Immune Response in Myocardial Injury: In Situ Hybridization and Immunohistochemistry Techniques for SARS-CoV-2 Detection in COVID-19 Autopsies.

Pek Yoon Chong,Jabed Iqbal,Paul Chui,Kian Sing Chan,Tar Choon Aw,Joe Yeong

doi:10.3389/fmolb.2021.658932

Abstract

Coronavirus disease-19 (COVID-19) is caused by the newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the lung remains the primary target site of COVID-19 injury, damage to myocardium, and other organs also contribute to the morbidity and mortality of this disease. There is also increasing demand to visualize viral components within tissue specimens. Here we discuss the cardiac autopsy findings of 12 intensive care unit (ICU) naïve and PCR-positive COVID-19 cases using a combination of histological, Immunohistochemical/immunofluorescent and molecular techniques. We performed SARS-CoV-2 qRT-PCR on fresh tissue from all cases; RNA-ISH and IHC for SARS-CoV-2 were performed on selected cases using FFPE tissue from heart. Eight of these patients also had positive post-mortem serology for SARS-CoV-2. Histopathologic changes in the coronary vessels and inflammation of the myocardium as well as in the endocardium were documented which support the reports of a cardiac component to the viral infection. As in the pulmonary reports, widespread platelet and fibrin thrombi were also identified in the cardiac tissue. In keeping with vaccine-induced activation of virus-specific CD4+ and CD8+ T cells, and release of cytokines such as interferon-gamma (IFNγ), we observed similar immune cellular distribution and cytokines in these patients. Immunohistochemical and immunofluorescent localisation for the viral Spike (S-protein) protein and the nucleocapsid protein (NP) were performed; presence of these aggregates may possibly contribute to cardiac ischemia and even remodelling.

Highlights

SARS-CoV-2 (Covid 19), a novel corona virus was first implicated as the cause of a rapidly spreading infectious upper respiratory illness in late 2019 (Zhu et al, 2020) resulting in an exponential increase in global infections (WHO, 2020)
Myocardial cells are a potential target of SARS-CoV-2, and myocarditis has been reported in a limited series in China, where 7% of deaths were attributed to myocardial damage with circulatory failure without a clear, definite diagnosis of myocarditis (Cheung et al, 2020)
Much of the published literature has focussed on the pulmonary changes, findings from our autopsy series demonstrate that significant cardiac pathology may be associated with COVID-19 infection

Summary

Introduction

SARS-CoV-2 (Covid 19), a novel corona virus was first implicated as the cause of a rapidly spreading infectious upper respiratory illness in late 2019 (Zhu et al, 2020) resulting in an exponential increase in global infections (WHO, 2020). There is much to be done as thenatural history of this disease has yet to be elucidated and whilst there has been an emphasis on pulmonary findings, there are Frontiers in Molecular Biosciences | www.frontiersin.org case No. Gender M. AGE BMI Ante mortem test (PCR) TEST TO DEATH INTERVAL (DAYS) PRIOR MEDICAL CONDITIONS. CIRCUMSTANCES OF DEATH HEART WT (gm) HEART GENERAL DESCRIPTION. SEROLOGY (IgM + IgG) Swab (Nasal) Swab (PNS) Swab (Tracheal) Swab (Ileal) Swab (CNS) NA YES 42 DAYS

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