Expert update on the SARS-CoV2 coronavirus causing the COVID-19 outbreak

18-03-2020

This expert update on the SARS-CoV2 coronavirus comes just six weeks after we asked two virologists to give us an expert statement on the then current status of the novel coronavirus outbreak, which was originating in Wuhan, China. With the World Health Organization (WHO) now reporting nearly 180,000 confirmed cases, over 7000 recorded deaths, and cases in 159 countries, areas or territories (as of 17 March), it is safe to say that the COVID-19 outbreak has developed rather significantly since then.

This could be the hardest public health battle of recent times, but humanity is poised to eventually win.”

We asked Alfredo Garzino-Demo (Twitter: @MicroviroB), who helped us draft the first expert statement, to give us an update on what more has been learned about the SARS-CoV2 virus, and the disease COVID-19:

Update 18 March 2020Our translation volunteer team have produced versions of this expert update in:

What more do we now know about the virus causing the COVID-19 outbreak, and what can scientists do to best respond?

”In the 15 weeks since the appearance of the SARS-CoV2 virus, and of the disease it causes, COVID-19, we have witnessed an emerging virus turning into a pandemic. There are lessons to be learned from this situation, which will hopefully be useful to avoid or contain a future emerging pathogen.

Nonetheless, there are some pieces of good news. The first of which is how fast epidemiologists, public health experts, health workers, industry, and research scientist have worked together to do their part to quash the pandemic as soon as humanly possible. As of March 15, 2020, a search on PubMed reveals that some 947 research articles have already been published (although many are commentaries and review articles); and many more have become available through preprints – the 21st century way to report data almost in real time.

Therefore, progress has been very expeditious, more so than probably any previous outbreak, and we have learned quite a few important features of this viral infection. Given the fast pace of progress, it is possible that some of the newest data is not included here, as we intend to highlight some aspects that we find particularly important, so this is by no means a comprehensive review of the field.

An important question is whether transmission will decrease as the weather becomes warmer in the northern hemisphere … The next few weeks will shed light on that intriguing, and welcome, possibility.”

A 3D model of SARS-CoV2 (public domain)

It is now common knowledge that there are asymptomatic infected individuals so that transmission can occur from apparently healthy subjects ([1], [2], [3], [4]); in addition, even when symptoms eventually occur, the asymptomatic period can last as long as two weeks, and in some cases even longer ([4], [5], [6]). There is evidence that, besides the respiratory system, the virus can infect cells in the gastrointestinal tract (mouth, esophagus, stomach and intestines), ([7], [8]).

Indirect transmission though fomites (objects) has been documented [9], and according to one study, the half-life of the virus on some surfaces (plastic) is more than 15 hours, and the virus can be detected up to 3 days later [10].

So far parenteral and maternal transmission have not been observed ([11], [12]). While it was known that older age is a risk factor for disease severity and fatal outcome, mortality in the 0-9 age group is virtually zero; and there is evidence that males have a higher risk for disease severity and death than females [13]. An important question is whether transmission will decrease as the weather becomes warmer in the northern hemisphere, since the initial focal points of the pandemic were in regions that had similar temperatures and absolute/specific humidity ranges [14]. The next few weeks will shed light on that intriguing, and welcome, possibility.

From a therapeutic viewpoint, the experimental drug Remdesivir can inhibit the related virus MERS-CoV (the cause of Middle East Respiratory Syndrome (MERS) in 2012 ([15], [16])) in in vitro and in vivo in animal models, and it is now being tested in clinical trials in the US and China, and is available for compassionate use against COVID-19 ([17], [18]). Preliminary evidence shows that Remdesivir has some efficacy in COVID-19 patients ([19], [20]). In addition, choroquine has shown efficacy in in vitro models, and is being widely used, as is a combination of Lopinavir and ritonavir, which has fewer studies supporting it ([18], [21], [22]).

As for prevention, the first clinical trial for a SARS-CoV2 vaccine is set to start, probably to be soon followed by other vaccine candidates [23]. It is noteworthy that rhesus macaques that were experimentally infected with SARS-CoV2 and resolved the infection resisted a subsequent re-infection challenge. That finding is very encouraging, as it suggests that it is possible to induce protective immunity against the virus [24].

…while the moment is dire and adherence to safe practices, starting with social distancing, is absolutely necessary, clinical, vaccine, and basic research are progressing with vigor (and generosity).”

Structure prediction of non-structural protein 4 (nsp4) of SARS-CoV2 (Estimate TM-score=0.53). Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. From Chengxin Zhang, Wei Zheng, Xiaoqiang Huang, Eric W. Bell, Xiaogen Zhou, Yang Zhang (2020).

Structural analyses for all viral proteins are now available [25], including studies on the interaction between the viral spike protein and Angiotensin Converting enzyme 2 (ACE2), which is the receptor on the human cell surface that the virus uses ([26], [27]); viral polymerase [28], and its major protease [29]. These structures will be important for rational drug design and in general to enable studies on preventive and therapeutic approaches.

In conclusion, while the moment is dire and adherence to safe practices, starting with social distancing, is absolutely necessary, clinical, vaccine, and basic research are progressing with vigor (and generosity). Scientists have been extremely proactive in responding to the SARS-CoV2 pandemic. Sharing data, and collaborations, including those between public institutions and the private sector, are needed to further boost the pace of progress.

This could be the hardest public health battle of recent times, but humanity is poised to eventually win.”

Alfredo Garzino-Demo is Associate Professor at the Institute of Human Virology, and the Department of Microbiology and Immunology of the University of Maryland School of Medicine (USA); and at the University of Padova (Italy), and is an Editor-in-Chief of our journal Pathogens and Disease.

Further resources:

World Health Organization (WHO) dashboard for tracking COVID-19 cases 

John Hopkins University (JHU) dashboard for tracking COVID-19 cases

Global MediXchange for Combating COVID-19

All expert reactions to the COVID-19 outbreak from the Science Media Centre UK: https://www.sciencemediacentre.org/tag/covid-19/

All expert reactions to the COVID-19 outbreak from the Science Media Center Germany (in German): https://www.sciencemediacenter.de/alle-angebote/coronavirus/

Research:

 

 

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