Expert statement on coronavirus

04-02-2020

The following commentary has been provided by Nicolas Locker, Professor of Virology, University of Surrey (UK) and Alfredo Garzino-Demo, an Editor-in-Chief of our journal Pathogens and Diease and Associate Professor of Microbiology and Immunology in the Institute of Human Virology at the University of Maryland School of Medicine (USA) and is also affiliated with the Department of Molecular Medicine, University of Padova (Italy).

Statement made 3 February 2020

Update 17 February 2020 Our journal, Pathogens and Disease, has published a priority paper on coronaviruses from a range of experts in response to the outbreak: Coronaviruses: a paradigm of new emerging zoonotic diseases

Update 28 February 2020 – Our translation volunteer team have produced versions of this statement in: Italian – Dichiarazione Di Esperti Del Coronavirus

What do we know about the virology of the 2019-nCoV coronavirus?

Since December 2019, more than 15000 people have been confirmed to be infected by a new coronavirus, 2019-nCoV causing pneumonia, clustered mainly in the Chinese Wuhan province. While China is reporting the majority of cases, 150 cases have now been reported in over 20 countries spreading from Thailand to France or the USA. Clinical symptoms manifest in patients with fever, dry cough, dyspnea, headache, and pneumonia. The onset of the disease will also lead to progressive respiratory failure due to alveolar damage and even death as seen in more than 300 cases. Virus-induced pneumonia, increased body temperature rising, lymphocytes number drop and new pulmonary infiltrates on chest radiography are all clinical scores for clinicians. Importantly most cases had a contact history with the Wuhan seafood market but human-to-human transmission is now established.” – Nicolas Locker

We know this is a virus that is related to a bat coronavirus, which is the ancestor of nCoV, i.e., there is no transmission from snakes, or accidental release of a lab-engineered virus. Angiotensin-converting enzyme 2 (ACE2) has been identified as nCoV receptor, and it is possible that ACE2 of different species may also function as a receptor, which may be important in transmission by intermediate hosts. There is evidence that cellular protease TMPRSS2 is also involved in nCoV replication in cells, and that inhibitors of TMPRSS2 are effective in reducing viral replication.” – Alfredo Garzino-Demo

Can you put this outbreak into context, how does it compare to previous viral outbreaks?

While usually responsible for common cold and mild illnesses, coronaviruses have caused two large-scale pandemics in the last two decades, SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). In particular SARS also emerged in China in 2002 and resulted in 8098 people to become ill, and 774 deaths, in 37 countries before it was extinguished. While the current outbreak has already surpassed SARS in number of cases, SARS had a ~10% mortality rate whereas 2019-nCoV is lower and estimated at 2%. However, because cases number are still subject to debate the mortality rate is hard to truly evaluate.” – Nicolas Locker

This outbreak is spreading faster than previous emerging or re-emerging viruses. Contributing factors could include presence of asymptomatic or mildly symptomatic individuals that might go undetected; the relatively central and connected geographic location of Wuhan; the increased ability of Chinese people to travel by plane and by train; the coincidence of the outbreak with the Chinese New Year, which is one of periods when Chinese people travel the most. – Alfredo Garzino-Demo

For active microbiologists, what is the most encouraging direction of research for finding potential treatments for this virus?

Within the past few weeks, owing to the rapid sharing of biological samples, scientists have already been able to sequence viruses and analyse its genome. More than 20 viral isolates have now been sequenced and analysed with scientists sharing their data analysis on social media and posting preprint to accelerate our understanding of the 2019-nCoV. Importantly, this has allowed virologists to publish a nucleic acid based diagnostic test for the new virus. This incredibly rapid outcome has accelerated the identification of infected patients and will help understand the origin of the virus. This can help explain why the number of reported cases has also rapidly exploded, owing to better detection. Others groups worldwide are developing simple to use antibody test.

On addition, few groups worldwide have reported successful attempt at propagating and recovering viral particles from Bronchoalveolar lavage fluid (BALF) of infected patients. Having viruses at hand will undoubtedly help proceed faster in the search and design for a vaccine. Best cases scenario estimate a vaccine ready within few months but clinical trials still would take time and another 18 months at best, before a vaccine can be rolled out.

So where does it come from? Like SARS, the Wuhan pneumonia cases are linked to live animal markets and appear to be caused by a virus that it related to ancestor viruses of SARS. While bats and civets are amongst suspected culprits, the identification of animal species harbouring the virus remain unknown. But having a test for the virus will help solve this question. Furthermore, while the number of cases is exploding in Hubei province, it remains relatively low in other countries, suggesting that human-to-human is low. However reported cases of transmission from asymptomatic patients are challenging this.” – Nicolas Locker

Clearly, a vaccine is the most important tool to prevent spreading of an infectious agent, and the quick availability of sequence data is very helpful. The same applies to development of neutralizing monoclonal antibodies, which could be useful for treatment. Antiviral compounds used in therapy for HIV, and Flu are being tested and early results suggest some efficacy against nCoV, which is encouraging for treatment of particularly severe infections.” – Alfredo Garzino-Demo

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