Research Sheds New Light on Genetic Risk Factors That Make Individuals More or Less Susceptible to Severe COVID-19

A growing body of genetic evidence from patients in China, Europe and the US links COVID-19 outcomes to variations in two regions of the human genome, although the statistical association fails to explain how the differences modulate disease. In order to do that, scientists need to understand which proteins these sections of the genome code for and the role these proteins play in the body in the context of disease.

Over the last decade, the BIDMC researchers have generated exactly such a database - an immense library of all the proteins and metabolites associated with various regions of the human genome. When the researchers looked up one genomic “hot spot” found to be associated with COVID-19 disease severity, they quickly realized that the very same region was linked to a protein that has recently been implicated in the process by which the SARS-CoV-2 virus infects human cells. The second region was linked to a poorly understood protein that appears to play a role attracting immune cells called lymphocytes to sites of infection, which also merits further study. Early analyses from their work also suggest that these genetic variants and proteins may vary across races. Taken together, these findings provide important contributions as the scientific community works rapidly to understand the mysteries of COVID-19.

“Groups are increasingly finding genomic hotspots related to diseases, but it’s often not clear how they impact the mechanisms of disease,” said Robert E. Gerszten, MD, Chief of the Division of Cardiovascular Medicine at BIDMC, who led the study. “We leveraged our huge database - it’s more than 100 terabytes’ worth of data - to very quickly determine that the protein most highly expressed by that region turned out to be a co-receptor for the virus that causes COVID-19, suggesting that this might be a target for therapeutic interventions. The so-called antibody cocktails currently available mostly target the spike proteins on the virus. In turn, our work identifies which proteins in the human body that SARS-CoV-2 and other coronaviruses latch on to.”

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Beth Israel Deaconess Medical Center (BIDMC)