COVID-19 and Seasonal Influenza Vaccination: Cross-Protection, Co-Administration, Combination Vaccines, and Hesitancy

Abstract

SARS-CoV-2 and influenza are the main respiratory viruses for which effective vaccines are currently available. Strategies in which COVID-19 and influenza vaccines are administered simultaneously or combined into a single preparation are advantageous and may increase vaccination uptake. Here, we comprehensively review the available evidence on COVID-19/influenza vaccine co-administration and combination vaccine candidates from the standpoints of safety, immunogenicity, efficacy, policy and public acceptance. While several observational studies have shown that the trained immunity induced by influenza vaccines can protect against some COVID-19-related endpoints, it is not yet understood whether co-administration or combination vaccines can exert additive effects on relevant outcomes. In randomized controlled trials, co-administration has proved safe, with a reactogenicity profile similar to that of either vaccine administered alone. From the immunogenicity standpoint, the immune response towards four influenza strains and the SARS-CoV-2 spike protein in co-administration groups is generally non-inferior to that seen in groups receiving either vaccine alone. Several public health authorities have advocated co-administration. Different combination vaccine candidates are in (pre)-clinical development. The hesitancy towards vaccine co-administration or combination vaccines is a multifaceted phenomenon and may be higher than the acceptance of either vaccine administered separately. Public health implications are discussed.

Flu and COVID-19 Vaccination: What Happens to the Flu Shot When the Campaigns Overlap? Experience from a Large Italian Research Hospital

“…Although some healthcare workers even opted for the coadministration, many others expressed concerns about the administration within a short period of time, therefore preferring to prioritize the SARS-CoV-2 vaccination and, thus, avoiding the flu one. The main reasons [49] seem to be the fear of the pandemic situation and especially in the uncertainty related to the consequences of a concurrent administration which may overload the immune system or may be more reactogenic, despite the availability of evidence-based recommendations demonstrating its safety and immunogenicity [50]. Moreover, another reason might be the spread of anti-vaccine movements, deriving from the COVID-19 vaccination campaign, even among HCWs, which might also affect the flu vaccination.…”

Transition to endemic: acceptance of additional COVID-19 vaccine doses among Canadian adults in a national cross-sectional survey

“…Thus, while more than 60% of all respondents agreed with COVID-19 vaccine co-administration, hesitancy towards co-administration is greater than hesitancy towards the COVID-19 vaccine alone. While there is some evidence to support this finding [ 12 ], one study found that a combination influenza/COVID-19 vaccine had higher acceptance than a COVID-19 vaccine alone [ 39 ]. More work is required to understand whether and how acceptance of co-administration differs from acceptance of combination vaccines, and whether these options differentially impact uptake across populations.…”

“…However, adult perceptions on ongoing booster doses (i.e., annual COVID-19 vaccination) are largely unknown, and evidence on additional vaccine dose acceptance among Canadian adults, particularly among populations who may be at greater risk for COVID-19 infection and/or severe illness, is required. To ensure that COVID-19 vaccination programs are both acceptable and sustainable, we need an understanding of perceptions on strategies used to promote vaccine uptake over the long term, including vaccination mandates and restrictions, vaccination locations, and COVID-19 vaccine co-administration with other vaccines [ 12 ].…”

Transition to Endemic: Acceptance of Additional COVID-19 Vaccine Doses Among Canadian Adults in A National Cross-Sectional Survey

“…To ensure that COVID-19 vaccination programs are both acceptable and sustainable, we need an understanding of perceptions on strategies used to promote vaccine uptake over the long term, including vaccination mandates and restrictions, vaccination locations, and COVID-19 vaccine co-administration with other vaccines. (12) The aim of this study was to determine Canadian adults' intention for receiving additional doses of COVID-19 vaccine (i.e., third or annual doses), and examine factors associated with acceptance. We further sought to understand influences on vaccination decision-making, and preferences around vaccine delivery location, and COVID-19 vaccine co-administration.…”

“…To ensure that COVID-19 vaccination programs are both acceptable and sustainable, we need an understanding of perceptions on strategies used to promote vaccine uptake over the long term, including vaccination mandates and restrictions, vaccination locations, and COVID-19 vaccine co-administration with other vaccines. (12)…”