LAUSR

Concomitant administration of the COVID-19 vaccine booster and the seasonal influenza vaccine could support uptake of both vaccines, augmenting protection against these preventable infectious diseases with potential implications for racial and ethnic disparities in vaccination rates.1 Vaccine coadministration could also introduce efficiencies in currently overburdened health care settings. Despite these many benefits, little is known about reactogenicity from concomitant dosing of COVID-19 and seasonal influenza vaccines. This situation is largely because, to avoid misattribution and more accurately estimate adverse event incidence, participants who had recently received other vaccines were excluded from early COVID-19 vaccine trials. COVID-19 and influenza vaccines have several known adverse events which could increase in frequency with coadministration and in turn negatively affect vaccine uptake. Although a 2021 phase 4 trial2 of simultaneous administration of Pfizer BioNTech and influenza vaccines in the UK raised no safety concerns, to date, there are no studies combining COVID-19 mRNA boosters with the influenza vaccine in the US. Hause et al3 examine adverse events in the week following simultaneous receipt of a COVID-19 mRNA booster and influenza vaccine in the US population. Using v-safe, the large vaccine surveillance self-report registry from the Centers for Disease Control and Prevention, Hause et al3 compared reactogenicity among respondents who received the Pfizer BioNTech or Moderna COVID-19 mRNA booster concomitant with a seasonal influenza vaccine with those who received the booster alone between September 22, 2021, and January 16, 2022. As was the case with COVID-19 vaccine booster trials,4 local and systemic adverse events with booster alone were reported to be mild to moderate and transient, occurring most often the day after vaccination. With coadministration of a booster with an influenza vaccine a small but significant increase in reactogenicity was observed; 8% among those who received the Pfizer mRNA booster and 11% among those who received the Moderna mRNA booster. The most frequently reported systemic reactions with vaccine coadministration were fatigue, headache, and myalgia. Local reactogenicity was dominated by pain at the injection site, and, as in the UK study, serious adverse events were infrequent. In addition, compared with those who received the Pfizer booster alone, those who simultaneously received the Pfizer booster and influenza vaccine were not more likely to report a health impact such as being unable to work, attend school, or perform normal activities. In contrast, those who received the Moderna booster and influenza vaccine were more likely to report a health impact in the following week than those who received the Moderna COVID-19 booster alone. Reactogenicity to vaccination is not wholly attributable to vaccine contents or delivery. In both influenza and COVID-19 vaccine clinical trials, substantial adverse events or so-called nocebo effects have been reported by participants randomized to the placebo arms of these trials. Nocebo effects may be affected by anxiety and expectation of adverse events. A meta-analysis5 of 45 380 participants in randomized COVID-19 vaccine clinical trials found that 76% of systemic and 24% of local reactogenicity could be attributed to nocebo effects. Thus, although Hause et al3 observed a slight but significant increase in adverse event reporting with vaccine coadministration, without a clinical trial and the requisite placebo controls, this increase cannot be simply attributed to the active agents in these vaccines. Further, by virtue of their acceptance of three COVID-19 vaccinations and an influenza vaccination, the v-safe participants studied by Hause et al3 may have lower expectation + Related article