
Darius Battle
Battle of Marathon
Establishment and spread of Christianity
"Justinian Code" handed down
Germanic peoples migration
Founding and demise of the Mayan civilization
The collapse of the Byzantine Empire
The rise of the Ottoman Empire
Hundred Years War
Renaissance
Opening of new routes
The European Reformation
Copernicus presented heliocentric
Newton discovered gravity
English bourgeois revolution
NYSE / capitalist development
Faraday invention motor
Reform of Peter I
The first industrial revolution
American Revolutionary
The French Revolution
The rise and fall of Napoleon
1848 European Revolution
Darwin's Theory of Evolution
Telephone and radio technology invention
{{Main part of world history events, individual controversial history of the world can be found in general history, world history and civilization classics Encyclopedia of network resources, the world's three encyclopedia}}.
Third technological revolution
After the Cold War new world-changing. Competitive countries in the world, the rapid development of modern science and technology productivity.
Genetic engineering, aerospace engineering, computer and information network engineering, materials engineering, energy engineering, mechatronics, biomedical engineering, agricultural engineering, intelligent robotics, marine technology, military engineering and technology applied to human society greatly.
Competition and conflict in various new challenges, new conflicts, civilization, religion, nationality, culture, etc. followed, the world order is facing change and innovation, a serious challenge to the consolidation and development of the turmoil in the world order - Transformation ago Row.
Humans - primates
Primates - physiological characteristics {evolutionary / biological human primate evolution, comparative study}
Primates primate skull
In primates inhabit trees common features, there are many differences. Including the holding force needed collarbone in the chest ribs, all angles to ensure freedom of movement of the shoulder, in front of the fingers, nails, touch sensitive finger (toe) end, the tendency smell degradation, the number of teeth is relatively degraded, complex visual system (visual sensitivity and color sense), and trunk disproportionate brain, the cerebral cortex expanded pairs of mammary gland, a common child, a longer gestation period and the like.
Usually highly social primates, and there is hierarchy. Pliocene period began monogamous primates, and form a stable patriarchal society.
Primate head has two eyes forward: This binocular can provide an accurate sense of distance. There are towering above the orbital brow.
There is a huge dome on primate skull - skull, which was unusual in its class. Skull protects the brain following the same difference. Human cranial cavity volume (space inside the skull) than non-human primates should be three times the largest cranial cavity, which show that humans have larger brains. The average human cranial volume is 1201 cubic centimeters, while gorillas are 469 cm3, 400 cm3 chimps, orangutans is 397 cubic centimeters. The primary direction of primate evolution is the brain, especially the neocortex. According to anthropologists and geneticists concluded that the evolution and mutation of the human brain in a few tens of thousand years after part of evolution, part may be degraded. to genetic variation, mutation, cells, enzymes, proteins and the like.
Primates generally have five toes on each forelimb (finger), the end of each toe has horny toenails. Hand, foot and toes very sensitive skin, constitute a well-developed sense of touch systems. Most primates are suitable for the thumb grip objects (opposable thumbs), which is characterized by iconic primates, but not unique. For example opossum there so fingers. For primates, such as finger nails is accompanied by short walk between the ancient trees of the product. Many methods thus developed upper limb walking out.
Primate of all ring-shaped neck sternum very obvious
Snout primates (lower jaw) showed shrinking trend. Technically speaking, the Old World and New World monkeys distinction lies in the structure of the nose, and the difference between the Old World monkeys and apes in the arrangement of the teeth. New World monkeys nostrils facing side, and old world monkeys are toward the lower nostril. Primates with a variety of teeth arranged manner. Hominid molar tip (the last tip) is in the early history of primates evolved, and this corresponds to the original lower molars tip (lower front tip) will disappear. Prosimians has its unique fixed upper lip, wet nose and lower front teeth inward.
Primate evolution and vision compared to most mammals was unusual. Primate ancestors developed trichromatic vision (can see three colors function), and nocturnal animals, warm-blooded animals and other mammals in the dinosaur ancestors of the period is lost in one third of the retinal cones.
Movement primates varied and useful arms, feet, jumping, arboreal, and walk on all fours on land, knuckles and other reptiles. Many of the original monkeys suborder animals vertical jumping and attached to trees, shrubs, including many monkeys, all indri. Humans are the only primates to fully upright.
Female migration system - born females leave the group. Male remained in the original population, while females and the collective is not closely linked.
Male exchange system - females remain in the original group and the males in adulthood Relocate. Allow polygamy society will fall into this category. Such social groups usually slightly larger, common in the ring-tailed lemurs, capuchin monkeys.
Monogamy - a male and a female stable structure, sometimes accompanied by heirs. Family care and social services (such as territorial defense) the work is divided into two sides. Parents will leave the territory after adult children. Such a society is more typical gibbon groups. However, where monogamy is not faithful representation of life.
Lonely type (for female) - together with the male will protect their territory, and which will include several female areas of activity. Such structures are found in apes.
Primates
Primate slower growth than other mammals. In addition to humans, primates cubs all rely on breastfeeding transfer of nutrients by the mother to protect, guide and support. Some species are also males, particularly his father, in charge of children's activities and safety. Other family members. encyclopedia site Wikipedia, Encyclopedia Britannica, Encyclopedia Americana and other information sites.]>
Primate mammals than the same size has a longer childhood (from weaning to sexual maturity). These are usually playing in knowledge gained. Later brought to maturity with the same size primate mammal compared to a longer life. And the average female life expectancy is longer than males.
Primate food source is very extensive. Most primates eat fruits, in order to absorb the digestible carbohydrates and fats for energy. However, other primates also need food, such as leaves or insects, for amino acids, vitamins and minerals (trace elements).
Baboon is the only major herbivorous primates. Tarsiers are the most carnivorous primates - eats insects, reptiles, and other animals. {Advanced intelligent life in the current scientific findings in humans with only other similar microbes in extreme environments - Extreme Life may find other planets or large in the universe, however, similar primate mammals in the visible Earth, the moon. Jupiter, Mars may not have even within the scope of these and other higher organisms. even if there had probably already extinct. As for whether within a larger universe, of course, can not all negative, however, there is the possibility, but not too much. extremophiles or other extreme life have then the possibility of a slightly larger universe in the development of change, extreme extreme biological life will produce and perish. everything is developing and changing universe, astrophysics, particle, expressing various forms of expression of life forms also is full of development and change.}.
Cosmic history summary table:
Temperature (K) Energy (eV) time (s) during physical Times
1032102810-44 Planck era
1028102410-35 grand unified era
10-35, -33 soaring inflation stage process
101310910-6 hadron era
101110710-2 lepton era .
10,101,061 neutrino neutrino decoupling decoupling
5 × 109 5 × 105 5 electron annihilation of electron-positron pairs
1,091,053 points nucleosynthesis era of light nuclides generated
400 million years of the formation of the first stars, reionization
Galaxies, large scale structure formation
2.725 3 × 10-4 137 billion years Modern
.
A brief history of the Earth's geology: for reference only, can be found in the relevant research monograph, the World Encyclopedia, Encyclopedia Britannica, Encyclopedia Americana, Wikipedia, Wikipedia and other websites on behalf of strata, representatives of the International Geological years.
Archean (AR, Archean Eon): about 4.567 billion to 25 billion years ago
Eoarchean (Ar0, Eoarchean Era): about 4.567 billion to 36 billion years ago
Paleoarchean (Ar1, Paleoarchean Era): about 3.6 billion to 32 billion years ago
The Archean (Ar2, Mesoarchean Era): about 32 billion to 2.8 billion years ago
Neoarchean (Ar3, Neoarchean Era): about 28 billion to 2.5 billion years ago
Proterozoic (PT, Proterozoic Eon): about 25 billion to 543 million years ago
Paleoproterozoic (Pt1, Paleoproterozoic Era): about 2.5 billion to 18 billion years ago
Before Hutuo discipline: about 2.5 billion to 23 billion years ago
Hutuo Ji (Ht): about 23 billion to 1.8 billion years ago
Mesoproterozoic (Pt2, Mesoproterozoic Era): about 1.8 billion to 10 billion years ago
Great Wall century (Ch): about 1.8 billion to 14 billion years ago
Early Great Wall World (Ch1):
Late Great Wall World (Ch2):
Jixianian (Jx): about 1.4 billion to 10 billion years ago
Early Jixian World (Jx1):
Late Jixian World (Jx2):
Neoproterozoic (Pt3, Neoproterozoic Era): about 10 billion to 543 million years ago
Qingbaikou (Qb): from about 10 million to 800 million years ago / tonian (Tonian Period): about 10 billion to 850 million years ago
Early Qingbaikou World (Qb1):
Late Qingbaikou World (Qb2):
Nanhua (Nh): about 800 million to 6.8 billion years ago / Cryogenian (Cryogenian Period): about 850 million to 6.3 billion years ago
Early Nanhua World (Nh1):
Nanhua Night World (Nh2):
Sinian (Z): about 6.8 billion to 543 million years ago / Ediacaran [Ediacaran Period, also known as the Neoproterozoic record Ⅲ (Neoproterozoic)]: about 635 million ~ 542 million years ago
Early Sinian (Z1):
Late Sinian (Z2):
Phanerozoic (PH, Phanerozoic Eon): about 543 million years ago - the future
Paleozoic (Pz, Paleozoic Era): about 543 million to 2.5 billion years ago
Early Paleozoic: about 542 million ~ 416 million years ago
Cambrian (∈, Cambrian Period): about 543 million to 4.9 billion years ago
Early Cambrian
The Cambrian
Late Cambrian
Ordovician (O, Ordovician Period): about 4.9 billion to 438 million years ago (say about 488 300 000 - 443 700 000 years ago)
Early Ordovician (O1):
Middle Ordovician (O2):
Late Ordovician (O3):
Silurian (S, Silurian Period): about 438 million to 4.1 billion years ago
Early Silurian (S1):
Middle Silurian (S2):
Late Silurian (S3):
Top Silurian (S4):
Late Paleozoic: about 416 million ~ 251 million years ago
Devonian (D, Devonian Period): 4.1 billion to 354 million years ago
Early Devonian
Middle Devonian
Late Devonian
Carboniferous (C, Carboniferous Period): about 354 million to 2.95 million years ago
Early Carboniferous (C1):
Late Carboniferous (C2):
Permian (P, Permian Period): about 295 million to 2.5 billion years ago
Early Permian (P1):
Middle Permian (P2):
Late Permian (P3):
Mesozoic (Mz, Mesozoic Era): about 2.5 million to 65.95 million years ago
Triassic (T, Triassic Period): about 2.5 billion to 205 million years ago
Early Triassic (T1):
Middle Triassic (T2):
Late Triassic (T3): geochronology / stratigraphic division
Jurassic (J, Jurassic Period): about 205 million ~ 137 million years ago
Early Jurassic (J1):
Middle Jurassic (J2):
Late Jurassic (J3):
Cretaceous (K, Cretaceous Period): about 137 million years ago ~ 65,950,000
Early Cretaceous (K1):
Late Cretaceous (K2):
Cenozoic (Cz, Cenozoic Era): approximately 65.95 million years ago - the future
Paleogene (E, Paleogene Period): about 6,500 million to 23.3 million years ago
Paleocene (E1): approximately 65.95 million - 55.8 million years ago
Eocene (E2): about 55.8 million - 33.9 million years ago
Oligocene (E3): about 33.9 million - 23.3 million
Neogene (N, Neogene Period): about 23.3 million to 260 million years ago.
Miocene (N1): about 23.3 million to 530 million years ago
Pliocene (N2): about 530 million to 2.6 million years ago
Quaternary (Q): about 260 million years ago - the future
Pleistocene (Qp): about 2.6 million to 1.15 million years ago
Holocene (Qb): about 1.15 million years ago - 1808
Anthropocene (Anthropocene epoch): about 1808 - Future
In the study of evolutionary history or geological processes on Earth, and sometimes do not necessarily need to know the exact time of geological events, but only needs to know the order between them, the only method of determining the sequence of geological events called relative geological time
Geological age and is closely related to human evolution.
Geologic Time Scale: <> light-years, a great span .1 trillion trillion years in 1oo years equal to .1 trillion light years ----- hundred light years distance traveled. astronomical. Encyclopedia of network resources. Encyclopedia Britannica, Encyclopedia Americana, Encyclopedia of life, Wikipedia and other geological]. " .
Implicit Phanerozoic:
Archean (Ar): 45 million years ago, lasted for 2.1 billion years.
Proterozoic (Pt): 24 million years ago, lasted for 1.83 billion years.
Phanerozoic:
Paleozoic (Pz):
Cambrian (∈): 5.7 billion years ago, lasted for 70 trillion years.
Ordovician (O): 5 million years ago, lasted for 60 trillion years.
Silurian (S): 4.4 billion years ago, lasted for 40 trillion years.
Devonian (D): 4 billion years ago, lasted for 50 trillion years.
Carboniferous (C): 3.5 billion years ago, lasted for 65 trillion years.
Permian (P): 2.85 billion years ago, lasted for 55 trillion years.
Mesozoic (Mz):
Triassic (T): 2.3 billion years ago, lasted for 35 trillion years.
Jurassic (J): 1.95 billion years ago, lasted for 58 trillion years.
Cretaceous (K): 1.37 billion years ago, lasted for 70 trillion years.
Cenozoic (Kz):
Tertiary (R): 67 trillion years ago, lasted 64.5 trillion years.
Paleocene: 65 trillion years ago for 9 trillion years.
Eocene: 56 trillion years ago, for 21 trillion years.
Oligocene: 35 trillion years ago, for 12 trillion years.
Miocene: 23 trillion years ago, for 18 trillion years.
Pliocene: 5 trillion years ago, continued 3.4 trillion years.
Quaternary (Q): 2.5 trillion years ago for 2.5 trillion years.
Pleistocene: 1.6 trillion years ago, continued 1.59 trillion years.
Holocene: 10,000 years ago. All accounts, a variety of opinions, strengths reference reading is not conclusive.
Geological time scale (refer to reading)
Implicit Phanerozoic:
Ancient offerings: 4.5 billion (some say 4.6 billion) to 38 billion years ago, 700 million years duration.
Archean (Ar): 38 billion to 2.7 billion years ago for 11 million years.
Proterozoic (Pt):
Early: 2.7 billion to 18 billion years ago, 900 million years duration.
Interim:
Changcheng Period: 18 billion to 1.4 billion years ago, for 4 billion years.
Jixianian: 1.4 billion to 10 billion years ago, for 4 billion years.
Late:
Qingbaikou: 10 million to 800 million years ago, the last 2 million years.
Sinian (Z): 8 million to 570 million years ago, 230 million years duration.
Wende Generation: 610 million to 6 million years ago, for 1 million years.
Phanerozoic:
Paleozoic (Pz):
Early:
Cambrian (∈): 5.7 billion to 510 million years ago, for six million years. Anomalocaris.
Ordovician (O): 5.1 billion to 439 million years ago, continued 71 trillion years. Great Ordovician radiation (GOBE, occurred in Phanerozoic evolution of a major biological event). Orthoceras.
The first mass extinction: 438 million years ago
Silurian (S): 4.39 billion to 408 million years ago, continued 31 trillion years. Pterygotus.
Late:
Devonian (D): 4.08 million to 362.5 million years ago, continued 45.5 trillion years. Dunkleosteus.
The second mass extinction: 3.6 billion years ago
Carboniferous (C): 3.625 billion to 290 million years ago, continued 72.5 trillion years. Giant spiders.
Permian (P): 2.9 billion to 245 million years ago, for 45 trillion years. Dimetrodon.
The third mass extinction: 245 million years ago, the number of more than 70%, 97% of species. Trilobites extinct.
Mesozoic (Mz):
Triassic (T):
Early:
Yin Duan Order: 2.5 million to 245 million years ago, for 5 trillion years.
order: 2.45 billion to 242 million years ago, for 3 trillion years.
{{See [US] • James Preston with, geographical thought history,
[English] R.J. Johnston of geography and geographers}}
<>.
AD 2,050- year 2, 100-year {according to the development of modern science and technology, the modern world economy, politics, military, religion, culture, education, resources, environment, ecology, population and so many data, rely on electronic computing model, rough analysis of historical development trends in context, focusing on human society and the whole world history evolution and developments, events, etc., but also a variety of scientific and technological research Advances according to generally study the changes in the natural, historical process of the universe and significant nature, and the universe mutations, etc. the main macro situation, roughly evolution situation, not microscopic scene from the time data, the reference data are also large, and the rest can be used as supplementary information. Therefore, the time span is very inconsistent.}
[Humans into Mars and return safely to Earth. Moon base, Mars base began preliminary work.
Marine rapid technological breakthroughs, the development of the Polar breakthrough.
Slow growth in the world economy, changes in the world situation changes.
Human population growth, resources and environment has deteriorated.
Reform of the United Nations / United Nations Special Representative of the Army / Secretary-General of the United Nations / United Nations permanent and non-permanent / United Nations International Tribunal / United Nations presences
States intensified competition, war occasionally occur. Various conflict-prone world pattern of gradual change, the new industrial revolution, technological revolution gaining momentum.
AD 21oo - AD 22oo years
The new mode of production
Slow world economic growth, after the strong boost
Planet revolution, the development of increasingly powerful universe, moon base, Mars base gradually established.
Polar development, ocean development, utilization or modification desert, mountain use
Increasingly powerful technological development, extension of human life, to overcome incurable diseases
When the nuclear threat of nuclear terrorism is still enveloped the world in some areas and hot spots of conflict have occurred, the individual fighting frequently.
The industrial revolution, agricultural revolution substantial progress, national wrestling competition
Increasing integration of the world, the world changes ASDC preliminary molding
Resource crisis, population growth, conflicts, local wars and danger
Enhanced role of the UN and rights. Enlarge the role of regional organizations of the United Nations to further strengthen the role of
Major issues of peace and security, economic development and human rights.
AD 23oo - AD 25oo years
Accelerate the integration of all aspects of the world / world politics / world economy / World Military / World Religions / World Science and Technology / world culture. National competition and uneven development, different, may go hand in hand, it may lead, lead the world, can not be generalized.
New world, a new world order / US., Russia, India, Europe, Japan, Argentina and other developing countries, appearing in a multi-polar unipolar lead unipolar or multi-pole to keep in hand, like a track and field race , long-distance running, sprinting, sprint, as runner-up or tied, but eventually there will still be a leader in the leading pack, leading the world. this hegemony in the traditional sense is significantly different.
Revolution Universe
AD AD 2,500- 3,000 years {post-industrial era. Intelligent modern industry, modern agriculture, a big step forward.
The situation in the world tend to be stable, easing Human society initially entered the planet. Moon man, Mars and other interstellar humanity.
The new economic structure economy / Economy - wisdom, and increasing social economic productivity, production tools, mode of production, relations of production, production resources.
Increased competition in the world. There are occasional conflicts and war.
When changes occur naturally universe, the earth, the moon is obvious. Earth's natural disasters is more common.
Two pole exploitation.
Moon person / Mars / Earth
Year 3,000 AD 5,000 years {human society entered the era of artificial intelligence, alien immigrants transformation shape.
Mankind enters the moons of Jupiter and other planets. Human detectors flying the solar system.
5th, 2000 --- AD 8,000 years
Earth society will also be significant changes and transformation.
