tetano
Editor, Senior Moderator
Ann Intern Med
. 2025 Nov 18.
doi: 10.7326/ANNALS-25-04028. Online ahead of print. Comparative Effectiveness and Harm of Seasonal Influenza Vaccines in Adults Who Are Not Pregnant or Immunocompromised: A Rapid Review for the American College of Physicians
Andreea I Dobrescu[SUP] 1 [/SUP], Amin Sharifan[SUP] 1 [/SUP], Isolde Sommer[SUP] 1 [/SUP], Camilla I A Neubauer-Bruckner[SUP] 1 [/SUP], Arianna Gadinger[SUP] 1 [/SUP], Irma Klerings[SUP] 1 [/SUP], Claus Nowak[SUP] 1 [/SUP], Gerald Gartlehner[SUP] 2 [/SUP]
Affiliations
Background: Seasonal influenza is a contagious viral respiratory illness that causes yearly epidemics.
Purpose: To assess the comparative effectiveness and harm of standard and newer and enhanced influenza vaccines in nonpregnant, nonimmunocompromised adults.
Data sources: Medline and Embase between May 2023 and July 2025, and a systematic review by the European Centre for Disease Prevention and Control (ECDC) to identify studies published before May 2023.
Study selection: Two investigators independently selected English-language randomized controlled trials (RCTs) and nonrandomized studies of interventions (NRSIs).
Data extraction: For newly included studies, one reviewer extracted data and assessed certainty of evidence (CoE), which was verified by a second reviewer; 2 reviewers independently assessed risk of bias. For studies from the ECDC report, original data and risk-of-bias assessments were used.
Data synthesis: The review included 35 RCTs and 5 NRSIs. Compared with standard vaccines, high-dose vaccines reduced laboratory-confirmed influenza in adults aged 65 years or older (high CoE) but increased the risk for fever in this group (high CoE). High-dose vaccines probably caused fewer serious adverse events in all adults and those aged 65 years or older (moderate CoE). Recombinant vaccines reduced laboratory-confirmed influenza in all adults and those younger than 65 years compared with standard vaccines (high CoE). Evidence from 2 RCTs indicated that mRNA vaccines may increase serious adverse events in all adults and those younger than 65 years compared with standard vaccines (low CoE).
Limitations: RCTs evaluating laboratory-confirmed influenza and influenza-related hospitalization or death are limited. Evidence was lacking for several comparisons and outcomes. Broad definitions of serious adverse events may have inflated risk estimates.
Conclusion: High-dose and recombinant vaccines improve protection compared with standard vaccines, but high-dose vaccines increase fever risk. Evidence for mRNA vaccines is limited and should be cautiously interpreted.
Primary funding source: American College of Physicians. (PROSPERO: CRD420251114496).
. 2025 Nov 18.
doi: 10.7326/ANNALS-25-04028. Online ahead of print. Comparative Effectiveness and Harm of Seasonal Influenza Vaccines in Adults Who Are Not Pregnant or Immunocompromised: A Rapid Review for the American College of Physicians
Andreea I Dobrescu[SUP] 1 [/SUP], Amin Sharifan[SUP] 1 [/SUP], Isolde Sommer[SUP] 1 [/SUP], Camilla I A Neubauer-Bruckner[SUP] 1 [/SUP], Arianna Gadinger[SUP] 1 [/SUP], Irma Klerings[SUP] 1 [/SUP], Claus Nowak[SUP] 1 [/SUP], Gerald Gartlehner[SUP] 2 [/SUP]
Affiliations
- PMID: 41248500
- DOI: 10.7326/ANNALS-25-04028
Background: Seasonal influenza is a contagious viral respiratory illness that causes yearly epidemics.
Purpose: To assess the comparative effectiveness and harm of standard and newer and enhanced influenza vaccines in nonpregnant, nonimmunocompromised adults.
Data sources: Medline and Embase between May 2023 and July 2025, and a systematic review by the European Centre for Disease Prevention and Control (ECDC) to identify studies published before May 2023.
Study selection: Two investigators independently selected English-language randomized controlled trials (RCTs) and nonrandomized studies of interventions (NRSIs).
Data extraction: For newly included studies, one reviewer extracted data and assessed certainty of evidence (CoE), which was verified by a second reviewer; 2 reviewers independently assessed risk of bias. For studies from the ECDC report, original data and risk-of-bias assessments were used.
Data synthesis: The review included 35 RCTs and 5 NRSIs. Compared with standard vaccines, high-dose vaccines reduced laboratory-confirmed influenza in adults aged 65 years or older (high CoE) but increased the risk for fever in this group (high CoE). High-dose vaccines probably caused fewer serious adverse events in all adults and those aged 65 years or older (moderate CoE). Recombinant vaccines reduced laboratory-confirmed influenza in all adults and those younger than 65 years compared with standard vaccines (high CoE). Evidence from 2 RCTs indicated that mRNA vaccines may increase serious adverse events in all adults and those younger than 65 years compared with standard vaccines (low CoE).
Limitations: RCTs evaluating laboratory-confirmed influenza and influenza-related hospitalization or death are limited. Evidence was lacking for several comparisons and outcomes. Broad definitions of serious adverse events may have inflated risk estimates.
Conclusion: High-dose and recombinant vaccines improve protection compared with standard vaccines, but high-dose vaccines increase fever risk. Evidence for mRNA vaccines is limited and should be cautiously interpreted.
Primary funding source: American College of Physicians. (PROSPERO: CRD420251114496).