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)

Abstract

Amid the ongoing global repercussions of SARS-CoV-2, it is 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 joins this 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-19 positive (n = 219,264), and COVID-19 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-19 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.

Fig 1. Final cohort selection by applying exclusion criteria.

Fig 2. SSPD hazard ratio comparisons.