The emergence and spread of the 2019 novel coronavirus (2019-nCoV)

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It has been about a month since the discovery and identification of the 2019 novel coronavirus (2019-nCoV) [1] and the numbers of cases and fatalities have been continuing to rise rapidly. Nearly all of the cases and deaths have been in patients in mainland China, which now stand (as of 10 Feb 2019) at over 40,000 cases identified with over 900 deaths [2,3].

Recently two landmark figures have been surpassed by the 2019-nCoV as compared its closest relative in humans, the severe acute respiratory syndrome coronavirus (SARS-CoV) of 2002–2003. These are the number of total confirmed cases (8096) and more recently, the number of deaths (774) [4]. However, according to these real-time monitoring websites, the rate of increase of new cases appears to be slowing [2,3].

So far 28 other countries have been reporting a slowly rising number of cases, initially, mostly imported. The highest numbers of such cases have been confirmed in mainly East and Southeast Asian countries close to China, including Japan, Singapore, Thailand, Hong Kong, South Korea, Taiwan, Malaysia and Vietnam, but Australia, Germany, the USA and France have also reported increasing numbers of cases [2].

Some characteristics of the new 2019-nCoV

The virus belongs to the Coronavirus (CoV) family of lipid-enveloped viruses with spike glycoproteins on the surface to bind to host cells. These viruses possess a positive-sense, single-stranded RNA genome of 30,000 base pairs (bp) (Figure 1), and include the common cold coronavirus (OC43, 229E, NL63 and HKU1), as well as the more virulent SARS- and MERS-associated coronaviruses. The current 2019-nCoV is the newest addition to this family that infects humans and appears to share the same cellular receptor as SARS-CoV, namely the ACE2 (angiotensin converting enzyme 2) [5]. Now that we have the complete nCoV sequence [6], it is possible to design PCR-based diagnostic assays to detect this virus in clinical samples [7], as well as designing specific antiviral drugs and vaccines against it.

This image shows the structure of the 2019-nCoV virus

Figure 1. Schematic showing the structure of coronaviruses. Note the spikes (S) on the outer surface of the virus, which give the impression of a ‘crown’ or ‘corona’ hence the name. Other virally-encoded proteins: E (envelope protein), M (membrane protein) and HE (haemagglutinin-esterase protein), also form part of the surface of the virus. [Image courtesy of the US CDC Public Health Image Library, which are free of any copyright restrictions: https://phil.cdc.gov/Details.aspx?pid=23313]

From the epidemic so far, additional epidemiological parameters have been estimated. Overall, the case-fatality rate (CFR) appears to be around 2–3%, though there are interesting debates on how best to estimate this and the resulting CFR estimates range over 5–21% in different affected populations [2,8]. The incubation period seems to be typically around 5 days with a range of 2–14 days, hence the upper limit of 14 days is used for the minimum quarantine period in current guidelines. The other useful parameter is the basic reproductive number (R0), which is the number of secondary cases arising when an infected case enters a fully susceptible population. Estimates from one team (Imperial College, London, UK) for R0 have ranged from 1–4, with a series of reports varying the value of R0 in sensitivity analyses to assess how this will affect the growth of the nCoV epidemic [9]. Their most recent report (number 4) focuses more on estimates of CFR, with ranges of 1–18% for different specific known affected populations, e.g. 18% within Hubei, China, to 5–6% outside of China, but dropping to below 1% if the estimates of the mildly or asymptomatic undiagnosed cases circulating in the community are also taken into account.

Where did this virus (2019-nCoV) come from?

Various teams have examined this question from different angles, but perhaps the most likely origin has been determined by analyzing the 2019-nCoV sequence and comparing it with other related CoVs obtained from other known animal hosts (i.e. viral phylogenetics), such as bat viruses, and human SARS-CoV and MERS-CoV [10]. Although one of the earliest papers suggested that the snake may be one of the natural hosts of this virus [11], the general consensus now is that this seems unlikely. Bats appear to be the original source of this nCoV, but the difference in the viral sequences between the closest bat CoVs and the nCoV seems too large just to be due to the new human host adaptation. Most researchers believe that another intermediate (likely mammalian) animal host is involved, possibly the pangolin, though this link is far from robust and needs further investigation [12].

Transmission to humans likely arose whilst preparing raw meat from these animal reservoir species for human consumption, and getting infected through skin abrasions and cuts. This process is similar to how Ebola and HIV were thought to emerge into the human population from the preparation of bush meat (i.e. meat from wild animals) in Africa [13].

Transmissibility of 2019-nCoV

One of the most impressive characteristics of this new nCoV is the speed with which it is spreading through the mainland Chinese population. Seasonal coronaviruses are thought to be mostly transmitted by large droplet, short-range aerosols, though other transmission routes appear to be available to SARS-CoV and MERS-CoV. During the 2003 SARS-CoV outbreaks there were some patient clusters that likely involved longer-range airborne transmission [14], which may also have explained some of the cases during the large clusters of hospital acquired MERS-CoV infections during the 2015 South Korean outbreak [15].

