Early influenza vaccination after MI reduces cardiovascular mortality

6th September 2021

Influenza vaccination given within 72 hours of a myocardial infarction (MI) reduced all-cause and cardiovascular mortality at 12 months.

Coronary heart diseases are the leading global cause of death and responsible for an estimated 17.9 million lives lost each year. The idea that influenza might contribute to the development of myocardial infarction (MI) and subsequent death, comes from autopsy studies of patients who died during influenza epidemics. In fact, a recent analysis of 364 hospitalisations for acute MI, confirmed a significant association between respiratory infections, especially influenza and MIs. It is therefore possible that administration of an influenza vaccination as both a primary or secondary preventative measure, could improve cardiovascular disease outcomes. However, a Cochrane review from 2015, concluded that among those with cardiovascular disease, influenza vaccination may reduce mortality and combined cardiovascular events but that more and higher-quality evidence is necessary to confirm these findings.

This need for more high-quality evidence was the reason for the Influenza vaccination After Myocardial Infarction (IAMI) trial undertaken by researchers from the Faculty of Health, Department of Cardiology, Orebro University, Sweden. The team hypothesised that influenza vaccination would reduce the incidence of death, further MIs and stent thrombosis, in patients with a recent MI or with high-risk coronary disease, which included those with stable coronary artery disease and 75 years of age or older with additional risk factors. Eligible patients for the trial were those with either ST-elevation myocardial infarction (STEMI) or non-STEMI. Patients were excluded if they had received an influenza vaccination during the previous 12 months. Participants were then randomised 1:1 to either influenza vaccine or placebo (saline) within 72 hours of their MI. The primary endpoint of interest was a composite of all-cause death, MI, or stent thrombosis at 12 months.

Findings
There were 2571 individuals with a mean age of 59.9 years (81% male) randomised to either arm. Overall, 54.5% of participants were admitted with STEMI and 45.2% with non-STEMI and 8 with stable coronary artery disease. Over the following 12 months, the primary outcome occurred in 5.3% of those vaccinated and 7.2% of those in the placebo group (hazard ratio, HR = 0.72, 95% CI 0.52 – 0.99, p = 0.04). The mortality rates were 2.9% (influenza vaccine) and 4.9% placebo (HR = 0.59, 95% CI 0.39 – 0.90, p = 0.014). In addition, within the influenza vaccination group, 2% experienced a subsequent MI compared to 2.4% in the placebo group (p = 0.57). None of the patients with stable coronary artery disease died.
Discussing their findings, the authors noted how the early administration of influenza vaccination led to a reduced risk of death compared to placebo. They concluded that the provision of influenza vaccination should form part of the in-hospital treatment received by patients following a myocardial infarction.

Citation

Frobert O et al. Influenza Vaccination after Myocardial Infarction:
A randomised, Double-Blind, Placebo-Controlled, multi-center Trial. Circulation 2021

Influenza vaccination protects against adverse outcomes in COVID-19 patients

7th August 2021

A large retrospective study has revealed a reduction in adverse outcomes in COVID-19 patients previously vaccinated against influenza.

The influenza vaccination has an effectiveness ranging from 30 to 60% for the three different influenza strains. However, over the course of the COVID-19 pandemic, there have been emerging data that suggests influenza vaccination confers some level of protection against COVID-19. For example, one US study found that among those who had not received an influenza vaccination, there was a two-fold higher risk of hospitalisation because of COVID-19. A further study appeared to confirm that having received a flu vaccination, reduced the risk of testing positive for COVID-19. Part of the reason for a potentially protective effect after influenza vaccination is related to the presence of MF59, an oil-in-water immunogenic adjuvant which appears to induce higher levels of antigen-specific antibody levels and ultimately, better protection.

While some preliminary data would suggest that receipt of an influenza vaccine protects against infection with COVID-19, no studies have examined whether vaccination mitigates any of the adverse outcomes associated with COID-19 infection. Using a retrospective design, a team from the Division of Plastic and Reconstructive Surgery, University of Miami, Florida, US, used propensity matching to compare the incidence of adverse outcomes between influenza vaccinated and unvaccinated individuals who had tested positive for COVID-19. They used a de-identified database and focused on individuals who had either received a flu vaccination six months and two weeks prior to the onset of symptoms or not. The two-week period was included because this is the length of time required to acquire immunity after an influenza vaccination. Additional data collected included demographics and co-morbidities and used these to propensity-match the two cohorts. Adverse outcomes were assessed within 30, 60, 90 and 120 days after a positive COVID-19 test result.

