Vaccination against both COVID-19 and influenza was well tolerated whether the vaccines were administered at the same time or separated by 1 to 2 weeks, in a placebo-controlled, randomized trial1 finding noninferiority between the schedules on measures of safety and reactogenicity.1
"In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 (inactivated influenza virus-quadrivalent) vaccines, reactogenicity was comparable in both groups," reported Emmanuel Walter, MD, MPH, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, and colleagues.
The investigators had randomized 335 adults on 1:1 ratio to receive either the COVID-19 and influenza vaccinations in different anatomical sites at the same time and placebo (saline) injection in 1 to 2 weeks, or the COVID-19 and placebo injections initially and the influenza vaccine in the subsequent visit.The injections were administered by unblinded staff, but participants and the study staff following them were blinded to the allocation.
"We initially chose a two-week interval to strike a balance between being able to distinguish between vaccine reactogenicity related to delivering both vaccines either simultaneously versus sequentially and not delaying the flu vaccine too long," Walter commented to Contagion.
"We did not want to leave people unvaccinated for too long and at risk of influenza. Ultimately, we shortened to 1 to 2 weeks so that we would be even more flexible about not delaying flu vaccine," Walter explained.
The study primary endpoint for noninferiority between groups was <10% difference in the proportion exhibiting a reactogenicity composite index comprising fever, chills, myalgia, and/or arthalgia of moderate or greater severity within 7 days after initial or subsequent vaccination visit. Secondary outcomes included solicited reactions and unsolicited adverse events, as well as serious adverse events reported throughout 121 days of follow-up.
Reaction were monitored on day 1 of vaccination through day 7 using a memory aid. Participants either submitted the memory aid information daily electronically, or brought it to the subsequent visit. Severity of each solicited reaction was graded based on criteria used in the mRNA COVID-18 vaccine trials. Serious adverse events, monitored through 121 days, were defined in accordance with the FDA.
What You Need to Know
A randomized trial demonstrated that administering mRNA COVID-19 and inactivated influenza (IIV4) vaccines simultaneously is as safe and well-tolerated as administering them sequentially (1-2 weeks apart).
The primary composite reactogenicity outcome (moderate-to-severe fever, chills, myalgia, and arthralgia within 7 days) occurred at similar rates in both groups—25.6% in the simultaneous group and 31.3% in the sequential group—supporting the feasibility of simultaneous administration.
Simultaneous vaccination offers a practical strategy to improve vaccine coverage during periods of high COVID-19 and influenza transmission.
Walter and colleagues reported non- inferiority between groups, with 25.6% (n=43) exhibiting primary composite reactogenicity outcome in the simultaneous group, compared to 31.3% (n-52) in the sequential group.They also noted that there were no significant group differences in adverse events.
"This trial lends support to the option of simultaneous administration of these vaccines," the investigators indicated, "which is a strategy to achieve high levels of vaccination coverage during anticipated periods of increased influenza and SAR-CoV-2 virus transmission."
Although the study focused on reactogenicity and safety and not on immunogenicity of the respective vaccine administration schedules, the investigators did find a numerical, but not statistically significant imbalance in the number of persons contracting COVID-19 illness in the simultaneous group (n=18) vs the sequential group (n=9).
Walter commented on the possibility of differences in immunogenicty between simultaneous and sequential administration. "I do not think this issue is settled," he said. "There are conflicting data, particularly with respect to COVID-19 immunogenicity. We hope to publish some immunogenicity data from this study in the future."
Reference
1.Walter EB, Schlaudecker EP, Talaat KR, et al. Safety of simultaneous vs sequential mRNA COVID-19 and inactivated influenza vaccines. A randomized clinical trial.JAMA Network Open. 2024;7(11):e2443166. doi:10.1001/jamanetworkopen.2024.43166.Accessed November 17, 2024.