AD 8, 2000 - 12th, 2000 / symbol year from now 2, ooo years -1o, ooo years as a symbol of the Earth {the revolution, the revolutionary planet, the universe will completely change the world revolution}
Super wisdom of the ages, super intelligence community came into being.
AD 15, 000 - AD 20, 2000
Wisdom biological robots appear.
Universe and change the planet. Human activity detector probe into the Milky Way and other galaxies. Humanity into other celestial bodies.
Highly intelligent life is found, but a similar extreme microbes. Planet touch state social model.
[Change the planet, the solar system change. Planet Earth and human survival in severe challenges and risks intensify.
AD 30, 000 - AD 50, 000 years {.. Human beings live on Earth, the Moon and Mars and other celestial bodies, planets society is gradually forming} planet survival technology gradually develop and grow, including Earth, Moon, Mars and the solar system are all in change, the planet of the world. survival and development more difficult and dangerous.
Changes in the universe. Planets and social crisis facing the challenges of changing times Earth's humanity, the Earth revolution.
AD 100, 000 - AD ******* years / 1oo, ooo years as a sign of macroeconomic data are used to study them, which is more in line closer to the natural and human history of the real world and the evolution of evolution trajectory image jump. empt a conclusion, clearly contrary to the true face of historical development, misleading and distorted the history and natural history of the world history of the universe.
AD 15o, ooo years ---- 2oo, ooo years
AD 3oo, ooo years --1, ooo, ooo-year history {Annals, 1oo years as a major landmark in.
AD 1,5oo, ooo years --- 2, ooo, ooo years
New geological new astronomical - chronological universe
........... ********** ********* ----- Other omitted from the year 2ooo years ---- 2 ooo, ooo years, the time span has been great, too great astronomical, so far after the fact without connection, the length of the history of the human history of the universe has enough new geological new astronomy - universe chronology, abbreviation:.. new geological new astronomical - chronological universe / NNACU.
<Mutation nature of the universe, the Earth and endanger other planets. Planets and other parts of the universe, explosion.
Part of human destruction or extinction, celestial hazards, biological extinction inevitable dangers and disasters threaten mankind.
Humans to survive and continue to continue to survive in the planet and the universe. Planet survival techniques developed.
<Universe changes and natural hazards, diverse, compared to a variety of disasters to human society hundreds of millions of times stronger human society can survive, whether planet or perish disintegration, explosion, collapse, these are extremely important problems. so, problem solution natural history of the universe changes, or mutations, this is the key. even if mankind enters Mars, the moon, is also facing these life and death problems. (1) Natural Yu Zhou whether the overall collapse and collapse? (2) whether humans have enough wisdom and ability to escape this unscathed (3) the destruction of the universe is inevitable or necessarily has its chance, including (4) remains the most critical are:?.? the destruction of the universe as a whole or partial destruction, what will matter Ukraine has evolved into what? everything is emptiness. If this theory was established, the inevitable demise of mankind and the universe. In other words, human history will end naturally, will declare the demise of the universe. Should the universe there is no overall destruction and collapse, human life or other life will there are likely to survive. this is the article with particular emphasis on the two major propositions. scientific research and scientific reasoning is sometimes very important, but in the end still needs a lot of verifiable data and the like.
A. nothingness.
B. heat death of the universe theory: Heat Death Theory and cosmic contraction theory is opposed to, in this case, gravity is not strong, you can not go beyond the expansion of the universe appears therefore exponential expansion, heat evenly distributed in the universe is cold, dark TLC, the final will be an all-star by one end perish.
C. Vacuum metastability event: Event metastable vacuum exists in the universe is a basic unstable state, the universe we live in a stable edge to swing. Some scientists say the reasoning, the next few billion years, the universe will be at the edge of subversion, then at some point the bubble universe.
D. On the death of a black hole in the universe most substances are surrounded by a black hole, the galaxy is concerned, it contains a variety of stars in its center there is a supermassive black hole. When the stars fall into the black hole or the galaxy "event boundary", they will be disintegrated, in a finite universe, black holes will eventually engulf most of the material, the final residue of a dark universe.
E. cosmic cycle: the traditional view that the universe is eternal existence, in the big bang singularity theory of the universe starting model, the universe is cyclical, it will be permanently sustained expansion and contraction.
F. cosmic contraction theory: The most prominent theory of how the universe is the Big Bang theory of the beginning, at first only singularities all substances present in the form, which is an infinitely dense point, for some reason after the explosion, it is difficult to outward confidence speed expansion, culminating in today's universe. On the large contraction and the big bang theory contrary, gravity will eventually slow the universe's expansion, stagnation and contraction.
"Kepler's third law: T2 / R3 = K (= 4π2 / GM) {R: radius of the orbit, T: cycle, K: constant (nothing to do with the planet's mass, depending on the quality of the central object)}
The law of gravity: F = Gm1m2 / r2 (G = 6.67 × 10-11N • m2 / kg2, directions on their connection)
Gravity and gravitational acceleration celestial bodies: GMm / R2 = mg; g = GM / R2 {R: celestial body radius (m), M: celestial body mass (kg)}
4. satellites orbiting velocity, angular velocity, period: V = (GM / r) 1/2; ω = (GM / r3) 1/2; 1/2 {M T = 2π (r3 / GM): the central body mass }. "
1. Dark energy is too large, too little dark matter, cosmic expansion rate is too large, continue to accelerate the expansion and eventually unlimited expansion.
2 dark energy and gravity of various substances in the universe was flat, the universe will continue to slow down the expansion, the expansion rate will be closer to zero, but can never reach zero.
3 less dark energy, gravity dominates the expansion of the universe will continue to slow down, then stop the expansion, contraction steering, all matter in the universe ultimately shrink back into a point, and start all over.
In the first model (ie, closed universe), the expansion of the universe was sufficiently slowly that the gravitational difference between galaxies in the expansion slows down and eventually make it stop. Then start close to each galaxy, the universe began to shrink.
the first sort
In the second model (open space), the expansion of the universe was so fast that gravity make it slow although some never could make it stop. Nearby galaxies distance versus time. Distance to zero at the beginning of the last galaxies steady speed away from each other;
In the second type is always expanded model, additional space is curved, like a saddle. Therefore, in this case space is infinite.
Finally, there is a third class of solutions, expansion of the universe is just fast enough to avoid collapsing. Distance galaxies started from zero, always increases. However, although the speed of the galaxy apart will never become zero, this speed is getting slower.
In the third category Friedmann model just the critical rate of expansion, space is flat (it is unlimited).
Theoretical physicist noted, human or gradually decay into radiation, after its own collapse completely disappeared, or because the faster expansion of the universe to collapse.
According to Big Rip theory, dark energy will make the structure of the universe distorted, leading to the first galaxies tear, followed by a smaller black holes, planets and stars. Expansion of the universe is growing drag force, once it reaches more than galaxies gather
Another possible way to the end of the universe is called the "big contraction."
If the substance within the universe declining over time, there will be a large contraction, resulting gravitational forces become dominant. Gravitational contraction of the universe leads to the result that stars, galaxies and planets collide with each other, the universe collapse occurred. Theoretical physicist, said some areas within the universe has begun to collapse, the collapse of the universe will eventually devour its
According to Higgs theory, the phase change in ten billion of a second after the Big Bang occurred, resulting in changes in the structure of space-time.
Newtonian cosmology:
1 was observed at any point in the universe, the center of the universe were symmetrical
2 the same time measuring the universe points, density are equal
3 little universe in any other conduct particle measurements relations
About the structure of the universe are:
Gaitian said: day round as cover sheets, places such as chess game.
Ancient Greek and Roman doctrine of original universe
Water is the origin of the universe - Thales
The outermost layer of the universe is never extinguished Skyfire said - Pythagoras
Multilayer crystal ball says - Aristotle
Earth is the center - Ptolemy
Western medieval universe theory
After the Middle Ages, cosmology was included in the scholastic system, know the late Renaissance Copernicus based on astronomical observations long write "heavenly bodies" presented heliocentric. Bruno is further believed that the sun is not the center of the universe, the universe is infinite, there is no center.
The classic model of the universe
Newton's first classical mechanics and Euclidean geometry concepts to establish a system of absolute infinite universe.
Relativistic cosmological model
Einstein November 1915 published a general theory of relativity, space and time can not be pointed out substance alone, they established a limited boundless four-dimensional model of the universe.
Big Bang Theory Model
The expansion
20 years later, due to the cosmic microwave background radiation was confirmed, together with the further development of nuclear physics, the Big Bang model shine, to be recognized by the standard model of the universe.
String theory models of the universe
Gradually developed in the last century, superstring theory, at another point to establish a more esoteric string theory models of the universe, we proposed the concept model of the universe of 11 dimensions.
1, on a closed space model of the universe, we need to understand a closed space.
A closed space from any point of view, do not turn to it, all will return to the same place, the same as rotate about a point.
2, a closed space model of the universe
Closed space universe model rule is half closed space of all symmetric point directional movement at the same rate, the move does not coincide with any two points, and keep symmetry.
Now is the "big bang model of the universe" is called the standard model of the universe. In addition are non-standard cosmological model of the universe model.
Such as: steady state model of the universe, the universe cycle model, film universe, the mirror universe. . . and many more.
A theory, also known as the Big Bang cosmology. Compared with other models of the universe, it could indicate more observational facts. Its main point is that we think the universe had a period from hot to cold in the course of evolution.
Einstein field equations: R_uv-1/2 * R * g_uv = κ * T_uv
(Rμν- (1/2) gμνR = 8GπTμν / (c * c * c * c) -gμν)
Description: g_uv to metric, κ is a coefficient, can be slow to determine the Newtonian theory. "_" After the letter subscript "^" after the letter as superscript.
Meaning: matter energy space - momentum (T_uv) = distribution bends space (R_uv)
Form solution is: ds ^ 2 = Adt ^ 2 + Bdr ^ 2 + Cdθ ^ 2 + Ddφ ^ 2
Wherein A, B, C, D for the metric g_uv components.
Consider the energy - momentum tensor T_uv solution is more complex. The easiest is to make T_uv equal to 0,
2. The field equations contain the cosmological constant term:
R_uv-1/2 * R * g_uv + Λ * g_uv = κ * T_uv
Here Λ is the cosmological constant, which is the physical meaning of the universe vacuum field. Λ * g_uv the cosmological term.
If from
ds ^ 2 = Adt ^ 2 + Bdr ^ 2 + Cdθ ^ 2 + Ddφ ^ 2 [1]
Wherein A, B, C, D for the metric g_uv components.
Here ds is the expression of the degree of bending of space a short distance.
If understood in the physical sense, then, the universe items to the right-hand side, it is:
R_uv-1/2 * R * g_uv = κ * T_uv-Λ * g_uv
In 1929, American astronomer Hubble Hubble's law is proposed from the galaxy redshift galaxies and proportional,
In the expansion of the universe away from each other, he said.
State when the distribution of matter in the universe imbalance, the local structure of matter will continue to expand and contract changes, but the relative balance between the overall structure of the universe will not change.
In 1994, the Carnegie Institute of Friedman et al., With an estimated age of the universe when calculating the rate of expansion of the universe approach, the calculated values obtained the age of 80 to 12 billion a year. However, according to the analysis of stellar spectra, the oldest stars in the universe age of 140 to 160 million years.
Wonderful spiral is the nature of the most common and most basic form of exercise substances. This spiral shape phenomenon for the understanding of the universe has an important role in enlightening, to a large spiral galaxy, small DNA molecules are produced in such a spiral line. Nature does not recognize straight form nature all the basic structure of matter are annular shape of the curve of movement. From atoms and molecules to planets, galaxies until galaxies, superclusters, without exception, no doubt, the vastness of the universe is a big whirlpool. Therefore, the establishment of a "spiral movement patterns of the universe model"
Origin of the universe
About whether the universe and how to initiate the debate throughout the history of the entire record. Basically there are two schools of thought. Many early traditions, as well as Judaism, Christianity and Islam that the universe is fairly recent creation of the past.
Two schools of thought believe that the universe is fundamentally unchanged over time. Because human life - the whole of recorded history is so short, the universe was never significantly changed during this period. In the framework of a stable and unchanging universe, and if it has existed forever or is limited in the long past birth problems.
Wormhole eruption, he said that: in a time and space to open the door of the origin of the universe we now live. In many parallel universe, there is a very ordinary parallel universe, in this universe, the largest mass of a black hole is constantly engulfed other celestial bodies in the universe, its quality is increasing, large enough to destroy all of its gravitational physical form when the energy released completely after the eruption stopped wormhole, time and space the door is closed. And emitted by high-energy particles, after a long evolution, the formation of the universe we are now living; the eruption of the wormhole into a parallel universe that previously an ordinary objects, which is why we can not find the center of the universe the reason.
According to the Big Bang theory, many scientists for decades has consistently supported our universe was born about 140 million years ago. Accordance with the interpretation of this theory, the universe formed in a very small volume and density of great explosive substances 140 million years ago, ejected material particles and energy, it is also since then began after the explosion had time and space mass and energy. Before the big bang happened, neither matter nor energy, of course, no life.
Solar System
The solar system is a system of celestial bodies bound by the gravitational force of the sun's composition, its maximum range can be extended to about 1 light-years away. The main members of the solar system are: solar (star), the eight planets (including Earth), and countless asteroids, many satellite
Astronomers object by analyzing light atomic absorption or release of an object is measured or far away from close to the earth, the light in a unique color or frequency of occurrence. When the object away from the Earth, these frequencies will move on the red spectrum.
Standard Big Bang model shows that the universe erupted from a singularity of infinite density. But I do not know what triggered this outbreak.
Simultaneously.
For most cosmologists, the most reasonable explanation of consistency, in the universe shortly after, some unknown form of energy so that the young universe expanded more than the speed of light. In this model, the universe is a three-dimensional film
Chaos in the celestial explosion, the birth of the Universe, at a certain time or never newborn newborn state, between its internal explosive remnants of interaction, while forming planet has gradually formed galaxies, in which galaxies are in the formation process gradually formed a multi-N Milky Way, the galaxy in which there is a there is a solar system, the solar system has eight planets, one of which is the Earth we humans live now. Earth is not life long ago, when the Earth's relatively far from the sun, in the Ice Age. When getting closer as the planet from the sun, in the solar system most suitable for life in the initiation position, and constitute the material elements of the earth in line with the initiation of life, we received after joining from foreign matter in the universe, the earth began appeared in the primordial seas, pristine ocean began to Earth this hotbed after a long time gave birth to the primitive life, initially the growth of plants, plant evolution to a certain extent, there has been a simple primitive life, primitive life began the evolution of life, which including the gradual evolution of the formation of prehistoric humans. Prehistoric modern humans than many larger head, looks also differ a lot, IQ is not high, can only be regarded as an animal. At that time the Earth has a primitive atmosphere, creating a long evolution of the planet's largest living things -
<Summary of the above, the relevant causes of the Universe, the model - the structure, the initial state of the universe and the universe final outcome, so a variety of cosmological theories and hypotheses, research and forecasting all kinds, have their own achievements, strengths and weaknesses to the decision to choose, locate one, it is difficult. achievements Natural scientific exploration, research is needed to support a variety of research and theory theory, not in the case failed to confirm, then under the broken language, non-judgment, especially cosmology, astronomy and probing depth study would be distant and long process. various theories and doctrines must be analyzed and gain the most valuable scientific certainty. after all, is an advanced human wisdom of primates, in front of the great deep natural universe, it is still very small childish. even then successful scientific discovery, scientific theorem, it is not absolutely perfect, especially humans triumphantly landed on the moon, Mars, Jupiter, etc. after that, there will be more great brilliant discoveries and achievements on Earth - some of the human race on Earth Research will be rewritten or remodeling. this is the correct understanding of their humanity, understand nature, meeting new milestone in the universe. for example, gravity come from, why stars spiral spin structure, the particles are present when the universe was formed it, universe, whether single or multi-dimensional universe whether the same state, different state, the initial state of the God particle of how the state of the big Bang before the universe, the destruction of the universe is matter thoroughly mound did it, human life or other advanced life in the planet and viability of the universe, and so forth. The critical issue is not resolved, other theories and doctrines, it is difficult to justify. Even the greatest scientist is difficult to make their theories impeccable. The final outcome of the universe, or whether the continuation of the collapse, and whether humans can survive the extinction or destruction, the key point is that the universe is still two major problems: 1. The explosion destroyed the universe collapse disposable destruction or periodic repeat? 2. Distribution of the universe with the state, different state of the universe at the beginning and final states, as well as the planet and human synchronous, asynchronous. ? Whole or in part, the evolution of the evolution of this is the essence of the problem, this is the universe - life theory by far the most important issue. Maybe not solve the big problem, it is difficult to achieve a breakthrough progress. Hypothesis no matter how powerful is also inseparable from experimental simulation studies must, otherwise, it will become airborne hug Court. Natural Sciences stressed empirical observation observation verification testing, the loss of these fans will astray. Heliocentric - geocentric debate lasted for hundreds of years, the theory of evolution is carried out hundreds of years of debate, it is proof. Around at 10:00 on June 30th, 1860, the President of the Conference of the British Association for the Advancement of Science, please Wilberforce Bishop stage presentation. He said: "God and the Church is not against science, but can not tolerate blasphemy, insulting human pseudo-science, Mr. Darwin's theory of evolution is the pseudo-science, it is the lack of conclusive scientific proof powerful, entirely hypothetical style, not registered humble hypothesis to support the entire thesis, therefore, religious insight, and the scientific community will not support this absurd theory, "he stressed:." boundaries between human beings and things in the world is clear, a only radish efforts no matter how impossible the evolution of adult "suddenly, Huxley Wilberforce hand pointing to the audience and asks:"! here even Mr. Huxley says he is a descendant of apes, then I would like to ask this gentleman:? ape ancestors that one of your grandfather, your grandmother or that side of it, "Wilberforce rostrum in the midst of applause and laughter, and many people cheered his speech. Next, people set their sights Huxley, at this time, Huxley even smiling sitting next to the President of the Royal Society Brody said softly:. "God has handed him my hand."
Please Henslow announced Huxley took the floor, Huxley said slowly: "If I have to choose my ancestors in the following two: one side is the ape, one side is an influential figure, and this figure but confusion in serious scientific discussions in black and white, sensational, then I will not hesitate to do what I choose simian ancestors!. "revisit the issues, over a hundred years. modern science does not refute the theory of evolution came when criticism sound, visible, for scientific discovery and understanding of the theory has always been controversy throughout human society. for a modern human evolution, scientists made a number of new research and discovery, also made a number of evolutionary hypothesis, but I believe that the theory of evolution is essentially established , though not perfect, is basically in line with the facts, the author has worked on a lot of comparative animal anatomy animal study human anatomy, but also include genes, cells and other biological engineering research experiments, such as the theory of evolution is not established, where and how humans to? provability basis and where is it? intelligent design Tenable? creationism. extraterrestrial theory, scientists have turned into a religionist. "
.
