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.1WHONovel coronavirus – Thailand (ex-China). Geneva: World Health Organization.https://www.who.int/csr/don/14-january-2020-novel-coronavirus-thailand/en/Date: Jan 14, 2020Date accessed: January 23, 2020Google Scholar, 2WHONovel Coronavirus – Japan (ex-China). Geneva: World Health Organization.https://www.who.int/csr/don/16-january-2020-novel-coronavirus-japan-ex-china/en/Date: Jan 16, 2020Date accessed: January 23, 2020Google Scholar, 3China National Health CommissionUpdate on the novel coronavirus pneumonia outbreak (Jan 24, 2020). Beijing: China National Health Commission.http://www.nhc.gov.cn/xcs/yqfkdt/202001/c5da49c4c5bf4bcfb320ec2036480627.shtmlDate: 2020Date accessed: January 24, 2020Google Scholar, 4WHONovel coronavirus – Republic of Korea (ex-China). Geneva: World Health Organization.https://www.who.int/csr/don/21-january-2020-novel-coronavirus-republic-of-korea-ex-china/en/Date: 2020Date accessed: January 24, 2020Google Scholar, 5US Centers for Disease Control and PreventionFirst travel-related case of 2019 novel coronavirus detected in United States. Atlanta, GA: US Centers for Disease Control and Prevention.https://www.cdc.gov/media/releases/2020/p0121-novel-coronavirus-travel-case.htmlDate: 2020Date accessed: January 24, 2020Google Scholar 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.3China National Health CommissionUpdate on the novel coronavirus pneumonia outbreak (Jan 24, 2020). Beijing: China National Health Commission.http://www.nhc.gov.cn/xcs/yqfkdt/202001/c5da49c4c5bf4bcfb320ec2036480627.shtmlDate: 2020Date accessed: January 24, 2020Google Scholar These cases detected outside Wuhan, together with the detection of infection in at least one household cluster—reported by Jasper Fuk-Woo Chan and colleagues6Chan JF-W Yuan S Kok K-H 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. 2020; (published online Jan 24.)https://doi.org/10.1016/S0140-6736(20)30154-9Summary Full Text Full Text PDF Scopus (6197) Google Scholar 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).3China National Health CommissionUpdate on the novel coronavirus pneumonia outbreak (Jan 24, 2020). Beijing: China National Health Commission.http://www.nhc.gov.cn/xcs/yqfkdt/202001/c5da49c4c5bf4bcfb320ec2036480627.shtmlDate: 2020Date accessed: January 24, 2020Google Scholar In The Lancet, Chaolin Huang and colleagues7Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30183-5Summary Full Text Full Text PDF Scopus (32861) Google Scholar 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.6Chan JF-W Yuan S Kok K-H 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. 2020; (published online Jan 24.)https://doi.org/10.1016/S0140-6736(20)30154-9Summary Full Text Full Text PDF Scopus (6197) Google Scholar 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. Of the 41 patients in this cohort, 22 (55%) developed severe dyspnoea and 13 (32%) required admission to an intensive care unit, and six died.7Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30183-5Summary Full Text Full Text PDF Scopus (32861) Google Scholar 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 on the spectrum of mild or asymptomatic infection becomes available, one case of which was documented by Chan and colleagues,6Chan JF-W Yuan S Kok K-H 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. 2020; (published online Jan 24.)https://doi.org/10.1016/S0140-6736(20)30154-9Summary Full Text Full Text PDF Scopus (6197) Google Scholar the case-fatality ratio is likely to decrease. Nevertheless, the 1918 influenza pandemic is estimated to have had a case-fatality ratio of less than 5%13Viboud C Eisenstein J Reid AH Janczewski TA Morens DM Taubenberger JK Age- and sex-specific mortality associated with the 1918–1919 influenza pandemic in Kentucky.J Infect Dis. 2013; 207: 721-729Crossref PubMed Scopus (72) Google Scholar but had an enormous impact due to widespread transmission, so there is no room for complacency.TableCharacteristics of patients who have been infected with 2019-nCoV, MERS-CoV, and SARS-CoV7Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; (published online Jan 24)https://doi.org/10.1016/S0140-6736(20)30183-5Summary Full Text Full Text PDF Scopus (32861) Google Scholar, 8Leung GM Hedley AJ Ho LM et al.The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients.Ann Intern Med. 2004; 141: 662-673Crossref PubMed Scopus (282) Google Scholar, 10WHOMiddle East respiratory syndrome coronavirus (MERS-CoV). Geneva: World Health Organization.http://www.who.int/emergencies/mers-cov/en/Date: 2020Date accessed: January 12, 2020Google Scholar, 11Assiri A Al-Tawfiq JA Al-Rabeeah AA et al.Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study.Lancet Infect Dis. 2013; 13: 752-761Summary Full Text Full Text PDF PubMed Scopus (1112) Google Scholar, 12WHOSummary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Geneva: World Health Organization.http://www.who.int/csr/sars/country/table2004_04_21/en/Date: 2004Date accessed: January 12, 2020Google Scholar2019-nCoV*Demographics and symptoms for 2019-nCoV infection are based on data from the first 41 patients reported by Chaolin Huang and colleagues (admitted before Jan 2, 2020).8 Case numbers and mortalities are updated up to Jan 21, 2020) as disclosed by the Chinese Health Commission.MERS-CoVSARS-CoVDemographicDateDecember, 2019June, 2012November, 2002Location of first detectionWuhan, ChinaJeddah, Saudi ArabiaGuangdong, ChinaAge, years (range)49 (21–76)56 (14–94)39·9 (1–91)Male:female sex ratio2·7:13·3:11:1·25Confirmed cases835†Data as of Jan 23, 2020.24948096Mortality25†Data as of Jan 23, 2020. (2·9%)858 (37%)744 (10%)Health-care workers16‡Data as of Jan 21, 2020.99·8%23·1%SymptomsFever40 (98%)98%99–100%Dry cough31 (76%)47%29–75%Dyspnoea22 (55%)72%40–42%Diarrhoea1 (3%)26%20–25%Sore throat021%13–25%Ventilatory support9·8%80%14–20%Data are n, age (range), or n (%) unless otherwise stated. 2019-nCoV=2019 novel coronavirus. MERS-CoV=Middle East respiratory syndrome coronavirus. SARS-CoV=severe acute respiratory syndrome coronavirus.* Demographics and symptoms for 2019-nCoV infection are based on data from the first 41 patients reported by Chaolin Huang and colleagues (admitted before Jan 2, 2020).8Leung GM Hedley AJ Ho LM et al.The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients.Ann Intern Med. 2004; 141: 662-673Crossref PubMed Scopus (282) Google Scholar Case numbers and mortalities are updated up to Jan 21, 2020) as disclosed by the Chinese Health Commission.† Data as of Jan 23, 2020.‡ Data as of Jan 21, 2020.9WHONovel coronavirus (2019-nCoV) situation report - 2 (22 January 2020). Geneva: World Health Organization.https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200122-sitrep-2-2019-ncov.pdfDate: 2020Date accessed: January 23, 2020Google Scholar Open table in a new tab Data are n, age (range), or n (%) unless otherwise stated. 2019-nCoV=2019 novel coronavirus. MERS-CoV=Middle East respiratory syndrome coronavirus. SARS-CoV=severe acute respiratory syndrome coronavirus. As an RNA virus, 2019-nCoV still has the inherent feature of a high mutation rate, although like other coronaviruses the mutation rate might be somewhat lower than other RNA viruses because of its genome-encoded exonuclease. This aspect provides the possibility for this newly introduced zoonotic viral pathogen to adapt to become more efficiently transmitted from person to person and possibly become more virulent. Two previous coronavirus outbreaks had been reported in the 21st century. The clinical features of 2019-nCoV, in comparison with SARS-CoV and Middle East respiratory syndrome (MERS)-CoV, are summarised in the table. The ongoing 2019-nCoV outbreak has undoubtedly caused the memories of the SARS-CoV outbreak starting 17 years ago to resurface in many people. In November, 2002, clusters of pneumonia of unknown cause were reported in Guangdong province, China, now known as the SARS-CoV outbreak. The number of cases of SARS increased substantially in the next year in China and later spread globally,14Zhong NS Zheng BJ Li YM et al.Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003.Lancet. 