White blood cells and severe COVID-19: a Mendelian randomization study

Abstract

Background: The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly emerged to seriously threaten public health. We aimed to investigate whether white blood cell traits have potential causal effects on severe COVID-19 using Mendelian randomization (MR). Methods: To evaluate the causal associations between various white blood cell traits and severe COVID-19, we conducted a two-sample MR analysis with summary statistics from recent large genome-wide association studies. Results: Our MR results indicated potential causal associations of white blood cell count, myeloid white blood cell count, and granulocyte count with severe COVID-19, with odds ratios (OR) of 0.84 (95% CI: 0.72-0.98), 0.81 (95% CI: 0.70-0.94), and 0.84 (95% CI: 0.71-0.99), respectively. Increasing eosinophil percentage of white blood cells was associated with a higher risk of severe COVID-19 (OR: 1.22, 95% CI: 1.03-1.45). Conclusions: Our results suggest the potential causal effects of lower white blood cell count, lower myeloid white blood cell count, lower granulocyte count, and higher eosinophil percentage of white blood cells on an increased risk of severe COVID-19.

Prioritizing Causal Risk Factors for Severe COVID-19: An Exhaustive Mendelian Randomization Study

“…In addition to direct evidence from neutrophils, sum basophil neutrophil counts and sum neutrophil eosinophil counts are directly related to neutrophils, and concordant causal effects were obtained using multiple MR methods. We also identi ed myeloid white blood cell counts and granulocyte counts as being inversely associated with the risk of severe COVID-19, which is consistent with our previous MR ndings 46 . In contrast to the negative associations in this MR study, previous observational studies have provided strong evidence that elevated white blood cells and neutrophils but depleted lymphocytes are common in COVID-19 patients [47][48][49][50] .…”

Liver and Kidney Function Biomarkers, Blood Cell Traits and Risk of Severe COVID-19: A Mendelian Randomization Study

“…In addition, a recent study showed that pre-existing lymphocytopenia before any possible exposure to SARS-CoV-2 is associated with an increased risk of dying from COVID-19 ( Burack et al, 2020 ). Beyond confirming the previous MR findings of the negative causality between white blood cell count and COVID-19 severity ( Sun et al, 2020 ), we extended these findings by implementing multiple well-established MR methods and assessing >2-fold GWAS sample size of COVID-19 patients (6,492 in our study vs. 3,199 in the prior report), and discovered that lymphocyte count have an independent causal role in the etiology of COVID-19 severity. The underlying mechanisms may involve complex immune responses.…”

“…In addition, a recent study showed that pre-existing lymphocytopenia before any possible exposure to SARS-CoV-2 is associated with an increased risk of dying from COVID-19 (Burack et al, 2020). Beyond confirming the previous MR findings of the negative causality between white blood cell count and COVID-19 severity (Sun et al, 2020), we extended these FIGURE 3 | Genetic correlation for eight risk factors and causal effects on severe COVID-19 estimated by multivariable MR analysis. (A) Pair-wise genetic correlations with significance at P < 0.05, P < 0.01, and P < 0.001 are marked with a single asterisk (*), double asterisk (**), and triple asterisk (***), respectively.…”

Quick COVID-19 Severity Index, CURB-65 and Quick SOFA Scores Comparison in Predicting Mortality and Risk Factors of COVID-19 Patients

“…However, studies show that normal or decreased WBC counts are more prevalent among COVID-19 patients than healthy individuals. 18 While neutrophils represent the innate immune response, lymphocytes are the marker of the inflammatory response. Thus, high NLR indicates an instability in the inflammatory response in sepsis and bacteremia.…”