SARS-Cov-2 fulminant myocarditis: an autopsy and histopathological case study

Abstract

The coronavirus disease 2019 (COVID-19), due to SARS-CoV-2, is primarily a respiratory disease, causing in most severe cases life-threatening acute respiratory distress syndrome (ARDS). Cardiovascular involvement can also occur, such as thrombosis or myocarditis, generally associated with pulmonary lesions. Little is known about SARS-CoV-2-induced myocarditis. We report the case of a 69-year-old man suffering from a refractory cardiogenic shock, without significant lung involvement. Prior to death, several nasopharyngeal swabs and distal bronchoalveolar lavage were sampled in order to perform RT-PCR analyses for SARS-CoV-2-RNA, which all gave negative results. Autopsy showed coronary atherosclerosis, without acute complication. Microscopic examination of the heart revealed the existence of an intense multifocal inflammatory infiltration, in both ventricles and septum, composed in its majority of macrophages and CD8+ cytotoxic T lymphocytes (CD4/CD8 ratio: 0.11). Immunohistochemistry for anti-SARS nucleocapsid protein antibody was strongly positive in myocardial cells, but not in lung tissue. RT-PCR was realized on formalin-fixed paraffin-embedded lung and heart tissue blocks: only heart tissue was positive for SARS-CoV-2 RNA. In conclusion, this exhaustive post-mortem pathological case study of fulminant myocarditis demonstrates the presence of SARS-CoV-2 RNA in heart tissue, without significant lung involvement. Immunohistochemistry showed that the virus was specifically localized in cardiomyocytes and induced a strong cytotoxic T cells inflammatory response. This case report thus gives new insight in the pathogenesis of SARS-CoV-2-induced myocarditis and emphasizes on the importance and reliability of post-mortem analyses in order to better understand the physiopathology of this worldwide spreading new viral disease.

Keywords: Autopsy; COVID-19; Histopathology; Myocarditis; SARS-Cov-2.

Fig. 1

(a) Abundant myocardium edema and interstitial inflammation, showing a predominance of mononucleated leucocytes, associated with cardiomyocytes dystrophies (hematoxylin, eosin, and saffron (HES), × 200). (b) Strong granular cytoplasmic staining of cardiomyocytes for SARS coronavirus nucleocapsid protein (immunohistochemistry, × 200)

Fig. 2

(a) Anti-CD163 antibody showing numerous interstitial macrophages. (b) Abundant T cell lymphocytes inflammation outlined by the anti-CD3 antibody. (c) Most of T cells are CD8-positive lymphocytes (CD4/CD8 ratio: 0.11). (d) Staining with anti-TIA-1 antibody (left), showing abundant cytotoxic T lymphocytes, part of them being activated, granzyme B positive (right) (immunohistochemistry, original magnification × 200)