pathophysiology photos on Flickr

My Feet Are Killing Me! by Karma Tharchen

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Being in nursing school, all I seem to think about is anatomy, physiology, and pathophysiology. So, when this week's Flickr Friday was announced, the only #Arches I could think of were these...

This image was taken in RAW and processed in Linux using RawTherapee.

Akay by Jeff Bowen

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I noticed her as I passed through the corridor of a university building in downtown Toronto and saw her as an excellent potential subject for my strangers photography project: The Human Family. She was sitting by the windows with two friends. By the time I approached her, the three of them stood up, linked hands in a circle, and engaged in what appeared to be a quiet prayer.

I waited until they finished and approached her as they were gathering their books and coats. I explained my photo project and invited her to participate. She asked if I had a card so she could contact me later because she and her friends were on their way to an exam for their Pathophysiology course.

I didn’t have time to explain that if we prearranged, she would no longer be a “stranger” but pushed my luck by asking if I could just take sixty seconds for a quick photo and then follow up by email. Her friends encouraged her to say yes. I thanked them for being on my side. She put down her things for a moment and agreed. Meet Akay. When I looked up her beautiful name I learned it is a Muslim girl's name of Turkish origin meaning "near the full moon."

Two photos later, as we walked down the hall, Akay said she was so glad this had happened. I told her I was too. I sensed that she had drawn a lesson about trust - and she seemed to quite like the photo.

I wished her and her friends the best of luck with their exam and invited her to use the card I gave her to contact me about the project by email. I hope she does that so I can send her a free copy of the photo.

This is my 858th submission to The Human Family Group on Flickr.

You can view more street portraits and stories by visiting The Human Family.

FOLLOW-UP:

I received a very nice email from Akay which told more about her and her background. As always, it's great when someone I meet takes the time to follow up. It also gave me a chance to reply with her photos. I will quote from the email:

"Hi Jeff,

I took a look at your online portfolio and love what i see so far.

I recently moved to Canada from Jamaica. It sort of like hitting the reset bottom on life if there was every one, not in a sense to erase the past, but like many immigrants to start from scratch as employers are looking for Canadian education and work experience. Its been quite a journey and one that is teaching me resilience.

I love nature and the changing seasons here in Canada and have met many wonderful people that have become like family. West Indian Groceries keep me connect to he food back home :).

I am currently in the Fast track public health program at Ryerson and really liking it and hoping to soon make positive contributions to the public health sector.

All the best,

Akay"

Série sobre Turim – Series about Turin – Torino – 17-01-2009 - IMG_20090117_9999_123 by Flávio Cruvinel Brandão

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Foto da foto do rosto de Cristo no Santo Sudário ou Sudário de Turim em tamanho real. Esta foto está em uma prateleira envidraçada de uma sala ao lado do altar da Igreja Real de São Lourenço (San Lorenzo) em Turim, Itália.

A seguir, texto, em português, da Wikipédia, a enciclopédia livre:

O Sudário de Turim, ou o Santo Sudário é uma peça de linho que mostra a imagem de um homem que aparentemente sofreu traumatismos físicos de maneira consistente com a crucificação. O Sudário está guardado fora das vistas do público na capela da catedral de São João Baptista em Turim, Itália.

O sudário é uma peça rectangular de linho com 4,4 metros de comprimento e 1,1 de largura. O tecido mostra as imagens frontal e dorsal de um homem nu, com as mãos pousadas sobre as partes baixas, consistentes com a projecção ortogonal, sem a projeção referente à parte lateral do corpo humano. As duas imagens apontam em sentidos opostos e unem-se na zona central do pano. O homem representado no sudário tem barba e cabelo comprido pela altura dos ombros, separado por uma risca ao meio. Tem um corpo bem proporcionado e musculado, com cerca de 1,75 de altura. O sudário apresenta ainda diversas nódoas encarnadas que, interpretadas como sangue, sugerem a presença de vários traumatismos

* ferida num dos punhos, de forma circular; o segundo punho está escondido em segundo plano;

* ferida na zona lateral, aparentemente provocada por instrumento cortante;

* conjunto de pequenas feridas em torno da testa; e

* série de feridas lineares nas costas e pernas.

A 28 de Maio de 1898, o fotógrafo italiano Secondo Pia tirou a primeira fotografia ao sudário e constatou que o negativo da fotografia assemelhava-se a uma imagem positiva do homem, o que significava que a imagem do sudário era, em si, um negativo. Esta descoberta lançou o mote para uma discussão científica que ainda hoje permanece aberta: o que representa o sudário?

As primeiras referências a um possível sudário surgem na própria Bíblia. O Evangelho de Mateus (27:59) refere que José de Arimateia envolveu o corpo de Jesus Cristo com "um pano de linho limpo". João (19:38-40) também descreve o evento, e relata que os apóstolos Pedro e João, ao visitar o túmulo de Jesus após a ressurreição, encontraram os lençóis dobrados (Jo 20:6-7). Embora depois desta descrição evangélica o sudário só tenha feito sua aparição definitiva no século XIV, para não mais ser perdido de vista, existem alguns relatos anteriores que contêm indicações bastante consistentes sobre a existência de um tal tecido em tempos mais antigos.

A primeira menção não-evangélica a ele data de 544, quando um pedaço de tecido mostrando uma face que se acreditou ser a de Jesus foi encontrado escondido sob uma ponte em Edessa. Suas primeiras descrições mencionam um pedaço de pano quadrado, mostrando apenas a face, mas São João Damasceno, em sua obra antiiconoclasta "Sobre as imagens sagradas", falando sobre a mesma relíquia, a descreve como uma faixa comprida de tecido, embora disesse que se tratava de uma imagem transferida para o pano quando Jesus ainda estava vivo.

Em 944, quando esta peça foi transferida para Constantinopla, Gregorius Referendarius, arquidiácono de Hagia Sophia pregou um sermão sobre o artefato, que foi dado como perdido até ser redescoberto em 2004 num manuscrito dos arquivos do Vaticano. Neste sermão é feita uma descrição do sudário de Edessa como contendo não só a face, mas uma imagem de corpo inteiro, e cita a presença de manchas de sangue. Outra fonte é o Codex Vossianus Latinus, também no Vaticano, que se refere ao sudário de Edessa como sendo uma impressão de corpo inteiro.

Outra evidência é uma gravura incluída no chamado Manuscrito Húngaro de Preces, datado de 1192, onde a figura mostra o corpo de Jesus sendo preparado para o sepultamento, numa posição consistente com a imagem impressa no sudário de Turim.

Em 1203, o cruzado Robert de Clari afirmou ter visto o sudário em Constantinopla nos seguintes termos: "Lá estava o sudário em que nosso Senhor foi envolto, e que a cada quinta-feira é exposto de modo que todos possam ver a imagem de nosso Senhor nele". Seguindo-se ao saque de Constantinopla, em 1205 Theodoros Angelos, sobrinho de um dos três imperadores bizantinos, escreveu uma carta de protesto ao papa Inocêncio III, onde menciona o roubo de riquezas e relíquias sagradas da capital pelos cruzados, e dizendo que as jóias ficaram com os venezianos e relíquias haviam sido divididas entre os franceses, citando explicitamente o sudário, que segundo ele havia sido levado para Atenas nesta época.

Dali, a partir de testemunhos de época de Geoffrey de Villehardouin e do mesmo Robert de Clari, o sudário teria sido tomado por Otto de la Roche, que se tornou Duque de Atenas. Mas Otto logo o teria transmitido aos Templários, que o teriam levado para a França. Apesar desses indícios de que o sudário de Edessa seja possivelmente o mesmo que o de Turim, o assunto ainda é objeto controvérsia.

Então começa a parte da história do sudário que é bem documentada. Ele aparece publicamente pela primeira vez em 1357, quando a viúva de Geoffroy de Charny, um templário francês, a exibiu na igreja de Lirey. Não foi oferecida nenhuma explicação para a súbita aparição, nem a sua veneração como relíquia foi imediatamente aceite. Henrique de Poitiers, arcebispo de Troyes, apoiado mais tarde pelo rei Carlos VI de França, declarou o sudário como uma impostura e proibiu a sua adoração. A peça conseguiu, no entanto, recolher um número considerável de admiradores que lutaram para a manter em exibição nas igrejas. Em 1389, o bispo Pierre d’Arcis (sucessor de Henrique) denunciou a suposta relíquia como uma fraude fabricada por um pintor talentoso, numa carta a Clemente VII (em Avinhão). D’Arcis menciona que até então tem sido bem sucedido em esconder o pano e revela que a verdade lhe fora confessada pelo próprio artista, que não é identificado. A carta descreve ainda o sudário com grande precisão. Aparentemente, os conselhos do bispo de Troyes não foram ouvidos visto que Clemente VII declarou a relíquia sagrada e ofereceu indulgências a quem peregrinasse para ver o sudário.

Em 1418, o sudário passou a ser propriedade de Umberto de Villersexel, Conde de La Roche, que o removeu para o seu castelo de Montfort, sob o argumento de proteger a peça de um eventual roubo. Depois da sua morte, o pároco de Lirey e a viúva travaram uma batalha jurídica pela custódia da relíquia, ganha pela família. A Condessa de La Roche iniciou então uma tournée com o sudário que incluiu as catedrais de Genebra e Liege. Em 1453, o sudário foi trocado por um castelo (não vendido porque a transacção comercial de relíquias é proibida) com o Duque Luís de Sabóia. A nova aquisição do duque tornou-se na atracção principal da recém construída catedral de Chambery, de acordo com cronistas contemporâneos, envolvida em veludo carmim e guardada num relicário com pregos de prata e chave de ouro.