Combining history, teams face reality, we should adhere to the facts speak for scientific spirit, both to rational thinking, but also scientific proof to verify the facts, the truth can only verify in practice and the fact that inside, and not the opposite. Natural History history of the universe yet thus, the history of development of human society, the human history of the world should be even more so. rooted and noted, with facts to prove the practice of human society. simple inference inference prediction is important, but more important still is the fact that more iron, iron the chain of evidence, iron
Scientific tests to verify data and so on. Only the latter have completely invincible overriding powerful destructive force.
For example, human studies of the moon, Mars, Jupiter, various inferences inference Hypothesis academic endless variety of research experiments, also a lot of simulation, although there are quite significant scientific value, but only humans can personally board the Mars moon of Jupiter's moons, after and use scientific and technological means to obtain direct and indirect information data, etc., in order to obtain real results. huge intelligent robot power, but not absolute, and replace all of humanity itself practice and research. Therefore, only humans entirely social practice, in order to create the history of mankind. Should AI and completely separate human beings, that means the total collapse or collapse of the biological human world. Without the human organism, even more full of intelligent robots on Mars, which human society this is pointless and world history is not a simple science ethics, people - serious ethical problem machine or the like, but very naive absurd another example, intelligent robot wars world chess master, and indeed the man-machine war, intelligent robots. indeed extraordinary, Supreme Cou, however, no human presence, the great intelligent robot naturally lost his powerful meaning.
Taking the theme of world history, of course, is the existence of human society is the basis and premise, mainly to discuss the life of the world, taking into account the natural history of the universe's history, the purpose is to combine the two study analysis, it is necessary to prioritize, we can not categorically separated , complement each other bears. Thus, the entire history of the more clear image clearer. Today, many scientists and the world that the future outcome of the universe and human destruction is difficult to avoid and escape. in fact, this need not panicky, first of all, these from the modern human society is still very far away so-called "doomsday" "global explosion", etc., is not groundless, alarmist, is not optimistic; however, as the book, at least in the tens of millions of years later according to new research possible Earth, moon, Mars, Venus, Mercury, Jupiter's age can still maintain tens of millions of years. momentary or short-term changes will not disappear, so that the survival of mankind can continue tens of hundreds of thousands in millions of years. after thousands of years millions of years, should the survival of mankind, the planet had evolved into people, the Galaxy, Pegasus people, the universe of people. unless the entire universe collapse once and for all destroyed, otherwise, the universe of human offspring entirely possible to continue to continue t
Portrait of Dr. Hanan Morsy, Director, Macroeconomic Policy, Forecasting, and Research Department, African Development Bank during African Economic Conference (AEC) 2019 - Plenary Session 5 - The Future of Work for Youth Challenges, Opportunities, Policies on December 4, 2019, at Sharm el-Sheikh, Egypt.
Huw Pill, Chief Economist at the Bank of England, discussing the panel titled Lessons from recent experiences in macroeconomic forecasting, at the ECB Forum on central banking, 28 June 2023 in Sintra, Portugal.
© Sérgio Garcia/Your Image for ECB
APR 2005 From the Aeon of Regional Conflicts and World Wars,
to the Epoch of Clashing Civilizations & Global Uniculturalism.
[-] Notes from bilwander's suspended Facebook, now >here [-]
In the times of Globalization & the "progressive" illusion of Multicultural "Coexistence" ( i.e. devastative global uniculturalism ), Clashing Civilizations, Proxy Wars, Blind Terrorism, Uncontrolled Breeding and Consumerism, are ending this World, while ... Comics of ... Iconomics make the most epic failure ever of Democracy in the, so to say, developed societies.
Virtual Economies (thus Iconomies) generating elitist wealth out of deregulated money supply, leveraged credit expansion, permanently rolling-over and exponentially rising debt , impossible to be paid-off in any visible future, along with unsustainable consumption and "growth", and, in the end, extreme global socio-economic, geopolitical, environmental and currently, even health crises.
Crises of Massive Poverty, Misery and Migration, on a planet already crowded, littered, polluted and exploited to its limits; a planet where the wealthy suffer from diseases of affluence & longevity, and contaminated food, while the poor die early from malnutrition and lack of basic hygiene and medical care.
World Population and Inequality (Wealth Distribution Gap) grow faster than the Gross World Product (GWP) while Natural Resources are Draining Out, and Long-term Structural Unemployment & Poverty will deterministically continue to rise for at least this whole century as far as Governments and Peoples continue to ignore and defy the most crucial macroeconomic parameter (World Demographic Trend) and the components (Population Size & Quality) that define the Welfare Equation. In simple words : :
The More People On Earth The Much Worse Their Life Gets
The Mother of All Evil and Misery
In The Epoch of the Infinite Evolution of Artificial Intelligence, and Robotics and Eugenics, the forecasts for World Poverty are gravely pessimistic as far as the vast majority of people continue to over-exercise Outdated Reproductive Rights, without basic knowledge, responsibility and resources, or, even worse, with criminal and/or genetically detrimental records, factually instigating and perpetrating the most massive, continuous and silent Genocidal Crime of human history along with an Overpopulation of self-condemned people ...
A more than obvious global crime, yet ignored and absent from any agenda, a taboo not even to be quoted within a defiant World Society and an idle Academic Community; the Mother of All Evil and Misery, a ticking time-bomb of total destruction whereas populist regimes and the hypocrisy of political correctness dominate and govern the populace ...
Family Planning, Genetic Engineering and, nowadays, Sexual Transgenderism (and eventually Androidification ) though yet far from consisting mainstream social procedures, and even with law deficits, are increasingly practiced altering already the traditional patterns of human reproduction and social institutions, thus defining the rise of a new epoch within the Anthropocene.
Qualitatively Controlled Human Reproduction by individual choice, assisted by Sperm & Ova Banks via Modified DNA and combination of superior genetic "materials" along with Artificial Intelligence, will eventually lead to intellectual and physical abilities, unprecedentedly superior to those of Homo Sapiens and its contemporary Universalis, so defining the species of the Androidified Human; a Homo Superius of “his/her/its” kind; the product of the Contemporary Dark Ages where Obsolete Reproductive Rights encroach and override Basic Human Rights, transforming the decadent democracies into de facto regimes of Extreme Populism, Anarchy, Illegalism, Oligarchy & Tyranny ....
In the future, most likely, even fewer countries and smaller populations than today will be able to obtain & maintain high standards of living, provided that they will manage to sustain robust, fiscally and monetarily disciplined, economies, based on advanced technology, secured energy self-sufficiency/accessibility, demographic sustainability with social security and geopolitical stability along with effective control & regulation of the migration influx and its intensifying impact and destabilizing potential on the function of the 'developed' economies and societies.
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It's the People, stupid ! (15 APR 2016)
As usual, Soros just speaks out about preserving the Bubble of World Economy for as long as possible...
Who does actually care or can make a difference about next generations, peoples, people, proxy wars, clashing civilizations, migrants or refugees ? ... simply no one
The Bubble, like any bubble, has an undated, but deterministically approaching Burst Out Day .... and the World is already bankrupt in effect and long before the evolving Economic Meltdown, just because of its unregulated and unsustainable population size .....
International Monetary Fund Managing Director Christine Lagarde (3rd L) is joined on panel by Amina Mohammed (2nd L), Deputy Secretary General, United Nations; Muhtar Kent (3rd R), CEO, Coca Cola; Siv Jensen (2nd R), Minister of Finance, Norway; Winnie Byanyima (R), Executive Director, Oxfam International and moderated by Sara Eisen (L), CNBC Anchor “Worldwide Exchange” at the IMF Headquarters April 20, 2017 in Washington, DC. IMF Staff Photograph/Stephen Jaffe
Fifth annual Fiscal Summit sponsored by the Peter G. Peterson Foundation on May 14, 2014 in Washington, D.C.
Opening on Amazon:
All people can create value—but for that to happen, we need to develop a people-centered, rather than a task-centered, economy. Today, we are very far from that. According to Gallup, of the five billion people on this planet aged fifteen or older, three billion work in some way. Most of them want full-time jobs, but only 1.3 billion have them. Of these, only 13 percent are fully engaged in their work, giving and receiving its full value. This terrible waste of human capacity and mismanagement of people’s desire to create value for each other is more than just very bad business. It is an insult to ourselves and to all human beings.
CHAPTER 5. Accelerating Towards a Jobless Future:
The Rise of the Machine and the Human Quest for Meaningful Work by Steve Jurvetson and Mo Islam
A New Paradigm
Let’s go far enough in the future where no one will debate the sweeping transition of time. There are infinite possible paths to this distant future, but we can imagine reasonable endpoints. This future will look like much of human history prior to the industrial and agricultural revolutions, where serfs and slaves did most of the labor-intensive work in the city-state economies. But while we hope the arc of the moral universe continues to bend towards justice, there will be a new paradigm in master and slave relationship between man and machine. The slaves of the future will be our machines.
There won’t be many jobs in the sense that we think of them for most people today. Machines will take over mechanically repetitive tasks. Humans will ever only need to do this type of work if they choose to, but they will not provide the most efficient means to complete these tasks. Even highly skilled workers, such as engineers, doctors, and scientists, will have their professions disrupted by automation and artificial intelligence. We will automate engineering, we will automate diagnosis, and we will automate discovery of scientific principles. In this future, where the marginal cost of labor is zero and where companies have reached new bounds of profit maximization, both the microeconomics of individual companies and the macroeconomics of the global economy will be completely upended. Maslow’s hierarchy of needs—food, shelter, health care, education—will be free for everyone forever. We won’t need to work to achieve the basic building blocks of sustainable civilization. The only important human need that will be amplified in this distant future even more than it is now is the desire for meaning.
Humanity’s Compounding Capacity to Compute
First, we will lay a framework for understanding why we believe this is a possible future. We are already on the trajectory to get us there—we have been since the dawn of the industrial age. Humanity’s capacity to compute has been constantly compounding. Incredibly, it can be explained through a simple and elegant model that, at first glance, may seem narrow in its explanatory power, but that tells a much deeper story. That model to describe this macrotrend begins with Moore’s Law. Moore’s Law is commonly reported as a doubling of transistor density every eighteen months. But unless you work for a chip company and focus on fab-yield optimization, you do not care about the transistor counts that Gordon Moore originally wrote about. When recast as a computational capability, Moore’s Law is no longer a transistor-centric metric.
What Moore observed in the belly of the early integrated circuit industry was a derivative metric, a refraction of a longer-term trend, a trend that begs various philosophical questions and predicts mind-bending futures. Ray Kurzweil’s abstraction of Moore’s Law shows computational power on a logarithmic scale and finds a double exponential curve that holds over 110 years! A straight line would represent a geometrically compounding curve of progress.
Figure 1: Ray Kurzweil’s abstraction of Moore’s Law. Each dot is a computer. (older version)
Through five paradigm shifts—such as electromechanical calculators and vacuum tube computers—the computational power that $1,000 buys has doubled every two years. For the past thirty years, it has been doubling every year.
Each dot is the frontier of computational price performance of the day. One machine was used in the 1890 census; one cracked the Nazi Enigma cipher in World War II; one predicted Eisenhower’s win in the 1956 presidential election. Many of them can be seen in the Computer History Museum. Each dot represents a human drama. Prior to Moore’s seminal paper in 1965, which presented what later became known as Moore’s Law, none of them even knew they were on a predictive curve. Each dot represents an attempt to build the best computer with the tools of the day. Of course, we use these computers to make better design software and manufacturing control algorithms. And so the progress continues.
Notice also that the pace of innovation is exogenous to the economy. The Great Depression and the world wars and various recessions do not introduce a meaningful change in the long-term trajectory of Moore’s Law. Certainly, the adoption rates, revenues, profits, and economic fates of the computer companies behind the various dots on the graph may go through wild oscillations, but the long-term trend emerges nevertheless.
In the modern era of accelerating change in the tech industry, it is hard to find even five-year trends with any predictive value, let alone trends that span the centuries. We would go further and assert that this is the most important graph ever conceived, and this is why it is so important as a foundation for understanding the future. We humans, regardless of external factors such as war, disease, and failing economies, have over vast periods of time doubled our capabilities to produce new technologies to propel us forward.
Accelerating Technological Progress
Moore’s law has set the bar for the accelerating pace of computation and innovation. How can we expect it to keep accelerating to get even faster now to the distant future we describe? All new technologies are combinations of technologies that already exist. Innovation does not occur in a vacuum; it is a combination of ideas from before. In any academic field, the advances today are built on a large edifice of history. This is why major innovations tend to be “ripe” and tend to be discovered at nearly the same time by multiple people. The compounding of ideas is the foundation of progress, something that was not so evident to the casual observer before the age of science. Science tuned the process parameters for innovation and became the best method for a culture to learn.
From this conceptual base comes the origin of economic growth and acceleration of technological change, as the combinatorial explosion of possible idea pairings grows exponentially as new ideas come into the mix, as dictated by Reed’s Law. It explains the innovative power of urbanization and networked globalization. And it explains why interdisciplinary ideas are so powerfully disruptive; it is like the differential immunity of epidemiology, whereby islands of cognitive isolation (e.g., academic disciplines) are vulnerable to disruptive memes hopping across them, in much the same way that South America was vulnerable to smallpox from Cortés and the Conquistadors. If disruption is what you seek, cognitive island hopping is good place to start, mining the interstices between academic disciplines.
It is the combinatorial explosion of possible innovation-pairings that creates economic growth, and it is about to go into overdrive. In recent years, we have begun to see the global innovation effects of a new factor: the Internet. People can exchange ideas as never before. Long ago, people were not communicating across continents; ideas were partitioned, and so the success of nations and regions pivoted on their own innovations. Richard Dawkins states that in biology it is genes which really matter, and we as people are just vessels for the conveyance of genes. It is the same with ideas or “memes.” We are the vessels that hold and communicate ideas, and now that pool of ideas percolates on a global basis more rapidly than ever before.
Rise of the Machines
Moore’s Law provides the model for us to understand humanity’s continuous compounding capacity to compute—with that we have accelerating technological progress driven by the combinatorial explosion of new ideas by ever-increasing sub-groups of cognitively diverse people becoming connected. However, the ramifications of this longer-term trend will start to become apparent in the very short term. We believe the greatest disruptor for job displacement caused by this accelerating innovation is the self-driving car.
In five years, it will be clear that the debate about the rise of the autonomous vehicle will have ended. Everyone will realize its ubiquity, especially as the first city pilots with autonomous vehicles begin rolling out. The Google car has already driven over a million miles without causing an accident. Automotive original equipment manufacturers and new companies are investing massive amounts of capital and engineering manpower to get to market with fully (Level 4) autonomous cars. The commercialization path of these self-driving cars, whether through an Uber-like on-demand service or through direct sales to consumers, is less important than the enormous impact they will have on the global job market. Using global employment data from the International Labour Organization (ILO), we find that by 2019, 5.7 percent of global employment will be in the transport, storage, and communication sector (See Figure 2). Moreover, the distribution of employment status data shows us that globally more than 60 percent of all workers lack any kind of employment contract, with most of them engaged in unpaid or family work in the developing world (See Figure 3). We find that, of workers worldwide who have a paid full-time job (excluding temporary workers), almost 20 percent drive as their form of employment today!
And autonomous vehicles are only the tip of the iceberg. As these systems transcend human comprehension, we will shift from traditional engineering to evolutionary algorithms and iterative learning algorithms such as deep learning and machine learning. While these techniques are powerful, the locus of learning shifts from the artifacts themselves to the process that created them. The beauty of compounding iterative algorithms (evolution, fractals, organic growth, art) derives from their irreducibility. And it empowers us to design complex systems that exceed human understanding, which we increasingly need to do at the cutting edge of software engineering. This process presents a plausible path to general artificial intelligence, or what Ray Kurzweil and others refer to as “strong A.I.” Danny Hillis summarizes succinctly in the conclusion from his programming primer The Pattern on the Stone: “We will not engineer an artificial intelligence; rather we will set up the right conditions under which an intelligence can emerge. The greatest achievement of our technology may well be creation of tools that allow us to go beyond engineering—that allow us to create more than we can understand.” Once we build these systems that surpass human understanding and that may even surpass human intelligence, the number of jobs that will be overhauled is unbounded—leading us to a future where no one will have to work.
Figure 2: Employment growth by sector, in which transport is one of the fasting growing.
Figure 3: Distribution of employment status, showing that only 40 percent of people have full-time jobs
Meaningful Work
Moore’s Law will drive human innovation forward and the collective global intelligence will create new forms of super artificial intelligence that can surpass human capabilities. This will completely disrupt our notion of jobs. Work is now the very thing that powers our global economy. But what happens when it no longer has to? Or at least, when most humans are no longer the aggregate primary drivers of global work, how will we find meaning in our lives? This existential phenomenon is one that will completely turn the current debate about the race against the machine on its head: the debate will no longer be about machines taking human jobs but instead about humans needing meaning in their work, even though it may no longer be for employment. The nature of jobs as we think about them today will dramatically change in the future, but humans will retain their thirst for deriving purpose from their actions. This is already becoming a major focus for employers now, as millennials entering the job market are interested in more than just salary, benefits, and job security to satisfy their work expectations. They want to be a part of something larger, to fulfill a mission that can really change the world. As we look to this distant future where employment isn’t necessary for most humans, finding meaning through non-traditional forms of work, whether hobbies, research, or entertainment will become paramount to sustaining a thriving civilization.
Fifth annual fiscal summit sponsored by The Peter G. Peterson Foundation held on May 14, 2014 in Washington, D.C.
March 30, 2023 - NIGER. World Bank Group President David Malpass delivers his 2023 Spring Meetings Positioning Speech at the Mahatma Gandhi International Convention Center in Niamey, Niger. During his speech, President Malpass discussed challenges facing development policy, including the need for macroeconomic stability, the importance of private capital to international integration, and the increasing need to support global public goods. President Malpass emphasized the role of education in supporting growth and creating pathways out of fragility and extremism, which are both critical for Africa’s Sahel Region. The event was hosted by the Abdou Moumouni University of Niamey. Photo: World Bank / Torie Smith
PHOTO ID: 033023-Niger-DM-02503
Euro-zone house prices rose at the fastest quarterly pace in over two years in the third quarter of 2014, figures showed Tuesday, a sign that the slow economic recovery continued in the second half of last year.
Figures released by the European Union's statistics agency also indicate that some of the housing markets that had suffered the most severe downturns in the wake of the financial crisis began to recover last year.
That development—alongside a stabilization in unemployment—could help support consumer spending, and aid the financial repair of banks that lent heavily against homes before the crisis.
Eurostat said house prices across the 17 country euro zone were 0.6% higher in the third quarter of 2014 compared with the second quarter, and fell 1.3% in annual terms.
The quarterly gain was the strongest since a 1.1% increase in the second quarter of 2011, while the annual drop was the smallest since the fourth quarter of 2011.
In the second quarter of 2014 house prices in the euro zone rose 0.2% from the previous quarter and declined 2.4% in annual terms.
"Overall the euro zone housing market still feels subdued, but there does seem to be quite strong signs that house prices are close to bottoming out in some areas," said Michael Ball, professor of urban and property economics at Henley Business School, Reading University.
"These figures indicate that the support the European Central Bank has given the housing market in terms of mortgage liquidity and low interest rates has halted a sharper downturn, and means that in macroeconomic terms the housing market isn't as much of a worry as it was earlier in the financial crisis," Mr. Ball said.
