The Wuhan Virus

As I write this article, the viral epidemic that started in a seafood market in Wuhan in Dec 2019 has claimed at least 40 lives and infected at least 1300 others in China. Cases are now being reported from Thailand, Singapore, Malaysia, South Korea, Japan, Vietnam, Nepal, France, Australia and even as far as the US. This is an eerie reminder of the SARS epidemic from 17 years ago. That epidemic also started from an animal market in China and then spread rapidly to infect ~8000 people across 37 countries, killing ~10% of those infected. What is different today is the speed with which the viral genome sequence in affected individuals has been obtained and used to identify and track the virus in question.

On Jan 10 2020, while news of the first fatality was barely trickling in, the 29,903 letters constituting the viral genome from an affected individual in Wuhan had already been elucidated (even though a few corrections were made subsequently). The first thousand or so letters appear below.

Unintelligible gobbledygook perhaps, but very useful nevertheless for multiple reasons.

First, this sequence in invaluable for diagnosing the cause of disease when an individual presents with suspicious symptoms, typically cough, fever, and shortness of breath. Is this just a harmless common cold, or could it progress to fatal pneumonia? If the latter, then is the culprit the Wuhan virus or some other agent of even greater virulence? Different viruses have differing letter sequences and determining the specific viral sequence in the affected person helps pinpoint the cause. Diagnostic tests based on this viral sequence are now being used to confirm those affected specifically with the Wuhan virus.

Second, comparing the sequence of this new virus with those from previous epidemics can give us a hint of what to expect. A "family tree" [ref] of various known viral genome sequences below

suggests that the Wuhan virus (called 2019-nCov above) is a close cousin of the viruses responsible for two other well-known epidemic outbreaks in this century: the SARS virus from the 2003 epidemic in China, and the MERS virus from the 2012 epidemic in Saudi Arabia. The similarity between their sequences is roughly 80% [ref] so all three viruses have a not very ancient common origin and can be expected to have somewhat similar effects on humans. Interestingly, all three are more distant cousins of the harmless common cold causing Rhinoviruses A and B.

The third use is to pinpoint the source of the virus—where was it hiding before it suddenly broke loose into humans in the seafood market in Wuhan a month ago? The answer is imminent, as exemplified by the analysis performed during the SARS outbreak in 2003 [ref]. Viral sequences obtained from patients were compared to those obtained from various animals sold in live animal markets in an effort to identify the original source of the infection. Palm civets and racoon dogs emerged as likely candidates in this analysis. However, unlike their unfortunate counterparts in the market, palm civets and racoon dogs in the wild did not carry the virus. This suggests that they were mere intermediaries in the transmission process and not the natural reservoir for the virus. Further surveillance work found very similar viral sequences in certain species of wild bats, implicating these bats as the natural reservoir for the SARS virus. Perhaps, the virus jumped from bats to palm civets and racoon dogs, and thence to humans, fine-tuning itself along the way its ability to infect humans. Culling of palm civets and racoon dogs in live markets helped eliminate the source of the epidemic.

A similar analysis after the MERS outbreak in Saudi Arabia in 2012 suggested that the MERS virus could also have originated in bats but used a different intermediary, the camel, before it jumped to humans. Culling camels is not an option in the middle east for cultural reasons, so outbreaks continue from time to time.

This process is still ongoing for the Wuhan virus. Nevertheless, the close similarity of the Wuhan virus genome sequence with other viral genomes in bats (~92%) suggests that this virus too originated from bats and then jumped to an unknown intermediary prior to jumping into humans. The intermediary, though still unknown, could be determined soon, and culling from live markets may again be key to eliminating the source of the virus.

But how do we know that the source of the virus is sharply concentrated in certain animals in certain live markets and not a lot more widespread? If the latter, then culling in certain areas would not be of much use and the risk of newer outbreaks would continue. Encouraging evidence comes from viral genome sequences released into GISAID from at least 25 other individuals infected with the Wuhan virus. Most individuals are from China while some are from other countries. Included in this list are individuals who were in Wuhan but not at or near the seafood market and could potentially have been infected from a very different source. Of course, one expects all these viral genomes to be very similar to each other, but not necessarily identical, because the virus continues to mutate with time. Similar to what extent is the question. Even a modest amount of difference between the sequences could suggest that either the virus jumped into humans a while ago or perhaps it jumped to humans multiple times from different animal populations. Fortunately, neither is the case.

All the viral genome sequences from affected individuals are very very close to each other. Several are identical and none has more than 5 differences (99.983% similarity). This strongly suggests that transmission into humans came from a single pointed source and happened very recently, between Sep-Dec 2019.

Given what we are learning from viral genome sequencing above, and given all the emergency measures being put in place in China in particular and around the world in general, there is every reason to believe that the epidemic will be controlled shortly. Meanwhile, the virulence of the Wuhan virus remains lower than that of the SARS and MERS viruses as measured by deaths caused among those infected: 3-4% as opposed to 10% and 35% respectively, with the brunt being borne by individuals with significant existing co-morbidities and/or older age.

Of course, what is it in these 29,903 characters of the Wuhan virus that enables this tiny virus to bring down a human with trillions of cells and a 6 billion character genome sequence remains a topic of much research.