Cardiac microstructure and the immune-inflammatory response to SARS-CoV-2

PROJECT SUMMARY Amidst the rapidly growing body of evidence regarding risks and outcomes associated with coronavirus disease 2019 (COVID-19), many knowledge gaps persist. We and others have reported on how certain comorbidities, including cardiovascular risk factors, predispose some individuals more than others to the severest forms of COVID-19 illness. The natural history, diversity, and determinants of end-organ sequelae following COVID-19 illness remain unknown. Extending beyond lung injury, accumulating data have highlighted not only short-term but also potentially long-term adverse effects involving the heart. In fact, multiple reports have indicated a high prevalence of subclinical as well as clinical abnormalities in cardiac structure and function seen among patients recovering from even mild cases of COVID-19 illness. Based on the emerging evidence and our own clinical experience to date, we hypothesize that SARS-Cov-2 provokes a systemic immune-inflammatory response that leads to under-recognized myocardial disease in a large proportion of infected individuals – in a manner that persists over time and represents elevated risk for the longer-term post-acute sequelae of COVID-19. Thus, we propose to expand the application of novel cardiac imaging methods to comprehensively characterize the post- infectious cardiac effects of COVID-19. Our specific aims are: (1) to identify and characterize the longitudinal trajectories of cardiac disease and associated outcomes following the post-acute phase of COVID-19 illness; and, (2) to characterize the longitudinal trajectories of immune-inflammatory response to COVID-19 illness, and their relations with post-infectious cardiac disease and associated outcomes. From our growing source sample of >12,500 hospitalized treated since 3/8/2020 for rt-PCR confirmed positive or negative COVID-19 status, we will prospectively enroll COVID-19 positive patients (cases) representing the spectrum of COVID-19 illness severity; we will simultaneously enroll hospitalized COVID-19 negative patients (controls) matched on age, sex, ethnicity/race, comorbidities, and illness severity. We will use serial multi-modality imaging to characterize trajectories of persistent cardiac disease versus functional and structural recovery over time. We will also use advanced high-throughput mass spectrometry methods to serially profile bioactive lipid eicosanoids, which are recognized as upstream molecular mediators of the systemic immune-inflammatory response to stress (including COVID-19). We will relate eicosanoid measures with trajectories of post-infectious cardiac disease persistence versus recovery. For significant associations, will examine heterogeneity in trajectories by sex, age, race/ethnicity, socioeconomic status, and host-environment modifiers.