O sudário foi mais uma vez declarado como relíquia verdadeira pelo Papa Júlio II em 1506. Em 1532, o sudário foi danificado por um incêndio que afectou a sua capela e pela água das tentativas de o controlar. Por volta de 1578 a peça foi transferida para Turim em Itália, onde se encontra até aos dias de hoje na Cappella della Sacra Sindone do Palazzo Reale di Torino. A casa de Sabóia foi a proprietária do sudário até 1983, data da sua doação ao Vaticano. A última exibição da peça foi no ano 2000, a próxima está agendada para 2010. Em 2002, o sudário foi submetido a obras de restauro.

As primeiras análises ao sudário foram realizadas em 1977 por uma equipe de cientistas da Universidade de Turim que usou métodos de microscopia. Os resultados demonstraram que o linho do sudário contém inúmeras gotículas de tinta fabricada a partir de ocre. Entretanto, a hipótese de uma pintura realizada por ação humana foi completamente descartada por experimentos posteriores.

Em 1978, a equipe americana do STURP (Shoud of Turin Research Project) teve acesso ao sudário durante 120 horas. A equipe era composta por 40 cientistas, dos quais apenas 7 católicos e um ateu, Walter C. McCrone, que retirou-se logo no início das investigações. Foram realizados muitos experimentos que envolveram diversas áreas da ciência, como fotografias com diferentes tipos de filme, radiografia de raios X, raio X com fluorescência, espectroscopia, infravermelho e retirada de amostras com fita.

Depois de três anos de análise do STURP, ficou provado que existia sangue humano no sudário e que as gotículas de tinta ocre eram resultado de contaminação. Existiram diversas tentativas de se recriar algo semelhante ao sudário, realizadas durante os séculos, feitas por dezenas de pintores, mas que nunca chegaram a um resultado minimamente próximo ao sudário examinado pelo STURP. Quando questionados sobre se o sudário não era a mortalha de Jesus Cristo, de forma unânime, foi afirmado que nenhum dos resultados dos estudos contradisse a narrativa dos evangelhos. Entretanto, como cientistas, também não podiam afirmar que a mortalha era verdadeira porque essa é uma hipótese não falseável.

Cientistas do STURP também mostraram a completa improbabilidade de aquela ser uma imagem gerada pela ação de um artista, ou seja, é humanamente impossível que o sudário seja uma pintura. A habilidade e equipamentos necessários para gerar uma falsificação daquela natureza são completamente incompatíveis com o período da Idade Média, época em que o sudário apareceu e foi guardado.

As principais conclusões científicas do STURP após cerca de 100.000 horas de pesquisa sobre o artefato foram as seguintes:

a) as marcas do Sudário são um duplo negativo fotográfico do corpo inteiro de um homem. Existe a imagem de frente e de dorso. O sangue do Sudário é positivo;

b) a figura do Sudário, ao contrário de todas as outras figuras bidimensionais já testadas até então, contém dados tridimensionais;

c) o material de cor vermelha do Sudário é sangue;

d) não existe ainda explicação científica de como as imagens do Sudário foram feitas; e

e) o Sudário está historicamente de acordo com os Evangelhos, pois mostra nas imagens as marcas da paixão de Cristo com precisão.

Na época, o STURP não foi autorizado a fazer o teste por datação carbono-14.

A Igreja Católica não emitiu nenhuma opinião acerca da autenticidade desta alegada relíquia. A posição oficial a esta questão é a de que a resposta deve ser uma decisão pessoal do crente. O Papa João Paulo II confessou-se pessoalmente comovido e emocionado com a imagem do sudário, mas afirmou que uma vez que não se trata de uma questão de fé, a Igreja não se pode pronunciar, ao mesmo tempo que convidou as comunidades científicas a continuar a investigação. O grande problema reside na dificuldade de acesso ao sudário, que não é de propriedade da Igreja Católica, mas de uma fundação italiana que alega que novos e constantes testes podem danificar o material da suposta relíquia. A Catholic Encyclopedia, editada pela Igreja Católica, no seu artigo sobre o Sudário de Turim afirma que o sudário está além da capacidade de falsificação de qualquer falsário medieval.

Following, a text, in english, from Wikipedia, the free encyclopedia:

The Shroud of Turin (or Turin Shroud)

The Shroud of Turin (or Turin Shroud) is a linen cloth bearing the image of a man who appears to have been physically traumatized in a manner consistent with crucifixion. It is kept in the royal chapel of the Cathedral of Saint John the Baptist in Turin, Italy. It is believed by many to be the cloth placed on the body of Jesus at the time of his burial.

The image on the shroud is much clearer in black-and-white negative than in its natural sepia color. The striking negative image was first observed on the evening of May 28, 1898, on the reverse photographic plate of amateur photographer Secondo Pia, who was allowed to photograph it while it was being exhibited in the Turin Cathedral. According to Pia, he almost dropped and broke the photographic plate from the shock of seeing an image of a person on it.

The shroud is the subject of intense debate among scientists, people of faith, historians, and writers regarding where, when, and how the shroud and its images were created. From a religious standpoint, in 1958 Pope Pius XII approved of the image in association with the Roman Catholic devotion to the Holy Face of Jesus, celebrated every year on Shrove Tuesday. Some believe the shroud is the cloth that covered Jesus when he was placed in his tomb and that his image was recorded on its fibers at or near the time of his resurrection. Skeptics, on the other hand, contend the shroud is a medieval forgery; others attribute the forming of the image to chemical reactions or other natural processes.

Various tests have been performed on the shroud, yet the debates about its origin continue. Radiocarbon dating in 1988 by three independent teams of scientists yielded results published in Nature indicating that the shroud was made during the Middle Ages, approximately 1300 years after Jesus lived.[4] Claims of bias and error in the testing were raised almost immediately and were addressed by Harry E. Gove.[5] Follow-up analysis published in 2005, for example, claimed that the sample dated by the teams was taken from an area of the shroud that was not a part of the original cloth. The shroud was also damaged by a fire in the Late Middle Ages which could have added carbon material to the cloth, resulting in a higher radiocarbon content and a later calculated age. This analysis itself is questioned by skeptics such as Joe Nickell, who reasons that the conclusions of the author, Raymond Rogers, result from "starting with the desired conclusion and working backward to the evidence".[6] Former Nature editor Philip Ball has said that the idea that Rogers steered his study to a preconceived conclusion is "unfair" and Rogers "has a history of respectable work".

However, the 2008 research at the Oxford Radiocarbon Accelerator Unit may revise the 1260–1390 dating toward which it originally contributed, leading its director Christopher Ramsey to call the scientific community to probe anew the authenticity of the Shroud.[7][8] "With the radiocarbon measurements and with all of the other evidence which we have about the Shroud, there does seem to be a conflict in the interpretation of the different evidence" Gordan said to BBC News in 2008, after the new research emerged.[9] Ramsey had stressed that he would be surprised if the 1988 tests were shown to be far off, let alone "a thousand years wrong", and insisted that he would keep an open mind.

The shroud is rectangular, measuring approximately 4.4 × 1.1 m (14.3 × 3.7 ft). The cloth is woven in a three-to-one herringbone twill composed of flax fibrils. Its most distinctive characteristic is the faint, yellowish image of a front and back view of a naked man with his hands folded across his groin. The two views are aligned along the midplane of the body and point in opposite directions. The front and back views of the head nearly meet at the middle of the cloth. The views are consistent with an orthographic projection of a human body, but see Analysis of the image as the work of an artist.

The "Man of the Shroud" has a beard, moustache, and shoulder-length hair parted in the middle. He is muscular and tall (various experts have measured him as from 1.75 m, or roughly 5 ft 9 in, to 1.88 m, or 6 ft 2 in). For a man of the first century (the time of Jesus' death), or of the Middle Ages (the time of the first uncontested report of the shroud's existence and the proposed time of a possible forgery), these figures present an above-average although not abnormal height. Reddish brown stains that have been said to include whole blood are found on the cloth, showing various wounds that correlate with the yellowish image, the pathophysiology of crucifixion, and the Biblical description of the death of Jesus:

* one wrist bears a large, round wound, apparently from piercing (the second wrist is hidden by the folding of the hands)

* upward gouge in the side penetrating into the thoracic cavity, a post-mortem event as indicated by separate components of red blood cells and serum draining from the lesion

* small punctures around the forehead and scalp

* scores of linear wounds on the torso and legs claimed to be consistent with the distinctive dumbbell wounds of a Roman flagrum.

* swelling of the face from severe beatings

* streams of blood down both arms that include blood dripping from the main flow in response to gravity at an angle that would occur during crucifixion

* no evidence of either leg being fractured

* large puncture wounds in the feet as if pierced by a single spike

Other physical characteristics of the shroud include the presence of large water stains, and from a fire in 1532, burn holes and scorched areas down both sides of the linen due to contact with molten silver that burned through it in places while it was folded. Some small burn holes that apparently are not from the 1532 event are also present. In places, there are permanent creases due to repeated foldings, such as the line that is evident below the chin of the image.

