COVID-19 (SARS-CoV2)

Onde estamos? Unai Tupinambás

Professor Associado do Departamento de Clínica Médica

Faculdade de Medicina - UFMG

Declaração conflito de interesse

• Não recebi apoio ou incentivo para aulas, participação em congressos e outros eventos da indústria farmacêutica nos últimos 10 anos

• Membro do Comitê Assessor do Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis

• Funcionário público federal

Roteiro da aula

• Histórico infecções coronavírus e riscos de pandemias

• Agente etiológico • SARS CoV • MERS CoV • SARS-CoV2

• Situação epidemiologia SARS-CoV2 (COVID-19)

• Enfrentando epidemia: • Definição de casos • Uso racional de Equipamentos de Proteção Individual (EPI)

• Quadro clínico COVID-19

“não sei de nada, mas desconfio de muita

coisa”

Fala do jagunço Riobaldo in “Grande Sertão: Veredas”

João Guimarães Rosa

Vírus zoonóticos - transmitidos por animais aos seres humanos

Kreuder J et al. Spillover and pandemic properties of zoonotic viruses with high host plasticity. Sci Rep 5, 14830 (2015)

Transporte aéreo mundial

24,5 milhões de passageiros (avião) ao ano Wuham Trens-bala 2,31 bilhões de passageiros em 2019*

*Wilson ME, Chen LH. Travelers give wings to novel coronavirus (2019-nCoV). J

Travel Med. J Travel Med. 2020 Feb 3

Destruição natureza

Grandes aglomerações

Iniquidade e saneamento básico

Histórico coronavírus • Coronavírus: RNA vírus envelopados

• Alta capacidade de mutações

• 4 gêneros: alfa, beta, delta e gama • Alfa e beta infectam seres humanos • 4 são endêmicos em todo mundo (resfriado comum)

• HCoV 299E, LM63, OC43 e HKU1

• São diversos, com grande variedade reino animal principalmente em morcegos

• A partir de 2002: 3 novos coronavírus com alta taxa mortalidade e potencial para causar pandemia

Novos coronavírus • Séc. XXI:

• eclosão de 3 novos coronavírus: SARS-Cov, MERS-CoV, 2019-CoV

Transmissão hospitalar

(SARS, MERS)

SARS-CoV 2002

MERS-CoV 2012

SARS-CoV2 2019

SARS-CoV (Nov/2002)

• Pneumonia atípica. Guangdong (China) • Março/2003: identificado SARS-CoV • Espalhou por 29 países • Custos: US$30 a 100 bilhões • Vírus SARS-CoV: reservatório natural:

morcegos • Julho/2003: OMS declara fim da epidemia,

8.096 casos com 774 mortes

Distribuição global SARS - 2003

MERS-CoV

• Set/2012: • novo coronavírus identificado. Arábia Saudita e região

MERS-CoV

• OMS: 2012-2019: • 2.494 casos com 858 mortes em 27 países • Restrito Península Arábica • Transmissão zoonótica esporádica, sem sustentação de

transmissão comunidade • Surtos localizados: Coreia do Sul • Importância infecção hospitalar

Distribuição global MERS - 2012

Características patogênicas e transmissibilidades dos vírus recentemente emergentes

Vírus Fatalidade (%) Pandemia Contida Observações

SARS-CoV2 Desconhecida ( <2-3?)