Findings
Two propensity matched cohorts of 37,377 patients with a median age of 52.5 years (58% female) were included in the analysis. Compared with unvaccinated individuals 60 days after testing positive, COVID-19 patients who received the influenza vaccine experienced significantly less sepsis (risk ratio, RR = 1.38, 95% CI 1.17–1.63, p < 0.01) and stroke (RR = 1.45), admission to an intensive care unit (RR = 1.16) and deep vein thrombosis (RR = 1.53). Furthermore, there was an overall lower number of emergency department visits at 120 days after infection (RR = 1.28). However, mortality did not differ at any of the time points between the two cohorts.
In their conclusion, while accepting the limitation imposed by a retrospective design and the potential for errors in data coding, the authors called for this potential protective effect of influenza vaccination against adverse outcomes in those testing positive for COVID-19, to be validated in further studies.

Citation

Taghioff SM et al. Examining the potential benefits of the influenza vaccine against SARS-CoV-2: A retrospective cohort analysis of 74,754 patients. PloS ONE 2021

Co-administration of influenza and COVID-19 vaccines shown to be effective

17th June 2021

Whether co-administration of a COVID-19 and influenza vaccine leads to immune interference is unclear but possibly relevant for future vaccination programmes.

The international rollout of the COVID-19 vaccination programme is starting to break the link between infection and severe illness and hospitalisation. Whether or not an annual booster COVID-19 vaccination will be required in the future is yet to be determined. Nevertheless, in some countries, it is possible that the COVID-19 vaccination schedule could overlap with the influenza season, with a potential for an overlap in vaccine administration. As the Phase III COVID-19 vaccination trials excluded those who had a recent or planned receipt of another vaccine, there is a lack of data on the impact of co-vaccination. This led a team from the Novavax Institute, Gaithersburg, USA and St George’s University Hospital, London, UK, to consider the effect of simultaneous administration of the first dose of the NVX-CoV2373 (Novavax COVID-19 vaccine) and an influenza vaccination, in a subgroup of patients included in the Phase III efficacy trial of NVX-CoV2373. Subgroup patients were required to be in good health and not already received an influenza vaccination or any other live vaccine within 4 weeks. These individuals were randomised to receive a concomitant dose of influenza with their first NVX-CoV2373 dose or influenza and placebo. Although the main study was observer-blind, the influenza vaccine was administered in an open-label manner and reactogenicity was evaluated using an electronic diary for 7 days post-vaccination and the team assessed the antibody titres to both influenza and COVID-19 after 21 days.

Findings
Although the main trial recruited over 15,000 participants, only 431 were randomised to influenza vaccine or placebo. A total of 217 participants with a mean age of 39 years (43.3% female) and 75.1% of White ethnicity received the seasonal influenza vaccine and 214 received the influenza vaccine and placebo. Reactogenicity was more common in the co-vaccinated group compared to NVX-CoV2373 alone, with 70.1% versus 57.6% reporting tenderness, pain at the injection site (39.7% vs 29.3%), fatigue (27.7% vs 19.4%) and muscle pain (28.3% vs 21.4%). Although the influenza vaccine response was satisfactory, the COVID-19 vaccine efficacy was 87.5% in the co-vaccinated subgroup compared with 89.8% in the main group. The rates of adverse effects were low and balanced between those given NVX-CoV2373, influenza vaccine or both.

Commenting on these findings, the authors noted how this was the first direct evidence that co-vaccination still resulted in acceptable vaccine efficacy. While there was an increase in the reported incidence of local reactogenicity in the co-vaccinated group, symptoms were generally mild in severity. They concluded that the study had generated to early safety concerns over co-vaccination.

Citation
Toback S et al. Safety, immunogenicity and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines. MedRxiv 2021