Scientists unravel why some people are more susceptible to Covid-19

A team of researchers from India and the US, led by a scientist at the Chennai-headquartered private genome research foundation, has found why some individuals are more susceptible to Covid-19 infection than others.

Researchers from MedGenome Inc and SciGenom Research Foundation (SGRF) jointly anlaysed the DNA sequence and variation data from over 300,000 individuals belonging to 400 different populations to predict susceptibility to the Covid-19 disease caused by the SARS-CoV-2 virus. Nearly 1 per cent of the samples are from people of Indian origin.

The team led by Sekhar Seshagiri, President of Chennai-based SGRF India, identified variations in the angiotensin-converting enzyme 2 (ACE-2) protein gene that are predicted to make individuals more susceptible to the virus. Their findings are published online on the Biorxiv.org portal. However, the study is yet to be peer-reviewed.

The study found that individuals carrying certain variants of the ACE2 gene would be protected against the Covid-19 infection, which has symptoms that include fever, chills, cough, diarrhoea and pneumonia. While some infected individuals are asymptomatic, about 10 per cent need hospitalisation and 1-5 per cent of the cases are fatal.

Understanding why some individuals are more severely affected by the virus than others is important for managing those at risk. In the current study, the team attempted to understand how genetic factors affect the susceptibility to the virus.

How the virus attacks

SARS-CoV-2 enters human cells by binding to ACE2, a cell surface protein that functions like a door to the virus. ACE2, an enzyme created by the ACE2 protein, usually plays a role in maintaining blood pressure but is tricked by the virus. One of the reasons why the SARS-CoV-2 virus is highly infectious is because it can bind to the ACE2 cell receptor with higher affinity compared to the SARS-CoV virus that caused the SARS  epidemic in 2003. Scientists, in fact, found out that the spike protein which helps SARS-CoV-2 bind to ACE2 has undergone several mutations that has increased its affinity to the human ACE2 by nearly 10-15 times compared to SARS-CoV S-protein, making it highly infectious.

Natural human ACE2 protein variation encoded in an individual’s DNA allows the virus to bind to ACE2 either strongly or weakly, altering the susceptibility to the disease, which has caused the current pandemic.

The scientists who analysed ACE2 protein variants from  the sample data identified those variants that bind to the virus less tightly, making some individuals less susceptible to Covid-19, said Seshagiri, the lead  author. “The converse is also true; in this data set, we found ACE2 variants that will render individuals more susceptible to the virus,” said Eric Stawiski, Vice-President Bioinformatics at MedGenome in the US.

“Besides identifying people who may be vulnerable due to ACE2 variants, the findings from the study can be used to make a drug for Covid-19. We can rationally engineer ACE2 recombinantly and use it as a drug for treating Covid-19 patients — it’s like an antibody therapy. In other words, we can turn ACE2 into a weapon against the virus,” Seshagiri told BusinessLine .

For instance, “we can use a modified ACE2 enzyme that is produced like insulin (that is administered for diabetic patients) and give it to patients with, perhaps, serious symptoms. It will act like a sink, adsorb the virus and prevent it from entering the cells and thus provide relief to patients until the immune system kicks in and takes care of the virus for good,” Seshagiri said.

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