Although the most recent phylogenetic analysis indicates that this virus only entered the human population in China (Wuhan) relatively recently in October 2019, it appears to have adapted to the human host remarkably quickly. Several studies have reported how it seems to be relatively easily transmitted between individuals within families and other close contacts [8,16,17].

Thus, a worrying, though perhaps not unexpected, recent development is the increasing numbers of new cases in other countries around the world with no travel history to China. These are most likely due to local transmission, which is something that has been already happening in China probably since the beginning of January 2020 when reports about a ‘pneumonia of unknown aetiology’ began to emerge [1,8,18,19].

This has also raised the concerns about emergence of possible ‘superspreaders’, i.e. infected individuals who are able to spread their infection to large numbers of others, creating multiple secondary cases that disseminate the virus even more widely. Such individuals were also identified during the SARS-CoV outbreaks in 2003 [20] and have the potential to completely change the epidemiology of an outbreak in local [14,15], and wider global populations where they have access to international travel [21].

One possible candidate for an nCoV ‘superspreader’ might be the third confirmed case in the UK. This was British man who acquired the nCoV infection from a business meeting in Singapore, who then went skiing in France, sharing a chalet with other families and infecting five of their members, before returning to the UK (Brighton), where he was diagnosed with nCoV infection. Another contact of his from the same French ski resort, who had travelled on to Spain and become ill with nCoV, has since been identified as the 4th UK nCoV case [22].

Clinical features and management of 2019-nCoV-infected cases

Recently published case series of nCoV-infected patients [18,19,23,24] indicate that acute nCoV infections present very similarly to seasonal influenza with fever, cough, shortness of breath and muscle aches being the most common symptoms. Generally, patients would present to hospital on day 7 of illness then progress to acute respiratory distress syndrome by day 8 and requiring intensive care support by days 8–10. Again, similar to seasonal influenza, the more vulnerable patients were the elderly and those with chronic diseases and other comorbidities. In contrast, one study from Beijing described a younger series of patients who were otherwise healthy with no comorbidities, whose illness was relatively mild [24].

Acute haematology and biochemical markers are typical for an acute viral infection, with some degree of lymphopenia and thrombocytopenia in many patients, as well as a mild to moderate hepatitis. High neutrophil counts and CRP (C-reactive protein – an acute inflammatory marker) can be seen in those with secondary bacterial infections. Radiological imaging is also mostly as expected with fine ground glass shadowing for the initial stages of acute viral pneumonitis with consolidation being evident with secondary bacterial infection, though some nCoV cases can also present with no radiological abnormalities.

Currently, there is no antiviral treatment or vaccine available for nCoV and management is mainly supportive, including empirical antibiotics to cover any secondary bacterial infections. Some new (re-purposed) drug combinations have been suggested, such as lopinavir/ritonavir (Kaletra) with or without ribavirin and/or interferon, including the use of a new drug remdesivir [25]. However, clinical data is currently limited for the effectiveness of these drug combinations and the potential benefits versus adverse effects of their use for individual patients need to be considered carefully. Finally, a recent article dictates that the use of steroid therapy for patients with acute respiratory distress, lung injury or shock due to nCoV, SARS-CoV or MERS-CoV infections should not be routine, as it may do more harm than good [26].

 Tentative predictions

What we have seen so far with the nCoV is that is seems to transmit more readily than SARS-CoV or MERS-CoV, with a generally lower CFR of ~2% compared with SARS-CoV (~10%) [4] and MERS (~35%) [27]. So, it seems that nCoV may be adapting quicker to the human host with a higher transmissibility and a lower lethality than either SARS-CoV or MERS-CoV.

The question is whether it will:

  1. disappear from the human population completely like SARS-CoV has thus far, to return and remain within the confines of its zoonotic origins;
  2. continue to infect humans sporadically like MERS-CoV, avian A(H5N1) and A(H7N9) influenza viruses, which continue to cause significant morbidity and mortality though to relatively few people;
  3. become a truly seasonal human respiratory virus, like the former pandemic influenza virus A(H1N1)pdm09, and the other seasonal coronaviruses, which circulate annually with less severe morbidity and mortality

Hopefully over the next few months, one of these scenarios will start to emerge, which will help us to optimize our approach to dealing with this epidemic.

