Post-traumatic stress disorder and risk for hospitalization and death following COVID-19 infection

The COVID-19 pandemic has caused substantial global morbidity and mortality. Prior research suggests that psychiatric disorders may increase risk for severe COVID-19 outcomes via higher rates of medical comorbidities, adverse health behaviors, and immune dysregulation. Meta-analyses have linked psychiatric disorders to higher risks of hospitalization and death from COVID-19. Despite the increased prevalence of traumatic stressors during the pandemic and biological and behavioral features of PTSD that could worsen infectious disease outcomes, it was unknown whether PTSD specifically confers higher risk for severe COVID-19 sequelae. This study tested the hypothesis that VA patients with PTSD would have increased risk of hospitalization and death within 60 days following a positive SARS-CoV-2 test compared with patients without psychiatric disorders and with those having psychiatric disorders other than PTSD, accounting for socio-demographic factors, medical comorbidities, and smoking.

Emerging large-scale studies and meta-analyses indicate psychiatric disorders are associated with greater COVID-19 severity, with adjusted odds ratios around 1.75 for hospitalization and 1.26–1.38 for death. Mechanistically, PTSD is linked to unhealthy behaviors (smoking, alcohol use, inactivity, poor diet), elevated chronic inflammation, reduced anti-inflammatory glucocorticoid signaling, and accelerated cellular aging, all potentially exacerbating COVID-19 pathophysiology including cytokine storm. PTSD is also associated with medical conditions that increase COVID-19 risk (cardiovascular disease, hypertension, diabetes, obesity). One VA study early in the pandemic found patients with PTSD were more likely to be tested but less likely to test positive for SARS-CoV-2, leaving uncertain whether PTSD affects outcomes once infected. This evidence motivated evaluating PTSD-specific risks for hospitalization and death following COVID-19 infection.

Design: Retrospective cohort study using the U.S. Department of Veterans Affairs (VA) Corporate Data Warehouse (CDW) and the VA COVID-19 Shared Data Repository (VHA RSR 15-437). Population: VA patients with a recorded positive SARS-CoV-2 test between February 2020 and August 17, 2021. Inclusion: Positive SARS-CoV-2 test recorded in VA systems (including outside tests recorded in the EHR). Exclusions: Records with positive test dates outside the 60-day risk window for outcomes and missing diagnosis information (n = 21,334 excluded). Final analytic sample: 228,367 patients. Exposure: Psychiatric diagnoses within 5 years prior to the positive test, identified via inpatient/outpatient ICD-9-CM/ICD-10-CM codes requiring at least two occurrences. Diagnoses grouped into: (1) PTSD (alone or comorbid with other psychiatric disorders); (2) other psychiatric disorders (depression, anxiety, adjustment disorder, alcohol use disorder, substance use disorder, bipolar disorder, psychotic disorder, ADHD, dissociative disorder, eating disorder) without PTSD; (3) no psychiatric disorders. Outcomes: Any acute inpatient hospitalization and all-cause death within 60 days following the positive SARS-CoV-2 test. Hospitalizations included acute inpatient admissions with patient isolation; long-term care and psychiatric/spinal cord injury admissions were not considered acute COVID-19 hospitalizations. Deaths captured from VA records within 60 days of positive test. Covariates: Socio-demographics (age, age squared, sex, race, ethnicity); medical comorbidities recorded within 2 years pre-test (obesity defined by BMI >30 at test date; diabetes; cardiovascular disease including hypertension; obstructive sleep apnea; COPD; cancer; chronic kidney disease; liver disease; HIV); smoking status (never, current, former/new). Statistical analysis: Descriptive comparisons by psychiatric group used t-tests/chi-square tests. Multivariable generalized linear models (Poisson with robust variance) estimated relative risks (RRs) for hospitalization and death. Model 1 adjusted for socio-demographics (age, age squared, sex, race, ethnicity). Model 2 additionally adjusted for obesity, medical comorbidities, and smoking. Analyses compared PTSD and other psychiatric disorders to no psychiatric disorder, and directly compared PTSD versus other psychiatric disorders. Age-stratified analyses (<65 vs ≥65 years) assessed effect modification. Secondary analyses further stratified by additional age bands (e.g., <40, 60–94). Sensitivity analyses: (a) examining PTSD versus adjustment disorder due to high co-occurrence; (b) excluding breakthrough infections defined as positive tests >14 days after any COVID-19 vaccine dose (n = 7,918 excluded). Data preparation used SAS 9.4; modeling used Stata 15.1; two-sided tests with p<0.05.

