Direct and indirect associations linking COVID-19 severity to internalizing disorders and symptoms among participants in New Haven, CT.

While COVID-19 has a negative impact on mental health, the understanding of its association with distinct psychiatric disorders and symptoms is still limited. Leveraging the PsychGenCOV19 cohort including 1132 participants enrolled in New Haven, CT, we observed that moderate COVID-19 severity was associated with greater odds of internalizing disorders (major depressive disorder, MDD OR = 3.74; generalized anxiety disorder, GAD OR = 2.85; and post-traumatic stress disorder, PTSD OR = 2.32) and with lower odds of panic disorder (OR = 0.44). After modeling comorbidities among these mental health outcomes, the association between moderate COVID-19 severity and MDD remained statistically significant (OR = 2.89, p = 0.006). Investigating internalizing traits, we observed several associations with COVID-19 moderate severity even after accounting for MDD diagnosis (e.g., "lost interest in most things lasting two weeks or more" OR = 3.84; "Feeling nervous, anxious or on edge" OR = 1.82). In the multivariable model accounting for the co-occurrence of PTSD symptoms, moderate COVID-19 severity was also inversely related to "being super-alert or watchful or on guard" (OR = 0.45). In addition to MDD symptoms, certain GAD and PTSD symptoms (e.g., "Feeling jumpy or easily startled", "Feeling nervous, anxious or on edge", "Worrying too much about different things") mediated the association between COVID-19 severity and MDD (proportion mediated 9% to 27%). Finally, a latent class analysis identified PsychGenCOV19 participants characterized by severity patterns of COVID-19 and internalizing symptoms. These findings highlight the symptom-specific association of COVID-19 severity with mental health, underscoring possible transdiagnostic effects across the internalizing spectrum.