? > ! Não Risco eminente pandemia

pH1N1 0,02-0,4 Sim Não Epidemias (outono/inverno)

H7N9 39 Não Não

NL63 ? ? Não

SARS-CoV 9,5 Não Sim 58% infecção hospitalar

MERS-CoV 34,4 Não Não 70% infecção hospitalar

Ebola vírus (West Africa)

63 Não Sim

Adaptado: NEJM 24 Jan.2020

SARS-CoV2 - COVID 3º coronavírus emergente em 2 décadas

• OMS 2018 sobre os coronavírus: • patógenos prioritários de interesse

• Posição OMS 30 de janeiro 2020: • declarada condição como “Emergência de Saúde Pública de

Importância Internacional (ESPII)"

• Conhecimentos adquiridos com surtos anteriores SARS e MERS

• Resposta autoridades chinesas: • desde identificação do agente pronta cooperação OMS, proibição

temporária venda animais silvestres, fechamento mercado Wuhan, cancelamento festas Ano-novo chinês

• Wuhan e outras cidades província em quarentena: • população atingida: 40 milhões

Resposta da China

COVID-19 Linha do tempo

Adaptado: Lancet 24 Jan.2020

Comment

www.thelancet.com Published online January 24, 2020 https://doi.org/10.1016/S0140-6736(20)30185-9 1

A novel coronavirus outbreak of global health concern

In December, 2019, Wuhan, Hubei province, China,

became the centre of an outbreak of pneumonia

of unknown cause, which raised intense attention

not only within China but internationally. Chinese

health authorities did an immediate investigation

to characterise and control the disease, including

isolation of people suspected to have the disease, close

monitoring of contacts, epidemiological and clinical

data collection from patients, and development of

diagnostic and treatment procedures. By Jan 7, 2020,

Chinese scientists had isolated a novel coronavirus

(CoV) from patients in Wuhan. The genetic sequence

of the 2019 novel coronavirus (2019-nCoV) enabled

the rapid development of point-of-care real-time

RT-PCR diagnostic tests specific for 2019-nCoV (based

on full genome sequence data on the Global Initiative

on Sharing All Influenza Data [GISAID] platform). Cases

of 2019-nCoV are no longer limited to Wuhan. Nine

exported cases of 2019-nCoV infection have been

reported in Thailand, Japan, Korea, the USA, Vietnam,

and Singapore to date, and further dissemination

through air travel is likely.1–5 As of Jan 23, 2020, confirmed

cases were consecutively reported in 32 provinces,

municipalities, and special administrative regions in

China, including Hong Kong, Macau, and Taiwan.3

These cases detected outside Wuhan, together with the

detection of infection in at least one household cluster—

reported by Jasper Fuk-Woo Chan and colleagues6 in

The Lancet—and the recently documented infections in

health-care workers caring for patients with 2019-nCoV

indicate human-to-human transmission and thus

the risk of much wider spread of the disease. As of

Jan 23, 2020, a total of 835 cases with laboratory-

confirmed 2019-nCoV infection have been detected

in China, of whom 25 have died and 93% remain in

hospital (figure).3

In The Lancet, Chaolin Huang and colleagues7 report

clinical features of the first 41 patients admitted to the

designated hospital in Wuhan who were confirmed to

be infected with 2019-nCoV by Jan 2, 2020. The study

findings provide first-hand data about severity of the

emerging 2019-nCoV infection. Symptoms resulting

from 2019-nCoV infection at the prodromal phase,

including fever, dry cough, and malaise, are non-

specific. Unlike human coronavirus infections, upper

respiratory symptoms are notably infrequent. Intestinal

presentations observed with SARS also appear to be

uncommon, although two of six cases reported by Chan

and colleagues had diarrhoea.6 Common laboratory

findings on admission to hospital include lymphopenia

and bilateral ground-glass opacity or consolidation in

chest CT scans. These clinical presentations confounded

early detection of infected cases, especially against

a background of ongoing influenza and circulation

of other respiratory viruses. Exposure history to the

Huanan Seafood Wholesale market served as an

important clue at the early stage, yet its value has

decreased as more secondary and tertiary cases have

appeared.

