Large-scale study could help inform new COVID-19 treatment strategies

A new analysis of data from the Veterans Affairs Million Veteran Program has discovered genetic links between the severity of COVID-19 and certain medical conditions that are known risk factors for severe COVID-19. Anurag Verma of Corporal Michael Crescenz VA Medical Center in Philadelphia, Pennsylvania, USA, and colleagues present these results April 28 in the open-access journal PLOS genetics.

Some people with COVID-19 experience the disease more severely than others. Previous research has identified some specific human gene variants that are associated with someone with more severe COVID-19. Some of these variants may also be associated with other medical conditions which may already be well understood; identifying these shared variants could improve understanding of COVID-19 and inform potential new avenues of treatment.

To identify shared variants, Verma and her colleagues used an unprecedented dataset of genotypic information linked to electronic health record (EHR) data for more than 650,000 US veterans. They conducted a type of analysis known as a phenome-wide association study (PheWAS) to examine links between variants often found in veterans who experienced severe COVID-19 and variants associated with a wide selection of medical conditions.

The analysis revealed that some variants associated with COVID-19 are also associated with known risk factors for COVID-19. Particularly strong links were found for variants associated with venous embolism and thrombosis, as well as type 2 diabetes and ischemic heart disease – two known risk factors for COVID-19.

The analysis also found genetic links between severe COVID-19 and neutropenia for veterans of African and Hispanic descent; these links did not appear for those of European ancestry.

Among respiratory conditions, idiopathic pulmonary fibrosis and chronic alveolar lung disease shared genetic links with severe COVID-19, but not other respiratory infections and chronic obstructive pulmonary disease (COPD). Some variants associated with severe COVID-19 were also associated with a reduced risk of autoimmune diseases, such as psoriasis and lupus. These findings underscore the need to carefully weigh various aspects of the immune system when developing new treatments.

Despite some limitations of the PheWAS method, these results could help deepen the understanding of COVID-19 and guide the development of new treatments.

Verma concludes, “The study demonstrates the value and impact of large biobanks linking genetic variations to EHR data in the public health response to current and future pandemics. MVP is one of the most diverse cohorts in the United States. We had a unique opportunity to analyze thousands of conditions documented before the COVID-19 pandemic. We gained insights into the genetic architecture of COVID-19 risk factors and disease complication.

“One thing that stood out to us was the high number of immune-mediated diseases that shared a genetic architecture with severe manifestations of COVID-19,” adds co-author Katherine Liao. “The nature of the associations has shed light on how the SARS-CoV2 virus exerts pressure on the human immune system and its constant balance to fight infection while maintaining sufficient control that it does not also become a process. autoimmune, attacking itself.”

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