key: cord-319158-n8e2n30b authors: Mackenzie, John S; Smith, David W title: COVID-19: a novel zoonotic disease caused by a coronavirus from China: what we know and what we don’t date: 2020-03-17 journal: Microbiol Aust DOI: 10.1071/ma20013 sha: doc_id: 319158 cord_uid: n8e2n30b nan subgenus Sarbecovirus in the Orthocoronavirinae subfamily [3] [4] [5] [6] [7] . Phylogenetic studies of the new virus showed it shared about 79% nucleotide homology with SARS-CoV 4-7 , as well as to two SARS-like coronaviruses isolated from Chinese horseshoe bats (Rhinolophus sinicus) in Zhoushan, with which it shared 89% nucleotide homology 3, [5] [6] [7] [8] , and to a third SARS-like coronavirus from an Intermediate horseshoe bat (R. affinis), with which it shared 96% nucleotide homology 4, 9 . Based on established practice, the new virus was named SARS-CoV-2 by the Coronavirus Study Group of the International Committee for the Taxonomy of Viruses 10 , and the disease it causes as COVID-19 by WHO 11 . How this virus moved from animal to human populations is yet to be determined. The outbreak clearly began epidemiologically at the Wuhan market, and a number of environmental samples from around the live animal section of the market were subsequently found to be positive for SARS-CoV-2 12 , but based on current evidence, it may not have actually emerged in the market. The earliest recognised case of infection with SARS-CoV-2 was an elderly and infirm man who developed symptoms on 1 December 2019. None of his family members became infected, and the source of his virus remains unknown 13 . Furthermore, 14 of the first 41 cases had no contact with the seafood market 13 . In another report, five of the first seven cases of COVID-19 had no link to the seafood market 14 . Thus, it seems very likely that the virus was amplified in the market, but the market might not have been the site of origin nor the only source of the outbreak. A recent phylo-epidemiological study has suggested that the virus was circulating but unrecognised in November, and was imported to the seafood market from elsewhere, where it subsequently was amplified 15 . Angiotensin-converting enzyme II (ACE2) was known to be the cell receptor for SARS-CoV, and also for some SARS-like bat coronaviruses 16 . Sequence studies found that the receptor-binding domain of the SARS-CoV-2 virus was sufficiently similar to that of SARS-CoV to indicate it could efficiently use the human ACE2 receptor for entry to human cells 6, 7 . Infectivity experiments were undertaken with HeLa cells expressing or not expressing ACE2 from humans, bats, civets, pigs and mice, and the results confirmed that SARS-CoV-2 virus was able to use entry receptors on all ACE2-expressing cells other than mice 5 . Molecular modelling has indicated that the binding affinity of SARS-CoV-2 to ACE-2 may be even higher than that of SARS-CoV and it may therefore be more efficient at infecting human cells 17 [3] [4] [5] [6] [7] , but this information was not widely available until a sequence was reported on 12 January 2020. Interestingly, this was the first time that NGS had alerted the world to a new zoonotic virus before the virus had been isolated, and it suggests that a new procedure for reporting outbreaks based on NGS rather than pathogen isolation and identification needs to be considered 19 . Transmission Human-to-human transmission of SARS-CoV-2 has been widely shown in health care, community and family settings. The dominant mode of transmission is from the respiratory tract via droplets or indirectly via fomites, and to a lesser extent via aerosols. In addition, as SARS-CoV and MERS-CoV can infect the human gastrointestinal tract 21, 22 , it has been suggested that faecal-oral spread may occur for SARS-CoV-2 23 . The reproduction number (Ro) is generally thought to be between 2.0 and 2.8 20,24-27 , although higher reproduction numbers have been suggested in some reports. The mean incubation time appears to be between 4.75 and 7 days 20,23,24,26,28 , ranging from 3 days to an upper limit of around 11-14 days. There is increasing knowledge about the virus load. In one study of symptomatic patients, higher viral loads were detected soon after symptom onset, with the viral loads higher in the nose than in the throat. In a single asymptomatic patient, the viral load was similar to the symptomatic patients 29 . In a second and more detailed study, the virus load was investigated over Hot Topic consecutive days in two patients from the time of their hospitalisation, with serial samples throat swabs, sputum, urine and stools. The viral loads peaked around 5-6 days after symptom onset, with 10 4 to 10 7 copies/mL. The authors also studied the viral loads in throat swabs, sputum and stool samples in other patients, and found viral loads were as high as 10 11 copies/mL in throat samples, but with a median of 7.99 Â 10 4 , and 7.52 Â 10 5 in sputum. In addition, virus was detected by RT-PCR in stools from 9 of 17 confirmed cases, but at titres lower than in respiratory samples 30 . Several studies have indicated that transmission may occur during the incubation period 31,32 and from asymptomatic or very mild infections 29, 33, 34 . There are a number of important questions still