Mechanistic registry to study whether infection with Corona Virus Disease 2019 (COVID-19) alters atherosclerotic plaque progression

Project Summary / Abstract The primary objective of the corona virus disease 2019 (COVID-19) (COVID-CT) registry is to determine if infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus which causes COVID-19, results in marked progression of coronary atherosclerotic plaque in patients with previously defined anatomic coronary artery disease (CAD). COVID-19 induces a pro-inflammatory cytokine release and pro- thrombotic processes that we hypothesize will accelerate atherosclerotic plaque progression. Coronary computed tomographic angiography (CCTA) is a robust noninvasive method uniquely capable of measuring angiographic stenosis and quantifying and characterizing atherosclerotic plaque. Our group has extensive experience in large multicenter trials and registries using CCTA to identify key atherosclerotic plaque features associated with progression and major CAD events. Moreover, we propose use of a novel CT marker of coronary artery inflammation - the perivascular fat attenuation index (FAI) - a marker highly predictive of acute CAD events and to assess serial changes in coronary inflammation. COVID-19 is rapidly becoming a leading cause of death with substantial evidence that pre-existing CAD increases risk of serious illness and mortality from COVID-19. By enrolling patients with high risk, atherosclerotic plaque, findings from the COVID-CT registry will inform this link between the inflammatory response sustained during COVID-19 to accelerated atherosclerotic plaque progression. If our hypotheses are confirmed, then clinicians and patients will have clear information that viral infections, such as SARS-CoV-2, alter the inflammatory milieu and accelerate progression of atherosclerosis. Importantly, a connection between COVID- 19 and CAD will broadly impact preventive risk assessment for the ~7 million patients infected with SARS-CoV- 2 and millions more yet to be tested in the United States. To date, evidence is lacking as to whether the COVID-19 results in marked atherosclerotic plaque progression among racially and ethnically diverse patients with CCTA-defined CAD who reside across a socioeconomically- diverse, urban setting. The present proposal constitutes a comprehensive approach assessing the clinical importance of atherosclerotic plaque progression following COVID-19. Currently, the implications of epicardial coronary injury following SARS-CoV-2 infection is unknown. Yet, the inflammatory pathway of atherosclerotic plaque progression is well studied and, as such, our hypotheses are supported by this knowledge base. The proposed COVID-19 registry is poised to provide an improved mechanistic understanding of the role of viral infection on alterations in atherosclerotic plaque.