Influenza Vaccination During COVID-19 Could Reduce Cardiovascular Risks

Preparations for a "twindemic" of influenza and COVID-19 respiratory viral infections should include recognition of potential cardiovascular complications, and the susceptibility of those with pre-existing cardiovascular conditions to a more severe course of illness, according to a JACC (Journal of the American College of Cardiology) State-of-the-Art review.

Bahar Behrouzi, MD/PhD student at the Department of Medicine, Women's College Hospital and the Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada, and colleagues consider the cardiovascular risks associated with influenza, and the evidence supporting wide-spread vaccination to reduce infections and mitigate the associated morbidity and mortality.

"One of our main intentions with this State-of-the-Art review was to provide a primer for cardiologists on the strongest evidence from the past 2 decades that support the cardioprotective effect of seasonal flu vaccines," Behrouzi told Contagion.

Behrouzi and colleagues point out that the increase in cardiovascular mortality with respiratory infection has been reported since the 1918 pandemic.Among the contemporary reports they cite is an investigation that accessed the United Kingdom General Practice Research Database to determine that within 3 days of presenting with respiratory tract infection, these patients had an approximate 4-fold higher rate of hospitalization for acute myocardial infarction (MI) and approximate 3-fold increase in rate of stroke.

Several mechanisms for a causal association between influenza and cardiovascular complications were noted in the review, including the viral illness destablizing patients with pre-existing cardiovascular disease (CVD) through increased metabolic demand.

"When complemented by hypoxemia, influenza infection may exacerbate underlying CVD through increased vascular tone via activation of the sympathetic nervous system, inadquae coronary artery blood flow with fever and tachycardia, potential volume overload, and arrhythmia," Behrouzi and colleagues explain.

In addition, they note, influenza virus may precipitate acute cardiovascular events by stimulating a potent acute inflammatory response, which can trigger acute plaque rupture and global myocardial depression.

The reviewers describe 3 ongoing influenza vaccine cardiovascular outcome trials (COVT) that they expect will characterize cardioprotective effects of vaccinations and could also provide a platform and infrastructure to study therapies for primary and secondary prevention of COVID-19.

"The 3 influenza vaccine CVOTs we describe are powered to give us definitive answers on the effectiveness of different flu shot formulations in reducing poor cardiovascular outcomes in high-risk patients," Behrouzi said.

"To date, these trials are the largest and most diverse global platform of investigators and high-risk patient participants in this arena," Behrouzi observed. "In contrast, we know that all the current COVID-19 vaccine trials exclude older patients, either directly or indirectly, which ironically are the patients who stand to gain the most from them"

Behrouzi and colleagues suggest that the CVOTs could determine that the effect size from influenza vaccination is comparable to existing secondary cardiovascular prevention strategies.

"Since healthcare providers play an important role in creating a safe space to promote vaccine acceptance and combat misinformation, it is our hope that armed with the evidence, cardiologists and other healthcare practitioners can better engage in meaningful and transparent conversations with patients, especially those who may tend towards being vaccine hesitant," Behrouzi said.