to be answered about the transmission dynamics. These include information about the infectivity during the incubation period; the length of time and virus load during incubation and during the symptomatic period of virus shedding; the incidence and infectiousness of asymptomatic cases, the risk of vertical transmission from mother to fetus 35 , and other modes of transmission, such as from faeces, saliva and urine. There is some evidence that virus can be isolated from saliva 36 The case fatality rates have varied depending on the population affected. Initial estimates that were based on severely ill patients were high, but more recent estimates are around 2.3% on average, but significantly higher in the elderly and particularly those aged 80 years and over 41 . As many milder or asymptomatic infections are likely to have been missed, the mortality rate is expected to be lower than published figures as more information becomes available. Clinical diagnosis has largely been based on clinical and exposure history, and laboratory and chest imaging findings. The laboratory findings will vary with the severity of disease, but a low lymphocyte count is common and persisting low counts is associated with poorer outcomes 13, 39, 40 . Testing for other respiratory pathogens should be undertaken to exclude viral and bacterial co-infections. to identify any genetic drift that may affect test sensitivity. We also need to be able to transfer the tests onto platforms that can be delivered outside major laboratories, in resource poor settings, near to the patient, and quickly. The lack of serological assays hampers our ability to understand the true epidemiology of this virus and its impact, and to identify PCR-negative infections. The authors declare no conflicts of interest. Report of clustering pneumonia of unknown etiology in Wuhan City Novel coronavirus (2019-nCoV) A novel coronavirus from patients with pneumonia in China A pneumonia outbreak associated with a new coronavirus of probable bat origin Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding A new coronavirus associated with human respiratory disease in China A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster Genomic variance of the 2019-nCoV coronavirus Severe acute respiratory syndrome-related coronavirus: the species and its viruses -a statement of the Coronavirus Study Group Novel coronavirus (2019-nCoV) China's CDC detects a large number of new coronaviruses in the South China seafood market in Wuhan Clinical features of patients infected with 2019 novel coronavirus in Wuhan Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia Decoding evolution and transmissions of novel pneumonia coronavirus (SARS-CoV-2) using the whole genomic data Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor Structure analysis of the receptor binding of 2019-nCoV Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China From Hendra to Wuhan: what has been learned in responding to emerging zoonotic viruses Estimating the unreported number of novel coronavirus (2019-nCoV) cases in China in the first half of January 2020: a data-driven modelling analysis of the early outbreak Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study Reporting, epidemic growth, and reproduction numbers for the 2019 novel coronavirus (2019-nCoV) epidemic An interim review of the epidemiological characteristics of 2019 novel coronavirus Report 3: Transmissibility of 2019-nCoV. WHO Collaborating Centre for Infectious Disease Modelling, MRC Centre for Global Infectious Disease Analysis Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China SARS-CoV-2 viral load in upper respiratory specimens of infected patients Viral load of SARS-CoV-2 in clinical samples Evidence of SARS-CoV-2 infection in returning travelers from Wuhan A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period Presumed asymptomatic carrier transmission of COVID-19 Asymptomatic cases in a family cluster with SARS-CoV-2 infection Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records Consistent detection of 2019 novel coronavirus in saliva Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes Emerg. Microbes Infect Isolation of 2019-nCoV from a stool specimen of a laboratory-confirmed case of the coronavirus disease 2019 (COVID-19) China CDC Weekly 2 Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. (2020) The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) -China Evolving status of the 2019 novel coronavirus infection: proposal of conventional serologic assays for disease diagnosis and infection monitoring COVID-19): CDNA National Guidelines for Public Health Units Clinical management of severe acute respiratory infection when Novel coronavirus (2019-nCoV) infection is suspected: Interim Guidance 28 World Health Organization (2020) Coronavirus disease 2019 (COVID-19) Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV) Relative sensitivity of international surveillance, WHO Collaborating Centre for Infectious Disease Modelling, MRC Centre for Global Infectious Disease Analysis, Abdul Latif Jameel Institute for Disease and Emergency Analytics (J-IDEA) A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus This research did not receive any specific funding.