  1. Wu P, Hao X, Lau EHY, Wong JY, Leung KSM, Wu JT, Cowling BJ, Leung GM. Real-time tentative assessment of the epidemiological characteristics of novel coronavirus infections in Wuhan, China, as at 22 January 2020. Euro Surveill. 25(3), doi:10.2807/1560-7917.ES.2020.25.3.2000044 (2020).
  2. Wuhan coronavirus outbreak. www.worldometers.info/coronavirus/ (Accessed 9 Feb 2020)
  3. Johns Hopkins CSSE. Coronavirus 2019-CVoV Global Cases. https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 (Accessed 9 Feb 2020)
  4. World Health Organization (WHO). Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. www.who.int/csr/sars/country/table2004_04_21/en/ (Accessed 9 Feb 2020)
  5. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. Virol. pii:JVI.00127-20. doi:10.1128/JVI.00127-20 (2020). [Epub ahead of print]
  6. Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Microbes Infect. 9(1), 221-236. doi:10.1080/22221751.2020.1719902 (2020).
  7. Corman VM, Landt O, Kaiser M, Molenkamp R et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 25(3). doi:10.2807/1560-7917.ES.2020.25.3.2000045 (2020).
  8. Li Q, Guan X, Wu P, Wang X et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. Engl. J. Med. doi:10.1056/NEJMoa2001316 (2020). [Epub ahead of print]
  9. Imperial College, London, UK. Report 4: Severity of 2019-novel coronavirus (nCoV). www.imperial.ac.uk/mrc-global-infectious-disease-analysis/news–wuhan-coronavirus/ (Accessed 10 Feb 2020)
  10. ARTIC Network. Novel 2019 coronavirus. nCoV Genomic Epidemiology. Phylodynamic Analysis. 67 genomes. 08 Feb 2020. http://virological.org/t/phylodynamic-analysis-67-genomes-08-feb-2020/356 (Accessed 9 Feb 2020)
  11. Ji W, Wang W, Zhao X, Zai J, Li X. Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. J Virol. Doi:10.1002/jmv.25682 (2020). [Epub ahead of print]
  12. The Straits Times. Coronavirus: Scientists question work suggesting pangolin link. www.straitstimes.com/asia/east-asia/china-scientists-identify-pangolin-as-possible-coronavirus-host (Accessed 9 Feb 2020)
  13. Wolfe ND, Daszak P, Kilpatrick AM, Burke DS. Bushmeat hunting, deforestation, and prediction of zoonoses emergence. Infect. Dis. 11(12), 1822–7 (2005).
  14. Tellier R, Li Y, Cowling BJ, Tang JW. Recognition of aerosol transmission of infectious agents: a commentary. BMC Infect Dis. 19(1), 101. doi:10.1186/s12879-019-3707-y (2019).
  15. Kim KH, Tandi TE, Choi JW, Moon J Kim MS. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications. Hosp. Infect. 95(2), 207–213. doi:10.1016/j.jhin.2016.10.008 (2017).
  16. Chan JF, Yuan S, Kok KH, To KK 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 doi:10.1016/S0140-6736(20)30154-9 (2020). [Epub ahead of print]
  17. Phan LT, Nguyen TV, Luong QC, Nguyen TV, Nguyen HT, Le HQ, Nguyen TT, Cao TM, Pham QD. Importation and human-to-human transmission of a novel coronavirus in Vietnam. Engl. J. Med. doi:10.1056/NEJMc2001272 (2020). [Epub ahead of print]
  18. Chen N, Zhou M, Dong X et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet doi:10.1016/S0140-6736(20)30211-7 (2020). [Epub ahead of print]
  19. Huang C, Wang Y, Li X, Ren L et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. doi: 10.1016/S0140-6736(20)30183-5 (2020). [Epub ahead of print]
  20. Bassetti S, Bischoff WE, Sherertz RJ. Are SARS superspreaders cloud adults? Infect. Dis. 11(4), 637–8 (2020).
  21. Wong G, Liu W, Liu Y, Zhou B, Bi Y, Gao GF. MERS, SARS, and Ebola: The role of super-spreaders in infectious disease. Cell Host Microbe. 18(4), 398–401, doi:10.1016/j.chom.2015.09.013 (2015).
  22. The Telegraph. Coronavirus: Briton tests positive in Spain as fourth case is confirmed in UK. www.telegraph.co.uk/news/2020/02/09/coronavirus-news-uk-outbreak-china-virus-latest/ (Accessed 10 Feb 2020)
  23. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. doi:10.1001/jama.2020.1585 (2020). [Epub ahead of print]
  24. Chang, Lin M, Wei L, Xie L, Zhu G, Dela Cruz CS, Sharma L. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA. doi:10.1001/jama.2020.1623 (2020). [Epub ahead of print]
  25. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. doi:10.1038/s41422-020-0282-0 (2020). [Epub ahead of print]
  26. Russell CD, Millar JW, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet doi:10.1016/S0140-6736(20)30317-2 (2020). [Epub ahead of print]
  27. World Health Organization (WHO). Middle East respiratory syndrome coronavirus (MERS-CoV). www.who.int/en/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov) (Accessed 9 Feb 2020)

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3 Comments

  1. Maria S Salvato on

    First of all COVID has been renamed SARS2 because it is so close to the SARS in sequence. Second of all, ACE2 inhibitors are FDA approved to block the ACE (receptors for SARS2) and should be re-purposed as antivirals.

    • Hi Maria,

      I believe the disease is named COVID-19, and the virus is named SAR-CoV-2, so there is a distinction there. But you’re corrected that the nomenclature of 2019-nCoV has now been replaced. As you can see this piece was published on February 10th and all information is correct as-of that date.

    • John Plaschke on

      Yes there a few other researchers thst say ace inhibitors may help

      Many papers say sar-cov-2 enters cells via ace2 one paper I read stated the receptor of sars2 is more flexible which is thought to make it more infectious

      Sar1 and sar2 are from what I recall 90% similar in genetic sequence

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