Publication date: Aug 15, 2024

While existing studies have suggested an increased risk of COVID-19 in patients with depression, the causal impact of MDD on the severity of COVID-19 remains to be validated. Additionally, the potential impact of antidepressant medication on the risk of COVID-19 is not known. In our study, we applied a Mendelian Randomization (MR) method, leveraging summary data from GWAS, to evaluate the potential causal effects of depression on three COVID-19 outcomes. Furthermore, we investigated the causal effects of antidepressants on COVID-19 outcomes. The COVID-19 datasets contain information on various stages of the disease, including SARS-CoV-2 infection (N = 2,597,856), hospitalized COVID-19 (N = 2,095,324), and critical COVID-19 (N = 1,086,211). Datasets for depression and antidepressants were comprised of 1,349,887 and 106,785 participants, respectively. Employing the inverse variance-weighted (IVW) method, we show a causal association between depression and three COVID-19 outcomes. Specifically, we found that genetic liability to depression is linked to critical COVID-19 (OR: 1. 28, 95 % CI: 1. 13-1. 46), hospitalized COVID-19 (OR: 1. 23, 95 % CI: 1. 13-1. 34), and SARS-CoV-2 infection (OR: 1. 06, 95 % CI: 1. 02-1. 10). Interestingly, the use of antidepressants was not associated with COVID-19, with the odds ratios for critical COVID-19 (OR: 1. 05, 95 % CI: 0. 88-1. 26), hospitalization (OR: 1. 01, 95 % CI: 0. 90-1. 13), and SARS-CoV-2 infection (OR: 1. 03, 95 % CI: 0. 99-1. 08) indicating no causal impact. Our study indicates that genetic liability to depression may increase the susceptibility to COVID-19 and its severe forms. The lack of causal effect of antidepressant use on COVID-19 implies antidepressant medication may counteract the detrimental effect of depression on COVID-19.

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