Myocardial Injury in Severe COVID-19 Infections

The rapid emergence and spread of COVID-19 caused by SAR-CoV-2 has put a heavy burden on scientists and clinicians to try to figure out, in real-time, the direct and indirect impact that viral infection has on tissue and organ systems. Originally thought to be a syndrome associated with the acute lung injury characteristic of infection, it is now apparent that severe COVID-19 infection also has direct myocardial effects such as thromboembolic disease and arrhythmia, particularly in patients predisposed or already presenting with heart disease.

Here at Lifeline®, we want to present industry research and perspective as it relates to real-world situations. In keeping with our recent blog focused on endothelial cells, we thought it would be pertinent to review one of the Journal of the American College of Cardiology’s focus seminars to examine the mechanism behind myocardial injury resulting from inflammation, endothelial activation, and microvascular thrombosis patients hospitalized with severe COVID-19 infections.

In the seminar entitled Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia, the authors noted that myocardial and cardiovascular injury was observed in ~25% of hospitalized COVID-19 patients, which is linked to a higher incidence of needing mechanical ventilator support and higher in-hospital mortality. The central pathophysiology underlying cardiovascular injury is the binding of SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) receptor and the impact this has on the body’s innate immune, and vascular, response to the resulting cytokine production.

Endothelial cells line the blood vessels of the body’s circulatory system and are one of the main cell types of the heart. These cells express high levels of ACE2 receptor and as such, during viral infection, cytokine release from innate immune responses promotes endothelial activation with the expression of cell adhesion molecules. Inflamed and dysfunctional endothelium soon becomes pro-adhesive and prothrombotic resulting in coronary vasoconstriction, thrombosis, and other myocardial injuries. What appears to be critical determinants of the severity of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities.

The authors discuss the link between troponin levels and survivorship of hospitalized COVID-19 patients. Myocardial injury increases serum troponin levels and in patients with pre-existing injury that also present with COVID-19 infection, this elevated troponin correlates with increased mortality rates. In looking at 2 studies from China, patients with high troponin levels at the time of infection showed increased mortality of 60% and 51%, whereas patients with normal troponin levels showed 5% and 9% mortality, respectively.

While there are direct and indirect impacts on the cardiovascular system resulting from viral infection, it is likely the key differentiator between severe disease and mild or asymptomatic infection in patients lies with each individual’s immune response. A patient with low levels of innate immunity, as characterized by weak interferon production, coupled with robust cytokine production (e.g., IL-6, IL-1) leads to an inability to clear the virus resulting in systemic endothelial/vascular inflammation and poor clinical outcomes. The authors speculate that this impaired innate immune response is the missing link between COVID-19 infection, inflammation, thrombosis, and myocardial injury particularly in elderly patients and those individuals with compromised immune systems.

Whether these effects are simply associated with poor patient outcomes, including death, or directly contribute to patient mortality is as yet uncertain. The lingering impact that endothelial activation, hypercoagulability, microvascular thrombosis, and myocardial injury will have on a patient long-term are similarly unknown and warrant further research on longitudinal follow-up studies.

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