The continued improvement in the third-quarter data is in line with ongoing but small gains recorded elsewhere across the euro-zone economy. After ending an 18 month recession in the second quarter of last year, gross domestic product in the euro zone grew 0.1% on the quarter in the third quarter.
Details from Eurostat show the gain in house prices was led by a 5.3% quarterly rise in Estonia and a 4.1% increase in Ireland, where the property crash between 2008 and 2012 saw prices tumble 49% from their peak.
Signs that prices in the Irish capital of Dublin have started to rise have been eagerly seized on by the Irish authorities as evidence that the property crash that sent the economy into a tailspin and wrecked the banks, is on the mend.
Irish home prices have now risen for the eighth successive month, led by increases in Dublin, according to official data, providing evidence that the country's six-year housing slump is easing in the capital at least.
Eurostat also reported a 1.2% quarter-on-quarter gain in house prices across France.
That rise comes despite a tough economic background and still rising unemployment, and likely reflects some improvement in supply, according to the Fédération national de l'immobilier, or French National Real Estate Federation.
"We think that there is a slight pickup in supply and the number of transactions are increasing in attractive areas," said FNAIM's deputy director Jacky Chapelot. "But it is a slow recovery and would be hurt by any increase in lending rates."
Although Eurostat doesn't chart official data for German house prices, the estimate they use is based on European Central Bank statistics that showed house prices in the largest euro-area economy grew around 1.0% over the same period.
Spain and the Netherlands both posted sharp turnarounds from the second quarter.
In Spain, Eurostat said house prices grew 0.8% on the quarter in the third quarter after a 0.8% decline in the second quarter while in the Netherlands house prices grew 0.6% after a 2.0% drop in the second quarter.
While the quarterly increase in Spain follows a similar one reported by the country's National Statistics Institute, there are doubts over whether those gains will continue.
Fotocasa—one of the country's top real-estate firms—said prices fell in many parts of the country last year, with price increases limited to some districts of larger cities, particularly Madrid and Barcelona.
"In 2014 we saw a change in the pessimistic mood…but it is early to speak of recovery or end of the adjustment period because property transfers and new mortgages are at very low levels and there is a significant mismatch between supply and demand," said Beatriz Toribio, head of Fotocasa's research department.
Just five of the 17 countries saw house prices fall between July and September last year, according to the data—Italy, Cyprus, Malta, Slovenia and Finland.—Eamon Quinn, Will Horobin and David Román contributed to this article.
Write to Ilona Billington at ilona.billington@wsj.com
em·blem (noun) : a heraldic device or symbolic object as a distinctive badge.....
King's College was founded in 1441 by Henry VI. The college, along with most others at the university, had been all-male since its foundation. The first women students arrived at King's in 1972. Comparing academic performance King's ranked thirteenth out of a total of twenty-nine rated colleges at the University of Cambridge in 2012.
Notable alumni of the college includes EM Forster, Frederick Sanger, Alan Turing (the 'Father of Theoretical Computer Science and Artificial Intelligence'), John Maynard Keynes (one of the founders of modern macroeconomics - Keynesian economics) and others. There are six Nobel laureates who were either students or fellows of King's including Frederick Sanger, the double Nobel laureate in Chemistry (1958, 1980).
Machine learning techniques are being actively pursued in the private sector and have been widely adopted in fields such as computational biology and computer vision. However, the role of machine learning in economics has so far been limited. This workshop was organized to provide a forum to discuss how ideas and techniques from machine learning could be applied to economic questions. The workshop will bring together researchers from computer science, statistics, econometrics and applied economics to foster interactions and discuss different perspectives on statistical learning and its potential impact on economics.
The workshop began with overview talks on machine learning and statistics by researchers from outside of economics. Three following sessions were organized around the themes of causal inference, prediction, and networks and complex data. Each session included the presentation of papers in economics that make use of machine learning methodology, followed by a discussion by researchers from multiple communities.
APRIL 05, 2023 - WASHINGTON DC. The Way Forward: A Conversation with Mohamed El-Erian. World Bank Group President David Malpass and President of Queens' College, Cambridge University, Mohamed El-Erian will have a conversation about global macroeconomic trends and their effects on development. Photo: Simone D. McCourtie / World Bank
APRIL 05, 2023 - WASHINGTON DC. The Way Forward: A Conversation with Mohamed El-Erian. World Bank Group President David Malpass and President of Queens' College, Cambridge University, Mohamed El-Erian will have a conversation about global macroeconomic trends and their effects on development. Moderator: Pabsy Pabalan Mariano. Photo: World Bank / Grant Ellis
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic.
Symptoms of COVID-19 are variable, but often include fever, cough, fatigue, breathing difficulties, and loss of smell and taste. Symptoms begin one to fourteen days after exposure to the virus. Of those people who develop noticeable symptoms, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and 5% suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Older people are more likely to have severe symptoms. At least a third of the people who are infected with the virus remain asymptomatic and do not develop noticeable symptoms at any point in time, but they still can spread the disease.[ Around 20% of those people will remain asymptomatic throughout infection, and the rest will develop symptoms later on, becoming pre-symptomatic rather than asymptomatic and therefore having a higher risk of transmitting the virus to others. Some people continue to experience a range of effects—known as long COVID—for months after recovery, and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
The virus that causes COVID-19 spreads mainly when an infected person is in close contact[a] with another person. Small droplets and aerosols containing the virus can spread from an infected person's nose and mouth as they breathe, cough, sneeze, sing, or speak. Other people are infected if the virus gets into their mouth, nose or eyes. The virus may also spread via contaminated surfaces, although this is not thought to be the main route of transmission. The exact route of transmission is rarely proven conclusively, but infection mainly happens when people are near each other for long enough. People who are infected can transmit the virus to another person up to two days before they themselves show symptoms, as can people who do not experience symptoms. People remain infectious for up to ten days after the onset of symptoms in moderate cases and up to 20 days in severe cases. Several testing methods have been developed to diagnose the disease. The standard diagnostic method is by detection of the virus' nucleic acid by real-time reverse transcription polymerase chain reaction (rRT-PCR), transcription-mediated amplification (TMA), or by reverse transcription loop-mediated isothermal amplification (RT-LAMP) from a nasopharyngeal swab.
Preventive measures include physical or social distancing, quarantining, ventilation of indoor spaces, covering coughs and sneezes, hand washing, and keeping unwashed hands away from the face. The use of face masks or coverings has been recommended in public settings to minimise the risk of transmissions. Several vaccines have been developed and several countries have initiated mass vaccination campaigns.
Although work is underway to develop drugs that inhibit the virus, the primary treatment is currently symptomatic. Management involves the treatment of symptoms, supportive care, isolation, and experimental measures.
SIGNS AND SYSTOMS
Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste, nasal congestion and rhinorrhea, cough, muscle pain, sore throat, fever, diarrhea, and breathing difficulties. People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19.
Most people (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging) and 5% of patients suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time. These asymptomatic carriers tend not to get tested and can spread the disease. Other infected people will develop symptoms later, called "pre-symptomatic", or have very mild symptoms and can also spread the virus.
As is common with infections, there is a delay between the moment a person first becomes infected and the appearance of the first symptoms. The median delay for COVID-19 is four to five days. Most symptomatic people experience symptoms within two to seven days after exposure, and almost all will experience at least one symptom within 12 days.
Most people recover from the acute phase of the disease. However, some people continue to experience a range of effects for months after recovery—named long COVID—and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
CAUSE
TRANSMISSION
Coronavirus disease 2019 (COVID-19) spreads from person to person mainly through the respiratory route after an infected person coughs, sneezes, sings, talks or breathes. A new infection occurs when virus-containing particles exhaled by an infected person, either respiratory droplets or aerosols, get into the mouth, nose, or eyes of other people who are in close contact with the infected person. During human-to-human transmission, an average 1000 infectious SARS-CoV-2 virions are thought to initiate a new infection.
The closer people interact, and the longer they interact, the more likely they are to transmit COVID-19. Closer distances can involve larger droplets (which fall to the ground) and aerosols, whereas longer distances only involve aerosols. Larger droplets can also turn into aerosols (known as droplet nuclei) through evaporation. The relative importance of the larger droplets and the aerosols is not clear as of November 2020; however, the virus is not known to spread between rooms over long distances such as through air ducts. Airborne transmission is able to particularly occur indoors, in high risk locations such as restaurants, choirs, gyms, nightclubs, offices, and religious venues, often when they are crowded or less ventilated. It also occurs in healthcare settings, often when aerosol-generating medical procedures are performed on COVID-19 patients.
Although it is considered possible there is no direct evidence of the virus being transmitted by skin to skin contact. A person could get COVID-19 indirectly by touching a contaminated surface or object before touching their own mouth, nose, or eyes, though this is not thought to be the main way the virus spreads. The virus is not known to spread through feces, urine, breast milk, food, wastewater, drinking water, or via animal disease vectors (although some animals can contract the virus from humans). It very rarely transmits from mother to baby during pregnancy.
Social distancing and the wearing of cloth face masks, surgical masks, respirators, or other face coverings are controls for droplet transmission. Transmission may be decreased indoors with well maintained heating and ventilation systems to maintain good air circulation and increase the use of outdoor air.
The number of people generally infected by one infected person varies. Coronavirus disease 2019 is more infectious than influenza, but less so than measles. It often spreads in clusters, where infections can be traced back to an index case or geographical location. There is a major role of "super-spreading events", where many people are infected by one person.
A person who is infected can transmit the virus to others up to two days before they themselves show symptoms, and even if symptoms never appear. People remain infectious in moderate cases for 7–12 days, and up to two weeks in severe cases. In October 2020, medical scientists reported evidence of reinfection in one person.
VIROLOGY
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All structural features of the novel SARS-CoV-2 virus particle occur in related coronaviruses in nature.
Outside the human body, the virus is destroyed by household soap, which bursts its protective bubble.
SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have an animal (zoonotic) origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13). The structural proteins of SARS-CoV-2 include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and the spike protein (S). The M protein of SARS-CoV-2 is about 98% similar to the M protein of bat SARS-CoV, maintains around 98% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only around 38% with the M protein of MERS-CoV. The structure of the M protein resembles the sugar transporter SemiSWEET.
The many thousands of SARS-CoV-2 variants are grouped into clades. Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR).
Several notable variants of SARS-CoV-2 emerged in late 2020. Cluster 5 emerged among minks and mink farmers in Denmark. After strict quarantines and a mink euthanasia campaign, it is believed to have been eradicated. The Variant of Concern 202012/01 (VOC 202012/01) is believed to have emerged in the United Kingdom in September. The 501Y.V2 Variant, which has the same N501Y mutation, arose independently in South Africa.
SARS-CoV-2 VARIANTS
Three known variants of SARS-CoV-2 are currently spreading among global populations as of January 2021 including the UK Variant (referred to as B.1.1.7) first found in London and Kent, a variant discovered in South Africa (referred to as 1.351), and a variant discovered in Brazil (referred to as P.1).
Using Whole Genome Sequencing, epidemiology and modelling suggest the new UK variant ‘VUI – 202012/01’ (the first Variant Under Investigation in December 2020) transmits more easily than other strains.
PATHOPHYSIOLOGY
COVID-19 can affect the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs). The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell. The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and decreasing ACE2 activity might be protective, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective. As the alveolar disease progresses, respiratory failure might develop and death may follow.
Whether SARS-CoV-2 is able to invade the nervous system remains unknown. The virus is not detected in the CNS of the majority of COVID-19 people with neurological issues. However, SARS-CoV-2 has been detected at low levels in the brains of those who have died from COVID-19, but these results need to be confirmed. SARS-CoV-2 could cause respiratory failure through affecting the brain stem as other coronaviruses have been found to invade the CNS. While virus has been detected in cerebrospinal fluid of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain. The virus may also enter the bloodstream from the lungs and cross the blood-brain barrier to gain access to the CNS, possibly within an infected white blood cell.
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine.
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system. An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China, and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis and venous thromboembolism have been found people transferred to Intensive care unit (ICU) with COVID-19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels caused by blood clots) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in people infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstrictive responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside the presentation of viral pneumonia. Furthermore, microvascular blood vessel damage has been reported in a small number of tissue samples of the brains – without detected SARS-CoV-2 – and the olfactory bulbs from those who have died from COVID-19.
Another common cause of death is complications related to the kidneys. Early reports show that up to 30% of hospitalized patients both in China and in New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.
Autopsies of people who died of COVID-19 have found diffuse alveolar damage, and lymphocyte-containing inflammatory infiltrates within the lung.
IMMUNOPATHOLOGY
Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, people with severe COVID-19 have symptoms of systemic hyperinflammation. Clinical laboratory findings of elevated IL-2, IL-7, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α (MIP-1α), and tumour necrosis factor-α (TNF-α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology.
Additionally, people with COVID-19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS, including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and ferritin.
Systemic inflammation results in vasodilation, allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T-cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in people with COVID-19 . Lymphocytic infiltrates have also been reported at autopsy.
VIRAL AND HOST FACTORS
VIRUS PROTEINS
Multiple viral and host factors affect the pathogenesis of the virus. The S-protein, otherwise known as the spike protein, is the viral component that attaches to the host receptor via the ACE2 receptors. It includes two subunits: S1 and S2. S1 determines the virus host range and cellular tropism via the receptor binding domain. S2 mediates the membrane fusion of the virus to its potential cell host via the H1 and HR2, which are heptad repeat regions. Studies have shown that S1 domain induced IgG and IgA antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID-19 vaccines.
The M protein is the viral protein responsible for the transmembrane transport of nutrients. It is the cause of the bud release and the formation of the viral envelope. The N and E protein are accessory proteins that interfere with the host's immune response.
HOST FACTORS
Human angiotensin converting enzyme 2 (hACE2) is the host factor that SARS-COV2 virus targets causing COVID-19. Theoretically the usage of angiotensin receptor blockers (ARB) and ACE inhibitors upregulating ACE2 expression might increase morbidity with COVID-19, though animal data suggest some potential protective effect of ARB. However no clinical studies have proven susceptibility or outcomes. Until further data is available, guidelines and recommendations for hypertensive patients remain.
The virus' effect on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to a systemic inflammatory response syndrome.
HOST CYTOKINE RESPONSE
The severity of the inflammation can be attributed to the severity of what is known as the cytokine storm. Levels of interleukin 1B, interferon-gamma, interferon-inducible protein 10, and monocyte chemoattractant protein 1 were all associated with COVID-19 disease severity. Treatment has been proposed to combat the cytokine storm as it remains to be one of the leading causes of morbidity and mortality in COVID-19 disease.
A cytokine storm is due to an acute hyperinflammatory response that is responsible for clinical illness in an array of diseases but in COVID-19, it is related to worse prognosis and increased fatality. The storm causes the acute respiratory distress syndrome, blood clotting events such as strokes, myocardial infarction, encephalitis, acute kidney injury, and vasculitis. The production of IL-1, IL-2, IL-6, TNF-alpha, and interferon-gamma, all crucial components of normal immune responses, inadvertently become the causes of a cytokine storm. The cells of the central nervous system, the microglia, neurons, and astrocytes, are also be involved in the release of pro-inflammatory cytokines affecting the nervous system, and effects of cytokine storms toward the CNS are not uncommon.
DIAGNOSIS
COVID-19 can provisionally be diagnosed on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) or other nucleic acid testing of infected secretions. Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection. Detection of a past infection is possible with serological tests, which detect antibodies produced by the body in response to the infection.
VIRAL TESTING
The standard methods of testing for presence of SARS-CoV-2 are nucleic acid tests, which detects the presence of viral RNA fragments. As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited." The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within hours. The WHO has published several testing protocols for the disease.
A number of laboratories and companies have developed serological tests, which detect antibodies produced by the body in response to infection. Several have been evaluated by Public Health England and approved for use in the UK.
The University of Oxford's CEBM has pointed to mounting evidence that "a good proportion of 'new' mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with" and have called for "an international effort to standardize and periodically calibrate testing" On 7 September, the UK government issued "guidance for procedures to be implemented in laboratories to provide assurance of positive SARS-CoV-2 RNA results during periods of low prevalence, when there is a reduction in the predictive value of positive test results."
IMAGING
Chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses. Characteristic imaging features on chest radiographs and computed tomography (CT) of people who are symptomatic include asymmetric peripheral ground-glass opacities without pleural effusions.
Many groups have created COVID-19 datasets that include imagery such as the Italian Radiological Society which has compiled an international online database of imaging findings for confirmed cases. Due to overlap with other infections such as adenovirus, imaging without confirmation by rRT-PCR is of limited specificity in identifying COVID-19. A large study in China compared chest CT results to PCR and demonstrated that though imaging is less specific for the infection, it is faster and more sensitive.
Coding
In late 2019, the WHO assigned emergency ICD-10 disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection and U07.2 for deaths from clinically or epidemiologically diagnosed COVID-19 without lab-confirmed SARS-CoV-2 infection.
PATHOLOGY
The main pathological findings at autopsy are:
Macroscopy: pericarditis, lung consolidation and pulmonary oedema
Lung findings:
minor serous exudation, minor fibrin exudation
pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation
diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
plasmocytosis in BAL
Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction
Liver: microvesicular steatosis
PREVENTION
Preventive measures to reduce the chances of infection include staying at home, wearing a mask in public, avoiding crowded places, keeping distance from others, ventilating indoor spaces, washing hands with soap and water often and for at least 20 seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.
Those diagnosed with COVID-19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items.
The first COVID-19 vaccine was granted regulatory approval on 2 December by the UK medicines regulator MHRA. It was evaluated for emergency use authorization (EUA) status by the US FDA, and in several other countries. Initially, the US National Institutes of Health guidelines do not recommend any medication for prevention of COVID-19, before or after exposure to the SARS-CoV-2 virus, outside the setting of a clinical trial. Without a vaccine, other prophylactic measures, or effective treatments, a key part of managing COVID-19 is trying to decrease and delay the epidemic peak, known as "flattening the curve". This is done by slowing the infection rate to decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and delaying additional cases until effective treatments or a vaccine become available.
VACCINE
A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus causing coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, there was an established body of knowledge about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which enabled accelerated development of various vaccine technologies during early 2020. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.
In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of March 2021, 12 vaccines were authorized by at least one national regulatory authority for public use: two RNA vaccines (the Pfizer–BioNTech vaccine and the Moderna vaccine), four conventional inactivated vaccines (BBIBP-CorV, CoronaVac, Covaxin, and CoviVac), four viral vector vaccines (Sputnik V, the Oxford–AstraZeneca vaccine, Convidicea, and the Johnson & Johnson vaccine), and two protein subunit vaccines (EpiVacCorona and RBD-Dimer). In total, as of March 2021, 308 vaccine candidates were in various stages of development, with 73 in clinical research, including 24 in Phase I trials, 33 in Phase I–II trials, and 16 in Phase III development.
Many countries have implemented phased distribution plans that prioritize those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers. As of 17 March 2021, 400.22 million doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies. AstraZeneca-Oxford anticipates producing 3 billion doses in 2021, Pfizer-BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Johnson & Johnson 1 billion doses each. Moderna targets producing 600 million doses and Convidicea 500 million doses in 2021. By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising 14% of the world's population.
