The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected millions of individuals and has claimed more than 5 million lives worldwide. According to the World Health Organization, globally, around 290000–650000 people die from influenza every year. Previous studies have indicated that individuals above 65 years and children below two years are most severely infected by influenza, which can also cause death.
Study: Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial. Image Credit: Prostock-studio/Shutterstock
Background
In many countries, influenza vaccination has been recommended as a preventive measure. Researchers have pointed out that the COVID-19 vaccination program could coincide with influenza vaccination programs in most countries, as the timing of both vaccinations might overlap. To date, no studies on the co-administration of COVID-19 vaccines with other vaccines are available. This is because, during the phase 3 trials of COVID-19 vaccines, scientists had either excluded candidates who were recently vaccinated or would receive vaccines within a week of receiving the COVID-19 vaccine. However, it is extremely important to understand the effects of co-administration of a vaccine on immune responses and safety where simultaneous vaccination programs could occur.
According to the current guidance in the UK, individuals can take both vaccines with at least seven days gap between the two. The US Centers for Disease Control (CDC) recommends a 14-day interval between these vaccines. However, the need for multiple visits to health care clinics for vaccination might reduce compliance and vaccination uptake. Therefore, it might be important to encourage people to take the vaccines, i.e., COVID-19 and influenza, in one visit rather than on separate days.
Scientists have conducted a substudy within a phase 3 UK trial and have reported the safety, immunogenicity, and efficacy of the NVX-CoV2373 COVID-19 vaccine when co-administered with licensed seasonal influenza vaccines. This report has been published in Lancet Respiratory Medicine.
Main findings
The authors claim that this substudy is the first to document the safety, immunogenicity, and efficacy of any COVID-19 vaccine when co-administered with a seasonal influenza vaccine or any other vaccination. This study found no proof of the interference of the COVID-19 vaccine with the quadrivalent influenza cell-based vaccine. This exploratory study was conducted between September 28th, 2020, and November 28th, 2020, and comprised a total of 15187 participants. The participants were young, radically diverse, and had less comorbidity.
Solicited local and systemic reactogenicity events such as tenderness or pain at the injection site, fatigue, and muscle pain were more common in the co-administration group compared to the group that received only the NVX-CoV2373 vaccine. Occurrences of unsolicited adverse events or serious adverse effects that required medical attention were found to be low in both groups. Scientists revealed no clinically meaningful pattern of increased reactogenicity was observed in all the study groups.
In the study cohort, no event of anaphylaxis or deaths was observed. Importantly, co-administration of COVID-19 and influenza vaccine led to no change in immune response related to influenza vaccine, but a reduction in antibody responses to the NVX-CoV2373 vaccine was observed. The efficacy of the NVX-CoV2373 vaccine in the substudy, including individuals of age group between 18 and 65 years, was 87.5% and control showed 89.8% efficacy.
Strengths and limitations
Researchers emphasized that the main strength of this substudy is its placebo-controlled study design. Another advantage of this study is its alignment with the UK’s national influenza vaccine policy in using both types of influenza vaccines (adjuvanted and unadjuvanted).
One of the main limitations of this substudy is its small sample size, with very few participants above the age of 65 years. Further limitations of the study include lack of randomization in recruiting the influenza substudy participants, a small number of substudy efficacy endpoints, absence of formal pre-specified statistical assessment of immunogenicity, etc. Future studies could construct more robust randomized groups, such as NVX-CoV2373 plus influenza vaccine, NVX-CoV2373 plus placebo, influenza vaccine plus placebo, and placebo plus placebo groups. Scientists also pointed out that the assessment of neutralizing antibody titers could have been beneficial for the immunogenicity investigation. Lastly, the open-label study design in administering the influenza vaccine was also a limitation, as pointed out by researchers.
Conclusion
This study is the first to document the safety, immunogenicity, and efficacy of a COVID-19 vaccine when administered in conjunction with a seasonal influenza vaccine. The data obtained showed no adverse effects of administering both the NVX-CoV2373 and influenza vaccines together. In other words, the immunogenicity of the influenza vaccine was preserved; however, scientists observed that a slight reduction occurred in the immunogenicity of the NVX-CoV2373 vaccine. Another striking observation among the age group 18-65 was that the vaccine efficacy was preserved in individuals who received both the vaccines, compared to those who received only NVX-CoV2373.
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