Peripheral blood indicators and COVID-19: an observational and Mendelian randomization study

Blood are critical for human health, underpinning multifarious physiological processes such as immune response and oxygen transport, which when impaired cause a considerable global health burden. Although recent observational studies have identified correlations between common blood clinical indicators and COVID-19, they cannot provide causal inference due to residual confounding and reverse causality. To identify indicators affecting COVID-19, we retrospectively collected the clinical data (n=2,293, aged 18–65years) about 58 indicators in the first affiliated hospital of Guangzhou medical university from 2022 to date, and revealed significant differences in 34 indicators between healthy controls and COVID-19 patients after multiple corrections. To assess the causal nature of these candidate markers for COVID‐19, we then performed Mendelian randomization (MR) and meta-analyses by integrating data (N > 2,461,591) from the COVID‐19 Host Genetic Initiative, Blood Cell Consortium, UK Biobank, and other large-scale Genome-wide association studies, and found that 6 blood indicators were causally associated with the risk of COVID‐19, five of which is consistent with our observational findings. Troponin I (OR, 1.07; 95% CI, 1.01–1.14) and platelet distribution width (OR, 1.04; 95% CI, 1.01–1.07) were significantly associated with a higher risk of COVID‐19 while hematocrit (OR, 0.89; 95% CI, 0.82–0.98), haemoglobin concentration (OR, 0.91; 95% CI, 0.85–0.97), and neutrophil count (OR, 0.94; 95% CI, 0.89–0.99) were significantly associated with a lower risk of COVID‐19. These findings may help identify high-risk individuals and provide further direction on the management of COVID‐19.