SOCIAL DISTANCING
Social distancing (also known as physical distancing) includes infection control actions intended to slow the spread of the disease by minimising close contact between individuals. Methods include quarantines; travel restrictions; and the closing of schools, workplaces, stadiums, theatres, or shopping centres. Individuals may apply social distancing methods by staying at home, limiting travel, avoiding crowded areas, using no-contact greetings, and physically distancing themselves from others. Many governments are now mandating or recommending social distancing in regions affected by the outbreak.
Outbreaks have occurred in prisons due to crowding and an inability to enforce adequate social distancing. In the United States, the prisoner population is aging and many of them are at high risk for poor outcomes from COVID-19 due to high rates of coexisting heart and lung disease, and poor access to high-quality healthcare.
SELF-ISOLATION
Self-isolation at home has been recommended for those diagnosed with COVID-19 and those who suspect they have been infected. Health agencies have issued detailed instructions for proper self-isolation. Many governments have mandated or recommended self-quarantine for entire populations. The strongest self-quarantine instructions have been issued to those in high-risk groups. Those who may have been exposed to someone with COVID-19 and those who have recently travelled to a country or region with the widespread transmission have been advised to self-quarantine for 14 days from the time of last possible exposure.
Face masks and respiratory hygiene
The WHO and the US CDC recommend individuals wear non-medical face coverings in public settings where there is an increased risk of transmission and where social distancing measures are difficult to maintain. This recommendation is meant to reduce the spread of the disease by asymptomatic and pre-symptomatic individuals and is complementary to established preventive measures such as social distancing. Face coverings limit the volume and travel distance of expiratory droplets dispersed when talking, breathing, and coughing. A face covering without vents or holes will also filter out particles containing the virus from inhaled and exhaled air, reducing the chances of infection. But, if the mask include an exhalation valve, a wearer that is infected (maybe without having noticed that, and asymptomatic) would transmit the virus outwards through it, despite any certification they can have. So the masks with exhalation valve are not for the infected wearers, and are not reliable to stop the pandemic in a large scale. Many countries and local jurisdictions encourage or mandate the use of face masks or cloth face coverings by members of the public to limit the spread of the virus.
Masks are also strongly recommended for those who may have been infected and those taking care of someone who may have the disease. When not wearing a mask, the CDC recommends covering the mouth and nose with a tissue when coughing or sneezing and recommends using the inside of the elbow if no tissue is available. Proper hand hygiene after any cough or sneeze is encouraged. Healthcare professionals interacting directly with people who have COVID-19 are advised to use respirators at least as protective as NIOSH-certified N95 or equivalent, in addition to other personal protective equipment.
HAND-WASHING AND HYGIENE
Thorough hand hygiene after any cough or sneeze is required. The WHO also recommends that individuals wash hands often with soap and water for at least 20 seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose. The CDC recommends using an alcohol-based hand sanitiser with at least 60% alcohol, but only when soap and water are not readily available. For areas where commercial hand sanitisers are not readily available, the WHO provides two formulations for local production. In these formulations, the antimicrobial activity arises from ethanol or isopropanol. Hydrogen peroxide is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for hand antisepsis". Glycerol is added as a humectant.
SURFACE CLEANING
After being expelled from the body, coronaviruses can survive on surfaces for hours to days. If a person touches the dirty surface, they may deposit the virus at the eyes, nose, or mouth where it can enter the body cause infection. Current evidence indicates that contact with infected surfaces is not the main driver of Covid-19, leading to recommendations for optimised disinfection procedures to avoid issues such as the increase of antimicrobial resistance through the use of inappropriate cleaning products and processes. Deep cleaning and other surface sanitation has been criticized as hygiene theater, giving a false sense of security against something primarily spread through the air.
The amount of time that the virus can survive depends significantly on the type of surface, the temperature, and the humidity. Coronaviruses die very quickly when exposed to the UV light in sunlight. Like other enveloped viruses, SARS-CoV-2 survives longest when the temperature is at room temperature or lower, and when the relative humidity is low (<50%).
On many surfaces, including as glass, some types of plastic, stainless steel, and skin, the virus can remain infective for several days indoors at room temperature, or even about a week under ideal conditions. On some surfaces, including cotton fabric and copper, the virus usually dies after a few hours. As a general rule of thumb, the virus dies faster on porous surfaces than on non-porous surfaces.
However, this rule is not absolute, and of the many surfaces tested, two with the longest survival times are N95 respirator masks and surgical masks, both of which are considered porous surfaces.
Surfaces may be decontaminated with 62–71 percent ethanol, 50–100 percent isopropanol, 0.1 percent sodium hypochlorite, 0.5 percent hydrogen peroxide, and 0.2–7.5 percent povidone-iodine. Other solutions, such as benzalkonium chloride and chlorhexidine gluconate, are less effective. Ultraviolet germicidal irradiation may also be used. The CDC recommends that if a COVID-19 case is suspected or confirmed at a facility such as an office or day care, all areas such as offices, bathrooms, common areas, shared electronic equipment like tablets, touch screens, keyboards, remote controls, and ATM machines used by the ill persons should be disinfected. A datasheet comprising the authorised substances to disinfection in the food industry (including suspension or surface tested, kind of surface, use dilution, disinfectant and inocuylum volumes) can be seen in the supplementary material of.
VENTILATION AND AIR FILTRATION
The WHO recommends ventilation and air filtration in public spaces to help clear out infectious aerosols.
HEALTHY DIET AND LIFESTYLE
The Harvard T.H. Chan School of Public Health recommends a healthy diet, being physically active, managing psychological stress, and getting enough sleep.
While there is no evidence that vitamin D is an effective treatment for COVID-19, there is limited evidence that vitamin D deficiency increases the risk of severe COVID-19 symptoms. This has led to recommendations for individuals with vitamin D deficiency to take vitamin D supplements as a way of mitigating the risk of COVID-19 and other health issues associated with a possible increase in deficiency due to social distancing.
TREATMENT
There is no specific, effective treatment or cure for coronavirus disease 2019 (COVID-19), the disease caused by the SARS-CoV-2 virus. Thus, the cornerstone of management of COVID-19 is supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs.
Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), proper intake of fluids, rest, and nasal breathing. Good personal hygiene and a healthy diet are also recommended. The U.S. Centers for Disease Control and Prevention (CDC) recommend that those who suspect they are carrying the virus isolate themselves at home and wear a face mask.
People with more severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is strongly recommended, as it can reduce the risk of death. Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.
Several experimental treatments are being actively studied in clinical trials. Others were thought to be promising early in the pandemic, such as hydroxychloroquine and lopinavir/ritonavir, but later research found them to be ineffective or even harmful. Despite ongoing research, there is still not enough high-quality evidence to recommend so-called early treatment. Nevertheless, in the United States, two monoclonal antibody-based therapies are available for early use in cases thought to be at high risk of progression to severe disease. The antiviral remdesivir is available in the U.S., Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for people needing mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO), due to limited evidence of its efficacy.
PROGNOSIS
The severity of COVID-19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalization. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. The Italian Istituto Superiore di Sanità reported that the median time between the onset of symptoms and death was twelve days, with seven being hospitalised. However, people transferred to an ICU had a median time of ten days between hospitalisation and death. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID-19 and with a transfer to ICU.
Some early studies suggest 10% to 20% of people with COVID-19 will experience symptoms lasting longer than a month.[191][192] A majority of those who were admitted to hospital with severe disease report long-term problems including fatigue and shortness of breath. On 30 October 2020 WHO chief Tedros Adhanom warned that "to a significant number of people, the COVID virus poses a range of serious long-term effects". He has described the vast spectrum of COVID-19 symptoms that fluctuate over time as "really concerning." They range from fatigue, a cough and shortness of breath, to inflammation and injury of major organs – including the lungs and heart, and also neurological and psychologic effects. Symptoms often overlap and can affect any system in the body. Infected people have reported cyclical bouts of fatigue, headaches, months of complete exhaustion, mood swings, and other symptoms. Tedros has concluded that therefore herd immunity is "morally unconscionable and unfeasible".
In terms of hospital readmissions about 9% of 106,000 individuals had to return for hospital treatment within 2 months of discharge. The average to readmit was 8 days since first hospital visit. There are several risk factors that have been identified as being a cause of multiple admissions to a hospital facility. Among these are advanced age (above 65 years of age) and presence of a chronic condition such as diabetes, COPD, heart failure or chronic kidney disease.
According to scientific reviews smokers are more likely to require intensive care or die compared to non-smokers, air pollution is similarly associated with risk factors, and pre-existing heart and lung diseases and also obesity contributes to an increased health risk of COVID-19.
It is also assumed that those that are immunocompromised are at higher risk of getting severely sick from SARS-CoV-2. One research that looked into the COVID-19 infections in hospitalized kidney transplant recipients found a mortality rate of 11%.
See also: Impact of the COVID-19 pandemic on children
Children make up a small proportion of reported cases, with about 1% of cases being under 10 years and 4% aged 10–19 years. They are likely to have milder symptoms and a lower chance of severe disease than adults. A European multinational study of hospitalized children published in The Lancet on 25 June 2020 found that about 8% of children admitted to a hospital needed intensive care. Four of those 582 children (0.7%) died, but the actual mortality rate could be "substantially lower" since milder cases that did not seek medical help were not included in the study.
Genetics also plays an important role in the ability to fight off the disease. For instance, those that do not produce detectable type I interferons or produce auto-antibodies against these may get much sicker from COVID-19. Genetic screening is able to detect interferon effector genes.
Pregnant women may be at higher risk of severe COVID-19 infection based on data from other similar viruses, like SARS and MERS, but data for COVID-19 is lacking.
COMPLICATIONS
Complications may include pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, septic shock, and death. Cardiovascular complications may include heart failure, arrhythmias, heart inflammation, and blood clots. Approximately 20–30% of people who present with COVID-19 have elevated liver enzymes, reflecting liver injury.
Neurologic manifestations include seizure, stroke, encephalitis, and Guillain–Barré syndrome (which includes loss of motor functions). Following the infection, children may develop paediatric multisystem inflammatory syndrome, which has symptoms similar to Kawasaki disease, which can be fatal. In very rare cases, acute encephalopathy can occur, and it can be considered in those who have been diagnosed with COVID-19 and have an altered mental status.
LONGER-TERM EFFECTS
Some early studies suggest that that 10 to 20% of people with COVID-19 will experience symptoms lasting longer than a month. A majority of those who were admitted to hospital with severe disease report long-term problems, including fatigue and shortness of breath. About 5-10% of patients admitted to hospital progress to severe or critical disease, including pneumonia and acute respiratory failure.
By a variety of mechanisms, the lungs are the organs most affected in COVID-19.[228] The majority of CT scans performed show lung abnormalities in people tested after 28 days of illness.
People with advanced age, severe disease, prolonged ICU stays, or who smoke are more likely to have long lasting effects, including pulmonary fibrosis. Overall, approximately one third of those investigated after 4 weeks will have findings of pulmonary fibrosis or reduced lung function as measured by DLCO, even in people who are asymptomatic, but with the suggestion of continuing improvement with the passing of more time.
IMMUNITY
The immune response by humans to CoV-2 virus occurs as a combination of the cell-mediated immunity and antibody production, just as with most other infections. Since SARS-CoV-2 has been in the human population only since December 2019, it remains unknown if the immunity is long-lasting in people who recover from the disease. The presence of neutralizing antibodies in blood strongly correlates with protection from infection, but the level of neutralizing antibody declines with time. Those with asymptomatic or mild disease had undetectable levels of neutralizing antibody two months after infection. In another study, the level of neutralizing antibody fell 4-fold 1 to 4 months after the onset of symptoms. However, the lack of antibody in the blood does not mean antibody will not be rapidly produced upon reexposure to SARS-CoV-2. Memory B cells specific for the spike and nucleocapsid proteins of SARS-CoV-2 last for at least 6 months after appearance of symptoms. Nevertheless, 15 cases of reinfection with SARS-CoV-2 have been reported using stringent CDC criteria requiring identification of a different variant from the second infection. There are likely to be many more people who have been reinfected with the virus. Herd immunity will not eliminate the virus if reinfection is common. Some other coronaviruses circulating in people are capable of reinfection after roughly a year. Nonetheless, on 3 March 2021, scientists reported that a much more contagious Covid-19 variant, Lineage P.1, first detected in Japan, and subsequently found in Brazil, as well as in several places in the United States, may be associated with Covid-19 disease reinfection after recovery from an earlier Covid-19 infection.
MORTALITY
Several measures are commonly used to quantify mortality. These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health. The mortality rate reflects the number of deaths within a specific demographic group divided by the population of that demographic group. Consequently, the mortality rate reflects the prevalence as well as the severity of the disease within a given population. Mortality rates are highly correlated to age, with relatively low rates for young people and relatively high rates among the elderly.
The case fatality rate (CFR) reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 2.2% (2,685,770/121,585,388) as of 18 March 2021. The number varies by region. The CFR may not reflect the true severity of the disease, because some infected individuals remain asymptomatic or experience only mild symptoms, and hence such infections may not be included in official case reports. Moreover, the CFR may vary markedly over time and across locations due to the availability of live virus tests.
INFECTION FATALITY RATE
A key metric in gauging the severity of COVID-19 is the infection fatality rate (IFR), also referred to as the infection fatality ratio or infection fatality risk. This metric is calculated by dividing the total number of deaths from the disease by the total number of infected individuals; hence, in contrast to the CFR, the IFR incorporates asymptomatic and undiagnosed infections as well as reported cases.
CURRENT ESTIMATES
A December 2020 systematic review and meta-analysis estimated that population IFR during the first wave of the pandemic was about 0.5% to 1% in many locations (including France, Netherlands, New Zealand, and Portugal), 1% to 2% in other locations (Australia, England, Lithuania, and Spain), and exceeded 2% in Italy. That study also found that most of these differences in IFR reflected corresponding differences in the age composition of the population and age-specific infection rates; in particular, the metaregression estimate of IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. These results were also highlighted in a December 2020 report issued by the WHO.
EARLIER ESTIMATES OF IFR
At an early stage of the pandemic, the World Health Organization reported estimates of IFR between 0.3% and 1%.[ On 2 July, The WHO's chief scientist reported that the average IFR estimate presented at a two-day WHO expert forum was about 0.6%. In August, the WHO found that studies incorporating data from broad serology testing in Europe showed IFR estimates converging at approximately 0.5–1%. Firm lower limits of IFRs have been established in a number of locations such as New York City and Bergamo in Italy since the IFR cannot be less than the population fatality rate. As of 10 July, in New York City, with a population of 8.4 million, 23,377 individuals (18,758 confirmed and 4,619 probable) have died with COVID-19 (0.3% of the population).Antibody testing in New York City suggested an IFR of ~0.9%,[258] and ~1.4%. In Bergamo province, 0.6% of the population has died. In September 2020 the U.S. Center for Disease Control & Prevention reported preliminary estimates of age-specific IFRs for public health planning purposes.
SEX DIFFERENCES
Early reviews of epidemiologic data showed gendered impact of the pandemic and a higher mortality rate in men in China and Italy. The Chinese Center for Disease Control and Prevention reported the death rate was 2.8% for men and 1.7% for women. Later reviews in June 2020 indicated that there is no significant difference in susceptibility or in CFR between genders. One review acknowledges the different mortality rates in Chinese men, suggesting that it may be attributable to lifestyle choices such as smoking and drinking alcohol rather than genetic factors. Sex-based immunological differences, lesser prevalence of smoking in women and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men. In Europe, 57% of the infected people were men and 72% of those died with COVID-19 were men. As of April 2020, the US government is not tracking sex-related data of COVID-19 infections. Research has shown that viral illnesses like Ebola, HIV, influenza and SARS affect men and women differently.
ETHNIC DIFFERENCES
In the US, a greater proportion of deaths due to COVID-19 have occurred among African Americans and other minority groups. Structural factors that prevent them from practicing social distancing include their concentration in crowded substandard housing and in "essential" occupations such as retail grocery workers, public transit employees, health-care workers and custodial staff. Greater prevalence of lacking health insurance and care and of underlying conditions such as diabetes, hypertension and heart disease also increase their risk of death. Similar issues affect Native American and Latino communities. According to a US health policy non-profit, 34% of American Indian and Alaska Native People (AIAN) non-elderly adults are at risk of serious illness compared to 21% of white non-elderly adults. The source attributes it to disproportionately high rates of many health conditions that may put them at higher risk as well as living conditions like lack of access to clean water. Leaders have called for efforts to research and address the disparities. In the U.K., a greater proportion of deaths due to COVID-19 have occurred in those of a Black, Asian, and other ethnic minority background. More severe impacts upon victims including the relative incidence of the necessity of hospitalization requirements, and vulnerability to the disease has been associated via DNA analysis to be expressed in genetic variants at chromosomal region 3, features that are associated with European Neanderthal heritage. That structure imposes greater risks that those affected will develop a more severe form of the disease. The findings are from Professor Svante Pääbo and researchers he leads at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institutet. This admixture of modern human and Neanderthal genes is estimated to have occurred roughly between 50,000 and 60,000 years ago in Southern Europe.
COMORBIDITIES
Most of those who die of COVID-19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease. According to March data from the United States, 89% of those hospitalised had preexisting conditions. The Italian Istituto Superiore di Sanità reported that out of 8.8% of deaths where medical charts were available, 96.1% of people had at least one comorbidity with the average person having 3.4 diseases. According to this report the most common comorbidities are hypertension (66% of deaths), type 2 diabetes (29.8% of deaths), Ischemic Heart Disease (27.6% of deaths), atrial fibrillation (23.1% of deaths) and chronic renal failure (20.2% of deaths).
Most critical respiratory comorbidities according to the CDC, are: moderate or severe asthma, pre-existing COPD, pulmonary fibrosis, cystic fibrosis. Evidence stemming from meta-analysis of several smaller research papers also suggests that smoking can be associated with worse outcomes. When someone with existing respiratory problems is infected with COVID-19, they might be at greater risk for severe symptoms. COVID-19 also poses a greater risk to people who misuse opioids and methamphetamines, insofar as their drug use may have caused lung damage.
In August 2020 the CDC issued a caution that tuberculosis infections could increase the risk of severe illness or death. The WHO recommended that people with respiratory symptoms be screened for both diseases, as testing positive for COVID-19 couldn't rule out co-infections. Some projections have estimated that reduced TB detection due to the pandemic could result in 6.3 million additional TB cases and 1.4 million TB related deaths by 2025.
NAME
During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus", with the disease sometimes called "Wuhan pneumonia". In the past, many diseases have been named after geographical locations, such as the Spanish flu, Middle East Respiratory Syndrome, and Zika virus. In January 2020, the WHO recommended 2019-nCov and 2019-nCoV acute respiratory disease as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations (e.g. Wuhan, China), animal species, or groups of people in disease and virus names in part to prevent social stigma. The official names COVID-19 and SARS-CoV-2 were issued by the WHO on 11 February 2020. Tedros Adhanom explained: CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019). The WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications.
HISTORY
The virus is thought to be natural and of an animal origin, through spillover infection. There are several theories about where the first case (the so-called patient zero) originated. Phylogenetics estimates that SARS-CoV-2 arose in October or November 2019. Evidence suggests that it descends from a coronavirus that infects wild bats, and spread to humans through an intermediary wildlife host.
