Abstract
Despite of considerable variation in disease manifestations observed among coronavirus disease 2019 (COVID-19) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the risk factors predicting disease severity remain elusive. Recent studies suggest that peripheral blood cells play a pivotal role in COVID-19 pathogenesis. Here, we applied two-sample Mendelian randomization (MR) analyses to evaluate the potential causal contributions of blood cell indices variation to COVID-19 severity, using single-nucleotide polymorphisms (SNPs) as instrumental variables for seventeen indices from the UK Biobank and INTERVAL genome-wide association studies (N = 173,480). Data on the associations between the SNPs and very severe respiratory confirmed COVID-19 were obtained from the COVID-19 host genetics initiative (N = 8,779/1,001,875). We observed significant negative association between hematocrit (OR = 0.775, 95% CI = 0.635-0.915, P - value = 3.48E-04) or red blood cell count (OR = 0.830, 95% CI = 0.728-0.932, P - value = 2.19E-03) and very severe respiratory confirmed COVID-19, as well as nominal negative association of HGB (OR = 0.808, 95% CI = 0.673-0.943, P = 3.95E-03) with very severe respiratory confirmed COVID-19 (no effect survived multiple correction). In conclusion, the MR study supports a protective effect of high hematocrit and red blood cell count from very severe respiratory confirmed COVID-19, suggesting potential strategies to ameliorate/treat clinical conditions in very severe respiratory confirmed COVID-19.
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