On May 28, 1898, amateur Italian photographer Secondo Pia took the first photograph of the shroud and was startled by the negative in his darkroom.[3] Negatives of the image give the appearance of a positive image, which implies that the shroud image is itself effectively a negative of some kind. Pia was immediately accused of forgery, but was finally vindicated in 1931 when a professional photographer, Giuseppe Enrie, also photographed the shroud and his findings supported Pia

Image analysis by scientists at the Jet Propulsion Laboratory found that rather than being like a photographic negative, the image unexpectedly has the property of decoding into a 3-D image of the man when the darker parts of the image are interpreted to be those features of the man that were closest to the shroud and the lighter areas of the image those features that were farthest. This is not a property that occurs in photography, and researchers could not replicate the effect when they attempted to transfer similar images using techniques of block print, engravings, a hot statue, and bas-relief.

Many people, including author Robin Cook,[42] have put forth the suggestion that the image on the shroud was produced by a side effect of the Resurrection of Jesus, purposely left intact as a rare physical aid to understanding and believing in Jesus' dual nature as man and God. Some have asserted that the shroud collapsed through the glorified body of Jesus, pointing to certain X-ray-like impressions of the teeth and the finger bones. Others assert that radiation streaming from every point of the revivifying body struck and discolored every opposite point of the cloth, forming the complete image through a kind of supernatural pointillism using inverted shades of blue-gray rather than primary colors. However, science has yet to find an example of a reviving body emitting radiation levels significant enough to produce these changes.

There are several reddish stains on the shroud suggesting blood. McCrone (see above) identified these as containing iron oxide, theorizing that its presence was likely due to simple pigment materials used in medieval times. This is in agreement with the results of an Italian commission investigating the shroud in the early 1970s. Serologists among the commission applied several different state-of-the-art blood tests which all gave a negative result for the presence of blood. No test for the presence of color pigments was performed by this commission.[57] Other researchers, including Alan Adler, a chemist specializing in analysis of porphyrins, identified the reddish stains as type AB blood and interpreted the iron oxide as a natural residue of hemoglobin. But the problem with a blood type AB for an authentic shroud is that it is today known that this type of blood is of relative recent origin. There is no evidence of the existence of this blood type before the year AD 700. It is today assumed that the blood type AB came into the existence by immigration and following intermingling of mongoloid people from central Asia with a high frequency of the blood type B to Europe and other areas where people with a relatively high frequency of the blood type A live.

As a depiction of Jesus, the image on the shroud corresponds to that found throughout the history of Christian iconography. For instance, the Pantocrator mosaic at Daphne in Athens is strikingly similar. This suggests that the icons were made while the Image of Edessa was available, with this appearance of Jesus being copied in later artwork, and in particular, on the Shroud. Art historian W.S.A. Dale proposed (before the radiocarbon dating of the Shroud) that the Shroud itself was an icon created in the 11th century for liturgical use. In opposition to this viewpoint, the locations of the piercing wounds in the wrists on the Shroud do not correspond to artistic representations of the crucifixion before close to the present time. In fact, the Shroud was widely dismissed as a forgery in the 14th century for the very reason that the Latin Vulgate Bible stated that the nails had been driven into Jesus' hands and Medieval art invariably depicts the wounds in Jesus' hands.

Although the Vatican newspaper Osservatore Romano covered the story of Secondo Pia's photograph of May 28 1898 in its June 15, 1898 edition, it did so with no comment and thereafter Church officials generally refrained from officially commenting on the photograph for almost half a century.

The first official connection between the image on the shroud and the Catholic Church was made in 1940 based on the formal request by Sister Maria Pierina De Micheli to the curia in Milan to obtain authorization to produce a medal with the image. The authorization was granted and the first medal with the image was offered to Pope Pius XII who approved the medal. The image was then used on what became known as the Holy Face Medal worn by many Catholics, initially as a means of protection during the Second World War. In 1958 Pope Pius XII approved of the image in association with the devotion to the Holy Face of Jesus, and declared its feast to be celebrated every year the day before Ash Wednesday.

In 1983 the Shroud was given to the Holy See by the House of Savoy. However, as with all relics of this kind, the Roman Catholic Church has made no pronouncements claiming whether it is Jesus' burial shroud, or if it is a forgery. As with other approved Catholic devotions, the matter has been left to the personal decision of the faithful, as long as the Church does not issue a future notification to the contrary. In the Church's view, whether the cloth is authentic or not has no bearing whatsoever on the validity of what Jesus taught nor on the saving power of his death and resurrection. The late Pope John Paul II stated in 1998, "Since we're not dealing with a matter of faith, the church can't pronounce itself on such questions. It entrusts to scientists the tasks of continuing to investigate, to reach adequate answers to the questions connected to this shroud." He showed himself to be deeply moved by the image of the shroud and arranged for public showings in 1998 and 2000. In his address at the Turin Cathedral on Sunday May 24 1998 (the occasion of the 100th year of Secondo Pia's May 28 1898 photograph), Pope John Paul II said: "... the Shroud is an image of God's love as well as of human sin" and "...The imprint left by the tortured body of the Crucified One, which attests to the tremendous human capacity for causing pain and death to one's fellow man, stands as an icon of the suffering of the innocent in every age."

Recent developments

On April 6, 2009, the Times of London reported that official Vatican researchers had uncovered evidence that the Shroud had been kept and venerated by the Templars since the 1204 sack of Constantinople. According to the account of one neophyte member of the order, veneration of the Shroud appeared to be part of the initiation ritual. The article also implies that this ceremony may be the source of the 'worship of a bearded figure' that the Templars were accused of at their 14th century trial and suppression.

On April 10, 2009, the Telegraph reported that original Shroud investigator, Ray Rogers, acknowledged the radio carbon dating performed in 1988 was flawed. The sample used for dating may have been taken from a section damaged by fire and repaired in the 16th century, which would not provide an estimate for the original material. Shortly before his death, Rogers said:

"The worst possible sample for carbon dating was taken."

"It consisted of different materials than were used in the shroud itself, so the age we produced was inaccurate."

"...I am coming to the conclusion that it has a very good chance of being the piece of cloth that was used to bury the historic Jesus."

A text, in english, about The Real Chiesa of S. Lorenzo and Turin:

The Real Chiesa of S. Lorenzo, restored on the occasion of the two Ostensionis of the Shroud (happened in 1998 and in 2000), he/she offers to the visitor, is assiduous, the vision is occasional marveled of this jewel of Guarino Guarini.

The Priests of the church of S. Lorenzo wish to each to bring itself, after having tasted how much the creation guariniana offers to the intelligence and the heart, that feelings of architectural and religious harmony that Guarino Guarini, father Teatino, knew how to amalgamate with his genius of architect and with the faith of the believer.

A visitor to the Church of San Lorenzo – a veritable work of art – reaches piazza Castello and sees no façade marking the church. Piazza Castello is a square with a theatre without a façade (Regio), a façade of a palace (Madama) with no corresponding palace, and a church without a façade. One in fact was designed but never built to maintain the architectural harmony of the square.

The church is next to the gates of the royal palace.

On the church front there is a plaque commemorating the dead on the Russian front and above a bell that strikes 10 times at 5.15 p.m. every day.

Why is this Royal Chapel dedicated to San Lorenzo (St. Lawrence)?

In 1557, Emmanuel Philibert, Duke of Savoy, and his cousin Phillip II, King of Spain, were fighting the French at Saint-Quentin in Flanders.

They made a votive offering to build a church in the name of the saint whose feast fell on the day of their eventual victory; that victory came on 10 August, St. Lawrence’s day.

Turin:

Turin, Torino in Italian, is an interesting and often overlooked city in the Piedmont region of Italy. Famous for the Shroud of Turin and Fiat auto plants, Turin has a lot more to offer. From its Baroque cafes and architecture to its arcaded shopping promenades and museums, Turin is a great city for wandering and exploring. Turin hosted the 2006 Winter Olympics and makes a good base for exploring nearby mountains and valleys.

Turin is in the northwest of Italy in the Piemonte region between the Po River and the foothills of the Alps.

Turin is served by a small airport, Citta di Torino - Sandro Pertini, with flights to and from Europe. There is bus service connecting Turin's airport with Turin and the main railway station. A railway links the airport to GTT Dora Railway Station in the northwest of Turin. The closest airport for flights from the United States is in Milan, a little over an hour away by train.

Turin is a major hub on the Italian train line and intercity buses provide transportation to and from Turin.

Turin has an extensive network of trams and buses that run from 5AM until midnight. There are also electric mini-buses in the city center. Bus and tram tickets can be bought in a tabacchi shop. A 28km metropolitan line is due for completion in 2006.

Turin's main railway station is Porta Nuova in central Turin at the Piazza Carlo Felice. The Porta Susa Station is the main station for trains to and from Milan and is connected to central Turin and the main station by bus.

There are tourist offices at the Porta Nuova Railway Station and at the airport. The main office is in Piazza Castello and there is also one in Piazza Solferino.

You can find landromats and internet points in Turin with Lavasciuga.

Turin discount cards: See Turin and Piedmont Card for information about discount passes and the ChocoPass for chocolate tastings.

