Section 5: Immune Responses to SARS-CoV-2 Infection and the Heart (from DOI: 10.1007/s11886-020-01292-3)
From publication: "Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response" published as Curr Cardiol Rep; 2020 04 21 ; 22 (5) 32. DOI: https://doi.org/10.1007/s11886-020-01292-3
Section 5: Immune Responses to SARS-CoV-2 Infection and the Heart
Early reports of fulminant myocarditis have alerted the medical and scientific communities that myocardial inflammation may play a role in cardiac injury during viral infection . However, the exact mechanism of this is currently unclear , as acute lymphocyte infiltrates were not noted in the myocardium of a SARS-CoV-2-infected ARDS patient autopsy, where only a few mononuclear inflammatory cells were seen. Currently, there is great interest in obtaining the pathological specimens from patients presenting with markedly elevated troponin and fulminant myocarditis in order to evaluate for lymphocyte-induced myocardial injury in SARS-CoV-2 infection. Consistent with this, no myocardial-specific epitopes have thus far been identified in the setting of SARS-CoV or SARS-CoV-2 infection. Several HLA-A*02:01-specific T cells recognizing SARS-CoV epitopes have been identified in the peripheral blood mononuclear cells (PBMC) of SARS-recovered individuals, including immunogenic epitopes localized to spike (S) and nucleocapsid (N) protein of SARS-CoV. Of note, MRI-verified acute myocarditis has been reported in association with MERS-CoV, although the exact mechanism by which it occurs is unknown.
Although no evidence of direct lymphocytic infiltration of the myocardium exists, the dysregulation of T cells can likely contribute to the cytokine storm and multi-organ damage in the setting of coronavirus infection. A recent retrospective, multi-center study of 150 patients confirmed that inflammatory markers, including elevated ferritin (mean 1297.6 ng/ml in non-survivors vs 614.0 ng/ml in survivors, p < 0.001) and IL-6 (p < 0.0001) were associated with more severe COVID-19 infection, suggesting that systemic inflammation may be a significant driver of multi-organ damage. A separate group has also reported that the serum cytokines IL-2R, IL-6, IL-10, and TNF-alpha are increased in patients with severe disease. This systemic release of cytokines, characterized by increased IL-2, IL-6, IL-10, GCSF, IFN-gamma, MCP-1, MIP-1-alpha, and TNF-alpha, likely contributes to cardiac injury in a situation analogous to cardiotoxicity in the setting of chimeric antigen receptor (CAR)-T cell therapy. A prior study demonstrated that cardiac injury and cardiovascular events in the form of elevated troponin and left ventricular systolic dysfunction are common post-CAR-T; in a cohort of 137 patients with post-CAR-T cytokine release syndrome (CRS), 21% had elevated troponin and 12% developed cardiovascular events including cardiac arrest, decompensated heart failure, and arrhythmias. Notably in this study, a shorter time from CRS onset to the administration of the IL-6 inhibitor tocilizumab was associated with a lower rate of cardiovascular events. Of note, tociluzumab may have some benefit in COVID-19 infection, suggesting a common mechanism of injury in the two settings. The exact mechanism by which cytokines/chemokines damage the myocardium is unknown, but cardiomyocyte and endothelial cell death in the presence of inflammatory cytokines such as TNF-alpha has been well documented in the literature .
