Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.12.15.22283507; this version posted December 20, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Antidepressant drug prescription and incidence of COVID-19: a retrospective cohort study Oleg O. Glebov1,2* Ph.D., Christoph Mueller2,3 M.D., Robert Stewart2,3 M.D., Dag Aarsland2,4 M.D., Gayan Perera2 Ph.D. 1 Institute of Neuroregeneration and Neurorehabilitation, Department Pathophysiology, School of Basic Medicine, Qingdao University, Shandong, China. of 2 Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. 3 South London and Maudsley NHS Foundation Trust, London, UK. 4 Centre for Age-related research, Stavanger University Hospital, Stavanger, Norway. * contact e-mail: oleg.glebov@kcl.ac.uk Word count: 1292 (Main Text) Key points Question Is there an association between prescription of antidepressants and incidence of COVID-19 in the general population? Findings In this retrospective cohort study of mental health outpatients with a recent (1-3 months) antidepressant prescription, there was a statistically significant 40% decrease in positive COVID-19 tests. This association was specifically observed for the most commonly prescribed antidepressant class, Selective Serotonin Reuptake Inhibitors, and remained when adjusted for socioeconomic parameters and physical health. Meaning Antidepressant prescription was associated with lower incidence of COVID-19 in the community, warranting further investigation as prophylactics in prospective clinical studies. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2022.12.15.22283507; this version posted December 20, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Abstract While antidepressant drugs (ADs) have shown some efficacy in treatment of COVID-19, their preventative potential remains unexplored. To investigate association between AD and COVID-19 incidence in the community, we analysed data from community-living, nonhospitalized adults admitted to inpatient care of the South London&Maudsley (SLaM) NHS Foundation Trust during the 1st wave of COVID-19 pandemic in the UK. Prescription of ADs within the period of 1 to 3 months before admission was associated with an approximately 40% decrease in positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was specifically observed for ADs of the Selective Serotonin Reuptake Inhibitor (SSRI) class. These results suggest that ADs, specifically SSRIs, may help prevent COVID-19 infection in the community. Definitive determination of AD preventative potential warrants prospective studies in the wider general population. Main text More than 2.5 years since the declaration of the global COVID-19 pandemic, it remains a major public health burden across the world, with further waves of infection more likely than not. To this day, the only available method for prevention of..