The Piedmont region has some of the best food in Italy. Over 160 types of cheese and famous wines like Barolo and Barbaresco come from here as do truffles, plentiful in fall. Turin has some outstanding pastries, especially chocolate ones. Chocolate for eating as we know it today (bars and pieces) originated in Turin. The chocolate-hazelnut sauce, gianduja, is a specialty of Turin.

Turin celebrates its patron saint in the Festa di San Giovanni June 24 with events all day and a huge fireworks display at night. Turin's big chocolate festival is in March. Turin has several music and theater festivals in summer and fall. During the Christmas season there is a 2-week street market and on New Year's Eve an open-air conert in the main piazza. The Turin Marathon in April attracts a huge number of international participants.

Turin has many museums. Walking around the city with its arcades, Baroque buildings, and beautiful piazzas can be very enjoyable.

* The Via Po is an interesting walking street with long arcades and many historic palaces and cafes. Start at Piazza Castello.

* Mole Antonelliana, a 167 meter tall tower built between 1798 and 1888, houses an excellent cinema museum. A panoramic lift takes you to the top of the tower for some expansive views of the city.

* Palazzo Carignano is the birthplace of Vittorio Emanuele II in 1820. The Unification of Italy was proclaimed here in 1861. It now houses the Museo del Risorgimento and you can see the royal apartments Royal Armoury, too.

* Museo Egizio is the third most important Egyptian museum in the world. It is housed in a huge baroque palace which also holds the Galleria Sagauda with a large collection of historic paintings.

* Piazza San Carlo, known as the "drawing room of Turin", is a beautiful baroque square with the twin churches of San Carlo and Santa Cristina as well as the above museum.

* Piazza Castello and Palazzo Reale are at the center of Turin. The square is a pedestrian area with benches and small fountains, ringed by beautiful, grand buildings.

* Il Quadrilatero is an interesting maze of backstreets with sprawling markets and splendid churches. This is another good place wo wander.

* Elegant and historic bars and cafes are everywhere in central Turin. Try a bicerin, a local layered drink made with coffee, chocolate, and cream. Cafes in Turin also serve other interesting trendy coffee drinks.

Just be beautiful mcr by al shep

26

The prefix pseudo- lying, false is used to mark something as false, fraudulent, or pretending to be something it is not. Psychosis refers to an abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality". People suffering from psychosis are described as psychotic. Psychosis (as a sign of a psychiatric disorder) is first and foremost a diagnosis of exclusion; that is, a new-onset episode of psychosis cannot be considered to be a symptom of a psychiatric disorder until other relevant and known causes of psychosis are properly excluded, or ruled out. Medical and biological laboratory tests should exclude central nervous system diseases and injuries, diseases and injuries of other organs, illicit substances, toxins, and prescribed medications as causes of symptoms of psychosis before any psychiatric illness can be diagnosed. In medical training, psychosis as a sign of illness, is often compared to "fever," since it can have multiple causes that aren't readily apparent. The term "psychosis" is very broad and can mean anything from relatively normal aberrant experiences through to the complex and catatonic expressions of schizophrenia and bipolar type 1 disorder. In properly diagnosed psychiatric disorders (where other causes have been excluded by extensive medical and biological laboratory tests), psychosis is a descriptive term for the hallucinations, delusions, sometimes violence, and impaired insight that may occur. Psychosis is generally given to noticeable deficits in normal behavior (negative signs) and more commonly to diverse types of hallucinations or delusional beliefs (e.g. grandiosity, delusions of persecution). An excess in dopaminergic signalling is hypothesized to be linked to the positive symptoms of psychosis, especially those of schizophrenia; however, this hypothesis has not been definitively supported. The dopaminergic mechanism is thought to involve the aberrant salience of environmental stimuli. Many antipsychotic drugs accordingly target the dopamine system; however, meta-analyses of placebo-controlled trials of these drugs show either no significant difference in effects between drug and placebo, or a very small effect size, suggesting that the pathophysiology of psychosis is much more complex than an overactive dopamine system. People experiencing psychosis may exhibit some personality changes and thought disorder. Depending on its severity, this may be accompanied by unusual or bizarre behavior, as well as difficulty with social interaction and impairment in carrying out daily life activities.

Solving Mysteries by Xavier J. Peg

32 17

Study becomes easy when you want to learn. When you are searching for solutions. Some people know me as a photographer, but I am also a nurse. As a nurse I am a detective. A health detective, able to see a reason for two seemingly diverse indicators such as trouble concentrating and consuming large quantities of ice. The foundation of arriving at solutions in healthcare lies in the study of pathophysiology. I enjoy my role in healthcare. I like finding root causes, solutions and bringing about improvements in people's lives.

So, if you hate studying, then change your way of thinking about it. Find a way to benefit yourself or others through your increasing knowledge. You won't be worth a damn at what you want to do if you don't understand what you're doing. Those indicators? Iron deficiency anemia. Quick and easy solution? Get rid of the copper and aluminum cookware and replace it with cast iron. If that isn't possible, increase the intake of beef, turkey and beans.

We're Here! : Everyone-hates-studying >.<

Running out of ideas for your 365 project? Join We're Here!

View Large and on Black

It's Not All Fun And Games by A Guy Named Nyal

9

While I was off exploring the ship the wife was putting in the work.

Her current class is Pathophysiology, which is according to Wikipedia, " is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury." Yay!

Of course, if you have to study why not do it in the comfort of the ships library? Much better than studying from home!

Avoid me by al shep

35 8

The prefix pseudo- lying, false is used to mark something as false, fraudulent, or pretending to be something it is not. Psychosis refers to an abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality". People suffering from psychosis are described as psychotic.

Psychosis (as a sign of a psychiatric disorder) is first and foremost a diagnosis of exclusion; that is, a new-onset episode of psychosis cannot be considered to be a symptom of a psychiatric disorder until other relevant and known causes of psychosis are properly excluded, or ruled out. Medical and biological laboratory tests should exclude central nervous system diseases and injuries, diseases and injuries of other organs, illicit substances, toxins, and prescribed medications as causes of symptoms of psychosis before any psychiatric illness can be diagnosed. In medical training, psychosis as a sign of illness, is often compared to "fever," since it can have multiple causes that aren't readily apparent.

The term "psychosis" is very broad and can mean anything from relatively normal aberrant experiences through to the complex and catatonic expressions of schizophrenia and bipolar type 1 disorder. In properly diagnosed psychiatric disorders (where other causes have been excluded by extensive medical and biological laboratory tests), psychosis is a descriptive term for the hallucinations, delusions, sometimes violence, and impaired insight that may occur. Psychosis is generally given to noticeable deficits in normal behavior (negative signs) and more commonly to diverse types of hallucinations or delusional beliefs (e.g. grandiosity, delusions of persecution).

An excess in dopaminergic signalling is hypothesized to be linked to the positive symptoms of psychosis, especially those of schizophrenia; however, this hypothesis has not been definitively supported. The dopaminergic mechanism is thought to involve the aberrant salience of environmental stimuli. Many antipsychotic drugs accordingly target the dopamine system; however, meta-analyses of placebo-controlled trials of these drugs show either no significant difference in effects between drug and placebo, or a very small effect size, suggesting that the pathophysiology of psychosis is much more complex than an overactive dopamine system.

People experiencing psychosis may exhibit some personality changes and thought disorder. Depending on its severity, this may be accompanied by unusual or bizarre behavior, as well as difficulty with social interaction and impairment in carrying out daily life activities.

Coronavirus disease 2019...Passive antibodies... immune systems... antibody-dependent cellular cytotoxicity...Sex differences...Gendered impact of the pandemic and mortality rates are different for men and women. by Hughes Songe

15

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[8] The disease was first identified in December 2019 in Wuhan, the capital of China's Hubei province, and has since spread globally, resulting in the ongoing 2019–20 coronavirus pandemic.[9][10] As of 26 April 2020, more than 2.89 million cases have been reported across 185 countries and territories, resulting in more than 203,000 deaths. More than 822,000 people have recovered.[7]

Common symptoms include fever, cough, fatigue, shortness of breath and loss of smell.[5][11][12] While the majority of cases result in mild symptoms, some progress to viral pneumonia, multi-organ failure, or cytokine storm.[13][9][14] More concerning symptoms include difficulty breathing, persistent chest pain, confusion, difficulty waking, and bluish skin.[5] The time from exposure to onset of symptoms is typically around five days but may range from two to fourteen days.[5][15]

The virus is primarily spread between people during close contact,[a] often via small droplets produced by coughing,[b] sneezing, or talking.[6][16][18] The droplets usually fall to the ground or onto surfaces rather than remaining in the air over long distances.[6][19][20] People may also become infected by touching a contaminated surface and then touching their face.[6][16] In experimental settings, the virus may survive on surfaces for up to 72 hours.[21][22][23] It is most contagious during the first three days after the onset of symptoms, although spread may be possible before symptoms appear and in later stages of the disease.[24] The standard method of diagnosis is by real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab.[25] Chest CT imaging may also be helpful for diagnosis in individuals where there is a high suspicion of infection based on symptoms and risk factors; however, guidelines do not recommend using it for routine screening.[26][27]

Recommended measures to prevent infection include frequent hand washing, maintaining physical distance from others (especially from those with symptoms), covering coughs, and keeping unwashed hands away from the face.[28][29] In addition, the use of a face covering is recommended for those who suspect they have the virus and their caregivers.[30][31] Recommendations for face covering use by the general public vary, with some authorities recommending against their use, some recommending their use, and others requiring their use.[32][31][33] Currently, there is not enough evidence for or against the use of masks (medical or other) in healthy individuals in the wider community.[6] Also masks purchased by the public may impact availability for health care providers.

