(C-254) Concomitant COVID-19 and Influenza Vaccination and the Risk of Psychiatric Adverse Events: a nationwide self-controlled case series study

Background: As COVID-19 transitions into an endemic state, annual concomitant administration of the COVID-19 vaccine with the influenza vaccine is recommended. While the safety of concomitant vaccination has been evaluated for reactogenic adverse events, evidence on the risk of psychiatric adverse events that might be attributed to systemic immune response remains limited.

Objectives: To assess whether concomitant COVID-19 and influenza vaccination is associated with the risk of psychiatric adverse events.

Methods: We conducted a self-controlled case series analysis using the National Health Insurance Database, linked with the Immunization Registry Information System from February 26, 2021 to July 31, 2023. The study population was defined as those who received both the COVID-19 and influenza vaccines within a 28-day interval and were subsequently diagnosed with psychiatric adverse events. Psychiatric adverse events were defined using ICD-10 codes, including anxiety/nervousness, mood disorder, perceptual disturbance/psychoses, aggression/behavioral disturbances, cognitive impairments, and sleep disorder. The risk window was defined as 28 days after each vaccination, and the overlap period as the risk window for concomitant. The control window encompassed the remaining observation period. For primary analysis, we assessed the risk of psychiatric adverse events in the risk window using conditional Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals. For secondary analysis, we conducted analyses stratified by the history of psychiatric disorder.

Results: Among 44,539,316 COVID-19 vaccine recipients and 21,614,811 influenza vaccine recipients, 521,024 concomitant patients were diagnosed with psychiatric adverse events. The primary analysis indicated that concomitant COVID-19 and influenza vaccination was associated with increased risk of anxiety/nervousness (IRR, 1.24; 95% CI, 1.20-1.28), mood disorder (1.10; 1.06-1.15), cognitive impairments (1.39; 1.33-1.44), and sleep disorder (1.38; 1.33-1.43), but was not associated with perceptual disturbance/psychoses (1.03; 0.92-1.15) or aggression/behavioral disturbances (1.00; 0.88-1.14). Secondary analyses stratified by the history of psychiatric disorders showed results consistent with our primary findings.

Conclusions: This nationwide study identified an increased risk of psychiatric adverse events following the concomitant COVID-19 and influenza vaccination, regardless of the history of psychiatric disorders. Continuous monitoring for psychiatric adverse events after concomitant vaccination is warranted, and further research is needed to elucidate the underlying immune-mediated mechanisms of psychiatric adverse events.