2003; 362: 1353-1358Summary Full Text Full Text PDF PubMed Scopus (1128) Google Scholar infecting at least 8096 people and causing 774 deaths.12WHOSummary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Geneva: World Health Organization.http://www.who.int/csr/sars/country/table2004_04_21/en/Date: 2004Date accessed: January 12, 2020Google Scholar The international spread of SARS-CoV in 2003 was attributed to its strong transmission ability under specific circumstances and the insufficient preparedness and implementation of infection control practices. Chinese public health and scientific capabilities have been greatly transformed since 2003. An efficient system is ready for monitoring and responding to infectious disease outbreaks and the 2019-nCoV pneumonia has been quickly added to the Notifiable Communicable Disease List and given the highest priority by Chinese health authorities. The increasing number of cases and widening geographical spread of the disease raise grave concerns about the future trajectory of the outbreak, especially with the Chinese Lunar New Year quickly approaching. Under normal circumstances, an estimated 3 billion trips would be made in the Spring Festival travel rush this year, with 15 million trips happening in Wuhan. The virus might further spread to other places during this festival period and cause epidemics, especially if it has acquired the ability to efficiently transmit from person to person. Consequently, the 2019-nCoV outbreak has led to implementation of extraordinary public health measures to reduce further spread of the virus within China and elsewhere. Although WHO has not recommended any international travelling restrictions so far,15WHOStatement on the meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). Geneva, World Health Organization.https://www.who.int/news-room/detail/23-01-2020-statement-on-the-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov)Date: Jan 23, 2020Date accessed: January 24, 2020Google Scholar the local government in Wuhan announced on Jan 23, 2020, the suspension of public transportation, with closure of airports, railway stations, and highways in the city, to prevent further disease transmission.16Announcement from the Headquarter for novel coronavirus pneumonia prevention and control (No 1). Beijing: China National Health Commission.http://www.gov.cn/xinwen/2020-01/23/content_5471751.htmDate: 2020Date accessed: January 23, 2020Google Scholar Further efforts in travel restriction might follow. Active surveillance for new cases and close monitoring of their contacts are being implemented. To improve detection efficiency, front-line clinics, apart from local centres for disease control and prevention, should be armed with validated point-of-care diagnostic kits. Rapid information disclosure is a top priority for disease control and prevention. A daily press release system has been established in China to ensure effective and efficient disclosure of epidemic information. Education campaigns should be launched to promote precautions for travellers, including frequent hand-washing, cough etiquette, and use of personal protection equipment (eg, masks) when visiting public places. Also, the general public should be motivated to report fever and other risk factors for coronavirus infection, including travel history to affected area and close contacts with confirmed or suspected cases. Considering that substantial numbers of patients with SARS and MERS were infected in health-care settings, precautions need to be taken to prevent nosocomial spread of the virus. Unfortunately, 16 health-care workers, some of whom were working in the same ward, have been confirmed to be infected with 2019-nCoV to date, although the routes of transmission and the possible role of so-called super-spreaders remain to be clarified.9WHONovel coronavirus (2019-nCoV) situation report - 2 (22 January 2020). Geneva: World Health Organization.https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200122-sitrep-2-2019-ncov.pdfDate: 2020Date accessed: January 23, 2020Google Scholar Epidemiological studies need to be done to assess risk factors for infection in health-care personnel and quantify potential subclinical or asymptomatic infections. Notably, the transmission of SARS-CoV was eventually halted by public health measures including elimination of nosocomial infections. We need to be wary of the current outbreak turning into a sustained epidemic or even a pandemic. The availability of the virus' genetic sequence and initial data on the epidemiology and clinical consequences of the 2019-nCoV infections are only the first steps to understanding the threat posed by this pathogen. Many important questions remain unanswered, including its origin, extent, and duration of transmission in humans, ability to infect other animal hosts, and the spectrum and pathogenesis of human infections. Characterising viral isolates from successive generations of human infections