Currently, there is no vaccine or specific antiviral treatment for COVID-19.[6] Management involves the treatment of symptoms, supportive care, isolation, and experimental measures.[34] The World Health Organization (WHO) declared the 2019–20 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC)[35][36] on 30 January 2020 and a pandemic on 11 March 2020.[10] Local transmission of the disease has occurred in most countries across all six WHO regions.[37]

File:En.Wikipedia-VideoWiki-Coronavirus disease 2019.webm

Video summary (script)

Contents

1Signs and symptoms

2Cause

2.1Transmission

2.2Virology

3Pathophysiology

3.1Immunopathology

4Diagnosis

4.1Pathology

5Prevention

6Management

6.1Medications

6.2Protective equipment

6.3Mechanical ventilation

6.4Acute respiratory distress syndrome

6.5Experimental treatment

6.6Information technology

6.7Psychological support

7Prognosis

7.1Reinfection

8History

9Epidemiology

9.1Infection fatality rate

9.2Sex differences

10Society and culture

10.1Name

10.2Misinformation

10.3Protests

11Other animals

12Research

12.1Vaccine

12.2Medications

12.3Anti-cytokine storm

12.4Passive antibodies

13See also

14Notes

15References

16External links

16.1Health agencies

16.2Directories

16.3Medical journals

Signs and symptoms

Symptom[4]Range

Fever83–99%

Cough59–82%

Loss of Appetite40–84%

Fatigue44–70%

Shortness of breath31–40%

Coughing up sputum28–33%

Loss of smell15[38] to 30%[12][39]

Muscle aches and pains11–35%

Fever is the most common symptom, although some older people and those with other health problems experience fever later in the disease.[4][40] In one study, 44% of people had fever when they presented to the hospital, while 89% went on to develop fever at some point during their hospitalization.[4][41]

Other common symptoms include cough, loss of appetite, fatigue, shortness of breath, sputum production, and muscle and joint pains.[4][5][42][43] Symptoms such as nausea, vomiting and diarrhoea have been observed in varying percentages.[44][45][46] Less common symptoms include sneezing, runny nose, or sore throat.[47]

More serious symptoms include difficulty breathing, persistent chest pain or pressure, confusion, difficulty waking, and bluish face or lips. Immediate medical attention is advised if these symptoms are present.[5][48]

In some, the disease may progress to pneumonia, multi-organ failure, and death.[9][14] In those who develop severe symptoms, time from symptom onset to needing mechanical ventilation is typically eight days.[4] Some cases in China initially presented with only chest tightness and palpitations.[49]

Loss of smell was identified as a common symptom of COVID‑19 in March 2020,[12][39] although perhaps not as common as initially reported.[38] A decreased sense of smell and/or disturbances in taste have also been reported.[50] Estimates for loss of smell range from 15%[38] to 30%.[12][39]

As is common with infections, there is a delay between the moment a person is first infected and the time he or she develops symptoms. This is called the incubation period. The incubation period for COVID‑19 is typically five to six days but may range from two to 14 days,[51][52] although 97.5% of people who develop symptoms will do so within 11.5 days of infection.[53]

A minority of cases do not develop noticeable symptoms at any point in time.[54][55] These asymptomatic carriers tend not to get tested, and their role in transmission is not yet fully known.[56][57] However, preliminary evidence suggests they may contribute to the spread of the disease.[58][59] In March 2020, the Korea Centers for Disease Control and Prevention (KCDC) reported that 20% of confirmed cases remained asymptomatic during their hospital stay.[59][60]

A number of neurological symptoms has been reported including seizures, stroke, encephalitis and Guillain-Barre syndrome.[61] Cardiovascular related complications may include heart failure, irregular electrical activity, blood clots, and heart inflammation.[62]

Cause

See also: Severe acute respiratory syndrome coronavirus 2

Transmission

Cough/sneeze droplets visualised in dark background using Tyndall scattering

Respiratory droplets produced when a man is sneezing visualised using Tyndall scattering

File:COVID19 in numbers- R0, the case fatality rate and why we need to flatten the curve.webm

A video discussing the basic reproduction number and case fatality rate in the context of the pandemic

Some details about how the disease is spread are still being determined.[16][18] The WHO and the U.S. Centers for Disease Control and Prevention (CDC) say it is primarily spread during close contact and by small droplets produced when people cough, sneeze or talk;[6][16] with close contact being within approximately 1–2 m (3–7 ft).[6][63] Both sputum and saliva can carry large viral loads.[64] Loud talking releases more droplets than normal talking.[65] A study in Singapore found that an uncovered cough can lead to droplets travelling up to 4.5 metres (15 feet).[66] An article published in March 2020 argued that advice on droplet distance might be based on 1930s research which ignored the effects of warm moist exhaled air surrounding the droplets and that an uncovered cough or sneeze can travel up to 8.2 metres (27 feet).[17]

Respiratory droplets may also be produced while breathing out, including when talking. Though the virus is not generally airborne,[6][67] the National Academy of Sciences has suggested that bioaerosol transmission may be possible.[68] In one study cited, air collectors positioned in the hallway outside of people's rooms yielded samples positive for viral RNA but finding infectious virus has proven elusive.[68] The droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.[16] Some medical procedures such as intubation and cardiopulmonary resuscitation (CPR) may cause respiratory secretions to be aerosolised and thus result in an airborne spread.[67] Initial studies suggested a doubling time of the number of infected persons of 6–7 days and a basic reproduction number (R0 ) of 2.2–2.7, but a study published on April 7, 2020, calculated a much higher median R0 value of 5.7 in Wuhan.[69]

It may also spread when one touches a contaminated surface, known as fomite transmission, and then touches one's eyes, nose or mouth.[6] While there are concerns it may spread via faeces, this risk is believed to be low.[6][16]

The virus is most contagious when people are symptomatic; though spread is may be possible before symptoms emerge and from those who never develop symptoms.[6][70] A portion of individuals with coronavirus lack symptoms.[71] The European Centre for Disease Prevention and Control (ECDC) says while it is not entirely clear how easily the disease spreads, one person generally infects two or three others.[18]

The virus survives for hours to days on surfaces.[6][18] Specifically, the virus was found to be detectable for one day on cardboard, for up to three days on plastic (polypropylene) and stainless steel (AISI 304), and for up to four hours on 99% copper.[21][23] This, however, varies depending on the humidity and temperature.[72][73] Surfaces may be decontaminated with many solutions (with one minute of exposure to the product achieving a 4 or more log reduction (99.99% reduction)), including 78–95% ethanol (alcohol used in spirits), 70–100% 2-propanol (isopropyl alcohol), the combination of 45% 2-propanol with 30% 1-propanol, 0.21% sodium hypochlorite (bleach), 0.5% hydrogen peroxide, or 0.23–7.5% povidone-iodine. Soap and detergent are also effective if correctly used; soap products degrade the virus' fatty protective layer, deactivating it, as well as freeing them from the skin and other surfaces.[74] Other solutions, such as benzalkonium chloride and chlorhexidine gluconate (a surgical disinfectant), are less effective.[75]

In a Hong Kong study, saliva samples were taken a median of two days after the start of hospitalization. In five of six patients, the first sample showed the highest viral load, and the sixth patient showed the highest viral load on the second day tested.[64]

Virology

Main article: Severe acute respiratory syndrome coronavirus 2

Illustration of SARSr-CoV virion

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus, first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan.[76] All features of the novel SARS-CoV-2 virus occur in related coronaviruses in nature.[77] Outside the human body, the virus is killed by household soap, which bursts its protective bubble.[26]

SARS-CoV-2 is closely related to the original SARS-CoV.[78] It is thought to have a 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).[47] In February 2020, Chinese researchers found that there is only one amino acid difference in the binding domain of the S protein between the coronaviruses from pangolins and those from humans; however, whole-genome comparison to date found that at most 92% of genetic material was shared between pangolin coronavirus and SARS-CoV-2, which is insufficient to prove pangolins to be the intermediate host.[79]

Pathophysiology

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.[80] The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and some have suggested that decreasing ACE2 activity might be protective,[81][82] though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective and these hypotheses need to be tested.[83] As the alveolar disease progresses, respiratory failure might develop and death may follow.[82]

The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium[84] as well as endothelial cells and enterocytes of the small intestine.[85]

ACE2 is present in the brain, and there is growing evidence of neurological manifestations in people with COVID‑19. It is not certain if the virus can directly infect the brain by crossing the barriers that separate the circulation of the brain and the general circulation. Other coronaviruses are able to infect the brain via a synaptic route to the respiratory centre in the medulla, through mechanoreceptors like pulmonary stretch receptors and chemoreceptors (primarily central chemoreceptors) within the lungs.[medical citation needed] It is possible that dysfunction within the respiratory centre further worsens the ARDS seen in COVID‑19 patients. Common neurological presentations include a loss of smell, headaches, nausea, and vomiting. Encephalopathy has been noted to occur in some patients (and confirmed with imaging), with some reports of detection of the virus after cerebrospinal fluid assays although the presence of oligoclonal bands seems to be a common denominator in these patients.[86]

