Clinical Heart and Vascular Center

Rapid-Fire Results from AHA Research on COVID-19

By James de Lemos, M.D.

Professor of Internal Medicine

Dr. James de Lemos

At #AHA21, I co-chaired a featured session with Dr. Mina Chung from the Cleveland Clinic in which the principal investigators of AHA-funded studies on COVID-19 and cardiovascular disease presented their preliminary findings in a “rapid fire” approach. Several of these translational research studies provide important new insights into mechanisms of cardiac injury in COVID-19. Two autopsy studies highlighted the finding that cardiac microthrombi appear to be the dominant cardiac feature of COVID-19.

Microthrombi were associated with markers of systemic inflammation, with pathological evidence of endothelial cell damage and a prothrombotic endothelial cell profile. Moreover, the endothelial cell activation appeared to be induced by hypoxia, providing a link between the respiratory and cardiac complications of COVID-19. A different study found that platelets can take up SARS-CoV-2 as part of their immune function, which may contribute to the propensity for arterial thrombosis seen in COVID-19. A study of endomyocardial biopsies from patients with COVID-19 and myocardial injury (i.e., elevated troponin levels) found decreased gene expression of angiotensin converting enzyme (ACE) 2 (a protective pathway) and increased expression of ACE (a harmful pathway) as compared with controls. There also was evidence for upregulated expression of inflammatory and thrombosis genes.

“Several of these translational research studies provide important new insights into mechanisms of cardiac injury in COVID-19.”

James de Lemos, M.D.

These findings provide the first human data to support the hypothesis that binding of the SARS-CoV-2 spike protein to the ACE 2 complex leads to dysregulation of ACE2/ACE, mediating cardiac damage in COVID-19. Finally, an innovative study reported preliminary results that leveraged new insights from network biology to identify existing drugs that might be successfully repurposed to target the SARS-CoV-2 virus. Other drug repurposing approaches have been successful in identifying remdesivir as an important agent to treat patients hospitalized with COVID-19, and there is hope such novel “in silico” strategies can identify additional effective agents.

Email: james.delemos@utsouthwestern.edu

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