Abstract
People hospitalized with COVID-19 often exhibit altered hematological traits associated with disease prognosis (e.g., lower lymphocyte and platelet counts). We investigated whether inter-individual variability in baseline hematological traits influences risk of acute SARS-CoV-2 infection or progression to severe COVID-19. We report inconsistent associations between blood cell traits with incident SARS-CoV-2 infection and severe COVID-19 in UK Biobank and the Vanderbilt University Medical Center Synthetic Derivative (VUMC SD). Since genetically determined blood cell measures better represent cell abundance across the lifecourse, we also assessed the shared genetic architecture of baseline blood cell traits on COVID-19 related outcomes by Mendelian randomization (MR) analyses. We found significant relationships between COVID-19 severity and mean sphered cell volume after adjusting for multiple testing. However, MR results differed significantly across different freezes of COVID-19 summary statistics and genetic correlation between these traits was modest (0.1), decreasing our confidence in these results. We observed overlapping genetic association signals between other hematological and COVID-19 traits at specific loci such as MAPT and TYK2. In conclusion, we did not find convincing evidence of relationships between the genetic architecture of blood cell traits and either SARS-CoV-2 infection or COVID-19 hospitalization, though we do see evidence of shared signals at specific loci.