The virus can cause acute myocardial injury and chronic damage to the cardiovascular system.[87] An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China,[88] and is more frequent in severe disease.[89] 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.[87] ACE2 receptors are highly expressed in the heart and are involved in heart function.[87][90] A high incidence of thrombosis (31%) and venous thromboembolism (25%) have been found in ICU patients with COVID‑19 infections and may be related to poor prognosis.[91][92] Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels) 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 patients 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 with the presentation of viral pneumonia.[93]

Another common cause of death is complications related to the kidneys[93]—SARS-CoV-2 directly infects kidney cells, as confirmed in post-mortem studies. Acute kidney injury is a common complication and cause of death; this is more significant in patients with already compromised kidney function, especially in people with pre-existing chronic conditions such as hypertension and diabetes which specifically cause nephropathy in the long run.[94]

Autopsies of people who died of COVID‑19 have found diffuse alveolar damage (DAD), and lymphocyte-containing inflammatory infiltrates within the lung.[95]

Immunopathology

Although SARS-COV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, patients 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.[96]

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.[97]

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 COVID‑19 patients.[98] Lymphocytic infiltrates have also been reported at autopsy.[95]

Diagnosis

Main article: COVID-19 testing

Demonstration of a nasopharyngeal swab for COVID-19 testing

CDC rRT-PCR test kit for COVID-19[99]

The WHO has published several testing protocols for the disease.[100] The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR).[101] The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used.[25][102] Results are generally available within a few hours to two days.[103][104] Blood tests can be used, but these require two blood samples taken two weeks apart, and the results have little immediate value.[105] Chinese scientists were able to isolate a strain of the coronavirus and publish the genetic sequence so laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus.[9][106][107] As of 4 April 2020, antibody tests (which may detect active infections and whether a person had been infected in the past) were in development, but not yet widely used.[108][109][110] The Chinese experience with testing has shown the accuracy is only 60 to 70%.[111] The FDA in the United States approved the first point-of-care test on 21 March 2020 for use at the end of that month.[112]

Diagnostic guidelines released by Zhongnan Hospital of Wuhan University suggested methods for detecting infections based upon clinical features and epidemiological risk. These involved identifying people who had at least two of the following symptoms in addition to a history of travel to Wuhan or contact with other infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count, or reduced lymphocyte count.[113]

A study asked hospitalised COVID‑19 patients to cough into a sterile container, thus producing a saliva sample, and detected the virus in eleven of twelve patients using RT-PCR. This technique has the potential of being quicker than a swab and involving less risk to health care workers (collection at home or in the car).[64]

Along with laboratory testing, 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.[26][27] Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection.[26] Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses.[26][114]

In late 2019, WHO assigned the 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.[115]

Typical CT imaging findings

CT imaging of rapid progression stage

Pathology

Few data are available about microscopic lesions and the pathophysiology of COVID‑19.[116][117] The main pathological findings at autopsy are:

Macroscopy: pleurisy, pericarditis, lung consolidation and pulmonary oedema

Four types of severity of viral pneumonia can be observed:

minor pneumonia: minor serous exudation, minor fibrin exudation

mild pneumonia: pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation

severe pneumonia: diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.

healing pneumonia: organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis

plasmocytosis in BAL[118]

Blood: disseminated intravascular coagulation (DIC);[119] leukoerythroblastic reaction[120]

Liver: microvesicular steatosis

Prevention

See also: 2019–20 coronavirus pandemic § Prevention, flatten the curve, and workplace hazard controls for COVID-19

Progressively stronger mitigation efforts to reduce the number of active cases at any given time—known as "flattening the curve"—allows healthcare services to better manage the same volume of patients.[121][122][123] Likewise, progressively greater increases in healthcare capacity—called raising the line—such as by increasing bed count, personnel, and equipment, helps to meet increased demand.[124]

Mitigation attempts that are inadequate in strictness or duration—such as premature relaxation of distancing rules or stay-at-home orders—can allow a resurgence after the initial surge and mitigation.[122][125]

Preventive measures to reduce the chances of infection include staying at home, avoiding crowded places, keeping distance from others, 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.[126][127][128] 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.[126] Proper hand hygiene after any cough or sneeze is encouraged.[126] The CDC has recommended the use of cloth face coverings in public settings where other social distancing measures are difficult to maintain, in part to limit transmission by asymptomatic individuals.[129] The U.S. 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 of the setting of a clinical trial.[130]

Social distancing strategies aim to reduce contact of infected persons with large groups by closing schools and workplaces, restricting travel, and cancelling large public gatherings.[131] Distancing guidelines also include that people stay at least 6 feet (1.8 m) apart.[132] There is no medication known to be effective at preventing COVID‑19.[133] After the implementation of social distancing and stay-at-home orders, many regions have been able to sustain an effective transmission rate ("Rt") of less than one, meaning the disease is in remission in those areas.[134]

As a vaccine is not expected until 2021 at the earliest,[135] a key part of managing COVID‑19 is trying to decrease the epidemic peak, known as "flattening the curve".[122] 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.[122][125]

According to the WHO, the use of masks is recommended only if a person is coughing or sneezing or when one is taking care of someone with a suspected infection.[136] For the European Centre for Disease Prevention and Control (ECDC) face masks "... could be considered especially when visiting busy closed spaces ..." but "... only as a complementary measure ..."[137] Several countries have recommended that healthy individuals wear face masks or cloth face coverings (like scarves or bandanas) at least in certain public settings, including China,[138] Hong Kong,[139] Spain,[140] Italy (Lombardy region),[141] and the United States.[129]

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.[30][142] The CDC 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, coughing or sneezing. It further recommends using an alcohol-based hand sanitiser with at least 60% alcohol, but only when soap and water are not readily available.[126]

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.[143]

Prevention efforts are multiplicative, with effects far beyond that of a single spread. Each avoided case leads to more avoided cases down the line, which in turn can stop the outbreak in its tracks.

File:COVID19 W ENG.ogv

Handwashing instructions

Management

People are managed with supportive care, which may include fluid therapy, oxygen support, and supporting other affected vital organs.[144][145][146] The CDC recommends that those who suspect they carry the virus wear a simple face mask.[30] Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration.[41][147] Personal hygiene and a healthy lifestyle and diet have been recommended to improve immunity.[148] Supportive treatments may be useful in those with mild symptoms at the early stage of infection.[149]

The WHO, the Chinese National Health Commission, and the United States' National Institutes of Health have published recommendations for taking care of people who are hospitalised with COVID‑19.[130][150][151] Intensivists and pulmonologists in the U.S. have compiled treatment recommendations from various agencies into a free resource, the IBCC.[152][153]

Medications

See also: Coronavirus disease 2019 § Research

As of April 2020, there is no specific treatment for COVID‑19.[6][133] Research is, however, ongoing. For symptoms, some medical professionals recommend paracetamol (acetaminophen) over ibuprofen for first-line use.[154][155][156] The WHO and NIH do not oppose the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for symptoms,[130][157] and the FDA says currently there is no evidence that NSAIDs worsen COVID‑19 symptoms.[158]

While theoretical concerns have been raised about ACE inhibitors and angiotensin receptor blockers, as of 19 March 2020, these are not sufficient to justify stopping these medications.[130][159][160][161] Steroids, such as methylprednisolone, are not recommended unless the disease is complicated by acute respiratory distress syndrome.[162][163]

Medications to prevent blood clotting have been suggested for treatment,[91] and anticoagulant therapy with low molecular weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).[164]

Protective equipment

See also: § Research

Research into potential treatments started in January 2020,[182] and several antiviral drugs are in clinical trials.[183][184] Remdesivir appears to be the most promising.[133] Although new medications may take until 2021 to develop,[185] several of the medications being tested are already approved for other uses or are already in advanced testing.[186] Antiviral medication may be tried in people with severe disease.[144] The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments.[187]

The FDA has granted temporary authorisation to convalescent plasma as an experimental treatment in cases where the person's life is seriously or immediately threatened. It has not undergone the clinical studies needed to show it is safe and effective for the disease.[188][189][190]

Information technology

See also: Contact tracing and Government by algorithm

In February 2020, China launched a mobile app to deal with the disease outbreak.[191] Users are asked to enter their name and ID number. The app can detect 'close contact' using surveillance data and therefore a potential risk of infection. Every user can also check the status of three other users. If a potential risk is detected, the app not only recommends self-quarantine, it also alerts local health officials.[192]

Big data analytics on cellphone data, facial recognition technology, mobile phone tracking, and artificial intelligence are used to track infected people and people whom they contacted in South Korea, Taiwan, and Singapore.[193][194] In March 2020, the Israeli government enabled security agencies to track mobile phone data of people supposed to have coronavirus. The measure was taken to enforce quarantine and protect those who may come into contact with infected citizens.[195] Also in March 2020, Deutsche Telekom shared aggregated phone location data with the German federal government agency, Robert Koch Institute, to research and prevent the spread of the virus.[196] Russia deployed facial recognition technology to detect quarantine breakers.[197] Italian regional health commissioner Giulio Gallera said he has been informed by mobile phone operators that "40% of people are continuing to move around anyway".[198] German government conducted a 48 hours weekend hackathon with more than 42.000 participants.[199][200] Two million people in the UK used an app developed in March 2020 by King's College London and Zoe to track people with COVID‑19 symptoms.[201] Also, the president of Estonia, Kersti Kaljulaid, made a global call for creative solutions against the spread of coronavirus.[202]

Psychological support

See also: Mental health during the 2019–20 coronavirus pandemic

Individuals may experience distress from quarantine, travel restrictions, side effects of treatment, or fear of the infection itself. To address these concerns, the National Health Commission of China published a national guideline for psychological crisis intervention on 27 January 2020.[203][204]

The Lancet published a 14-page call for action focusing on the UK and stated conditions were such that a range of mental health issues was likely to become more common. BBC quoted Rory O'Connor in saying, "Increased social isolation, loneliness, health anxiety, stress and an economic downturn are a perfect storm to harm people's mental health and wellbeing."[205][206]

Prognosis

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The severity of diagnosed cases in China

The severity of diagnosed COVID-19 cases in China[207]

Case fatality rates for COVID-19 by age by country.