The 41 patients in this cohort developed severe

dyspnoea and required admission to an intensive care

unit, and six patients died.7 Hence, the case-fatality

proportion in this cohort is approximately 14·6%, and

the overall case fatality proportion appears to be closer

to 3% (table). However, both of these estimates should

be treated with great caution because not all patients

have concluded their illness (ie, recovered or died) and

the true number of infections and full disease spectrum

are unknown. Importantly, in emerging viral infection

outbreaks the case-fatality ratio is often overestimated

in the early stages because case detection is highly

biased towards the more severe cases. As further data

Published Online

January 24, 2020

https://doi.org/10.1016/

S0140-6736(20)30185-9

See Online/Articles

https://doi.org/10.1016/

S0140-6736(20)30154-9 and

https://doi.org/10.1016/

S0140-6736(20)30183-5

For GISAID platform see

https://www.gisaid.org/

Figure: Timeline of early stages of 2019-nCoV outbreak

2019-nCoV=2019 novel coronavirus.

Dec 30, 2019

Cluster of cases of pneumonia

of unknown origin reported to

China National Health

Commission

Jan 7, 2020

Novel coronavirus

isolated

Jan 24, 2020

835 cases reported in China (549 from Hubei

province, 286 from the other 31 provinces,

municipalities, or special administrative regions)

Jan 11, 2020

First fatal

case reported

Jan 19, 2020

First case in Korea

reported; two cases

in Beijing and one

case in Guangdong

province reported

Jan 13, 2020

First case in

Thailand reported

Jan 1, 2020

Huanan Seafood Wholesale

market closed

Jan 16, 2020

First case in

Japan reported

Jan 12, 2020

Named as 2019-nCoV;

whole genome sequence

shared with WHO

Jan 20, 2020

Infection in

health-care workers

caring for 2019-nCoV

patients

30/Dez/2019 Casos de PNM causa desconhecida reportado pelas autoridades sanitárias da China

13/Jan/2020 1º caso fora China (Tailândia)

07/Jan/2019 Novo coronavirus é isolado

19/Jan/2020 1os casos Coréia, 2 casos em Pequim e 1 caso em Guangdong

24/Jan/2020 835 casos China (549 Hubei, 286 em outras 31 províncias ou regiões administrativas )

1º Jan/2020 Mercado de frutos do mar Huanan é fechado

11/Jan/2020 1º caso fatal

12/Jan/2020 Nomeado: 2019-nCoV. Sequencia genética e compartilhada com OMS

16/Jan/2020 1º caso no Japão

20/Jan/2020 Infecção em Trabalhadores saúde (lembrando padrão SARS-MERS)

Como estimar risco de pandemia SARS-CoV2

NEJM 24 Jan.2020

Dinâmica da transmissibilidade no início da epidemia

• Dados a partir de 4 de Jan/2020

• R0 > 1 indica possibilidade epidemia

• Papel pessoas assintomáticas na cadeia de transmissão

• R0 SARS-CoV2: 2,2 (?)

• Poucos casos em crianças e em trabalhadores da saúde (diferente da SARS e MERS)

• Estudos de soroincidência serão fundamentais para entender a dinâmica da transmissão

Viewpoint | Published 07 February 2020

Cite this as: Swiss Med Wkly. 2020;150:w20203

2019-Novel Coronavirus (2019-nCoV):estimating the case fatality rate – a word ofcaution

Battegay Manuela, Kuehl Richarda, Tschudin-Sutter Saraha, Hirsch Hans H.abc, Widmer Andreas F.a, Neher Richard A.d

a Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel, University of Basel, Switzerlandb Clinical Virology, Laboratory Medicine, University Hospital Basel, Switzerlandc Transplantation and Clinical Virology, Department Biomedicine, University of Basel, Switzerlandd Biozentrum, University of Basel, Switzerland

Estimating and predicting the extent and lethality of the

2019-Novel Coronavirus (2019-nCoV) outbreak, originat-

ing in Wuhan/China is obviously challenging, reflected by

many controversial statements and reports. Unsurpassed

to date, an ever-increasing flow of information, immedi-

ately available and accessible online, has allowed the de-

scription of this emerging epidemic in real-time [1]. The

first patients were reported in Wuhan on December 31st

2019 [2]. Only a few days later, Chinese researchers identi-

fied the etiologic agent now known as the 2019-nCoV and

published the viral sequence [3]. New data on the virus,

its characteristics and epidemiology become available 24/7

and are often shared via informal platforms and media [4].