Sample characteristics: 228,367 VA patients with positive SARS-CoV-2; mean age 60.6 years; 89.5% male; 67.4% White, 22.4% Black; 9.8% Hispanic/Latinx. Psychiatric morbidity: 25.6% had PTSD (n = 58,567); 28.2% had other psychiatric disorders (n = 64,395); high comorbidity with 82.2% of those with PTSD having at least one other psychiatric diagnosis. Outcomes within 60 days: 15.0% hospitalized (n = 34,354); 6.0% died (n = 13,661). Main associations (Model 1 socio-demographic adjusted; Model 2 fully adjusted): • PTSD vs no psychiatric disorder: Hospitalization RR 1.18 (95% CI 1.15–1.21), fully adjusted 1.09 (1.06–1.12); Death RR 1.13 (1.08–1.19), fully adjusted 1.08 (1.03–1.13). • Other psychiatric disorders vs no psychiatric disorder: Hospitalization RR 1.34 (1.31–1.37), fully adjusted 1.22 (1.19–1.24); Death RR 1.23 (1.18–1.27), fully adjusted 1.14 (1.10–1.19). • Direct comparison (PTSD vs other psychiatric disorders): Lower risk in PTSD group: Hospitalization RR 0.88 (0.86–0.91), fully adjusted 0.90 (0.87–0.92); Death RR 0.92 (0.88–0.97), fully adjusted 0.94 (0.90–0.99). Any psychiatric disorder (including PTSD) vs none: • Hospitalization: RR 1.27 (1.24–1.29) socio-demographic adjusted; 1.16 (1.14–1.19) fully adjusted. • Death: RR 1.19 (1.15–1.23) socio-demographic adjusted; 1.12 (1.08–1.16) fully adjusted. Age patterns: Absolute risks were higher in older patients (≥65 years: 21.6% hospitalized; 11.5% died) versus younger (<65 years: 9.3% hospitalized; 1.2% died). Associations of psychiatric disorders with hospitalization and death were evident across age groups after socio-demographic adjustment. Among older patients, other psychiatric disorders showed stronger associations with both outcomes than PTSD; among younger patients, magnitudes for PTSD and other psychiatric disorders were similar. Individual disorders: Each assessed disorder (e.g., major depressive disorder, anxiety, adjustment, alcohol and substance use, bipolar, psychotic) was associated with increased 60-day hospitalization and death risks versus no psychiatric disorder after socio-demographic adjustment. Larger effect sizes were observed for substance use, psychotic, and bipolar disorders (e.g., hospitalization RRs approximately 1.66–1.90; death RRs approximately 1.46–1.69), whereas PTSD showed more modest elevations (hospitalization RR ~1.18; death RR ~1.13).

Findings support the hypothesis that PTSD confers increased risk for severe COVID-19 outcomes (hospitalization and death) within 60 days following infection, independent of socio-demographics, medical comorbidities, and smoking. The results align with prior literature linking psychiatric disorders to worse infectious disease outcomes and suggest that PTSD-related behavioral and biological factors (e.g., higher prevalence of health risk behaviors, chronic inflammation, altered glucocorticoid signaling) may contribute to vulnerability. While all psychiatric disorders evaluated were associated with adverse outcomes, other psychiatric conditions—particularly psychotic, bipolar, and substance use disorders—showed larger effect sizes than PTSD, especially among older adults. Clinically, these findings underscore the need to recognize PTSD and other psychiatric disorders as markers of higher risk for severe COVID-19, informing prioritization for preventive strategies (e.g., vaccination, boosters), early testing and treatment access, and tailored counseling during infection surges. The data also suggest that ongoing public health guidance (e.g., CDC lists of conditions conferring higher risk) should consider including PTSD alongside mood and schizophrenia spectrum disorders.

In a large, national VA cohort of 228,367 COVID-19-positive patients, PTSD and other psychiatric disorders were independently associated with elevated 60-day risks of hospitalization and death. Although effect sizes for PTSD were modest relative to some other psychiatric conditions, the consistent associations after adjustment highlight psychiatric morbidity as an important risk marker for severe COVID-19 outcomes. These findings support prioritizing individuals with PTSD and other psychiatric disorders for preventive measures and early treatment. Future research should investigate mechanisms (behavioral, inflammatory, endocrine), evaluate interventions that mitigate risk in psychiatric populations, assess generalizability beyond VA and predominantly male samples, and incorporate richer social determinants of health and more precise phenotyping of psychiatric diagnoses.

Use of clinical record data limited characterization of key covariates, including social determinants of health. Potential misclassification of psychiatric diagnoses due to over- or underdiagnosis in routine care. Generalizability may be limited because the cohort included only VA patients who accessed VA healthcare and was predominantly male (~89.5%), a group potentially at higher risk for severe COVID-19 than women. Some psychiatric conditions had low prevalence, limiting precision of individual effect estimates. Residual confounding and measurement error are possible despite extensive adjustment. The evolving nature of COVID-19 (variants, vaccination) may influence outcomes over time, though sensitivity analyses excluding breakthrough infections were conducted.