Simultaneous COVID-19 mRNA, Flu Vaccination Linked to More Adverse Reactions

Anne M. Hause, PhD, MSPH

Simultaneous administration of a COVID-19 messenger RNA (mRNA) vaccine booster and a seasonal influenza vaccine may result in more adverse events than that of a lone mRNA booster dose, according to new findings.

In new research that makes consideration to the opportunity for dual immunization against COVID-19 and the flu annually, a team of investigators reported an approximate 10% increase in risk of systemic adverse events among individuals who received both a COVID-19 mRNA vaccine booster and flu shot in the same appointment during the 2021-22 flu season.

Led by Anne M. Hause, PhD, MSPH, of the Centers for Disease Control and Prevention (CDC) COVID-19 Response Team, the US-based research team sought to better describe the safety of simultaneous administration of COVID-19 and influenza vaccination during the first season of opportunity this past year. As they noted, the initial US Food and Drug Administration (FDA) emergency authorization expansions for Pfizer-BioNTech’s BNT162b2 and Moderna’s mRNA-1273—the first authorized COVID-19 mRNA vaccines globally—as booster doses for high-risk adults occurred in fall 2021.

They sought to characterize the safety outcomes of simultaneous COVID-19 vaccine booster and flu vaccine doses through adverse events and health impacts reported into the nationally-available smartphone surveillance system v-safe. Their assessment pertained to outcomes reported from 0-7 days following vaccination, from September 22, 2021 to May 1, 2022.

Hause and colleagues excluded persons who reported simultaneous administration of a third vaccination along with the COVID-19 and flu doses; those who reported a COVID-19 booster dose prior to FDA authorization; and those who reported an mRNA-1273 vaccination <18 years old or those who reported a BNT162b2 vaccination <12 years old. They compared calculated odds for any reported injection site (local) or systemic reactions, as well as health impacts, among simultaneously vaccinated persons with any such outcomes reported by those vaccinated with lone COVID-19 mRNA doses.

Their analysis included 92,023 v-safe respondents who reported a simultaneous receipt of COVID-19 mRNA booster and flu vaccination, versus 889,076 reported recipients of a lone COVID-19 mRNA booster vaccination. A majority (59.7%) of simultaneous recipients were female; they were primarily (40.6%) aged 12-49 years.

A majority of respondents to receive simultaneous vaccination with either BNT162b2 (58.9%) or mRNA-1273 (68.6%) with a flu shot reported systemic reactions within the week following administration. The most common reactions included fatigue, headaches, and myalgia; only fatigue, among patients administered mRNA-1273, was reported in a majority of patients. Another 64.9% and 74.4%, respectively, reported any local reaction—such as itching, pain, redness and swelling.

Among respondents to receive either lone BNT162b2 or mRNA-1273 in the observed time period, local reactions (64.0%, 71.7%, respectively) and systemic reactions (58.9%, 64.9%, respectively) were generally slightly lower than the simultaneous vaccination arms, respectively.

Respondents who received mRNA-1273 plus a flu shot were the most likely to report any health impact shortly following vaccination (26.8%), followed by those who received lone mRNA-1273 (25.3%). The most commonly reported impact across all 4 treatment arms was the inability to attend work or school.

Investigators confirmed that respondents who received mRNA-1273 plus a flu vaccination were 11% more likely to report any systemic reaction than those who received a lone COVID-19 booster (adjusted OR [aOR], 1.11; 95% CI, 1.08 – 1.14), while those who received BNT162b2 plus a flu vaccination were 8% more likely to report any systemic reaction (aOR, 1.08; 95% CI, 1.06 – 1.10). Reactions were generally mild in severity, they noted, and any vaccination-related hospitalization was not possible to determine based on available v-safe data.

“Our findings are generally consistent with results from the phase 3 trial of simultaneous

administration of an adjuvanted recombinant subunit vaccine for prevention of herpes zoster with substantial reactogenicity and quadrivalent inactivated influenza vaccine,” investigators wrote. “Participants aged 50 years or older who received simultaneous vaccination reported systemic reactions more frequently (60.9%) than participants who received adjuvanted recombinant subunit herpes zoster vaccine (52.1%) or influenza vaccine (33.6%) alone; however, this difference was not considered clinically meaningful by Schwarz et al.”

The team concluded the findings may help “better characterize the outcomes associated with simultaneously administered COVID-19 mRNA booster and influenza vaccines in the US population.”

The study, “Reactogenicity of Simultaneous COVID-19 mRNA Booster and Influenza Vaccination in the US,” was published online in JAMA Network Open.