In a recent publication in the journal Gene, scientists at the Indian Institute of Science Education and Research (IISER) in Mohali, Punjab, showed through a meta-analysis of globally published data that correlations exist between mutations in specific genes of patients and susceptibility and severity of COVID-19.
This is the first study that has synthesised all the published data from case-control studies seeking to establish association of variants in the host genetic make-up with COVID-19. The study found that while mutations in certain genes (ACE1, APOE, CCR5 and IFITM3) showed increased risk for infection, variants in others (ACE2, AGTR1 and TNFA) showed association with severe COVID.
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Why some people are more susceptible to COVID-19 and why only in some people the infection progresses to more severe manifestations has remained a puzzle. Risk factors such as age, sex, underlying comorbidities, and environmental factors do have an association with disease severity but do not on their own explain why only some young, healthy individuals suffer severe or life-threatening illness.
To identify the host genes that may have a role in COVID-19’s impact on an individual, many studies around the world examined possible correlations between variants of the “usual suspect” genes and COVID-19 susceptibility and severity.
After identifying 84 studies that investigated the association of 130 polymorphisms in 61 genes, the IISER Mohali team, which included three doctoral students and Indranil Banerjee, the principal investigator of this study, performed a meta-analysis of all the eligible studies. Seven genetic variants involving 15,550 cases and 4,44,007 controls were explored. Similarly, the data of 11 variants involving 6,702 patients with severe COVID-19 and 8,640 infected individuals with non-severe manifestations were studied for statistically significant association.
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“We believe that this study will have important implications in elucidating the mechanisms of SARS-CoV-2 infection, identifying susceptible individuals, and designing promising therapeutic strategies for COVID-19,” Banerjee said.