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      COVID-19: what is next for public health?

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      a , b , WHO Scientific and Technical Advisory Group for Infectious Hazards
      Lancet (London, England)
      Elsevier Ltd.

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          Abstract

          The WHO Scientific and Technical Advisory Group for Infectious Hazards (STAG-IH), working with the WHO secretariat, reviewed available information about the outbreaks of 2019 novel coronavirus disease (COVID-19) on Feb 7, 2020, in Geneva, Switzerland, and concluded that the continuing strategy of containment for elimination should continue, and that the coming 2–3 weeks through to the end of February, 2020, will be crucial to monitor the situation of community transmission to update WHO public health recommendations if required. Genetic analysis early in the outbreak of COVID-19 in China revealed that the virus was similar to, but distinct from, severe acute respiratory syndrome coronavirus (SARS-CoV), but the closest genetic similarity was found in a coronavirus that had been isolated from bats. 1 As there was in early January, 2020, scarce information available about the outbreak, knowledge from outbreaks caused by the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) formed the basis for WHO public health recommendations in mid-January. 2 However, the availability of more evidence in the past month has shown major differences between the outbreaks and characteristics of COVID-19 compared with those of SARS-CoV. Recognising the Wuhan-focused and nationwide outbreak responses in China, WHO has encouraged countries with heavy air travel exchange with Wuhan to take precautionary public health measures 2 and, if there is imported infection, to undertake activities that could lead to the elimination of the virus in human populations as occurred during the 2003 SARS outbreak. 3 After the SARS outbreak, a few follow-on outbreaks occurred, including accidents in laboratories researching SARS-CoV. 4 SARS-CoV is thought to have been eliminated from human populations during 2003, and there have been no reports in the medical literature about SARS-CoV circulation in human populations since then. The 2003 SARS outbreaks are thought to have originated from the spillover of a mutated coronavirus from animals sold in a live animal market in Guangdong province in China to a few humans, and it then surfaced as a large cluster of pneumonia in health-care settings in Guangdong province. 5 Although the causative agent was then unknown, an infected medical doctor who had been treating patients in Guangdong province travelled to Hong Kong when he became ill and became an index case for hospital-associated and community outbreaks in Hong Kong and in three countries outside of China. The causative agent was later identified as a coronavirus and named SARS-CoV. The SARS outbreaks were at times characterised by several superspreading events—eg, hotel-based transmission from one infected hotel guest to others who travelled to Canada, Singapore, and Vietnam. 6 One large apartment complex-based outbreak of SARS was later found to be caused by aerosolisation of virus contaminated sewage. 6 COVID-19 is thought to have been introduced to human populations from the animal kingdom in November or December, 2019, as suggested by the phylogeny of genomic sequences obtained from early cases. 7 The genetic epidemiology suggests that from the beginning of December, 2019, when the first cases were retrospectively traced in Wuhan, the spread of infection has been almost entirely driven by human-to-human transmission, not the result of continued spillover. There was massive transmission in a matter of weeks in Wuhan, and people in the resulting chains of transmission spread infection by national and international travel during the Chinese New Year holidays. COVID-19 seems to have different epidemiological characteristics from SARS-CoV. COVID-19 replicates efficiently in the upper respiratory tract and appears to cause less abrupt onset of symptoms, similar to conventional human coronaviruses that are a major cause of common colds in the winter season. 8 Infected individuals produce a large quantity of virus in the upper respiratory tract during a prodrome period, are mobile, and carry on usual activities, contributing to the spread of infection. By contrast, transmission of SARS-CoV did not readily occur during the prodromal period when those infected were mildly ill, and most transmission is thought to have occurred when infected individuals presented with severe illness, thus possibly making it easier to contain the outbreaks SARS-CoV caused, unlike the current outbreaks with COVID-19. 6 © 2020 Kyodo News/Contributor/Getty Images 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. COVID-19 also has affinity for cells in the lower respiratory tract and can replicate there, causing radiological evidence of lower respiratory tract lesions in patients who do not present with clinical pneumonia. 8 There seem to be three major patterns of the clinical course of infection: mild illness with upper respiratory tract presenting symptoms; non-life-threatening pneumonia; and severe pneumonia with acute respiratory distress syndrome (ARDS) that begins with mild symptoms for 7–8 days and then progresses to rapid deterioration and ARDS requiring advanced life support (WHO EDCARN clinical telephone conference on COVID-19, personal communication with Myoung-don Oh [Seoul National University Hospital] and Yinzhong Shen [Shanghai Public Health Clinical Center]) The case fatality ratio with COVID-19 has been difficult to estimate. The initial case definition in China included pneumonia but was recently adjusted to include people with milder clinical presentation and the current estimate is thought to be about 1–2%, which is lower than that for SARS (10%). 9 The actual case fatality ratio of infection with COVID-19 will eventually be based on all clinical illness and at the time of writing information on subclinical infection is not available and awaits the development of serological tests and serosurveys. Presently COVID-19 seems to spread from person to person by the same mechanism as other common cold or influenza viruses—ie, face to face contact with a sneeze or cough, or from contact with secretions of people who are infected. The role of faecal–oral transmission is yet to be determined in COVID-19 but was found to occur during the SARS outbreak. 10 The lock-down of Wuhan City seems to have slowed international spread of COVID-19; however, the effect is expected to be short-lived (WHO modelling group). Efforts are currently underway in China, in the 24 countries to which infected persons have travelled, and in public conveyances, such as cruise ships, to interrupt transmission of all existing and potential chains of transmission, with elimination of COVID-19 in human populations as the final goal. This WHO-recommended strategy is regularly assessed each week by STAG-IH on the basis of daily risk assessments by WHO as information becomes available from outbreak sites. A plausible scenario based on the available evidence now is that the newly identified COVID-19 is causing, like seasonal influenza, mild and self-limiting disease in most people who are infected, with severe disease more likely among older people or those with comorbidities, such as diabetes, pulmonary disease, and other chronic conditions. Health workers and carers are at high risk of infection, and health-care-associated amplification of transmission is of concern as is always the case for emerging infections. People in long-term care facilities are also at risk of severe health consequences if they become infected. Non-pharmaceutical interventions remain central for management of COVID-19 because there are no licensed vaccines or coronavirus antivirals. If the situation changes towards much wider community transmission with multiple international foci, the WHO strategy of containment for elimination could need to be adjusted to include mitigation strategies combined with the following activities currently recommended by STAG-IH on the WHO website. First, close monitoring is needed of changes in epidemiology and of the effectiveness of public health strategies and their social acceptance. Second, continued evolution is needed of enhanced communication strategies that provide general populations and vulnerable populations most at risk with actionable information for self-protection, including identification of symptoms, and clear guidance for treatment seeking. Third, continued intensive source control is needed in the epicentre in China—ie, isolation of patients and persons testing positive for COVID-19, contact tracing and health monitoring, strict health facility infection prevention and control, and use of other active public health control interventions with continued active surveillance and containment activities at all other sites where outbreaks are occurring in China. Fourth, continued containment activities are needed around sites outside China where there are infected people and transmission among contacts, with intensive study to provide information on transmissibility, means of transmission, and natural history of infection, with regular reporting to WHO and sharing of data. Fifth, intensified active surveillance is needed for possible infections in all countries using the WHO-recommended surveillance case definition. 11 Sixth, preparation for resilience of health systems in all countries is needed, as is done at the time of seasonal influenza, anticipating severe infections and course of disease in older people and other populations identified to be at risk of severe disease. Seventh, if widespread community transmission is established, there should then be consideration of a transition to include mitigation activities, especially if contact tracing becomes ineffective or overwhelming and an inefficient use of resources. Examples of mitigation activities include cancelling public gatherings, school closure, remote working, home isolation, observation of the health of symptomatic individuals supported by telephone or online health consultation, and provision of essential life support such as oxygen supplies, mechanical ventilators and extracorporeal membrane oxygenation (ECMO) equipment. Eighth, serological tests need to be developed that can estimate current and previous infections in general populations. Finally, continued research is important to understand the source of the outbreak by study of animals and animal handlers in markets to provide evidence necessary for prevention of future coronavirus outbreaks.

