Emergence of a novel coronavirus causing respiratory illness from Wuhan, China.

Dear Editor,

In previous reports, workers have characterized the presentation of Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) to aid clinical teams in the recognition, diagnosis and management of these cases. Now with the emergence of a novel coronavirus (CoV) from Wuhan, China (tentatively named as 2019-nCoV by The World Health Organization – WHO), , similar clinical, diagnostic and management guidance are required.

Available information at the time of writing indicates that the virus has now spread beyond China and infection has been confirmed in individuals without direct contact with the index Wuhan wet market (Huanan South China Seafood Market), where the sale of game meat from live animals was also available. This suggests that human-to-human transmission is not only possible but very likely. A full genome phylogenetic analysis of this 2019-nCoV indicates that it is closely related to bat SARS-like CoV (Fig. 1 ), compatible with a zoonotic origin for this virus, similar to SARS-CoV and MERS-CoV.

Fig. 1

A maximum likelihood tree using full genome coronavirus sequences (30–40 kbp in length) from GenBank was constructed using Fast Tree (v2.1) under a GTR model of evolution. Initial alignment was performed using the online multiple alignment program (MAFFT v.7: https://mafft.cbrc.jp/alignment/server/) with further manual editing. The final tree was displayed and annotated in FigTree v1.4.4. Large groups of similar sequences belong to HCoV OC43, HKU1, NL63, 229E ad SARS CoV have been collapsed for clarity. Figures on the branches are Shimodaira-Hasegawa-like support values, ranging from 0 to 1, with higher values indicating that the branch topologies (or ‘splits’) are more likely to be real. The Wuhan 2019-nCoV (GenBank Accession no. MN908947) is shown in red along with its closest relative bat SARS-like CoVs.

Two cases have now been confirmed to date in Thailand. The first was a 61-year old Chinese woman travelling with 5 family members in a 16-member tour group. She developed symptoms of fever, chills, headache and sore throat on 5 January 2020 and flew from Wuhan directly to Thailand on 8 January, where she was diagnosed and isolated. She reported regular visits to wet markets in Wuhan but not the index wet market from where most cases were reported.

The second case confirmed in Thailand was that of a 74-year old Chinese woman, who was laboratory-confirmed to be infected with the 2019-nCoV on 17 January 2020. This second case was not linked epidemiologically to the first case, and she had not visited any market in Wuhan. So far both cases are recovering well in the negative pressure isolation facilities at the Bamrasnaradura Institute in Thailand, and may be discharged soon. ,

In addition, one case of 2019-nCoV was confirmed in a male patient in his thirties in Japan who was staying in Wuhan during late December 2019 to early January 2020, and developed fever on 3 January. Although he had not visited any wet or live animal markets during his stay in Wuhan, he did report close contact with someone with pneumonia. On return to Japan on 6 January he visited a local clinic where he tested negative for influenza. Despite this, his symptoms of fever, cough, and sore throat continued, so he attended a local hospital on 10 January where he was admitted and found to have abnormal infiltrates on his chest X-ray. He remained febrile until 14 January and was eventually tested as positive for 2019-nCoV on 15 January. He became afebrile on the same day and was discharged home where he remains stable. This was the second 2019-nCoV case to be confirmed outside of China (being identified between the two cases from Thailand).

Thus, clinically, the symptoms of 2019-nCoV infection appear very non-specific and may be very similar to influenza, including fever, cough, fatigue, sore throat, runny nose, headache and shortness of breath, with possible ground glass shadowing on the chest X-ray. Importantly, such symptoms appear to persist longer in cases of 2019-nCoV infection than in most cases of uncomplicated influenza. Similar to SARS and MERS, there is still no specific, licensed antiviral treatment for CoVs and the clinical management is mainly supportive. Infection control guidance will be likely based on existing guidance for SARS and MERS, perhaps with some additional heightened precautions due to the largely unknown nature of this new virus.

Also similar to the SARS and MERS cases, there is likely a lot of variability in the clinical presentation, including mild or asymptomatic cases that may never present to healthcare services. Larger population level seroprevalence studies to test for past infection or exposure are required to determine how many such cases may exist. Whether “super-spreaders” who are associated with multiple secondary infections, as has occurred most prominently with SARS but also MERS, will be (or indeed may have already been) a feature of the epidemiology of this virus is not yet known.

No pediatric 2019-nCoV infections have been diagnosed so far, and infections in other vulnerable patient groups, such as transplant and other immunocompromised patients, pregnant women and those with chronic diseases (diabetes, liver, kidney, heart disease, etc.) and extremes of the body-mass index (BMI), are yet to be reported. Further data are awaited on such cases.

Based on the current and limited data available and the likelihood that many milder or asymptomatic cases have not presented to healthcare services, it is too early to compare case-fatality rates with SARS or MERS. So far, there have been two deaths out of a total of 48 cases reported from Wuhan and overseas, which have been in older patients with various comorbidities.

Most recently, a mathematical modelling study from Imperial College (London, UK) suggests that the number of unrecognized, undiagnosed cases could be as high as 4400–4500, though ∼1700 may be more realistic – assuming that the model assumptions are reasonably accurate. This situation is evolving and more updates will be forthcoming.

SARS was the first emerging infectious disease of the 21st century and it came and went quickly despite a tremendous global impact. MERS in contrast remains largely confined to the Middle East with occasional exported cases and has smouldered since 2012. We clearly have a lot to learn about these zoonotic bat coronaviruses (see Fig. 1), but hopefully the scientific, medical and public health worlds are now much better prepared this time round to deal with this new emerging threat.