Yet, key questions remain largely unanswered.

How is the virus transmitted, how long is the incubation

period, what is the role of asymptomatic infected, what

is the definite reproductive number R0, how long is viral

shedding persisting after fading of symptoms, who is at

risk for a severe course, and ultimately, how high is the

case fatality rate?

Accurate answers are critical for predicting the outbreak

dynamics, to tailor appropriate and effective prevention

measures, and to prepare for a potential pandemic. Precise

estimates of the case fatality rate and the fraction of in-

fections that require hospitalization are critical to balance

the socioeconomic burden of infection control interven-

tions against their potential benefit for mankind. Hence,

one of the most important figures to determine is the rate of

asymptomatic and mild cases allowing to put severe cours-

es and death rates into accurate context.

At present, it is tempting to estimate the case fatality rate

by dividing the number of known deaths by the number

of confirmed cases. The resulting number, however, does

not represent the true case fatality rate and might be off

by orders of magnitude. Diagnosis of viral infection will

precede recovery or death by days to weeks and the num-

ber of deaths should therefore be compared to the past case

counts – accounting for this delay increasing the estimate

of the case fatality rate. On the other hand, cases in offi-

cial statistics are likely a severe underestimate of the total

– accounting for this underestimate will decrease the case

fatality rate. The time between diagnosis and death/recov-

ery and the degree of underreporting will vary over time

as well as between cities and countries. A precise estimate

of the case fatality rate is therefore impossible at present.

Figure 1 illustrates how these uncertainties manifest them-

selves using currently available data.

Better estimates could be derived from large-scale investi-

gations, in particular, in the region of the epidemic’s origin.

Still, population-based testing of respiratory secretions by

nucleic acid amplification testing (NAT) for 2019-nCoV

would most likely underestimate the scale of the outbreak,

as asymptomatic patients or patients after recovery from

infection may no longer be NAT-positive. A sensitive

2019-nCoV-specific serological assay is needed to firmly

assess the rate of past exposure and may help to assess herd

immunity.

One intriguing aspect of the outbreak so far is the dis-

crepancy between the estimates of the case fatality rate

reported from Hubei province, from different regions of

China and from other countries. As of February 7, 2020,

30’536 have been confirmed. Thereof, 22’112 occurred in

the Hubei province of China with a death toll of 619 (=

2.8%). This contrasts with 16 deaths among 8’702 record-

ed cases in other regions of China and further countries,

suggesting at first glance a case fatality rate of 0.18%.

The uncertainties and spatio-temporal variation discussed

above could explain this divergence:

The higher case fatality rate reported fromWuhan may be overestimated

The true number of exposed cases affected in Wuhan may

be vastly underestimated. With a focus on thousands of

serious cases, mild or asymptomatic courses that possibly

account for the bulk of the 2019-nCoV infections might

remain largely unrecognized, in particular during the in-

fluenza season.

Correspondence:

Prof. Manuel Battegay,

MD, Division of Infectious

Diseases and Hospital Epi-

demiology, University Hos-

pital Basel, Petersgraben 4,

CH-4031 Basel,

manuel.battegay[at]usb.ch

Swiss Medical Weekly · PDF of the online version · www.smw.ch

Published under the copyright license “Attribution – Non-Commercial – No Derivatives 4.0”.

No commercial reuse without permission. See http://emh.ch/en/services/permissions.html.

Page 1 of 3

• Província de Hubei até 07/02: 22.112 casos com 619 mortes: 2,8% letalidade • Outras regiões China e mundo: 8.702 casos com 16

mortes: 0,18%

• Dados 4/3: Mortalidade Hubei 4,3% • Outras regiões China/mundo: 1,4%

Qual a prevalência de pessoas assintomáticas / oligossintomáticas?

