Abstract
Increasing evidence shows that white blood cells are associated with the risk of coronavirus disease 2019 (COVID-19), but the direction and causality of this association are not clear. To evaluate the causal associations between various white blood cell traits and the COVID-19 susceptibility and severity, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses with summary statistics from the largest and most recent genome-wide association studies. Our MR results indicated causal protective effects of higher basophil count, basophil percentage of white blood cells, and myeloid white blood cell count on severe COVID-19, with odds ratios (OR) per standard deviation increment of 0.75 (95% CI: 0.60–0.95), 0.70 (95% CI: 0.54–0.92), and 0.85 (95% CI: 0.73–0.98), respectively. Neither COVID-19 severity nor susceptibility was associated with white blood cell traits in our reverse MR results. Genetically predicted high basophil count, basophil percentage of white blood cells, and myeloid white blood cell count are associated with a lower risk of developing severe COVID-19. Individuals with a lower genetic capacity for basophils are likely at risk, while enhancing the production of basophils may be an effective therapeutic strategy.
Highlights
Coronavirus disease 2019 (COVID-19) is caused by infection of a novel virus calledSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has rapidly spread, causing irreversible damage or even death [1,2,3,4]
Elevated white blood cells (WBC) and neutrophil counts, and depleted lymphocyte count have been repeatedly observed in COVID-19 patients with severe outcomes, and the neutrophil-to-lymphocyte ratio has been proposed as prognostic biomarkers [1,5,13,14,15,16]
We first aimed to investigate the causal effects of WBC traits on COVID-19 severity and susceptibility via the forward Mendelian randomization (MR) analysis
Summary
Coronavirus disease 2019 (COVID-19) is caused by infection of a novel virus calledSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has rapidly spread, causing irreversible damage or even death [1,2,3,4]. A growing number of studies have found that immune cells may play important roles in the COVID-19 severity and susceptibility [5,6,7,8,9]. Since prior findings were based on observational studies, the causal associations between white blood cells (WBC) and COVID-19 remain unclear. Many observational studies have reported risk factors for COVID-19 susceptibility and severity. Findings from recent observational studies are inconsistent, and it is difficult to infer the causal roles of WBC in severe COVID-19 due to confounding and reverse causation [17,18,19]. Most existing studies measured blood cell counts in patients with confirmed infection of SARS-CoV-2 and as a result, the hematological indices could have been modified by immune responses [20]
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