Jacques Fellay, a professor at EPFL’s School of Life Sciences based at Campus Biotech, talks about mutations of the novel coronavirus, variants in the human genome, and how they might affect the current pandemic.

Has the SARS-CoV-2 virus mutated by now?

Like all viruses, SARS-CoV-2 evolves over time through random mutations of its genome (which is made of single-stranded RNA). These little changes can be used to draw up phylogenetic trees, a diagram that shows evolutionary relationships between coronaviruses, and can tell us about the virus’s spread. However, most mutations have no impact on viral fitness and ability to cause disease, and so far, there is no evidence of more or less virulent strains of SARS-CoV-2.

What did we learn from the genome of SARS-CoV-2?

First, we very quickly learned that the pathogen causing a severe pneumonia of unknown origin in the city of Wuhan was in fact a coronavirus. Second, sequencing of the viral RNA made it possible to estimate that the virus probably jumped from animal to human in November 2019, and to identify the bat as the most likely reservoir – sorry to disappoint, but it’s probably not the pangolin… Finally, the distribution of the random mutations detected in the virus’s genome makes it possible to reconstruct the temporal and geographical routes of viral propagation, which is important for informing public health policy.

Is there any correlation between genetics and symptom severity?

On the viral side, as said above, nothing suggests that the slight variations observed in the genome have an impact on symptoms and disease severity. On the human side, the short answer is “we don’t know yet”. As for all infectious diseases, human genetic variants are likely to explain some of the differences observed between patients. However, we don’t have any data yet.

Is it true that once you are infected the virus stays in your body forever in your DNA?

No. This is only true for retroviruses like HIV, which have the capacity to integrate into our own DNA and persist for life. Coronaviruses depend on our cellular machinery to replicate but they cannot colonize the human genome. Once someone is cured, the virus is completely eliminated.

How will this pandemic contribute to your research in human genomics and infections?

My lab aims at understanding how human genetic variation influences our response to infectious diseases. Hidden in our genome, we can find clues to better fight pathogens. We plan to sequence the genome of previously healthy patients, less than 50 years old, who develop life-threatening SARS-CoV-2 infections. The identification of genetic variants that explain this very unusual clinical presentation could shed light on the genes and pathways that play a crucial role in viral pathogenesis, thereby informing drug and vaccine development. 

Science publishing on the Corona topic is mostly published without being peer-reviewed. Is this a problem? Are the papers still useful?

During this pandemic, there is a clear need to rapidly disseminate scientific information about epidemiology, viral biology, clinical outcomes, prevention and therapy, etc. The classical model of peer-reviewed publishing just cannot cope. This has led to a flurry of coronavirus-related preprints posted online (>500 on bioRxiv and medRxiv over the past 3 months). Many of those have provided essential information about the epidemic, almost in real-time. So no, I don’t think it’s a problem. Of course, we must keep in mind that some preprints will be proven false, but the vast majority is scientifically sound – in fact, several of them end up in Nature or the New England Journal of Medicine every week – and play an essential role in the rapid dissemination of knowledge.

Do you think this pandemic could change the opinion of people regarding science?

To put in bluntly, the world now has no choice but to count on science to save lives, to predict the impact of various confinement or testing strategies, and to develop efficient antivirals and ultimately a vaccine. Whether this will be enough for society to listen more carefully to scientists in the future is less clear… One can only hope!