What we know about the Wuhan Coronavirus: To date

In the past 3 weeks, there has been massive media attention on a novel coronavirus strain which seems to be infecting and spreading at an accelerated rate. There is so much of internet content about it, with a majority of them being false news. Its time to write a piece on it and clear some air.

Figure 1: Structure of Coronavirus.
Source

Coronaviruses are enveloped non-segmented positive-sense RNA viruses belonging to the family Coronaviridae (Order Nidovirales). Historically, Coronavirus disease was first described in 1931. Only two human coronaviruses- HCoV-229E and HCoV-OC43 were known until the appearance of SARS-CoV and later MERS-CoV. Structurally, the coronavirus is spherically shaped with a few proteins (See Figure 1). Their RNA genome is one of the largest with about 30Kbp sequence packed into a helical capsid contributed by the nucleocapsid protein (N) and further surrounded by an envelope. The M (membrane), E (Envelope) and S (Spike) protein form the structural proteins. The S protein mediates cell entry through receptors most possibly by acting as a class I viral membrane fusion protein.

Table 1: Classification of Coronaviruses.

The complete set of known coronaviruses are currently classified into 4 genera. The details of these are summarised in Table 1. As can be seen, the beta coronaviruses have been the most problematic to humans. This is especially due to their adaptability to new environments through rapid mutation and recombination with relative ease.

Figure 2: Current Coronavirus Statistics. Source

The current growing epidemic of coronavirus designated as novel coronavirus 2019 was first reported in December 2019 from Wuhan in China viral pneumonia. Subsequently, a massive increase in the number of cases has been observed. At the time of writing this post, a total of 20,626 cases have been confirmed of which 2,790 (14%) are in critical condition. There have been 427 deaths and 653 cases have been confirmed to have recovered completely (Live update is available through this link). That makes the case fatality ratio to approximately 2.07%. The most recent available estimate of R0 for nCoV 2019 is approximately 4.08 (WHO estimates the value in the range of 1.4 - 2.5). That means the epidemic is currently in a growing stage. The epidemic was initially declared as a PHEIC (Public Health Emergency of International Concern) which has been now escalated to a level 4- Global emergency.

Figure 3: Geographic distribution of nCoV-2019. Source: ECDC

Figure 4: Phylogenetic tree showing Wuhan Coronavirus relationship.

Source.

There has been a lot of media coverage in recent times suggesting that the Wuhan Coronavirus is a product of bioweapon research program that has leaked. I must say the news agencies have shown irresponsible behaviour here. This was further fuelled by a paper posted in biorxiv suggesting that the nCoV sequences had been engineered with HIV Gag sequence inserted into it. Most people even believed leading to the widespread circulation of the news. Thankfully, the paper has been retracted owing to lack of scientific robustness (Link). There is currently no genomic level evidence that it is engineered. Indeed the phylogenetic tree clarifies that the sequence is very much similar to the Bat coronavirus sequence, thereby also indicating a possible origin source.

"Based on the virus genome and properties there is no indication whatsoever that it was an engineered virus. Most countries had largely abandoned their bioweapons research after years of work proved fruitless. The vast majority of new, nasty diseases come from nature".

-Richard Ebright & Tim Trevan. Source

Currently, the diagnosis of coronavirus has been done by RT-PCR from the respiratory samples (Link). Scientists from China have previously reported that it can be cultured in human cells and that it enters them through the same molecular receptor as the coronavirus that causes SARS. The virus is also cultured at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) in Melbourne have successfully cultured the coronavirus. Quoting Dr Druce on this “Chinese officials released the genome sequence of this novel coronavirus, which is helpful for diagnosis, however, having the real virus means we now have the ability to actually validate and verify all test methods, and compare their sensitivities and specificities - it will be a game changer for diagnosis. The virus will be used as positive control material for the Australian network of public health laboratories, and also shipped to expert laboratories working closely with the World Health Organization (WHO) in Europe.” Source

In approximately a month the number of papers published on the Wuhan Coronavirus has already climbed to more than 60 papers (Link), evidence that a lot of labs are actually working on the virus at an extreme pace and there is a lot of data on clinical presentation and transmission. However, as of date, there are no approved specific coronavirus antiviral drugs. A clinical trial using a combination of lopinavir and ritonavir (Anti HIV drugs) based on its previously demonstrated use against SARS-CoV is currently in process. Another drug- remdesivir is also under testing. There was news circulating that the anti-HIV drug Nelfinavir, can be used for treatment which is not true. Rather, oseltamivir is currently used for treatment as per the publications.

Currently, the infection is spreading at a very high rate and with global attention, it is unlikely that many cases are missed. However, recent reports suggesting that many number of cases are asymptomatic and these asymptomatic cases can be good spreaders has challenged the perceptions we have for this infection. It must be noted that most coronavirus cases currently seen have not caused serious health damage and only a subset of the cases who have other predisposing factors are probably entering a critical stage. The WHO has urged the public to take simple hygiene precautions such as frequent washing of hands to avoid catching an infection.

In summary, nCoV-2019 is currently an ascending epidemic slowly moving to pandemic proportions, with most cases still being reported from China. The case-fatality ratio is very low but early detection method is available. There are no specific antivirals but the research is currently in rapid progress.

References:

1. R Lu et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020. pii: S0140-6736(20)30251-8. Link

2. Huang et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020. Link

3. Rothe et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. NEJM. 2020. DOI: 10.1056/NEJMc2001468 Link

4. Li et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. NEJM. 2020. DOI: 10.1056/NEJMoa2001316 Link

5. Wu et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020. https://doi.org/10.1038/s41586-020-2008-3. Link