Follow up Post: Wuhan Coronavirus

I must admit that my previous post on Wuhan Coronavirus (nCoV 2019) is not in any way complete information. Some of the details I skipped deliberately to provide an overview and avoid long boring read. Apparently, I should have given more information, considering that there is so much information floating around.

Photo 1: R affinis bat. Source

To the best of my understanding, we have not really understood what was the source from which the infection was acquired. Based on the sequencing results, the best match that has been found to be a coronavirus sequence isolated from Rhinolophus affinis (More commonly known as the Intermediate Horseshoe Bat) which was isolated in Yunnan Province in 2013 (More than 96% identity of sequence). The sequence identity in itself cannot ascertain that the virus made the jump to humans through a bat, but the circumstantial evidence is indicative. There are some important details from the paper by Zhou et al. The nCoV whole-genome sequences show similarity to the SARS-CoV. Further, the spike gene which encodes for receptor binding protein- S was found to be highly different from other CoVs, though it still uses the same ACE2 receptor for entry. Figure 1, from the paper, shows that there are some important changes in the S protein which is involved in cell entry.

Figure 1: Amino acid changes in the S protein indicating significant changes. Source: Zhou et al.

Photo 2: Bat Soup. Source

Though the exact mechanism of how it jumped or when it made the jump is not clear at this point of time, the current running hypothesis is that the "jump" happened at the Huanan Fish Market which sells exotic wild meat some which are also illegal. Interestingly, about 45% of the initial cluster of cases were not connected to the Wuhan market. This brings up two possibilities. First, the Wuhan market is not the primary place where the W happened. Alternatively, the percentage of people who did not directly acquire it from Wuhan market probably got it through a human to human transmission (By contact with asymptomatic case). The most famous "bat soup theory" suggests that the virus was acquired and adapted by consuming bat soup. Personally, I have doubts over this since Coronaviruses, in general, are not resistant to heat. A more likely possibility is the consumption of raw exotic meat. The definitive evidence would be finding the virus sequence from bats in Wuhan market, where the ground zero is supposed to be. According to a Chinese newspaper, environmental sampling was done at the Wuhan seafood market for 585 samples. of these, 33 samples were found to be positive for nCoV. All of the positives were from the market’s western portion where the wildlife and exotic meat was sold.

That brings in the question if the first case was the one reported in December. This is something difficult to answer. The best answer that I can think is "we are not sure". The first case might have acquired it much earlier and been asymptomatic and simply not detected. There is no way to tell. We can just say, that first known case was the one reported. There is a fair chance that the virus was circulating much before in Wuhan. The very high number of reported cases spreading at a rapid rate can be indeed explained by the idea that the virus was in circulation much earlier before December. 

In the context of the question, if bats are the source Christian Walzer comments, “These animals are live. You will see a bird on top of a domestic pig, and you might have snake and bats, all stacked together in wire-mesh cages. virus-laden fluids and secretions can mix, helping create new viruses, especially when the animals are slaughtered right in front of customers. If you planned it and thought, ‘I am going to make new viruses, that is exactly how you would do it.”

The second question that comes up is the epidemic severity of the nCoV in comparison to SARS-CoV and MERS CoV. I have compiled a comparison table for yourself to see. As can be noted, the nCoV has the lowest mortality rate as of yet, with the highest being MERS. But nCoV is leading in the total number of cases. However, the outbreak cannot be taken lightly. Remember, 1918 flu had a mortality rate of approximately 2.5 %. However, it still is considered as one of the grave pandemics. This was due to an extremely high speed of spreading at the time.

Table 1: Comparison of SARS-CoV, MERS-CoV and nCoV-2019.

The most common clinical symptoms of the infection include fever, cough and myalgia or fatigue. In almost all cases, the symptoms appear within 14 days. However, only a subset of cases actually requires hospitalisation and intensive treatment. Fig 2, shows the timelines of clinical symptoms after the onset of illness. The laboratory diagnosis is currently performed using RT-PCR from respiratory samples. The WHO protocol uses 3 targets for identification- First-line screening detects the E gene; Confirmatory assay targets the RdRp gene and an additional confirmatory assay look for the N gene.

As discussed in the previous post, an experimental drug remdesivir is currently under investigation. The drug was first tried in the US for the first case detected. The patient improved in a day and within 4 days, the case was successfully treated by this drug. Another study by Wang et al tested the efficacy of ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine, remdesivir and favipiravir in an in-vitro model and found that remdesivir and chloroquine were highly effective. Remdesivir is an adenosine analogue, which incorporates into nascent viral RNA chains and results in premature termination, which has been previously demonstrated to be useful against SARS and MERS. Chloroquine has been previously shown to block SARS infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors. The recent research from Thailand reports on successful treatment with lopinavir and ritonavir with large doses of the flu drug oseltamivir.

The current scenario of the outbreak is not showing any signs of slowing down. A few experts based on the current data available suggest that the outbreak may escalate if sufficient measures are not taken. As Anthony S. FauciIt's comments, "it is very, very transmissible, and it almost certainly is going to be a pandemic. But will it be catastrophic? I don't know". 

References:

1. Zhou et al. Pneumonia outbreak associated with a new coronavirus of probable bat origin.  Nature. 2020. https://doi.org/10.1038/s41586-020-2012-7. Link

2. Holshue et al. First Case of 2019 Novel Coronavirus in the United States. NEJM. 2020. Link

2. Wang et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Nature. 2020. https://doi.org/10.1038/s41422-020-0282-0. Link