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          Most cited references2

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          Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

          Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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            A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

            Summary Background An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation Our 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. Funding The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
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              Author and article information

              Contributors
              Journal
              Lancet
              Lancet
              Lancet (London, England)
              Elsevier Ltd.
              0140-6736
              1474-547X
              13 February 2020
              22-28 February 2020
              13 February 2020
              : 395
              : 10224
              : 542-545
              Affiliations
              [a ]Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
              [b ]World Health Organization, Geneva, Switzerland
              Author notes
              [†]

              Members of the WHO Scientific and Technical Advisory Group for Infectious Hazards (STAG-IH) are Juliet Bedford (Anthrologica, Broughton, UK), Delia Enria (Buenos Aires, Argentina), Johan Giesecke (Karolinska Institute, Stockholm, Sweden), David Heymann (Chair), Chikwe Ihekweazu (Nigeria Centre for Disease Control, Abuja, Nigeria), Gary Kobinger (Infectious Disease Research Centre, Université Laval, Faculty of Medicine, Québec City, Canada), Clifford Lane (National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA), Ziad Memish (Alfaisal University, Riyadh, Saudi Arabia), Oh Myoung-don (J W Lee Center for Global Medicine, SNU College of Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea), Amadou Alpha Sall (Institut Pasteur de Dakar, Unité des Arbovirus et Virus de fièvres hémorragiques, Dakar, Senegal), Kum Ungchusak (Ministry of Health, Department of Diseases Control, Bangkok, Thailand), and Lothar Wieler (Robert Koch Institute, Berlin, Germany).

              Article
              S0140-6736(20)30374-3
              10.1016/S0140-6736(20)30374-3
              7138015
              32061313
              5361780b-eb13-412a-9f72-5abd8869e1d9
              © 2020 Elsevier Ltd. All rights reserved.

              Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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