Reactogenicity of Simultaneous COVID-19 mRNA Booster and Influenza Vaccination in the US

JAMA Netw Open. 2022 Jul 1;5(7):e2222241. doi: 10.1001/jamanetworkopen.2022.22241.


Importance: COVID-19 and seasonal influenza vaccines are essential in preventing respiratory infections and their potentially severe complications. Simultaneous administration of vaccines is efficient and may improve coverage with each vaccine. However, the safety of simultaneous administration of COVID-19 and influenza vaccines has not been well described.

Objective: To evaluate adverse events and health impacts associated with simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines in the US population.

Design, setting, and participants: In this retrospective cohort study, self-reported vaccine data were collected on days 0 to 7 after vaccination from September 22, 2021, through May 1, 2022, through v-safe, a voluntary smartphone-based monitoring system established by the Centers for Disease Control and Prevention. Participants were persons who voluntarily registered in v-safe following COVID-19 vaccination.

Exposure: Receipt of simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines or COVID-19 mRNA booster alone.

Main outcomes and measures: Local injection site and systemic reactions (eg, fatigue, headache, and myalgia) and health impacts reported by v-safe respondents in the week following COVID-19 mRNA booster vaccination. Adjusted odds ratios (aORs) were estimated for simultaneous administration compared with booster dose alone, controlling for sex, age, and week of vaccination.

Results: Of a total of 981 099 persons aged 12 years or older registered with v-safe, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was reported by 92 023 (9.4%) v-safe respondents; of these respondents, 54 926 (59.7%) were female, 36 234 (39.4%) were male, and sex was unknown for 863 (0.9%). In the week following vaccination, any systemic reactions were reported by 36 144 (58.9%) of 61 390 respondents who simultaneously received Pfizer-BioNTech booster and influenza vaccines and 21 027 (68.6%) of 30633 respondents who simultaneously received Moderna booster and influenza vaccines. Respondents who simultaneously received influenza and Pfizer-BioNTech booster vaccines (aOR, 1.08; 95% CI, 1.06-1.10) or influenza and Moderna booster vaccines (aOR, 1.11; 95% CI, 1.08-1.14) were slightly more likely to report any systemic reaction in the week following simultaneous vaccination than respondents who received only a COVID-19 mRNA vaccine booster.

Conclusions and relevance: In this study, compared with administration of COVID-19 mRNA booster vaccines alone, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was associated with significant increases in reports of systemic reactions during days 0 to 7 following vaccination. These results may help better characterize the outcomes associated with simultaneously administered COVID-19 booster and influenza vaccines in the US population.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • COVID-19 Vaccines* / adverse effects
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Influenza Vaccines* / adverse effects
  • Influenza, Human* / epidemiology
  • Influenza, Human* / prevention & control
  • Male
  • RNA, Messenger
  • Retrospective Studies
  • Vaccination / adverse effects
  • Vaccines, Synthetic
  • mRNA Vaccines


  • COVID-19 Vaccines
  • Influenza Vaccines
  • RNA, Messenger
  • Vaccines, Synthetic
  • mRNA Vaccine
  • mRNA Vaccines

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