Causal influences of osteoarthritis on COVID-19: a Mendelian randomization study

OBJECTIVE: Although observational and genetic studies have indicated a correlation between OA and COVID-19, it remains uncertain whether osteoarthritis (OA) contributes to the severity of COVID-19. Here, we aimed to investigate the potential causal links between the two. METHODS: In this study, we conducted Mendelian randomization (MR) analysis to investigate whether there is a potential causal connection between OA and COVID-19 outcomes. The analysis utilized publicly available GWAS summary datasets, incorporating data on OA (N = 455,221), SARS-CoV-2 infection (N = 2,597,856), hospitalized COVID-19 (N = 2,095,324), and critical COVID-19 (N = 1,086,211). Additionally, we performed a literature analysis to establish a molecular network connecting OA and COVID-19. RESULTS: The MR analysis showed causal effects of OA on hospitalized COVID-19 (OR: 1.21, 95% CI: 1.02–1.43, p = 0.026) and critical COVID-19 (OR: 1.35, 95% CI: 1.09–1.68, p = 0.006) but not on SARS-CoV-2 infection as such (OR: 1.00, 95% CI: 0.92–1.08, p = 0.969). Moreover, the literature-based pathway analysis uncovered a set of specific genes, such as CALCA, ACE, SIRT1, TNF, IL6, CCL2, and others, that were found to mediate the association between OA and COVID-19. CONCLUSION: Our findings indicate that OA elevates the risk of severe COVID-19. Therefore, larger efforts should be made in the prevention of COVID-19 in OA patients.