Lung cancer and COVID-19 susceptibility and severity: a Mendelian randomization analysis

It has been observed that lung cancer patients are more susceptible to COVID-19. Establishing the causal relationships between lung cancer and COVID-19 susceptibility and severity is challenging due to numerous confounding factors. Mendelian randomization (MR) is an effective method to investigate the causal association between exposure and outcome variables. However, different studies have yielded conflicting conclusions regarding the role of lung cancer in COVID-19 susceptibility and severity. Lung cancer subtypes exhibit heterogeneity in genetic susceptibility, which may influence the assessment of the true relationship between lung cancer and COVID-19 susceptibility and severity. In this study, we utilized the most recent COVID-19 association data from The COVID-19 Host Genetics Initiative with more than two million samples in total, in combination with genetic data of different lung cancer subtypes with more than eighty-five thousand samples, and conducted a two-sample Mendelian randomization study. We examined the associations between lung cancer and its four subtypes with COVID-19 susceptibility, hospitalization, and severity. Our data indicates that lung cancer, overall, does not have a causal association with COVID-19 susceptibility, hospitalization, or severity. However, lung cancer in ever smokers is nominally associated with COVID-19 hospitalization p-value 0.035, false discover rate (FDR) [Formula: see text] and increased severity [Formula: see text], [Formula: see text]. Additionally, small cell lung carcinoma is associated with increased COVID-19 severity [Formula: see text], [Formula: see text].