In our pooled analysis, almost one third of COVID–19 infected patients had ACI with a mortality rate of 53%. Although the exact mechanism by which COVID–19 causes ACI remain poorly understood. Potential mechanisms currently proposed either invoke a direct damage to myocytes as a result of systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells or the secondary effect of coronary plaque destabilization as well as the profound hypoxia these patients have as a result of the overwhelming pneumonia.4
Furthermore, Zhou et5 al have also demonstrated the relationship existing between COVID–19 and angiotensin-converting enzyme 2 (ACE2), which is a monocarboxypeptidase renin-angiotensin-aldosterone system enzyme that metabolizes several peptides, to enter ACE2-expressing cells. ACE2 is widely expressed in the endothelium of the heart and kidneys,6 and that might explain the prevalence of ACI and acute kidney injury among patients with COVID–19. Additionally, ACE2 generates angiotensin 1–7, which decreases myocardial levels of pro-inflammatory cytokines (i.e., TNFα and IL–6).7 One of the proposed mechanisms for ACI in COVID–19 is downregulation of ACE2 expression with subsequent accumulation of pro-inflammatory cytokines in the myocardium; however, the effect of COVID–19 on ACE2 serum level, tissue expression, and function is still not clear. Furthermore, COVID–19 is associated with a hypercoagulability state due to an increase in the procoagulant factors, such as fibrinogen.8,9 This hypercoagulability state may result in microthrombi formation, which precipitates ACI.
Regardless of the underlying mechanism, ACI was associated with a significantly higher mortality rate. More data is urgently required to better understand the apparent complex tropism that appears to link COVID–19 with ACI not only to identify patients at risk but also provide effective treatment options.
Aside from this being a retrospective study and that most studies were done on Chinese population, which makes generalizability another limitation; it is also important to recognize the relatively high heterogeneity as indicated by an I2 index value of 81%. Notwithstanding we cannot discard that fact even though this strain of SARS-CoV 2 has shown an increased propensity for developing extra-pulmonary complications, namely ACI, its reported involvement is most likely underestimated. First, initial focus from the outset of the pandemia was simply given to the more common respiratory symptoms. Second, cardiac involvement such myocarditis could have occurred and since in most cases is often self-limiting, would not have recorded. Third, there has been a large number of deaths occurring outside the hospital setting of patients that either decided to stay home or of individuals at other institutions, such as Nursing Homes, were the cause of death would never be known. Last, some case reports have reported patients presenting for other reasons, that were later found to be COVID–19 positive whose cardiac enzymes were probably never assessed and could have had subclinical manifestations.