SARS-CoV-2 Infection is Associated with an Increase in New Diagnoses of Schizophrenia Spectrum and Psychotic Disorder: A Study Using the US National COVID Cohort Collaborative (N3C) (preprint)

ABSTRACT

Amid the ongoing global repercussions of SARS-CoV-2, its crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joinsthis exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts ARDS (n = 222,337), COVID-positive (n = 219,264), and COVID-negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR 4.6; CI 3.7-5.7), 22-90 days (HR 2.9; CI 2.3 -3.8), beyond 90 days (HR 1.7; CI 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.