Based on a recent meta-analysis, which of the following viruses was associated with the HIGHEST rate of acute cardiac injury among critically ill patients?
- □ (A) Influenza A subtype H3N2
- □ (B) Influenza B
- □ (C) SARS-CoV-2
The course of illness for patients with COVID-19 caused by SARS-CoV-2 may be complicated by myocardial injury. The mechanism for this complication is unclear. However, a prevailing hypothesis is that the myocardial injury stems from the affinity of the virus for angiotensin-converting enzyme 2 (ACE2) and inhibition of the enzyme. The normal function of ACE2 is to cleave angiotensin II (a potent vasoconstrictor) and convert it to angiotensin (a protein with vasodilatory and anti-inflammatory effects). These receptors are expressed in the lung, heart, kidney, and endothelium, potentially explaining the commonly encountered involvement of lung, cardiac, and kidney injury in patients with COVID-19. Certain other viruses such as severe acute respiratory syndrome coronavirus 1 (SARS-CoV) and influenza A also bind to ACE2 receptors, but to a lesser degree (SARS-CoV-2 binds to ACE2 at a rate of 10 to 20 times more compared with SARS-CoV). The investigators of a recent meta-analysis examined the frequency of SARS-CoV-2-induced acute myocardial injury. In addition, they specifically examined whether myocardial injury is unique to SARS-CoV-2 among respiratory viruses, or if it is a common feature of other ACE2-binding viruses.
“The normal function of ACE2 is to cleave angiotensin II (a potent vasoconstrictor) and convert it to angiotensin (a protein with vasodilatory and anti-inflammatory effects). These receptors are expressed in the lung, heart, kidney, and endothelium, potentially explaining the commonly encountered involvement of lung, cardiac, and kidney injury in patients with COVID-19.”
This meta-analysis included peer-reviewed studies with cohorts of a minimum of 10 adult patients hospitalized with COVID-19 having evidence of acute cardiac injury as reported by cardiac biomarkers. Acute cardiac injury was defined by the authors of the original studies or by myocardial ischemia, new cardiac arrhythmia, or new or worsening heart failure on echocardiogram. For control patients, similar methodology, inclusion criteria, and data were collected for studies involving patients infected with other ACE2-binding viruses (influenza A subtypes H1N1, H5N1, and H7N9, and SARS-CoV). Data were also compared with other influenza viruses that do not bind ACE2 (influenza A subtype H3N2 and influenza B). Pooled estimates for the proportion of acute cardiac injury within each virus group and comparison of rates between groups were obtained. Analyses were performed for critically ill patients (defined by an intensive care unit admission, the need for invasive mechanical ventilation, or death) and for the overall study population.
For COVID-19 publications, 57 studies met inclusion criteria. For publications pertaining to other respiratory viruses, 23 studies met inclusion criteria. The following is a summary of the results:
- The pooled rate of acute cardiac injury among critically ill COVID-19 patients was 50% (95% CI, 44%-57%).
- The rate of acute cardiac injury for the overall population of patients with COVID-19 was 21% (95% CI, 18%-26%).
- In the 34,072 patients with COVID-19, the presence of comorbidities included 33% with hypertension, 18% with diabetes, 10% with cardiovascular disease, and 6% with chronic kidney disease.
- The frequency of acute cardiac injury among critically ill patients infected with H1N1, SARS-CoV, and H7N9 was 39% (95% CI, 25%-55%), 27% (95% CI, 12%-51%), and 40% (95% CI, 19%-65%), respectively. The pooled frequency was 37% (95% CI, 26%-49%).
- The rate of acute cardiac injury among critically ill patients was higher for those infected with COVID-19 compared to patients infected with respiratory viruses that do not bind ACE2. For viruses that do not bind ACE2 (influenza A subtype H3N2 and influenza B), the pooled rate of acute cardiac injury among critically ill patients was 12% (95% CI, 7%-22%).
Results from this meta-analysis appear to indicate that rates of acute cardiac injury align with the degree of viral ACE2 binding. The mechanism for this is unclear but may result from inhibition of ACE2 leading to increased angiotensin II, which is a potent vasoconstrictor that could potentially result in severe coronary vasoconstriction. Myocardial injury could also result from direct infection of endothelial cells or cardiomyocytes or from thromboembolic events.
In summary, this meta-analysis demonstrated that acute cardiac injury occurred at a relatively high frequency in critically ill patients with COVID-19. In addition, acute cardiac injury occurred at a higher rate in ACE2-binding viruses such as SARS-CoV-2 compared with viruses that do not bind ACE2.