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Old age, male sex, and underlying comorbidities have been found to predispose patients to increased disease severity in COVID-19. In this study, brother pairs with a shared phenotype offered an opportunity to evaluate the role of variants in genes located on the X chromosome. In the Netherlands, two pairs of brothers (family 1 of Dutch ancestry and family 2 of African ancestry) were diagnosed with severe COVID-19 requiring intensive care unit management; one of the four patients died. The investigators performed rapid whole-exome sequencing to identify possible genetic variants linked to this disease presentation.
Genetic analysis identified the X-chromosomal TLR7 as the plausible genetic link. The brothers in family 1 had a 4-nucleotide del…