Image_1_The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies.tiff (9.1 MB)
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posted on 05.11.2021, 04:43 authored by Camila Hartmann, Anna Flavia Ribeiro dos Santos Miggiolaro, Jarbas da Silva Motta, Lucas Baena Carstens, Caroline Busatta Vaz De Paula, Sarah Fagundes Grobe, Larissa Hermann de Souza Nunes, Gustavo Lenci Marques, Peter Libby, Lidia Zytynski Moura, Lucia de Noronha, Cristina Pellegrino Baena
Rationale

Myocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.

Objective

This histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.

Methods and Results

Postmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.

Conclusions

The pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.

History

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