This timely JACC state-of-the-art review addresses the potential cardioprotective effects of influenza vaccines in the context of the coronavirus disease 2019 (COVID-19) pandemic, and lessons from influenza-related research that can be applied to COVID-19. The following are 10 key points summarizing its findings:

1. The association between myocardial infarctions (MIs) and infections, notably respiratory, has been reproduced across numerous observational studies: the risk of acute MI within 7 days of testing positive for influenza is increased 5- to 10-fold. Influenza is estimated to account for 3-5% of the population-attributable risk of MI-associated deaths.
2. The risk of a hospitalization for MI post-respiratory infection is highest at 3 days following the infection, gradually diminishing until 28 days post-infection.
3. Potential mechanisms of influenza-associated MI are increased metabolic demand, volume overload, increased vascular tone, and a hyperinflammatory and prothrombotic microenvironment.
4. While influenza and COVID-19 have similar presenting symptoms, COVID-19 is more easily transmissible, and is associated with an approximately 10-fold higher hospitalization rate and about 5- to 10-fold higher mortality.
5. Myocardial injury (elevated troponin) is common in COVID-19 and associated with a 4-fold increase in risk of death.
6. The mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lead to myocardial injury are unclear and include direct infection of endothelial cells and myocytes through the angiotensin converting enzyme 2 (ACE2) receptor, and promoting a prothrombotic state such as the development of antiphospholipid antibodies.
7. The highest-risk patients in need of an effective vaccine against influenza infection or COVID-19 are older individuals (typically age 60 years and older) and those with chronic comorbidities. This same group tends to show reduced effectiveness of vaccination in inducing a sustained immune response; a phenomenon termed “immunosenescence.”
8. Compared to influenza in which vaccine aims to provide humoral immunity, the immune response to SARS-CoV-2 may be in large part cell-mediated.
9. Influenza vaccination is associated with a reduction in the risk of major cardiovascular events, notably in patients with recent MI. There are three ongoing trials comparing the effectiveness of various influenza vaccine formulations in reducing major cardiovascular events in: a) patients with heart failure, b) patients undergoing coronary angiography for MI, and c) patients with cardiovascular disease at high risk of a recurrent event.
10. These trials represent a unique opportunity to explore the association among immunosenescence and treatment effect, as substudies will analyze participants’ immune responses and assess genetic profiling as a tool for risk stratification; lessons that can be applied to COVID-19 and the inevitable future pandemics.

Clinical Topics: Acute Coronary Syndromes, COVID-19 Hub, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Acute Heart Failure, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, Coronary Angiography, Coronavirus, COVID-19, Endothelial Cells, Heart Failure, Immunity, Humoral, Influenza Vaccines, Influenza, Human, Myocardial Infarction, Peptidyl-Dipeptidase A, Respiratory Tract Infections, Secondary Prevention, severe acute respiratory syndrome coronavirus 2, Thrombosis, Troponin, Vascular Diseases

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