Casos notificados (que procuram atendimento médico)

Numerador casos assintomáticos / oligossintomáticos?

Situação epidemiologia SARS-CoV2 (COVID) 04/03/2020

https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200304-sitrep-44-covid-19.pdf?sfvrsn=783b4c9d_2

Situação epidemiologia SARS-CoV2 (COVID) 04/03/2020 • 28 países com transmissão local

http://plataforma.saude.gov.br/novocoronavirus/

Situação epidemiológica Brasil 04/03/2020

Situação no Brasil • Ainda na fase de contenção da epidemia

• Até o momento sem transmissão local - casos com vínculos

epidemiológicos: retorno de países com transmissão local, contato com pessoas suspeitas da infecção

• Chegada do outono/inverno: aumento dos casos de infecções vias aéreas

• Circulação de vários vírus respiratórios: influenza, rinovírus, adenovírus... SARS-CoV2(?)

• Papel da APS no enfrentamento da “Síndrome Respiratória Aguda”

Enfrentamento COVID-19 - Brasil

Ministério da Saúde. Boletim Epidemiológico n4. 04/03/2020

Ministério da Saúde. Boletim Epidemiológico n4. 04/03/2020

Instrumento contra “Fake News”

Uso racional de EPI Local atendimento Público-alvo

Tipo de atividade Tipo de EPI

Serviços de Saúde Enfermarias Trabalhadores saúde Contato direto com pessoas

COVID-19 Máscara cirúrgica Luvas / capote impermeável Proteção ocular

Procedimentos geradores de aerossol

Respirador N95 ou similar Luvas / capote Proteção ocular

Pessoal limpeza Limpeza enfermaria Máscara cirúrgica Luvas de limpeza / capote impermeável Proteção ocular Sapatos adequados

Acompanhantes Máscara cirúrgica Capote Luvas

Outras áreas de trânsito pessoas COVID-19

Sem contato com COVID-19 Sem EPI

Triagem Trabalhadores saúde Triagem sem contato Distância pelo menos 1m Sem EPI

Pessoas com sintomas respiratórios

Manter distância Máscara cirúrgica

Pessoas sem sintomas respiratórios

Sem EPI

WHO reference number: WHO/2019-nCov/IPC PPE_use/2020.1

Notificação de casos suspeitos

https://portalarquivos2.saude.gov.br/images/pdf/2020/fevereiro/11/protocolo-manejo-coronavirus.pdf

Apresentação clínica dos 1os casos COVID-19

This article was published on January 29, 2020, and updated on January 29, 2020, at NEJM.org. DOI: 10.1056/NEJMoa2001316

Características dos pacientes (n=1.099)

Idade 99,1% >15 anos

Trabalhadores saúde 3,5% (38)

Período incubação (dias) 4 (2-7)

Sintomas/sinais mais prevalentes

Tosse Febre admissão Cansaço

67,8% 43,8% 38,1%

Presença de comorbidades 23,7%

Achados radiológicos (%)

Alterações RX tórax 59%

Imagem em vidro fosco

20%

Condensação bilateral 36,5%

Infiltrado intersticial 4,4%

Mortalidade

1,4%

Achados tomografia computadorizada de tórax

Heshui Shi*, Xiaoyu Han*, Nanchuan Jiang*, Yukun Cao, Osamah Alwalid, Jin Gu, Yanqing Fan†, Chuansheng Zheng†

Lancet Infect Dis 2020Lancet Infect Dis 2020 Published Online February 24, 2020 https://doi.org/10.1016/ S1473-3099(20)30086-4

PAHO/WHO

Crianças: perfil epidemiológico

Idade (anos) - todos os estudos (n=67):

• Min - máx : 6 meses a 17 anos

Contatos com pessoas infectadas • Familiares: 64/67 (95%)