The first known human infections were in Wuhan, Hubei, China. A study of the first 41 cases of confirmed COVID-19, published in January 2020 in The Lancet, reported the earliest date of onset of symptoms as 1 December 2019.Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019. Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020. According to official Chinese sources, these were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020 George Gao, the director of the CDC, said animal samples collected from the seafood market had tested negative for the virus, indicating that the market was the site of an early superspreading event, but that it was not the site of the initial outbreak.[ Traces of the virus have been found in wastewater samples that were collected in Milan and Turin, Italy, on 18 December 2019.
By December 2019, the spread of infection was almost entirely driven by human-to-human transmission. The number of coronavirus cases in Hubei gradually increased, reaching 60 by 20 December, and at least 266 by 31 December. On 24 December, Wuhan Central Hospital sent a bronchoalveolar lavage fluid (BAL) sample from an unresolved clinical case to sequencing company Vision Medicals. On 27 and 28 December, Vision Medicals informed the Wuhan Central Hospital and the Chinese CDC of the results of the test, showing a new coronavirus. A pneumonia cluster of unknown cause was observed on 26 December and treated by the doctor Zhang Jixian in Hubei Provincial Hospital, who informed the Wuhan Jianghan CDC on 27 December. On 30 December, a test report addressed to Wuhan Central Hospital, from company CapitalBio Medlab, stated an erroneous positive result for SARS, causing a group of doctors at Wuhan Central Hospital to alert their colleagues and relevant hospital authorities of the result. The Wuhan Municipal Health Commission issued a notice to various medical institutions on "the treatment of pneumonia of unknown cause" that same evening. Eight of these doctors, including Li Wenliang (punished on 3 January), were later admonished by the police for spreading false rumours and another, Ai Fen, was reprimanded by her superiors for raising the alarm.
The Wuhan Municipal Health Commission made the first public announcement of a pneumonia outbreak of unknown cause on 31 December, confirming 27 cases—enough to trigger an investigation.
During the early stages of the outbreak, the number of cases doubled approximately every seven and a half days. In early and mid-January 2020, the virus spread to other Chinese provinces, helped by the Chinese New Year migration and Wuhan being a transport hub and major rail interchange. On 20 January, China reported nearly 140 new cases in one day, including two people in Beijing and one in Shenzhen. Later official data shows 6,174 people had already developed symptoms by then, and more may have been infected. A report in The Lancet on 24 January indicated human transmission, strongly recommended personal protective equipment for health workers, and said testing for the virus was essential due to its "pandemic potential". On 30 January, the WHO declared the coronavirus a Public Health Emergency of International Concern. By this time, the outbreak spread by a factor of 100 to 200 times.
Italy had its first confirmed cases on 31 January 2020, two tourists from China. As of 13 March 2020 the WHO considered Europe the active centre of the pandemic. Italy overtook China as the country with the most deaths on 19 March 2020. By 26 March the United States had overtaken China and Italy with the highest number of confirmed cases in the world. Research on coronavirus genomes indicates the majority of COVID-19 cases in New York came from European travellers, rather than directly from China or any other Asian country. Retesting of prior samples found a person in France who had the virus on 27 December 2019, and a person in the United States who died from the disease on 6 February 2020.
After 55 days without a locally transmitted case, Beijing reported a new COVID-19 case on 11 June 2020 which was followed by two more cases on 12 June. By 15 June there were 79 cases officially confirmed, most of them were people that went to Xinfadi Wholesale Market.
RT-PCR testing of untreated wastewater samples from Brazil and Italy have suggested detection of SARS-CoV-2 as early as November and December 2019, respectively, but the methods of such sewage studies have not been optimised, many have not been peer reviewed, details are often missing, and there is a risk of false positives due to contamination or if only one gene target is detected. A September 2020 review journal article said, "The possibility that the COVID-19 infection had already spread to Europe at the end of last year is now indicated by abundant, even if partially circumstantial, evidence", including pneumonia case numbers and radiology in France and Italy in November and December.
MISINFORMATION
After the initial outbreak of COVID-19, misinformation and disinformation regarding the origin, scale, prevention, treatment, and other aspects of the disease rapidly spread online.
In September 2020, the U.S. CDC published preliminary estimates of the risk of death by age groups in the United States, but those estimates were widely misreported and misunderstood.
OTHER ANIMALS
Humans appear to be capable of spreading the virus to some other animals, a type of disease transmission referred to as zooanthroponosis.
Some pets, especially cats and ferrets, can catch this virus from infected humans. Symptoms in cats include respiratory (such as a cough) and digestive symptoms. Cats can spread the virus to other cats, and may be able to spread the virus to humans, but cat-to-human transmission of SARS-CoV-2 has not been proven. Compared to cats, dogs are less susceptible to this infection. Behaviors which increase the risk of transmission include kissing, licking, and petting the animal.
The virus does not appear to be able to infect pigs, ducks, or chickens at all.[ Mice, rats, and rabbits, if they can be infected at all, are unlikely to be involved in spreading the virus.
Tigers and lions in zoos have become infected as a result of contact with infected humans. As expected, monkeys and great ape species such as orangutans can also be infected with the COVID-19 virus.
Minks, which are in the same family as ferrets, have been infected. Minks may be asymptomatic, and can also spread the virus to humans. Multiple countries have identified infected animals in mink farms. Denmark, a major producer of mink pelts, ordered the slaughter of all minks over fears of viral mutations. A vaccine for mink and other animals is being researched.
RESEARCH
International research on vaccines and medicines in COVID-19 is underway by government organisations, academic groups, and industry researchers. The CDC has classified it to require a BSL3 grade laboratory. There has been a great deal of COVID-19 research, involving accelerated research processes and publishing shortcuts to meet the global demand.
As of December 2020, hundreds of clinical trials have been undertaken, with research happening on every continent except Antarctica. As of November 2020, more than 200 possible treatments had been studied in humans so far.
Transmission and prevention research
Modelling research has been conducted with several objectives, including predictions of the dynamics of transmission, diagnosis and prognosis of infection, estimation of the impact of interventions, or allocation of resources. Modelling studies are mostly based on epidemiological models, estimating the number of infected people over time under given conditions. Several other types of models have been developed and used during the COVID-19 including computational fluid dynamics models to study the flow physics of COVID-19, retrofits of crowd movement models to study occupant exposure, mobility-data based models to investigate transmission, or the use of macroeconomic models to assess the economic impact of the pandemic. Further, conceptual frameworks from crisis management research have been applied to better understand the effects of COVID-19 on organizations worldwide.
TREATMENT-RELATED RESEARCH
Repurposed antiviral drugs make up most of the research into COVID-19 treatments. Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.
In March 2020, the World Health Organization (WHO) initiated the Solidarity trial to assess the treatment effects of some promising drugs: an experimental drug called remdesivir; anti-malarial drugs chloroquine and hydroxychloroquine; two anti-HIV drugs, lopinavir/ritonavir; and interferon-beta. More than 300 active clinical trials were underway as of April 2020.
Research on the antimalarial drugs hydroxychloroquine and chloroquine showed that they were ineffective at best, and that they may reduce the antiviral activity of remdesivir. By May 2020, France, Italy, and Belgium had banned the use of hydroxychloroquine as a COVID-19 treatment.
In June, initial results from the randomised RECOVERY Trial in the United Kingdom showed that dexamethasone reduced mortality by one third for people who are critically ill on ventilators and one fifth for those receiving supplemental oxygen. Because this is a well-tested and widely available treatment, it was welcomed by the WHO, which is in the process of updating treatment guidelines to include dexamethasone and other steroids. Based on those preliminary results, dexamethasone treatment has been recommended by the NIH for patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen but not in patients with COVID-19 who do not require supplemental oxygen.
In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19. The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID-19 (strong recommendation, based on moderate certainty evidence). The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence). The updated guidance was based on a meta-analysis of clinical trials of critically ill COVID-19 patients.
WIKIPEDIA
Recently, many economies have come under sharp foreign exchange pressures, reflecting large commodity price declines, volatile external financing conditions, and country-specific factors. This seminar will invite central bank officials from emerging and frontier markets to discuss their recent experiences in dealing with these pressures, including the role of exchange rate flexibility and constraints imposed by the overall macroeconomic policy frameworks and balance sheets.
THE DAILY TIMES
MARCH 23, 2023
Pakistan Simply has to Eliminate Tuberculosis
By
Dr Ghulam Nabi Kazi
Tuberculosis remains a dreaded disease even today although its causative organism Mycobacterium Tuberculosis was identified By Robert Koch in 1882. It has almost always been present in the human population, as evidenced by pathological signs found in bony fragments of Egyptian mummies from 2400 BC. The major brunt of the disease is faced by low to middle-income countries mainly in Asia, Africa and South America. Resistance to first-line drugs and HIV/AIDS is fuelling the pandemic of Tuberculosis. which continues unabated. According to the World Health Organization, 10.6 million people acquired active TB, while 1.6 million died due to it in 2021 globally.
Tuberculosis has caused enormous havoc in Pakistan’s national life and affected 611,000 people in 2021–fifth highest burden in the world-out of which service coverage was provided to only 55 per cent of them. The scenario is indicative of the adverse effects of climate change, torrential rains, flooding and COVID-19, which have jointly hampered TB work for nearly three consecutive years since March 2020. Currently, TB incidence is estimated at 264/100,000 in a population exceeding 231 million, while an estimated 50,100 persons died due to TB in Pakistan in 2021. The position of the 16,000 drug-resistant (DR) TB cases is more disturbing with a case notification rate of around 15 per cent, mainly owing to the low number of Programmatic Management of Drug-Resistant TB (PMDT) sites across the country.
There is yet hope that we can fulfil our targets of lowering TB incidence by 90 per cent in the next seven years (2030) and by 95 per cent in 12 years (2035); eliminating the disease as a public health problem in Pakistan in line with our national aspirations and international commitments. This optimism stems mostly from the rapid advances in technology for diagnosis, and availability of faster-acting medicines along with the enduring hope of an effective vaccine raising expectations of a breakthrough in the control and elimination of the disease. However, what is clear is that all this cannot be achieved with the current pace of effort and it cannot be business as usual.
In September 2018, Pakistan’s Foreign Minister pledged at the United Nations to do everything possible to curb the TB pandemic. Nearly five years later, and with the next high-level meeting due in September this year, there is not much good news to report. Meanwhile, macroeconomic issues threaten to slash nondevelopment funding, including that for healthcare and more specifically for TB.
TB stems from the deprivations of poverty and is more of a social problem than a clinical one. We have been treating TB sufferers with free diagnostics and medicines, not taking into account their other needs such as transport, days of work lost and travelling overnight for accessing DR-TB services to distant areas in addition to nutritional support, which contributes to substantial out-of-pocket expenditure, warranting urgent remedial action.
Recent actions for TB control in Pakistan include the formation of an End-TB Parliamentary Caucus, identifying private sector patients through private pharmacies while initiating community involvement through a rights-based approach. The President of Pakistan has presided over two TB Summits, the last in January 2022, while the First Lady has presided over a TB community rights and gender seminar in December 2022 as part of efforts to de-stigmatize the disease and raise awareness that the condition is eminently curable. These top-down approaches need to be complemented with community-led accountability mechanisms and inter-sectoral collaboration. The Constitution of Pakistan 1973 unequivocally stresses the Right to Life for which good health is an essential imperative and the Right to Education for all children. Simply by acting on this supreme charter and overarching legal umbrella, which completes 50 years next month, we can provide legal cover to TB patients by removing all barriers to TB care. The paucity of domestic funding is another sore issue with over 80 per cent of the TB care costs coming from donors, particularly The Global Fund, while some claim the figure is 92 per cent.
More importantly, we need a change in mindset. The association of tuberculosis with mental health symptoms, such as anxiety, psychosis and depression, has been repeatedly documented in Pakistan’s context affecting over 70 per cent of patients on TB medication, particularly in drug-resistant persons. When we add to it the plight of millions of persons displaced from their homes due to the massive floods and already in need of psychosocial support, the scenario becomes all the more critical. Then certain anti-TB drugs are implicated with mental side effects, while possible interactions with psychotic drugs could lead to a further deterioration of mental health. This nexus of TB care and mental health issues is unfortunate for patients in Pakistan, subjecting them to double jeopardy in accessing care as both conditions are highly stigmatized, particularly for women.
The World Health Organization has been calling for patient-centred care and it is therefore imperative to make TB care processes user-friendly while adopting a holistic approach substituting a clinical one and according to due importance to preventive aspects such as treatment of latent TB patients who do not manifest any symptoms and enabling adequate attention to vulnerable and at-risk populations like women, children, IDP, refugees and prisoners.
We also need to build partnerships across different sectors and social safety nets like health insurance and use innovative approaches for destigmatizing the disease, bridging system-wide barriers, amending policy guidelines and building synergies in the existing TB care system to make it more patient-friendly through the proper utilization of TB survivors, celebrities and civil society representatives, complemented with the use of digital technologies and innovative tools to improve TB treatment outcomes. To do anything less is not an option – and yes, we can do it!
*World TB Day is being observed on March 24, 2023
The writer is a senior public health specialist in Pakistan and Editor-in-Chief of the Public Health Action journal of the International Union Against TB and Lung Disease.
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic.
Symptoms of COVID-19 are variable, but often include fever, cough, fatigue, breathing difficulties, and loss of smell and taste. Symptoms begin one to fourteen days after exposure to the virus. Of those people who develop noticeable symptoms, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and 5% suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Older people are more likely to have severe symptoms. At least a third of the people who are infected with the virus remain asymptomatic and do not develop noticeable symptoms at any point in time, but they still can spread the disease.[ Around 20% of those people will remain asymptomatic throughout infection, and the rest will develop symptoms later on, becoming pre-symptomatic rather than asymptomatic and therefore having a higher risk of transmitting the virus to others. Some people continue to experience a range of effects—known as long COVID—for months after recovery, and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
The virus that causes COVID-19 spreads mainly when an infected person is in close contact[a] with another person. Small droplets and aerosols containing the virus can spread from an infected person's nose and mouth as they breathe, cough, sneeze, sing, or speak. Other people are infected if the virus gets into their mouth, nose or eyes. The virus may also spread via contaminated surfaces, although this is not thought to be the main route of transmission. The exact route of transmission is rarely proven conclusively, but infection mainly happens when people are near each other for long enough. People who are infected can transmit the virus to another person up to two days before they themselves show symptoms, as can people who do not experience symptoms. People remain infectious for up to ten days after the onset of symptoms in moderate cases and up to 20 days in severe cases. Several testing methods have been developed to diagnose the disease. The standard diagnostic method is by detection of the virus' nucleic acid by real-time reverse transcription polymerase chain reaction (rRT-PCR), transcription-mediated amplification (TMA), or by reverse transcription loop-mediated isothermal amplification (RT-LAMP) from a nasopharyngeal swab.
Preventive measures include physical or social distancing, quarantining, ventilation of indoor spaces, covering coughs and sneezes, hand washing, and keeping unwashed hands away from the face. The use of face masks or coverings has been recommended in public settings to minimise the risk of transmissions. Several vaccines have been developed and several countries have initiated mass vaccination campaigns.
Although work is underway to develop drugs that inhibit the virus, the primary treatment is currently symptomatic. Management involves the treatment of symptoms, supportive care, isolation, and experimental measures.
SIGNS AND SYSTOMS
Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste, nasal congestion and rhinorrhea, cough, muscle pain, sore throat, fever, diarrhea, and breathing difficulties. People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19.
Most people (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging) and 5% of patients suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time. These asymptomatic carriers tend not to get tested and can spread the disease. Other infected people will develop symptoms later, called "pre-symptomatic", or have very mild symptoms and can also spread the virus.
As is common with infections, there is a delay between the moment a person first becomes infected and the appearance of the first symptoms. The median delay for COVID-19 is four to five days. Most symptomatic people experience symptoms within two to seven days after exposure, and almost all will experience at least one symptom within 12 days.
Most people recover from the acute phase of the disease. However, some people continue to experience a range of effects for months after recovery—named long COVID—and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease.
CAUSE
TRANSMISSION
Coronavirus disease 2019 (COVID-19) spreads from person to person mainly through the respiratory route after an infected person coughs, sneezes, sings, talks or breathes. A new infection occurs when virus-containing particles exhaled by an infected person, either respiratory droplets or aerosols, get into the mouth, nose, or eyes of other people who are in close contact with the infected person. During human-to-human transmission, an average 1000 infectious SARS-CoV-2 virions are thought to initiate a new infection.
The closer people interact, and the longer they interact, the more likely they are to transmit COVID-19. Closer distances can involve larger droplets (which fall to the ground) and aerosols, whereas longer distances only involve aerosols. Larger droplets can also turn into aerosols (known as droplet nuclei) through evaporation. The relative importance of the larger droplets and the aerosols is not clear as of November 2020; however, the virus is not known to spread between rooms over long distances such as through air ducts. Airborne transmission is able to particularly occur indoors, in high risk locations such as restaurants, choirs, gyms, nightclubs, offices, and religious venues, often when they are crowded or less ventilated. It also occurs in healthcare settings, often when aerosol-generating medical procedures are performed on COVID-19 patients.
Although it is considered possible there is no direct evidence of the virus being transmitted by skin to skin contact. A person could get COVID-19 indirectly by touching a contaminated surface or object before touching their own mouth, nose, or eyes, though this is not thought to be the main way the virus spreads. The virus is not known to spread through feces, urine, breast milk, food, wastewater, drinking water, or via animal disease vectors (although some animals can contract the virus from humans). It very rarely transmits from mother to baby during pregnancy.
Social distancing and the wearing of cloth face masks, surgical masks, respirators, or other face coverings are controls for droplet transmission. Transmission may be decreased indoors with well maintained heating and ventilation systems to maintain good air circulation and increase the use of outdoor air.
The number of people generally infected by one infected person varies. Coronavirus disease 2019 is more infectious than influenza, but less so than measles. It often spreads in clusters, where infections can be traced back to an index case or geographical location. There is a major role of "super-spreading events", where many people are infected by one person.
A person who is infected can transmit the virus to others up to two days before they themselves show symptoms, and even if symptoms never appear. People remain infectious in moderate cases for 7–12 days, and up to two weeks in severe cases. In October 2020, medical scientists reported evidence of reinfection in one person.
VIROLOGY
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All structural features of the novel SARS-CoV-2 virus particle occur in related coronaviruses in nature.
Outside the human body, the virus is destroyed by household soap, which bursts its protective bubble.
SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have an animal (zoonotic) origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13). The structural proteins of SARS-CoV-2 include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and the spike protein (S). The M protein of SARS-CoV-2 is about 98% similar to the M protein of bat SARS-CoV, maintains around 98% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only around 38% with the M protein of MERS-CoV. The structure of the M protein resembles the sugar transporter SemiSWEET.
The many thousands of SARS-CoV-2 variants are grouped into clades. Several different clade nomenclatures have been proposed. Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR).
Several notable variants of SARS-CoV-2 emerged in late 2020. Cluster 5 emerged among minks and mink farmers in Denmark. After strict quarantines and a mink euthanasia campaign, it is believed to have been eradicated. The Variant of Concern 202012/01 (VOC 202012/01) is believed to have emerged in the United Kingdom in September. The 501Y.V2 Variant, which has the same N501Y mutation, arose independently in South Africa.
