tetano
Editor, Senior Moderator
Vaccine
. 2026 Jun 15:88:128821.
doi: 10.1016/j.vaccine.2026.128821. Online ahead of print.
Incidence of outcomes relevant to vaccine safety monitoring in the general population, after influenza vaccination, and after respiratory infections: a descriptive analysis of four US claims databases, 2022-2023
Christopher Bush[SUP] 1 [/SUP], Shaina Desai[SUP] 1 [/SUP], Huabo Wang[SUP] 2 [/SUP], Wei-Chun Hsu[SUP] 3 [/SUP], E Claire Newbern[SUP] 3 [/SUP], Astra Toyip[SUP] 1 [/SUP], Sarah Grace[SUP] 2 [/SUP], Katherine E Mues[SUP] 1 [/SUP], Brent Arakaki[SUP] 1 [/SUP], Vaishali Khamamkar[SUP] 3 [/SUP], Daina B Esposito[SUP] 3 [/SUP], Cindy Ke Zhou[SUP] 4 [/SUP]
Affiliations
Background: Background incidence rates (IRs) of safety outcomes in the absence of vaccination of interest and IRs following the infection targeted by the vaccine, are integral for contextualizing vaccine benefit-risk. As new respiratory vaccines are developed, contemporaneous IR estimates for outcomes commonly assessed in vaccine safety surveillance are needed in the COVID-19 endemic era.
Methods: This retrospective cohort study used four administrative claims data sources in the United States (HealthVerity Closed Claims, Optum's de-identified Clinformatics® Data Mart, Humana and Medicare Fee-For-Service) to estimate IRs for 30 safety outcomes across five organ systems between 1 August 2022 and 31 July 2023. Analyses were conducted overall and stratified by age and sex in five cohorts: the general population, influenza vaccine recipients, and those with medically attended SARS-CoV-2, respiratory syncytial virus, or influenza infection.
Results: IRs following influenza vaccination were generally similar to or lower than those in the general population, whereas rates after respiratory infections were generally higher and confounded by marked baseline differences. Among adults ≥65 years, heart failure, atrial fibrillation, ischemic coronary artery disease, and venous thromboembolism had the highest IRs across cohorts. Among adults aged 18-64 years, seizure, anaphylaxis and cardiovascular outcomes were most frequent after respiratory infections. The highest IRs in children were febrile seizures in those ≤5 years and seizures in <18 years; most other outcomes were rare. IRs were similar to or higher in males than females, except for autoimmune disorders.
Conclusion: This study estimated IRs for 30 safety outcomes relevant to vaccine safety monitoring in a COVID-19 endemic period. Variation across demographic groups and cohorts underscores the importance of accounting for confounders including age and sex when estimating expected rates. Elevated IRs after respiratory infections provide context for future benefit-risk assessments for vaccines targeting these viruses before more rigorous adjusted analyses become available.
Keywords: Background rates; Influenza; Respiratory syncytial virus; SARS-CoV-2; Safety outcomes; Vaccine safety surveillance.
. 2026 Jun 15:88:128821.
doi: 10.1016/j.vaccine.2026.128821. Online ahead of print.
Incidence of outcomes relevant to vaccine safety monitoring in the general population, after influenza vaccination, and after respiratory infections: a descriptive analysis of four US claims databases, 2022-2023
Christopher Bush[SUP] 1 [/SUP], Shaina Desai[SUP] 1 [/SUP], Huabo Wang[SUP] 2 [/SUP], Wei-Chun Hsu[SUP] 3 [/SUP], E Claire Newbern[SUP] 3 [/SUP], Astra Toyip[SUP] 1 [/SUP], Sarah Grace[SUP] 2 [/SUP], Katherine E Mues[SUP] 1 [/SUP], Brent Arakaki[SUP] 1 [/SUP], Vaishali Khamamkar[SUP] 3 [/SUP], Daina B Esposito[SUP] 3 [/SUP], Cindy Ke Zhou[SUP] 4 [/SUP]
Affiliations
- PMID: 42296834
- DOI: 10.1016/j.vaccine.2026.128821
Background: Background incidence rates (IRs) of safety outcomes in the absence of vaccination of interest and IRs following the infection targeted by the vaccine, are integral for contextualizing vaccine benefit-risk. As new respiratory vaccines are developed, contemporaneous IR estimates for outcomes commonly assessed in vaccine safety surveillance are needed in the COVID-19 endemic era.
Methods: This retrospective cohort study used four administrative claims data sources in the United States (HealthVerity Closed Claims, Optum's de-identified Clinformatics® Data Mart, Humana and Medicare Fee-For-Service) to estimate IRs for 30 safety outcomes across five organ systems between 1 August 2022 and 31 July 2023. Analyses were conducted overall and stratified by age and sex in five cohorts: the general population, influenza vaccine recipients, and those with medically attended SARS-CoV-2, respiratory syncytial virus, or influenza infection.
Results: IRs following influenza vaccination were generally similar to or lower than those in the general population, whereas rates after respiratory infections were generally higher and confounded by marked baseline differences. Among adults ≥65 years, heart failure, atrial fibrillation, ischemic coronary artery disease, and venous thromboembolism had the highest IRs across cohorts. Among adults aged 18-64 years, seizure, anaphylaxis and cardiovascular outcomes were most frequent after respiratory infections. The highest IRs in children were febrile seizures in those ≤5 years and seizures in <18 years; most other outcomes were rare. IRs were similar to or higher in males than females, except for autoimmune disorders.
Conclusion: This study estimated IRs for 30 safety outcomes relevant to vaccine safety monitoring in a COVID-19 endemic period. Variation across demographic groups and cohorts underscores the importance of accounting for confounders including age and sex when estimating expected rates. Elevated IRs after respiratory infections provide context for future benefit-risk assessments for vaccines targeting these viruses before more rigorous adjusted analyses become available.
Keywords: Background rates; Influenza; Respiratory syncytial virus; SARS-CoV-2; Safety outcomes; Vaccine safety surveillance.