COVID-19 and the Cardiovascular System: Observed complications and potential mechanisms

By Victoria Osinski

The outbreak of COVID-19 resulting from the transmission of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in many cases of illness typically manifesting in minor to severe respiratory symptoms. However, additional cardiovascular complications have been observed in a subset of patients as well, prompting further inquiry into the mechanisms of infection and response to SARS-CoV-2. While advancements have been made into answering these questions, it is still early in our understanding of this virus and disease and we should continue to follow new developments in research as time continues.

Troponin I was detected in immersion fixed paraffin-embedded sections of human heart using Mouse Anti-Human Troponin I Monoclonal Antibody (MAB68871) at 15 µg/mL overnight at 4 °C. Tissue was stained using the Anti-Mouse HRP-DAB Cell & Tissue Staining Kit (CTS002) (brown) and counterstained with hematoxylin (blue). Lower panel shows a lack of labeling when primary antibodies are omitted and tissue is stained only with secondary antibody followed by incubation with detection reagents. Specific staining was localized to cardiac muscle.

Observed cardiovascular complications

Cardiovascular complications (CVC) observed in patients with COVID-19 include thrombotic events, acute cardiac injury, heart failure, and cerebrovascular ischemia.^1-5 Acute injuries including myocarditis (inflammation in the heart muscle) and other myocardial injuries are associated with increased troponin levels and can affect the heart’s ability to function normally. Thrombotic events involve formation of blood clots in the heart, brain, or other tissues, such as the lungs, that interfere with normal blood flow. In a review of COVID autopsy reports, some patients had small thrombi in pulmonary capillaries or deep vein thrombosis.⁶ These reported complications are thought to be a result of SARS-CoV-2 infection, but it should be noted that the literature also reports that infected patients with pre-existing cardiovascular diseases are more likely to require critical care.⁴

Potential mechanisms driving observed pathologies

One protein of particular interest to those looking to understand the connection between SARS-CoV-2 and CVC is the angiotensin converting enzyme 2 (ACE-2) receptor. SARS-CoV-2 infection is triggered by the binding of the viral spike (S) protein to ACE2 on the surface of the host cell. Briefly, after S protein-ACE2 binding, the S protein is cleaved by transmembrane serine protease TMPRSS2 which allows for host-virus membrane fusion and viral entry into the cytoplasm.⁷ ACE2 is the protein that converts pro-inflammatory Angiotensin II to non-inflammatory forms and that SARS-CoV-2 binds to enter a cell.^8,9 ACE2 is expressed in many tissues including the lungs, heart, kidneys, gut, and brain.¹⁰ There are multiple means by which viral binding to ACE2 causes or exacerbates cardiovascular damage. One method is the broad expression of ACE2: with more available binding sites in more tissues, there is an increased opportunity for viral infection and resultant damage from viral-induced death or respondent inflammation. Another mechanism is the potentially reduced surface expression of ACE2 due to viral binding and resultant receptor internalization.¹⁰ Similar to what has been observed with SARS-CoV, SARS-CoV-2 may lead to the downregulation of ACE2 in the heart, and this downregulation could induce endothelial dysfunction.⁷ Endothelial dysfunction is a key initiation step in many cardiovascular injuries and diseases including cardiac dysfunction and atherosclerosis or the buildup of arterial cholesterol and fats.⁷

ACE‑2 was detected in perfusion fixed frozen sections of mouse kidney using 15 µg/mL Goat Anti-Mouse ACE‑2 Antigen Affinity- purified Polyclonal Antibody (AF3437) overnight at 4 °C. Tissue was stained (red) and counterstained (green.

Overall, early findings from COVID-19 patients suggest cardiovascular injury should be considered a notable potential complication in disease progression. Further characterization of disease outcomes and investigation into the roles that ACE2 and the endothelium play in CVC will be valuable in increasing our understanding of this new virus and resultant disease.

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Victoria Osinski, Doctoral Candidate   
University of Virginia
Victoria studies cellular mechanisms regulating vascular growth during peripheral artery disease and obesity.

References

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