SARS-CoV-2 VARIANTS
Three known variants of SARS-CoV-2 are currently spreading among global populations as of January 2021 including the UK Variant (referred to as B.1.1.7) first found in London and Kent, a variant discovered in South Africa (referred to as 1.351), and a variant discovered in Brazil (referred to as P.1).
Using Whole Genome Sequencing, epidemiology and modelling suggest the new UK variant ‘VUI – 202012/01’ (the first Variant Under Investigation in December 2020) transmits more easily than other strains.
PATHOPHYSIOLOGY
COVID-19 can affect the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs). The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell. The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and decreasing ACE2 activity might be protective, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective. As the alveolar disease progresses, respiratory failure might develop and death may follow.
Whether SARS-CoV-2 is able to invade the nervous system remains unknown. The virus is not detected in the CNS of the majority of COVID-19 people with neurological issues. However, SARS-CoV-2 has been detected at low levels in the brains of those who have died from COVID-19, but these results need to be confirmed. SARS-CoV-2 could cause respiratory failure through affecting the brain stem as other coronaviruses have been found to invade the CNS. While virus has been detected in cerebrospinal fluid of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain. The virus may also enter the bloodstream from the lungs and cross the blood-brain barrier to gain access to the CNS, possibly within an infected white blood cell.
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine.
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system. An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China, and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis and venous thromboembolism have been found people transferred to Intensive care unit (ICU) with COVID-19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels caused by blood clots) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in people infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstrictive responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside the presentation of viral pneumonia. Furthermore, microvascular blood vessel damage has been reported in a small number of tissue samples of the brains – without detected SARS-CoV-2 – and the olfactory bulbs from those who have died from COVID-19.
Another common cause of death is complications related to the kidneys. Early reports show that up to 30% of hospitalized patients both in China and in New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.
Autopsies of people who died of COVID-19 have found diffuse alveolar damage, and lymphocyte-containing inflammatory infiltrates within the lung.
IMMUNOPATHOLOGY
Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, people with severe COVID-19 have symptoms of systemic hyperinflammation. Clinical laboratory findings of elevated IL-2, IL-7, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α (MIP-1α), and tumour necrosis factor-α (TNF-α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology.
Additionally, people with COVID-19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS, including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and ferritin.
Systemic inflammation results in vasodilation, allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T-cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in people with COVID-19 . Lymphocytic infiltrates have also been reported at autopsy.
VIRAL AND HOST FACTORS
VIRUS PROTEINS
Multiple viral and host factors affect the pathogenesis of the virus. The S-protein, otherwise known as the spike protein, is the viral component that attaches to the host receptor via the ACE2 receptors. It includes two subunits: S1 and S2. S1 determines the virus host range and cellular tropism via the receptor binding domain. S2 mediates the membrane fusion of the virus to its potential cell host via the H1 and HR2, which are heptad repeat regions. Studies have shown that S1 domain induced IgG and IgA antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID-19 vaccines.
The M protein is the viral protein responsible for the transmembrane transport of nutrients. It is the cause of the bud release and the formation of the viral envelope. The N and E protein are accessory proteins that interfere with the host's immune response.
HOST FACTORS
Human angiotensin converting enzyme 2 (hACE2) is the host factor that SARS-COV2 virus targets causing COVID-19. Theoretically the usage of angiotensin receptor blockers (ARB) and ACE inhibitors upregulating ACE2 expression might increase morbidity with COVID-19, though animal data suggest some potential protective effect of ARB. However no clinical studies have proven susceptibility or outcomes. Until further data is available, guidelines and recommendations for hypertensive patients remain.
The virus' effect on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to a systemic inflammatory response syndrome.
HOST CYTOKINE RESPONSE
The severity of the inflammation can be attributed to the severity of what is known as the cytokine storm. Levels of interleukin 1B, interferon-gamma, interferon-inducible protein 10, and monocyte chemoattractant protein 1 were all associated with COVID-19 disease severity. Treatment has been proposed to combat the cytokine storm as it remains to be one of the leading causes of morbidity and mortality in COVID-19 disease.
A cytokine storm is due to an acute hyperinflammatory response that is responsible for clinical illness in an array of diseases but in COVID-19, it is related to worse prognosis and increased fatality. The storm causes the acute respiratory distress syndrome, blood clotting events such as strokes, myocardial infarction, encephalitis, acute kidney injury, and vasculitis. The production of IL-1, IL-2, IL-6, TNF-alpha, and interferon-gamma, all crucial components of normal immune responses, inadvertently become the causes of a cytokine storm. The cells of the central nervous system, the microglia, neurons, and astrocytes, are also be involved in the release of pro-inflammatory cytokines affecting the nervous system, and effects of cytokine storms toward the CNS are not uncommon.
DIAGNOSIS
COVID-19 can provisionally be diagnosed on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) or other nucleic acid testing of infected secretions. Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection. Detection of a past infection is possible with serological tests, which detect antibodies produced by the body in response to the infection.
VIRAL TESTING
The standard methods of testing for presence of SARS-CoV-2 are nucleic acid tests, which detects the presence of viral RNA fragments. As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited." The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within hours. The WHO has published several testing protocols for the disease.
A number of laboratories and companies have developed serological tests, which detect antibodies produced by the body in response to infection. Several have been evaluated by Public Health England and approved for use in the UK.
The University of Oxford's CEBM has pointed to mounting evidence that "a good proportion of 'new' mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with" and have called for "an international effort to standardize and periodically calibrate testing" On 7 September, the UK government issued "guidance for procedures to be implemented in laboratories to provide assurance of positive SARS-CoV-2 RNA results during periods of low prevalence, when there is a reduction in the predictive value of positive test results."
IMAGING
Chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses. Characteristic imaging features on chest radiographs and computed tomography (CT) of people who are symptomatic include asymmetric peripheral ground-glass opacities without pleural effusions.
Many groups have created COVID-19 datasets that include imagery such as the Italian Radiological Society which has compiled an international online database of imaging findings for confirmed cases. Due to overlap with other infections such as adenovirus, imaging without confirmation by rRT-PCR is of limited specificity in identifying COVID-19. A large study in China compared chest CT results to PCR and demonstrated that though imaging is less specific for the infection, it is faster and more sensitive.
Coding
In late 2019, the WHO assigned emergency ICD-10 disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection and U07.2 for deaths from clinically or epidemiologically diagnosed COVID-19 without lab-confirmed SARS-CoV-2 infection.
PATHOLOGY
The main pathological findings at autopsy are:
Macroscopy: pericarditis, lung consolidation and pulmonary oedema
Lung findings:
minor serous exudation, minor fibrin exudation
pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation
diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.
organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis
plasmocytosis in BAL
Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction
Liver: microvesicular steatosis
PREVENTION
Preventive measures to reduce the chances of infection include staying at home, wearing a mask in public, avoiding crowded places, keeping distance from others, ventilating indoor spaces, washing hands with soap and water often and for at least 20 seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands.
Those diagnosed with COVID-19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items.
The first COVID-19 vaccine was granted regulatory approval on 2 December by the UK medicines regulator MHRA. It was evaluated for emergency use authorization (EUA) status by the US FDA, and in several other countries. Initially, the US National Institutes of Health guidelines do not recommend any medication for prevention of COVID-19, before or after exposure to the SARS-CoV-2 virus, outside the setting of a clinical trial. Without a vaccine, other prophylactic measures, or effective treatments, a key part of managing COVID-19 is trying to decrease and delay the epidemic peak, known as "flattening the curve". This is done by slowing the infection rate to decrease the risk of health services being overwhelmed, allowing for better treatment of current cases, and delaying additional cases until effective treatments or a vaccine become available.
VACCINE
A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus causing coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, there was an established body of knowledge about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which enabled accelerated development of various vaccine technologies during early 2020. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19.
In Phase III trials, several COVID‑19 vaccines have demonstrated efficacy as high as 95% in preventing symptomatic COVID‑19 infections. As of March 2021, 12 vaccines were authorized by at least one national regulatory authority for public use: two RNA vaccines (the Pfizer–BioNTech vaccine and the Moderna vaccine), four conventional inactivated vaccines (BBIBP-CorV, CoronaVac, Covaxin, and CoviVac), four viral vector vaccines (Sputnik V, the Oxford–AstraZeneca vaccine, Convidicea, and the Johnson & Johnson vaccine), and two protein subunit vaccines (EpiVacCorona and RBD-Dimer). In total, as of March 2021, 308 vaccine candidates were in various stages of development, with 73 in clinical research, including 24 in Phase I trials, 33 in Phase I–II trials, and 16 in Phase III development.
Many countries have implemented phased distribution plans that prioritize those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers. As of 17 March 2021, 400.22 million doses of COVID‑19 vaccine have been administered worldwide based on official reports from national health agencies. AstraZeneca-Oxford anticipates producing 3 billion doses in 2021, Pfizer-BioNTech 1.3 billion doses, and Sputnik V, Sinopharm, Sinovac, and Johnson & Johnson 1 billion doses each. Moderna targets producing 600 million doses and Convidicea 500 million doses in 2021. By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising 14% of the world's population.
SOCIAL DISTANCING
Social distancing (also known as physical distancing) includes infection control actions intended to slow the spread of the disease by minimising close contact between individuals. Methods include quarantines; travel restrictions; and the closing of schools, workplaces, stadiums, theatres, or shopping centres. Individuals may apply social distancing methods by staying at home, limiting travel, avoiding crowded areas, using no-contact greetings, and physically distancing themselves from others. Many governments are now mandating or recommending social distancing in regions affected by the outbreak.
Outbreaks have occurred in prisons due to crowding and an inability to enforce adequate social distancing. In the United States, the prisoner population is aging and many of them are at high risk for poor outcomes from COVID-19 due to high rates of coexisting heart and lung disease, and poor access to high-quality healthcare.
SELF-ISOLATION
Self-isolation at home has been recommended for those diagnosed with COVID-19 and those who suspect they have been infected. Health agencies have issued detailed instructions for proper self-isolation. Many governments have mandated or recommended self-quarantine for entire populations. The strongest self-quarantine instructions have been issued to those in high-risk groups. Those who may have been exposed to someone with COVID-19 and those who have recently travelled to a country or region with the widespread transmission have been advised to self-quarantine for 14 days from the time of last possible exposure.
Face masks and respiratory hygiene
The WHO and the US CDC recommend individuals wear non-medical face coverings in public settings where there is an increased risk of transmission and where social distancing measures are difficult to maintain. This recommendation is meant to reduce the spread of the disease by asymptomatic and pre-symptomatic individuals and is complementary to established preventive measures such as social distancing. Face coverings limit the volume and travel distance of expiratory droplets dispersed when talking, breathing, and coughing. A face covering without vents or holes will also filter out particles containing the virus from inhaled and exhaled air, reducing the chances of infection. But, if the mask include an exhalation valve, a wearer that is infected (maybe without having noticed that, and asymptomatic) would transmit the virus outwards through it, despite any certification they can have. So the masks with exhalation valve are not for the infected wearers, and are not reliable to stop the pandemic in a large scale. Many countries and local jurisdictions encourage or mandate the use of face masks or cloth face coverings by members of the public to limit the spread of the virus.
Masks are also strongly recommended for those who may have been infected and those taking care of someone who may have the disease. When not wearing a mask, the CDC recommends covering the mouth and nose with a tissue when coughing or sneezing and recommends using the inside of the elbow if no tissue is available. Proper hand hygiene after any cough or sneeze is encouraged. Healthcare professionals interacting directly with people who have COVID-19 are advised to use respirators at least as protective as NIOSH-certified N95 or equivalent, in addition to other personal protective equipment.
HAND-WASHING AND HYGIENE
Thorough hand hygiene after any cough or sneeze is required. The WHO also recommends that individuals wash hands often with soap and water for at least 20 seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose. The CDC recommends using an alcohol-based hand sanitiser with at least 60% alcohol, but only when soap and water are not readily available. For areas where commercial hand sanitisers are not readily available, the WHO provides two formulations for local production. In these formulations, the antimicrobial activity arises from ethanol or isopropanol. Hydrogen peroxide is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for hand antisepsis". Glycerol is added as a humectant.
SURFACE CLEANING
After being expelled from the body, coronaviruses can survive on surfaces for hours to days. If a person touches the dirty surface, they may deposit the virus at the eyes, nose, or mouth where it can enter the body cause infection. Current evidence indicates that contact with infected surfaces is not the main driver of Covid-19, leading to recommendations for optimised disinfection procedures to avoid issues such as the increase of antimicrobial resistance through the use of inappropriate cleaning products and processes. Deep cleaning and other surface sanitation has been criticized as hygiene theater, giving a false sense of security against something primarily spread through the air.
The amount of time that the virus can survive depends significantly on the type of surface, the temperature, and the humidity. Coronaviruses die very quickly when exposed to the UV light in sunlight. Like other enveloped viruses, SARS-CoV-2 survives longest when the temperature is at room temperature or lower, and when the relative humidity is low (<50%).
On many surfaces, including as glass, some types of plastic, stainless steel, and skin, the virus can remain infective for several days indoors at room temperature, or even about a week under ideal conditions. On some surfaces, including cotton fabric and copper, the virus usually dies after a few hours. As a general rule of thumb, the virus dies faster on porous surfaces than on non-porous surfaces.
However, this rule is not absolute, and of the many surfaces tested, two with the longest survival times are N95 respirator masks and surgical masks, both of which are considered porous surfaces.
Surfaces may be decontaminated with 62–71 percent ethanol, 50–100 percent isopropanol, 0.1 percent sodium hypochlorite, 0.5 percent hydrogen peroxide, and 0.2–7.5 percent povidone-iodine. Other solutions, such as benzalkonium chloride and chlorhexidine gluconate, are less effective. Ultraviolet germicidal irradiation may also be used. The CDC recommends that if a COVID-19 case is suspected or confirmed at a facility such as an office or day care, all areas such as offices, bathrooms, common areas, shared electronic equipment like tablets, touch screens, keyboards, remote controls, and ATM machines used by the ill persons should be disinfected. A datasheet comprising the authorised substances to disinfection in the food industry (including suspension or surface tested, kind of surface, use dilution, disinfectant and inocuylum volumes) can be seen in the supplementary material of.
VENTILATION AND AIR FILTRATION
The WHO recommends ventilation and air filtration in public spaces to help clear out infectious aerosols.
HEALTHY DIET AND LIFESTYLE
The Harvard T.H. Chan School of Public Health recommends a healthy diet, being physically active, managing psychological stress, and getting enough sleep.
While there is no evidence that vitamin D is an effective treatment for COVID-19, there is limited evidence that vitamin D deficiency increases the risk of severe COVID-19 symptoms. This has led to recommendations for individuals with vitamin D deficiency to take vitamin D supplements as a way of mitigating the risk of COVID-19 and other health issues associated with a possible increase in deficiency due to social distancing.
TREATMENT
There is no specific, effective treatment or cure for coronavirus disease 2019 (COVID-19), the disease caused by the SARS-CoV-2 virus. Thus, the cornerstone of management of COVID-19 is supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs.
Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), proper intake of fluids, rest, and nasal breathing. Good personal hygiene and a healthy diet are also recommended. The U.S. Centers for Disease Control and Prevention (CDC) recommend that those who suspect they are carrying the virus isolate themselves at home and wear a face mask.
People with more severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is strongly recommended, as it can reduce the risk of death. Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.
Several experimental treatments are being actively studied in clinical trials. Others were thought to be promising early in the pandemic, such as hydroxychloroquine and lopinavir/ritonavir, but later research found them to be ineffective or even harmful. Despite ongoing research, there is still not enough high-quality evidence to recommend so-called early treatment. Nevertheless, in the United States, two monoclonal antibody-based therapies are available for early use in cases thought to be at high risk of progression to severe disease. The antiviral remdesivir is available in the U.S., Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for people needing mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO), due to limited evidence of its efficacy.
PROGNOSIS
The severity of COVID-19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalization. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. The Italian Istituto Superiore di Sanità reported that the median time between the onset of symptoms and death was twelve days, with seven being hospitalised. However, people transferred to an ICU had a median time of ten days between hospitalisation and death. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID-19 and with a transfer to ICU.
Some early studies suggest 10% to 20% of people with COVID-19 will experience symptoms lasting longer than a month.[191][192] A majority of those who were admitted to hospital with severe disease report long-term problems including fatigue and shortness of breath. On 30 October 2020 WHO chief Tedros Adhanom warned that "to a significant number of people, the COVID virus poses a range of serious long-term effects". He has described the vast spectrum of COVID-19 symptoms that fluctuate over time as "really concerning." They range from fatigue, a cough and shortness of breath, to inflammation and injury of major organs – including the lungs and heart, and also neurological and psychologic effects. Symptoms often overlap and can affect any system in the body. Infected people have reported cyclical bouts of fatigue, headaches, months of complete exhaustion, mood swings, and other symptoms. Tedros has concluded that therefore herd immunity is "morally unconscionable and unfeasible".
In terms of hospital readmissions about 9% of 106,000 individuals had to return for hospital treatment within 2 months of discharge. The average to readmit was 8 days since first hospital visit. There are several risk factors that have been identified as being a cause of multiple admissions to a hospital facility. Among these are advanced age (above 65 years of age) and presence of a chronic condition such as diabetes, COPD, heart failure or chronic kidney disease.
According to scientific reviews smokers are more likely to require intensive care or die compared to non-smokers, air pollution is similarly associated with risk factors, and pre-existing heart and lung diseases and also obesity contributes to an increased health risk of COVID-19.
It is also assumed that those that are immunocompromised are at higher risk of getting severely sick from SARS-CoV-2. One research that looked into the COVID-19 infections in hospitalized kidney transplant recipients found a mortality rate of 11%.
See also: Impact of the COVID-19 pandemic on children
Children make up a small proportion of reported cases, with about 1% of cases being under 10 years and 4% aged 10–19 years. They are likely to have milder symptoms and a lower chance of severe disease than adults. A European multinational study of hospitalized children published in The Lancet on 25 June 2020 found that about 8% of children admitted to a hospital needed intensive care. Four of those 582 children (0.7%) died, but the actual mortality rate could be "substantially lower" since milder cases that did not seek medical help were not included in the study.
Genetics also plays an important role in the ability to fight off the disease. For instance, those that do not produce detectable type I interferons or produce auto-antibodies against these may get much sicker from COVID-19. Genetic screening is able to detect interferon effector genes.
Pregnant women may be at higher risk of severe COVID-19 infection based on data from other similar viruses, like SARS and MERS, but data for COVID-19 is lacking.
COMPLICATIONS
Complications may include pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, septic shock, and death. Cardiovascular complications may include heart failure, arrhythmias, heart inflammation, and blood clots. Approximately 20–30% of people who present with COVID-19 have elevated liver enzymes, reflecting liver injury.
Neurologic manifestations include seizure, stroke, encephalitis, and Guillain–Barré syndrome (which includes loss of motor functions). Following the infection, children may develop paediatric multisystem inflammatory syndrome, which has symptoms similar to Kawasaki disease, which can be fatal. In very rare cases, acute encephalopathy can occur, and it can be considered in those who have been diagnosed with COVID-19 and have an altered mental status.
