The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies.

Autor:	Hartmann C; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil., Miggiolaro AFRDS; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil., Motta JDS; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil., Baena Carstens L; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil., Busatta Vaz De Paula C; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil., Fagundes Grobe S; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil., Hermann de Souza Nunes L; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil., Lenci Marques G; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil., Libby P; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States., Zytynski Moura L; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil., de Noronha L; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil., Pellegrino Baena C; School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.; Department of Medicine, Marcelino Champagnat Hospital, Curitiba, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Nov 05; Vol. 12, pp. 748417. Date of Electronic Publication: 2021 Nov 05 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.748417
Abstrakt:	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. Competing Interests: PL is an unpaid consultant to, or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Cartesian, Esperion, Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Novo Nordisk, Merck, Novartis, Pfizer, Sanofi-Regeneron. PL is a member of scientific advisory board for Amgen, Corvidia Therapeutics, Caristo, CSL Behring, DalCor Pharmaceuticals, Dewpoint, PlaqueTec, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, and XBiotech, Inc. PL’s laboratory has received research funding in the last 2 years from Novartis. PL is on the Board of Directors of XBiotech, Inc. PL has a financial interest in Xbiotech, a company developing therapeutic human antibodies. PL’s interests were reviewed and are managed by Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict of interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Hartmann, Miggiolaro, Motta, Baena Carstens, Busatta Vaz De Paula, Fagundes Grobe, Hermann de Souza Nunes, Lenci Marques, Libby, Zytynski Moura, de Noronha and Pellegrino Baena.)
Databáze:	MEDLINE
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