will be key to updating diagnostics and assessing viral evolution. Beyond supportive care,17WHOClinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. Geneva, World Health Organization.https://www.who.int/internal-publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspectedDate: 2020Date accessed: January 22, 2020Google Scholar no specific coronavirus antivirals or vaccines of proven efficacy in humans exist, although clinical trials of both are ongoing for MERS-CoV and one controlled trial of ritonavir-boosted lopinavir monotherapy has been launched for 2019-nCoV (ChiCTR2000029308). Future animal model and clinical studies should focus on assessing the effectiveness and safety of promising antiviral drugs, monoclonal and polyclonal neutralising antibody products, and therapeutics directed against immunopathologic host responses. We have to be aware of the challenge and concerns brought by 2019-nCoV to our community. Every effort should be given to understand and control the disease, and the time to act is now. This online publication has been corrected. The corrected version first appeared at thelancet.com on January 29, 2020 This online publication has been corrected. The corrected version first appeared at thelancet.com on January 29, 2020 FGH reports personal fees from University of Alabama Antiviral Drug Discovery and Development Consortium, and is a non-compensated consultant for Gilead Sciences, Regeneron, and SAB Biotherapeutics, which have investigational therapeutics for coronavirus infections. All other authors declare no competing interests. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family clusterOur findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Full-Text PDF Clinical features of patients infected with 2019 novel coronavirus in Wuhan, ChinaThe 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Full-Text PDF Department of ErrorWang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet 2020; published online Jan 24. https://dox.doi.org/S0140-6736(20)30185-9—In this Comment, the first sentence of the third paragraph should have read "Of the 41 patients in this cohort, 22 (55%) developed severe dyspnoea and 13 (32%) required admission to an intensive care unit, and six died." And in the table, the title of the third row should have read "Location of first detection". These corrections have been made to the online version as of Jan 29, 2020, and will be made to the printed version. Full-Text PDF The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirusIn December, 2019, a novel coronavirus outbreak of pneumonia emerged in Wuhan, Hubei province, China,1 and has subsequently garnered attention around the world.2 In the fight against the 2019 novel coronavirus (2019-nCoV), medical workers in Wuhan have been facing enormous pressure, including a high risk of infection and inadequate protection from contamination, overwork, frustration, discrimination, isolation, patients with negative emotions, a lack of contact with their families, and exhaustion. Full-Text PDF Mental health care for medical staff in China during the COVID-19 outbreakIn December, 2019, an outbreak of a novel coronavirus pneumonia occurred in Wuhan (Hubei, China), and subsequently attracted worldwide attention.1 By Feb 9, 2020, there were 37 294 confirmed and 28 942 suspected cases of 2019 coronavirus disease (COVID-19) in China.2 Facing this large-scale infectious public health event, medical staff are under both physical and psychological pressure.3 To better fight the COVID-19 outbreak, as the largest top-class tertiary hospital in Hunan Province, the Second Xiangya Hospital of Central South University undertakes a considerable part of the investigation of suspected patients. Full-Text PDF Emerging understandings of 2019-nCoV"There is an emergency in China, but it has not yet become a global health emergency...WHO is following this outbreak every minute of every day", said Dr Tedros Ghebreyesus, Director-General of WHO, on Jan 23. A novel coronavirus (2019-nCoV) outbreak is emerging, but it is not yet a Public Health Emergency of International Concern (PHEIC). As we went to press, more than 500 cases have been confirmed in China, as well as in Japan, South Korea, Thailand, and the US. The virus can cause a severe respiratory illness, like SARS and MERS, and human-to-human transmission has been confirmed. Full-Text PDF