LONGER-TERM EFFECTS
Some early studies suggest that that 10 to 20% of people with COVID-19 will experience symptoms lasting longer than a month. A majority of those who were admitted to hospital with severe disease report long-term problems, including fatigue and shortness of breath. About 5-10% of patients admitted to hospital progress to severe or critical disease, including pneumonia and acute respiratory failure.
By a variety of mechanisms, the lungs are the organs most affected in COVID-19.[228] The majority of CT scans performed show lung abnormalities in people tested after 28 days of illness.
People with advanced age, severe disease, prolonged ICU stays, or who smoke are more likely to have long lasting effects, including pulmonary fibrosis. Overall, approximately one third of those investigated after 4 weeks will have findings of pulmonary fibrosis or reduced lung function as measured by DLCO, even in people who are asymptomatic, but with the suggestion of continuing improvement with the passing of more time.
IMMUNITY
The immune response by humans to CoV-2 virus occurs as a combination of the cell-mediated immunity and antibody production, just as with most other infections. Since SARS-CoV-2 has been in the human population only since December 2019, it remains unknown if the immunity is long-lasting in people who recover from the disease. The presence of neutralizing antibodies in blood strongly correlates with protection from infection, but the level of neutralizing antibody declines with time. Those with asymptomatic or mild disease had undetectable levels of neutralizing antibody two months after infection. In another study, the level of neutralizing antibody fell 4-fold 1 to 4 months after the onset of symptoms. However, the lack of antibody in the blood does not mean antibody will not be rapidly produced upon reexposure to SARS-CoV-2. Memory B cells specific for the spike and nucleocapsid proteins of SARS-CoV-2 last for at least 6 months after appearance of symptoms. Nevertheless, 15 cases of reinfection with SARS-CoV-2 have been reported using stringent CDC criteria requiring identification of a different variant from the second infection. There are likely to be many more people who have been reinfected with the virus. Herd immunity will not eliminate the virus if reinfection is common. Some other coronaviruses circulating in people are capable of reinfection after roughly a year. Nonetheless, on 3 March 2021, scientists reported that a much more contagious Covid-19 variant, Lineage P.1, first detected in Japan, and subsequently found in Brazil, as well as in several places in the United States, may be associated with Covid-19 disease reinfection after recovery from an earlier Covid-19 infection.
MORTALITY
Several measures are commonly used to quantify mortality. These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health. The mortality rate reflects the number of deaths within a specific demographic group divided by the population of that demographic group. Consequently, the mortality rate reflects the prevalence as well as the severity of the disease within a given population. Mortality rates are highly correlated to age, with relatively low rates for young people and relatively high rates among the elderly.
The case fatality rate (CFR) reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 2.2% (2,685,770/121,585,388) as of 18 March 2021. The number varies by region. The CFR may not reflect the true severity of the disease, because some infected individuals remain asymptomatic or experience only mild symptoms, and hence such infections may not be included in official case reports. Moreover, the CFR may vary markedly over time and across locations due to the availability of live virus tests.
INFECTION FATALITY RATE
A key metric in gauging the severity of COVID-19 is the infection fatality rate (IFR), also referred to as the infection fatality ratio or infection fatality risk. This metric is calculated by dividing the total number of deaths from the disease by the total number of infected individuals; hence, in contrast to the CFR, the IFR incorporates asymptomatic and undiagnosed infections as well as reported cases.
CURRENT ESTIMATES
A December 2020 systematic review and meta-analysis estimated that population IFR during the first wave of the pandemic was about 0.5% to 1% in many locations (including France, Netherlands, New Zealand, and Portugal), 1% to 2% in other locations (Australia, England, Lithuania, and Spain), and exceeded 2% in Italy. That study also found that most of these differences in IFR reflected corresponding differences in the age composition of the population and age-specific infection rates; in particular, the metaregression estimate of IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. These results were also highlighted in a December 2020 report issued by the WHO.
EARLIER ESTIMATES OF IFR
At an early stage of the pandemic, the World Health Organization reported estimates of IFR between 0.3% and 1%.[ On 2 July, The WHO's chief scientist reported that the average IFR estimate presented at a two-day WHO expert forum was about 0.6%. In August, the WHO found that studies incorporating data from broad serology testing in Europe showed IFR estimates converging at approximately 0.5–1%. Firm lower limits of IFRs have been established in a number of locations such as New York City and Bergamo in Italy since the IFR cannot be less than the population fatality rate. As of 10 July, in New York City, with a population of 8.4 million, 23,377 individuals (18,758 confirmed and 4,619 probable) have died with COVID-19 (0.3% of the population).Antibody testing in New York City suggested an IFR of ~0.9%,[258] and ~1.4%. In Bergamo province, 0.6% of the population has died. In September 2020 the U.S. Center for Disease Control & Prevention reported preliminary estimates of age-specific IFRs for public health planning purposes.
SEX DIFFERENCES
Early reviews of epidemiologic data showed gendered impact of the pandemic and a higher mortality rate in men in China and Italy. The Chinese Center for Disease Control and Prevention reported the death rate was 2.8% for men and 1.7% for women. Later reviews in June 2020 indicated that there is no significant difference in susceptibility or in CFR between genders. One review acknowledges the different mortality rates in Chinese men, suggesting that it may be attributable to lifestyle choices such as smoking and drinking alcohol rather than genetic factors. Sex-based immunological differences, lesser prevalence of smoking in women and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men. In Europe, 57% of the infected people were men and 72% of those died with COVID-19 were men. As of April 2020, the US government is not tracking sex-related data of COVID-19 infections. Research has shown that viral illnesses like Ebola, HIV, influenza and SARS affect men and women differently.
ETHNIC DIFFERENCES
In the US, a greater proportion of deaths due to COVID-19 have occurred among African Americans and other minority groups. Structural factors that prevent them from practicing social distancing include their concentration in crowded substandard housing and in "essential" occupations such as retail grocery workers, public transit employees, health-care workers and custodial staff. Greater prevalence of lacking health insurance and care and of underlying conditions such as diabetes, hypertension and heart disease also increase their risk of death. Similar issues affect Native American and Latino communities. According to a US health policy non-profit, 34% of American Indian and Alaska Native People (AIAN) non-elderly adults are at risk of serious illness compared to 21% of white non-elderly adults. The source attributes it to disproportionately high rates of many health conditions that may put them at higher risk as well as living conditions like lack of access to clean water. Leaders have called for efforts to research and address the disparities. In the U.K., a greater proportion of deaths due to COVID-19 have occurred in those of a Black, Asian, and other ethnic minority background. More severe impacts upon victims including the relative incidence of the necessity of hospitalization requirements, and vulnerability to the disease has been associated via DNA analysis to be expressed in genetic variants at chromosomal region 3, features that are associated with European Neanderthal heritage. That structure imposes greater risks that those affected will develop a more severe form of the disease. The findings are from Professor Svante Pääbo and researchers he leads at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institutet. This admixture of modern human and Neanderthal genes is estimated to have occurred roughly between 50,000 and 60,000 years ago in Southern Europe.
COMORBIDITIES
Most of those who die of COVID-19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease. According to March data from the United States, 89% of those hospitalised had preexisting conditions. The Italian Istituto Superiore di Sanità reported that out of 8.8% of deaths where medical charts were available, 96.1% of people had at least one comorbidity with the average person having 3.4 diseases. According to this report the most common comorbidities are hypertension (66% of deaths), type 2 diabetes (29.8% of deaths), Ischemic Heart Disease (27.6% of deaths), atrial fibrillation (23.1% of deaths) and chronic renal failure (20.2% of deaths).
Most critical respiratory comorbidities according to the CDC, are: moderate or severe asthma, pre-existing COPD, pulmonary fibrosis, cystic fibrosis. Evidence stemming from meta-analysis of several smaller research papers also suggests that smoking can be associated with worse outcomes. When someone with existing respiratory problems is infected with COVID-19, they might be at greater risk for severe symptoms. COVID-19 also poses a greater risk to people who misuse opioids and methamphetamines, insofar as their drug use may have caused lung damage.
In August 2020 the CDC issued a caution that tuberculosis infections could increase the risk of severe illness or death. The WHO recommended that people with respiratory symptoms be screened for both diseases, as testing positive for COVID-19 couldn't rule out co-infections. Some projections have estimated that reduced TB detection due to the pandemic could result in 6.3 million additional TB cases and 1.4 million TB related deaths by 2025.
NAME
During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus", with the disease sometimes called "Wuhan pneumonia". In the past, many diseases have been named after geographical locations, such as the Spanish flu, Middle East Respiratory Syndrome, and Zika virus. In January 2020, the WHO recommended 2019-nCov and 2019-nCoV acute respiratory disease as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations (e.g. Wuhan, China), animal species, or groups of people in disease and virus names in part to prevent social stigma. The official names COVID-19 and SARS-CoV-2 were issued by the WHO on 11 February 2020. Tedros Adhanom explained: CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019). The WHO additionally uses "the COVID-19 virus" and "the virus responsible for COVID-19" in public communications.
HISTORY
The virus is thought to be natural and of an animal origin, through spillover infection. There are several theories about where the first case (the so-called patient zero) originated. Phylogenetics estimates that SARS-CoV-2 arose in October or November 2019. Evidence suggests that it descends from a coronavirus that infects wild bats, and spread to humans through an intermediary wildlife host.
The first known human infections were in Wuhan, Hubei, China. A study of the first 41 cases of confirmed COVID-19, published in January 2020 in The Lancet, reported the earliest date of onset of symptoms as 1 December 2019.Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019. Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020. According to official Chinese sources, these were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020 George Gao, the director of the CDC, said animal samples collected from the seafood market had tested negative for the virus, indicating that the market was the site of an early superspreading event, but that it was not the site of the initial outbreak.[ Traces of the virus have been found in wastewater samples that were collected in Milan and Turin, Italy, on 18 December 2019.
By December 2019, the spread of infection was almost entirely driven by human-to-human transmission. The number of coronavirus cases in Hubei gradually increased, reaching 60 by 20 December, and at least 266 by 31 December. On 24 December, Wuhan Central Hospital sent a bronchoalveolar lavage fluid (BAL) sample from an unresolved clinical case to sequencing company Vision Medicals. On 27 and 28 December, Vision Medicals informed the Wuhan Central Hospital and the Chinese CDC of the results of the test, showing a new coronavirus. A pneumonia cluster of unknown cause was observed on 26 December and treated by the doctor Zhang Jixian in Hubei Provincial Hospital, who informed the Wuhan Jianghan CDC on 27 December. On 30 December, a test report addressed to Wuhan Central Hospital, from company CapitalBio Medlab, stated an erroneous positive result for SARS, causing a group of doctors at Wuhan Central Hospital to alert their colleagues and relevant hospital authorities of the result. The Wuhan Municipal Health Commission issued a notice to various medical institutions on "the treatment of pneumonia of unknown cause" that same evening. Eight of these doctors, including Li Wenliang (punished on 3 January), were later admonished by the police for spreading false rumours and another, Ai Fen, was reprimanded by her superiors for raising the alarm.
The Wuhan Municipal Health Commission made the first public announcement of a pneumonia outbreak of unknown cause on 31 December, confirming 27 cases—enough to trigger an investigation.
During the early stages of the outbreak, the number of cases doubled approximately every seven and a half days. In early and mid-January 2020, the virus spread to other Chinese provinces, helped by the Chinese New Year migration and Wuhan being a transport hub and major rail interchange. On 20 January, China reported nearly 140 new cases in one day, including two people in Beijing and one in Shenzhen. Later official data shows 6,174 people had already developed symptoms by then, and more may have been infected. A report in The Lancet on 24 January indicated human transmission, strongly recommended personal protective equipment for health workers, and said testing for the virus was essential due to its "pandemic potential". On 30 January, the WHO declared the coronavirus a Public Health Emergency of International Concern. By this time, the outbreak spread by a factor of 100 to 200 times.
Italy had its first confirmed cases on 31 January 2020, two tourists from China. As of 13 March 2020 the WHO considered Europe the active centre of the pandemic. Italy overtook China as the country with the most deaths on 19 March 2020. By 26 March the United States had overtaken China and Italy with the highest number of confirmed cases in the world. Research on coronavirus genomes indicates the majority of COVID-19 cases in New York came from European travellers, rather than directly from China or any other Asian country. Retesting of prior samples found a person in France who had the virus on 27 December 2019, and a person in the United States who died from the disease on 6 February 2020.
After 55 days without a locally transmitted case, Beijing reported a new COVID-19 case on 11 June 2020 which was followed by two more cases on 12 June. By 15 June there were 79 cases officially confirmed, most of them were people that went to Xinfadi Wholesale Market.
RT-PCR testing of untreated wastewater samples from Brazil and Italy have suggested detection of SARS-CoV-2 as early as November and December 2019, respectively, but the methods of such sewage studies have not been optimised, many have not been peer reviewed, details are often missing, and there is a risk of false positives due to contamination or if only one gene target is detected. A September 2020 review journal article said, "The possibility that the COVID-19 infection had already spread to Europe at the end of last year is now indicated by abundant, even if partially circumstantial, evidence", including pneumonia case numbers and radiology in France and Italy in November and December.
MISINFORMATION
After the initial outbreak of COVID-19, misinformation and disinformation regarding the origin, scale, prevention, treatment, and other aspects of the disease rapidly spread online.
In September 2020, the U.S. CDC published preliminary estimates of the risk of death by age groups in the United States, but those estimates were widely misreported and misunderstood.
OTHER ANIMALS
Humans appear to be capable of spreading the virus to some other animals, a type of disease transmission referred to as zooanthroponosis.
Some pets, especially cats and ferrets, can catch this virus from infected humans. Symptoms in cats include respiratory (such as a cough) and digestive symptoms. Cats can spread the virus to other cats, and may be able to spread the virus to humans, but cat-to-human transmission of SARS-CoV-2 has not been proven. Compared to cats, dogs are less susceptible to this infection. Behaviors which increase the risk of transmission include kissing, licking, and petting the animal.
The virus does not appear to be able to infect pigs, ducks, or chickens at all.[ Mice, rats, and rabbits, if they can be infected at all, are unlikely to be involved in spreading the virus.
Tigers and lions in zoos have become infected as a result of contact with infected humans. As expected, monkeys and great ape species such as orangutans can also be infected with the COVID-19 virus.
Minks, which are in the same family as ferrets, have been infected. Minks may be asymptomatic, and can also spread the virus to humans. Multiple countries have identified infected animals in mink farms. Denmark, a major producer of mink pelts, ordered the slaughter of all minks over fears of viral mutations. A vaccine for mink and other animals is being researched.
RESEARCH
International research on vaccines and medicines in COVID-19 is underway by government organisations, academic groups, and industry researchers. The CDC has classified it to require a BSL3 grade laboratory. There has been a great deal of COVID-19 research, involving accelerated research processes and publishing shortcuts to meet the global demand.
As of December 2020, hundreds of clinical trials have been undertaken, with research happening on every continent except Antarctica. As of November 2020, more than 200 possible treatments had been studied in humans so far.
Transmission and prevention research
Modelling research has been conducted with several objectives, including predictions of the dynamics of transmission, diagnosis and prognosis of infection, estimation of the impact of interventions, or allocation of resources. Modelling studies are mostly based on epidemiological models, estimating the number of infected people over time under given conditions. Several other types of models have been developed and used during the COVID-19 including computational fluid dynamics models to study the flow physics of COVID-19, retrofits of crowd movement models to study occupant exposure, mobility-data based models to investigate transmission, or the use of macroeconomic models to assess the economic impact of the pandemic. Further, conceptual frameworks from crisis management research have been applied to better understand the effects of COVID-19 on organizations worldwide.
TREATMENT-RELATED RESEARCH
Repurposed antiviral drugs make up most of the research into COVID-19 treatments. Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.
In March 2020, the World Health Organization (WHO) initiated the Solidarity trial to assess the treatment effects of some promising drugs: an experimental drug called remdesivir; anti-malarial drugs chloroquine and hydroxychloroquine; two anti-HIV drugs, lopinavir/ritonavir; and interferon-beta. More than 300 active clinical trials were underway as of April 2020.
Research on the antimalarial drugs hydroxychloroquine and chloroquine showed that they were ineffective at best, and that they may reduce the antiviral activity of remdesivir. By May 2020, France, Italy, and Belgium had banned the use of hydroxychloroquine as a COVID-19 treatment.
In June, initial results from the randomised RECOVERY Trial in the United Kingdom showed that dexamethasone reduced mortality by one third for people who are critically ill on ventilators and one fifth for those receiving supplemental oxygen. Because this is a well-tested and widely available treatment, it was welcomed by the WHO, which is in the process of updating treatment guidelines to include dexamethasone and other steroids. Based on those preliminary results, dexamethasone treatment has been recommended by the NIH for patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen but not in patients with COVID-19 who do not require supplemental oxygen.
In September 2020, the WHO released updated guidance on using corticosteroids for COVID-19. The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID-19 (strong recommendation, based on moderate certainty evidence). The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID-19 (conditional recommendation, based on low certainty evidence). The updated guidance was based on a meta-analysis of clinical trials of critically ill COVID-19 patients.
WIKIPEDIA
Rebecca Patterson, Director of Investment Research, Bridgewater Associates
Paul Hamill, Global Head of FICC Distribution, Citadel Securities
Chen Chen, Technical Assistance Advisor, IMF Fiscal Affairs Department, and Irene Yackovlev, Senior Economist, IMF Communications Department, introduce the new IMF course on the macroeconomics of climate change, at the International Monetary Fund.
IMF Photo/Allison Shelley
19 April 2022
Washington, DC, United States
Photo ref: AS220419035.cr3
www.youtube.com/watch?v=44-ShN1i5SM&feature=related
sun
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No corn hog cycle macroeconomics here mon ami randall J der ( RJ )
:-)
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Billie Holiday featured in Djazz tribute - St Germain des prés café
James McCormack
Global Head, Sovereign and Supranational Group, Fitch Ratings
Seema Shah
Senior Global Investment Strategist, Principal Global Investors
No prizes for the correct answer. xD
So this is one of her latest begging/stare spots. Her fear of heights is long gone. :| This is on top of her cage...
Surprisingly she does not disapprove of macroecons.
[vet messaged me about pancake's passing when i was typing this. lost the mood halfway. sorry.]
The purpose of this workshop is to take stock of emerging best practices on big data and facilitate peer-learning across the membership. The discussion brings together government agencies, international organizations, and the private sector at the forefront of using big data and new technology to produce macroeconomic and financial indicators.
The PricewaterhouseCoopers report, entitled 'The World in 2050: Beyond the BRICs (Brazil, Russia, India and China)', also shows that the Chinese economy is anticipated to grow to about 130 per cent of that of the US by 2050.
John Hawksworth, head of macroeconomics at PricewaterhouseCoopers, said: "The global centre of economic gravity is already shifting to China, India and other large emerging economies and our analysis suggests that this process has a lot further to run.
"Our latest projections suggest that China could overtake the US in around 2025 to become the world's largest economy." (read all)
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Looks better enlarged
Captured during a visit to Shanghai in May 2007 (as seen from a 66th floor corner suite in Grand Hyatt Shanghai, Jin Mao building; it's a shame the window was so dirty.)