• Visita em área acometida (22/66)

Razão de sexo (M/F)

- 28/39

Procedência dos casos:

• China (66) e Cingapura (1)

PAHO/WHO

Comorbidade • Sem comorbidade relatada

Complicações

• Amigdalite supurativa aguda: 1/31

• Derrame pleural (0/15)

• Pneumotórax (0/15)

Evolução

Óbitos: nenhum

Internados na UTI: nenhum

Sequelas: nenhuma

Crianças: evolução clínica e evolução

Estudos utilizados (crianças)

1. Wang D, Ju XL, Xie F, Lu Y, Li FY, Huang HH, et al. Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China. Zhonghua Er Ke Za Zhi. 2 de março de 2020;58(4):E011

2. Feng K, Yun YX, Wang XF, Yang GD, Zheng YJ, Lin CM, et al. Analysis of CT features of 15 Children with 2019 novel coronavirus infection. Zhonghua Er Ke Za Zhi. 16 de fevereiro de 2020;58(0):E007

3. Cai J, Xu J, Lin D, Yang Z, Xu L, Qu Z, et al. A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis [Internet]. [citado 3 de março de 2020]

4. Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang Z-J. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. JAMA [Internet]. 14 de fevereiro de 2020

5. Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 15 de fevereiro de 2020;395(10223):514–23

6. Kam K, Yung CF, Cui L, Lin Tzer Pin R, Mak TM, Maiwald M, et al. A Well Infant with Coronavirus Disease 2019 (COVID-19) with High Viral Load. Clin Infect Dis [Internet]

PAHO/WHO

Quadro clínico no início

• Febre (19/21) • Antes ou no momento da

admissão: 15/19

• Tosse (9/21)

• Dor de garganta (3/18*)

• Diarreia (2/18*)

• Mialgia (3/9*)

• Fraqueza (2/9*)

• Dispneia (1/9*)

Resultados de imagem

• Pneumonia como opacidade difusa em vidro fosco, consolidação irregular dos pulmões e bordas borradas, na Tomografia computadorizada (TC)

• Bilateral (17/21)

• Unilateral (4/21)

• Derrame pleural (1/21)

Gestantes: Perfil clínico

* O denominador é partir dos artigos que refiram a presença da caraterística

PAHO/WHO

Cesarianas: (18/21) Indicação da cesariana: Pneumonia por COVID-19, mais outras patologias (11/12) Transmissão vertical: 0/21 com RT-PCR Óbitos maternos: 0/21 Óbitos fetais: 0/21 Óbitos de RN: 1/21

Gestantes: Evolução

Caraterização das publicações

Nome do primeiro autor

Número de pacientes

(n=21)

Hospital Data da captação dos pacientes

Revista

Chen H 9 Hospital de Zhongnan 20 jan a 31 jan Lancet

Zhu H 9 Multicêntrico - 5 Hospitais de Hubei

20 jan a 5 fev Translational Paediatrics

Liu W 3 Hospital Tongji 2 fev a 5 fev Pré-print

1. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The Lancet [Internet]. 2020 2. Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr 2020; 9(1):51-60 3. Liu W, Wang Q, Zhang Q, Chen L, Chen J, Zhang B, et al. Coronavirus Disease 2019 (COVID-19) During Pregnancy: A Case Series. Preprints [Internet] 2020

https://portalarquivos2.saude.gov.br/images/pdf/2020/fevereiro/11/protocolo-manejo-coronavirus.pdf

Uso de antivirais

• Experiência com pacientes com SARS e MERS sugerem que CORTICOIDE não teve impacto na mortalidade e atrasou o clareamento viral

• Uso de Loppinavir-ritonavir em pacientes com SARS e MERS demonstrou benefícios clínicos

• Antiviral de amplo espectro – Remdesivir – mostrou alguma eficácia na SARS e MERS