Case fatality rates by age group:

China, as of 11 February 2020[208]

South Korea, as of 15 April 2020[209]

Spain, as of 24 April 2020[210]

Italy, as of 23 April 2020[211]

Case fatality rate depending on other health problems

Case fatality rate in China depending on other health problems. Data through 11 February 2020.[208]

Case fatality rate by country and number of cases

The number of deaths vs total cases by country and approximate case fatality rate[212]

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. 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.[47]

Children make up a small proportion of reported cases, with about 1% of cases being under 10 years, and 4% aged 10-19 years.[22] They are likely to have milder symptoms and a lower chance of severe disease than adults; in those younger than 50 years, the risk of death is less than 0.5%, while in those older than 70 it is more than 8%.[213][214][215] Pregnant women may be at higher risk for severe infection with COVID-19 based on data from other similar viruses, like SARS and MERS, but data for COVID-19 is lacking.[216][217] In China, children acquired infections mainly through close contact with their parents or other family members who lived in Wuhan or had traveled there.[213]

In some people, COVID‑19 may affect the lungs causing pneumonia. In those most severely affected, COVID-19 may rapidly progress to acute respiratory distress syndrome (ARDS) causing respiratory failure, septic shock, or multi-organ failure.[218][219] Complications associated with COVID‑19 include sepsis, abnormal clotting, and damage to the heart, kidneys, and liver. Clotting abnormalities, specifically an increase in prothrombin time, have been described in 6% of those admitted to hospital with COVID-19, while abnormal kidney function is seen in 4% of this group.[220] Approximately 20-30% of people who present with COVID‑19 demonstrate elevated liver enzymes (transaminases).[133] Liver injury as shown by blood markers of liver damage is frequently seen in severe cases.[221]

Some studies have found that the neutrophil to lymphocyte ratio (NLR) may be helpful in early screening for severe illness.[222]

Most of those who die of COVID‑19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease.[223] The Istituto Superiore di Sanità reported that out of 8.8% of deaths where medical charts were available for review, 97.2% of sampled patients had at least one comorbidity with the average patient having 2.7 diseases.[224] According to the same report, the median time between the onset of symptoms and death was ten days, with five being spent hospitalised. However, patients transferred to an ICU had a median time of seven days between hospitalisation and death.[224] In a study of early cases, the median time from exhibiting initial symptoms to death was 14 days, with a full range of six to 41 days.[225] In a study by the National Health Commission (NHC) of China, men had a death rate of 2.8% while women had a death rate of 1.7%.[226] Histopathological examinations of post-mortem lung samples show diffuse alveolar damage with cellular fibromyxoid exudates in both lungs. Viral cytopathic changes were observed in the pneumocytes. The lung picture resembled acute respiratory distress syndrome (ARDS).[47] In 11.8% of the deaths reported by the National Health Commission of China, heart damage was noted by elevated levels of troponin or cardiac arrest.[49] According to March data from the United States, 89% of those hospitalised had preexisting conditions.[227]

The availability of medical resources and the socioeconomics of a region may also affect mortality.[228] Estimates of the mortality from the condition vary because of those regional differences,[229] but also because of methodological difficulties. The under-counting of mild cases can cause the mortality rate to be overestimated.[230] However, the fact that deaths are the result of cases contracted in the past can mean the current mortality rate is underestimated.[231][232] Smokers were 1.4 times more likely to have severe symptoms of COVID‑19 and approximately 2.4 times more likely to require intensive care or die compared to non-smokers.[233]

Concerns have been raised about long-term sequelae of the disease. The Hong Kong Hospital Authority found a drop of 20% to 30% in lung capacity in some people who recovered from the disease, and lung scans suggested organ damage.[234] This may also lead to post-intensive care syndrome following recovery.[235]

Case fatality rates (%) by age and country

Age0–910–1920–2930–3940–4950–5960–6970–7980-8990+

China as of 11 February[208]0.00.20.20.20.41.33.68.014.8

Denmark as of 25 April[236]0.24.515.524.940.7

Italy as of 23 April[211]0.20.00.10.40.92.610.024.930.826.1

Netherlands as of 17 April[237]0.00.30.10.20.51.57.623.230.029.3

Portugal as of 24 April[238]0.00.00.00.00.30.62.88.516.5

S. Korea as of 15 April[209]0.00.00.00.10.20.72.59.722.2

Spain as of 24 April[210]0.30.40.30.30.61.34.413.220.320.1

Switzerland as of 25 April[239]0.90.00.00.10.00.52.710.124.0

Case fatality rates (%) by age in the United States

Age0–1920–4445–5455–6465–7475–8485+

United States as of 16 March[240]0.00.1–0.20.5–0.81.4–2.62.7–4.94.3–10.510.4–27.3

Note: The lower bound includes all cases. The upper bound excludes cases that were missing data.

Estimate of infection fatality rates and probability of severe disease course (%) by age based on cases from China[241]

0–910–1920–2930–3940–4950–5960–6970–7980+

Severe disease0.0

(0.0–0.0)0.04

(0.02–0.08)1.0

(0.62–2.1)3.4

(2.0–7.0)4.3

(2.5–8.7)8.2

(4.9–17)11

(7.0–24)17

(9.9–34)18

(11–38)

Death0.0016

(0.00016–0.025)0.0070

(0.0015–0.050)0.031

(0.014–0.092)0.084

(0.041–0.19)0.16

(0.076–0.32)0.60

(0.34–1.3)1.9

(1.1–3.9)4.3

(2.5–8.4)7.8

(3.8–13)

Total infection fatality rate is estimated to be 0.66% (0.39–1.3). Infection fatality rate is fatality per all infected individuals, regardless of whether they were diagnosed or had any symptoms. Numbers in parentheses are 95% credible intervals for the estimates.

Reinfection

As of March 2020, it was unknown if past infection provides effective and long-term immunity in people who recover from the disease.[242] Immunity is seen as likely, based on the behaviour of other coronaviruses,[243] but cases in which recovery from COVID‑19 have been followed by positive tests for coronavirus at a later date have been reported.[244][245][246][247] These cases are believed to be worsening of a lingering infection rather than re-infection.[247]

History

Main article: Timeline of the 2019–20 coronavirus pandemic

The virus is thought to be natural and has an animal origin,[77] through spillover infection.[248] The actual origin is unknown, but by December 2019 the spread of infection was almost entirely driven by human-to-human transmission.[208][249] A study of the first 41 cases of confirmed COVID‑19, published in January 2020 in The Lancet, revealed the earliest date of onset of symptoms as 1 December 2019.[250][251][252] Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019.[253] Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020.[254][255]

Epidemiology

Main article: 2019–20 coronavirus pandemic

Several measures are commonly used to quantify mortality.[256] 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.[257]

The death-to-case ratio 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 7.0% (203,044/2,899,830) as of 26 April 2020.[7] The number varies by region.[258]

Other measures include the case fatality rate (CFR), which reflects the percent of diagnosed individuals who die from a disease, and the infection fatality rate (IFR), which reflects the percent of infected individuals (diagnosed and undiagnosed) who die from a disease. These statistics are not time-bound and follow a specific population from infection through case resolution. Many academics have attempted to calculate these numbers for specific populations.[259]

Total confirmed cases over time

Total deaths over time

Total confirmed cases of COVID‑19 per million people, 10 April 2020[260]

Total confirmed deaths due to COVID‑19 per million people, 10 April 2020[261]

Infection fatality rate

Our World in Data states that as of March 25, 2020, the infection fatality rate (IFR) cannot be accurately calculated.[262] In February, the World Health Organization estimated the IFR at 0.94%, with a confidence interval between 0.37 percent to 2.9 percent.[263] The University of Oxford Centre for Evidence-Based Medicine (CEBM) estimated a global CFR of 0.72 percent and IFR of 0.1 percent to 0.36 percent.[264] According to CEBM, random antibody testing in Germany suggested an IFR of 0.37 percent there.[264] Firm lower limits to local infection fatality rates were established, such as in Bergamo province, where 0.57% of the population has died, leading to a minimum IFR of 0.57% in the province. This population fatality rate (PFR) minimum increases as more people get infected and run through their disease.[265][266] Similarly, as of April 22 in the New York City area, there were 15,411 deaths confirmed from COVID-19, and 19,200 excess deaths.[267] Very recently, the first results of antibody testing have come in, but there are no valid scientific reports based on them available yet. A Bloomberg Opinion piece provides a survey.[268][269]

