Mechanisms Underlying Cardiovascular Consequences Associated with COVID-19 and Long COVID

The American Heart Association (AHA) announces a Request for Applications (RFA) to study mechanisms that underly cardiovascular and cerebrovascular effects of COVID-19 and/or Long COVID.

The COVID-19 (Coronavirus Disease 2019) pandemic has had a devastating global impact, resulting in over 5,000,000 deaths.  In the United States alone, nearly 800,000 individuals have died from COVID-19.  Like other diseases associated with the coronavirus family such as SARS (Severe Acute Respiratory Syndrome), COVID-19 is a disease of the respiratory system.  COVID-19 often results in an extensive array of clinical symptoms, however, and those most likely to succumb to COVID-19 often have a number of co-morbidities, including hypertension and cardiovascular disease.  

In response to the coronavirus pandemic, the international scientific enterprise has acted rapidly.  This has resulted in advances in understanding of the biological effects of coronavirus, and in significant advances in combating its effects.  For example, vaccines developed for COVID-19 are extremely efficacious, resulting in a substantial decrease in infection and death.  Recent data from the Center for Disease Control and Prevention (CDC) indicate unvaccinated individuals are 6.1 times more likely to get COVID-19, and they are 11.3 times more likely to die from it (https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status).  

Also promising are the development of therapeutics that appear to be effective in minimizing hospitalizations and death from COVID.  A number of monoclonal antibodies have received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) for treating mild or moderate COVID in those who are at high risk for serious complications.  In addition, the antiviral drug remdesivir has been approved by the FDA to treat those hospitalized with COVID.   As of November 2021, the FDA is considering approval of two oral antiviral agents for EUA.  Initial results show these agents can significantly reduce hospitalization or death in high-risk patients compared to placebo.     
        
Despite the advances in vaccination and treatment, the likelihood that COVID-19 remains a prominent health challenge is high.  Indeed, there is a developing consensus that COVID-19 will not be eliminated.  A number of factors underly this expectation, including the possible emergence of novel strains that may be resistant to vaccines, uneven vaccination rates globally, and lack of broad availability of effective treatments.  This point has been driven home recently with the emergence of the novel omicron variant.  This variant has dozens of mutations, some of which could result in reduced efficacy of currently available vaccines.   This variant has spread rapidly through communities in South Africa, where it is believed to have emerged.     

It thus remains critically important to understand the mechanism through which COVID-19 acts.  Cardiovascular complications of COVID-19 include venous thrombosis, myocarditis, arrhythmias, heart failure, and myocardial infarction (Tomidokoro and Hiroi, J Cardiol, https://doi.org/10.1016/j.jjcc.2021.09.010, 2021). Whereas our understanding of the biology of coronavirus has grown, including its effects on the heart and vasculature, major gaps remain in understanding mechanism(s) underlying these consequences of COVID-19.   

To better understand both COVID-19 and Long COVID, the American Heart Association (AHA) invites research proposals that will contribute to understanding the mechanism(s) underlying cardiac, vascular and cerebrovascular effects of these conditions, as well as mechanisms that contribute to differential susceptibility to Long COVID.  Proposals are sought that will utilize contemporary and innovative approaches to assess tissue damage and/or dysfunction of the heart and vasculature/cerebrovascular, and/or potential associated dysregulation of various signaling pathways and systems.  Proposals directed toward leveraging basic mechanistic discoveries, including identification of biomarkers, to develop therapeutic approaches for cardiovascular consequences of COVID are also of interest.  Due to the heterogeneity of Long COVID, important insights into key mechanistic underpinnings and potential treatment strategies are most likely to be achieved in participant populations with well-characterized phenotypes.        

Because of the racial and ethnic disparities associated with COVID-19 and Long COVID noted above,  proposals should have a strong focus on inclusion of demographically diverse subject populations.  Applicants proposing studies engaging individuals who have active Long COVID are encouraged to consider utilization of a patient-centered approach in designing, conducting and disseminating their studies (https://www.pcori.org/research-results/2021/using-body-mapping-develop-patient-centered-research-agenda-about-long-covid).