• Medicina Tradicional Chinesa: mais de 15 ensaios clínicos em andamento

Huang C, et al. Lancet 2020; 1-10

Referências

• Mandel, Douglas and Bennett’s. Principles and Practice of Infectious Diseaes. 7th Edition. Philadelphia. USA Elsevier

• Na Zhu, Ph.D, et al. A Novel Coronavirus from Patients with Pneumonia in China,2019. NEJM, 24 Jan. 2020

• Vincent J. Munster, Ph.D et al. A Novel Coronavirus Emerging in China. Key Questions for Impact Assessment. NEJM, 24 Jan 2020. DOI: 10.1056/NEJMp2000929

• Chaolin Huang et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 24 Jan 2020

• Stanley Perlman and Jason Netland. Coronaviruses post-SARS: Update on replication and pathogenesis Nat Rev Microbiol. 2009 June ; 7(6): 439–450. doi:10.1038/nrmicro2147

• Nanshan Chen, Min Zhou et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study . Lancet, 29 Jan 2020. https://doi.org/10.1016/

Referências

• Yudong Yini and Richard G. WunderinkI. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology (2018) 23, 130–137 doi: 10.1111/resp.13196

• To Sing Fung and Ding Xiang Liu. Human Coronavirus: Host-Pathogen Interaction. Annu. Rev. Microbiol. 2019. 73:529–57. https://doi.org/10.1146/annurev-micro-020518-115759

• Zhiqi Song, Yanfeng Xu et al. From SARS to MERS, Thrusting Coronaviruses into the Spotlight. Viruses 2019, 11, 59; doi:10.3390/v11010059

• Yu Chen, Qianyun Liu, Deyin Guo. Coronaviruses: genome structure, replication, and pathogenesis. doi: 10.1002/jmv.25681

• Editorial. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China. International Journal of Infectious Diseases 91 (2020) 264–266

• Esam I. Azhar, PhD, FRCPa, David S.C. Hui. The Middle East Respiratory Syndrome (MERS). Infect Dis Clin N Am 33 (2019) 891–905

• David S.C. Hui, Alimuddin Zumla. Severe Acute Respiratory Syndrome. Historical, Epidemiologic, and Clinical Features. Infect Dis Clin N Am 33 (2019) 869–889

Referências • Chen Wang, Peter W Horby, Frederick G Hayden, George F Gao. A novel coronavirus

outbreak of global health concern. Lancet. January 24, 2020 https://doi.org/10.1016/S0140-6736(20)30185-9.\

• Emerging understandings of 2019-nCoV. Editorial. Lancet. January 24, 2020 https://doi.org/10.1016/ S0140-6736(20)30186-0

• Jasper Fuk-Woo Chan, Shuofeng Yuan et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. January 24, 2020 https://doi.org/10.1016/S0140-6736(20)30154-9

• https://promedmail.org/. Último acesso 29 janeiro de 2020

• https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 Último acesso 29 de janeiro de 2020

• https://www.who.int/emergencies/diseases/novel-coronavirus-2019 Último acesso 29 de janeiro de 2020

• https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html Último acesso 29 de janeiro de 2020

• BBRASIL. Ministerio da Saúde. Novo coronavirus (2019-nCoV). Boletim epidemiologico, Brasilia, v. 51, n. 4, Jan./2020

“O inferno dos vivos não é algo que será; se existe, é aquele

que já está aqui, o inferno no qual vivemos todos os dias, que formamos estando juntos. Existem duas maneiras de não sofrer. A primeira é fácil para a maioria das pessoas: aceitar o inferno e tornar-se parte deste até o ponto de deixar de percebê-lo. A segunda é arriscada e exige atenção e aprendizagem contínuas: tentar saber reconhecer quem e o que, no meio do inferno, não é inferno, e preservá-lo, e abrir espaço”.

Ítalo Calvino. In Cidades Invisíveis. Ed. Companhia das Letras

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