Sex differences

Main article: Gendered impact of the 2019–20 coronavirus pandemic

The impact of the pandemic and its mortality rate are different for men and women.[270] Mortality is higher in men in studies conducted in China and Italy.[271][272][273] The highest risk for men is in their 50s, with the gap between men and women closing only at 90.[273] In China, the death rate was 2.8 percent for men and 1.7 percent for women.[273] The exact reasons for this sex-difference are not known, but genetic and behavioural factors could be a reason.[270] Sex-based immunological differences, a lower 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.[273] In Europe, of those infected with COVID‑19, 57% were men; of those infected with COVID‑19 who also died, 72% were men.[274] As of April 2020, the U.S. government is not tracking sex-related data of COVID‑19 infections.[275] Research has shown that viral illnesses like Ebola, HIV, influenza, and SARS affect men and women differently.[275] A higher percentage of health workers, particularly nurses, are women, and they have a higher chance of being exposed to the virus.[276] School closures, lockdowns, and reduced access to healthcare following the 2019–20 coronavirus pandemic may differentially affect the genders and possibly exaggerate existing gender disparity.[270][277]

Society and culture

Name

During the initial outbreak in Wuhan, China, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus",[278][279][280] with the disease sometimes called "Wuhan pneumonia".[281][282] In the past, many diseases have been named after geographical locations, such as the Spanish flu,[283] Middle East Respiratory Syndrome, and Zika virus.[284]

In January 2020, the World Health Organisation recommended 2019-nCov[285] and 2019-nCoV acute respiratory disease[286] 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 to prevent social stigma.[287][288][289]

The official names COVID‑19 and SARS-CoV-2 were issued by the WHO on 11 February 2020.[290] WHO chief Tedros Adhanom Ghebreyesus explained: CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019).[291] The WHO additionally uses "the COVID‑19 virus" and "the virus responsible for COVID‑19" in public communications.[290] Both the disease and virus are commonly referred to as "coronavirus" in the media and public discourse.

Misinformation

Main article: Misinformation related to the 2019–20 coronavirus pandemic

After the initial outbreak of COVID‑19, conspiracy theories, misinformation, and disinformation emerged regarding the origin, scale, prevention, treatment, and other aspects of the disease and rapidly spread online.[292][293][294][295]

Protests

Beginning April 17, 2020, news media began reporting on a wave of demonstrations protesting against state-mandated quarantine restrictions in in Michigan, Ohio, and Kentucky.[296][297]

Other animals

Humans appear to be capable of spreading the virus to some other animals. A domestic cat in Liège, Belgium, tested positive after it started showing symptoms (diarrhoea, vomiting, shortness of breath) a week later than its owner, who was also positive.[298] Tigers at the Bronx Zoo in New York, United States, tested positive for the virus and showed symptoms of COVID‑19, including a dry cough and loss of appetite.[299]

A study on domesticated animals inoculated with the virus found that cats and ferrets appear to be "highly susceptible" to the disease, while dogs appear to be less susceptible, with lower levels of viral replication. The study failed to find evidence of viral replication in pigs, ducks, and chickens.[300]

Research

Main article: COVID-19 drug development

No medication or vaccine is approved to treat the disease.[186] International research on vaccines and medicines in COVID‑19 is underway by government organisations, academic groups, and industry researchers.[301][302] In March, the World Health Organisation initiated the "SOLIDARITY Trial" to assess the treatment effects of four existing antiviral compounds with the most promise of efficacy.[303]

Vaccine

Main article: COVID-19 vaccine

There is no available vaccine, but various agencies are actively developing vaccine candidates. Previous work on SARS-CoV is being used because both SARS-CoV and SARS-CoV-2 use the ACE2 receptor to enter human cells.[304] Three vaccination strategies are being investigated. First, researchers aim to build a whole virus vaccine. The use of such a virus, be it inactive or dead, aims to elicit a prompt immune response of the human body to a new infection with COVID‑19. A second strategy, subunit vaccines, aims to create a vaccine that sensitises the immune system to certain subunits of the virus. In the case of SARS-CoV-2, such research focuses on the S-spike protein that helps the virus intrude the ACE2 enzyme receptor. A third strategy is that of the nucleic acid vaccines (DNA or RNA vaccines, a novel technique for creating a vaccination). Experimental vaccines from any of these strategies would have to be tested for safety and efficacy.[305]

On 16 March 2020, the first clinical trial of a vaccine started with four volunteers in Seattle, United States. The vaccine contains a harmless genetic code copied from the virus that causes the disease.[306]

Antibody-dependent enhancement has been suggested as a potential challenge for vaccine development for SARS-COV-2, but this is controversial.[307]

Medications

Main article: COVID-19 drug repurposing research

At least 29 phase II–IV efficacy trials in COVID‑19 were concluded in March 2020 or scheduled to provide results in April from hospitals in China.[308][309] There are more than 300 active clinical trials underway as of April 2020.[133] Seven trials were evaluating already approved treatments, including four studies on hydroxychloroquine or chloroquine.[309] Repurposed antiviral drugs make up most of the Chinese research, with nine phase III trials on remdesivir across several countries due to report by the end of April.[308][309] Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2.[309]

The COVID‑19 Clinical Research Coalition has goals to 1) facilitate rapid reviews of clinical trial proposals by ethics committees and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data and 4) facilitate sharing of clinical trial outcomes before publication.[310][311]

Several existing medications are being evaluated for the treatment of COVID‑19,[186] including remdesivir, chloroquine, hydroxychloroquine, lopinavir/ritonavir, and lopinavir/ritonavir combined with interferon beta.[303][312] There is tentative evidence for efficacy by remdesivir, as of March 2020.[313][314] Clinical improvement was observed in patients treated with compassionate-use remdesivir.[315] Remdesivir inhibits SARS-CoV-2 in vitro.[316] Phase III clinical trials are underway in the U.S., China, and Italy.[186][308][317]

In 2020, a trial found that lopinavir/ritonavir was ineffective in the treatment of severe illness.[318] Nitazoxanide has been recommended for further in vivo study after demonstrating low concentration inhibition of SARS-CoV-2.[316]

There are mixed results as of 3 April 2020 as to the effectiveness of hydroxychloroquine as a treatment for COVID‑19, with some studies showing little or no improvement.[319][320] The studies of chloroquine and hydroxychloroquine with or without azithromycin have major limitations that have prevented the medical community from embracing these therapies without further study.[133]

Oseltamivir does not inhibit SARS-CoV-2 in vitro and has no known role in COVID‑19 treatment.[133]

Anti-cytokine storm

Cytokine release syndrome (CRS) can be a complication in the later stages of severe COVID‑19. There is preliminary evidence that hydroxychloroquine may have anti-cytokine storm properties.[321]

Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small study was completed.[322][323] It is undergoing a phase 2 non-randomised trial at the national level in Italy after showing positive results in people with severe disease.[324][325] Combined with a serum ferritin blood test to identify cytokine storms, it is meant to counter such developments, which are thought to be the cause of death in some affected people.[326][327][328] The interleukin-6 receptor antagonist was approved by the FDA to undergo a phase III clinical trial assessing the medication's impact on COVID‑19 based on retrospective case studies for the treatment of steroid-refractory cytokine release syndrome induced by a different cause, CAR T cell therapy, in 2017.[329] To date, there is no randomised, controlled evidence that tocilizumab is an efficacious treatment for CRS. Prophylactic tocilizumab has been shown to increase serum IL-6 levels by saturating the IL-6R, driving IL-6 across the blood-brain barrier, and exacerbating neurotoxicity while having no impact on the incidence of CRS.[330]

Lenzilumab, an anti-GM-CSF monoclonal antibody, is protective in murine models for CAR T cell-induced CRS and neurotoxicity and is a viable therapeutic option due to the observed increase of pathogenic GM-CSF secreting T-cells in hospitalised patients with COVID‑19.[331]

The Feinstein Institute of Northwell Health announced in March a study on "a human antibody that may prevent the activity" of IL-6.[332]

Passive antibodies

Transferring purified and concentrated antibodies produced by the immune systems of those who have recovered from COVID‑19 to people who need them is being investigated as a non-vaccine method of passive immunisation.[333] This strategy was tried for SARS with inconclusive results.[333] Viral neutralisation is the anticipated mechanism of action by which passive antibody therapy can mediate defence against SARS-CoV-2. Other mechanisms, however, such as antibody-dependent cellular cytotoxicity and/or phagocytosis, may be possible.[333] Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development.[333] Production of convalescent serum, which consists of the liquid portion of the blood from recovered patients and contains antibodies specific to this virus, could be increased for quicker deployment.[334]

en.wikipedia.org/wiki/Coronavirus_disease_2019

Série sobre Turim – Series about Turin – Torino – 17-01-2009 - IMG_20090117_9999_119 by Flávio Cruvinel Brandão

19 29

Esta réplica, da coroa de espinhos usada por Jesus Cristo, se encontra em uma sala ao lado do altar da Igreja Real de São Lourenço (San Lorenzo) em Turim, Itália.