Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients.

Dickson W L Wong,Christopher Werlein,Saskia Von Stillfried,M Cherelle Timm,Barbara M Klinkhammer,Danny Jonigk,Sophia Villwock,Ruth Knüchel-Clarke,Edgar Dahl,Roman D Bülow,Sonja Djudjaj,Claudio Cacchi,Sophie Wucherpfennig,Eva M Buhl,Till Braunschweig,Peter Boor

doi:10.3390/cells10081900

Dickson W L Wong, Christopher Werlein + Show 14 more

Open Access

https://doi.org/10.3390/cells10081900

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Abstract

Multiorgan tropism of SARS-CoV-2 has previously been shown for several major organs. We have comprehensively analyzed 25 different formalin-fixed paraffin-embedded (FFPE) tissues/organs from autopsies of fatal COVID-19 cases (n = 8), using histopathological assessment, detection of SARS-CoV-2 RNA using polymerase chain reaction and RNA in situ hybridization, viral protein using immunohistochemistry, and virus particles using transmission electron microscopy. SARS-CoV-2 RNA was mainly localized in epithelial cells across all organs. Next to lung, trachea, kidney, heart, or liver, viral RNA was also found in tonsils, salivary glands, oropharynx, thyroid, adrenal gland, testicles, prostate, ovaries, small bowel, lymph nodes, skin and skeletal muscle. Viral RNA was predominantly found in cells expressing ACE2, TMPRSS2, or both. The SARS-CoV-2 replicating RNA was also detected in these organs. Immunohistochemistry and electron microscopy were not suitable for reliable and specific SARS-CoV-2 detection in autopsies. These findings were validated using in situ hybridization on external COVID-19 autopsy samples (n = 9). Apart from the lung, correlation of viral detection and histopathological assessment did not reveal any specific alterations that could be attributed to SARS-CoV-2. In summary, SARS-CoV-2 and its replication could be observed across all organ systems, which co-localizes with ACE2 and TMPRSS2 mainly in epithelial but also in mesenchymal and endothelial cells. Apart from the respiratory tract, no specific (histo-)morphologic alterations could be assigned to the SARS-CoV-2 infection.

Highlights

Since late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has caused a pandemic with major impacts on virtually all aspects of life
We have identified several respiratory cells that were positive for SARS-CoV-2 genomic (S gene; sense) and replicating (S gene: antisense) RNA, angiotensin-converting enzyme 2 (ACE2), and transmembrane protease serine subtype 2 (TMPRSS2)
We have comprehensively analyzed a multitude of tissues and cells for SARS-CoV-2 presence to perform a detailed correlation of virus presence and potential pathology findings

Summary

Introduction

Since late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has caused a pandemic with major impacts on virtually all aspects of life. Despite extensive research, understanding of the organic and cellular manifestations of COVID-19 remains incomplete. To the typical clinical symptoms of respiratory infection [1], including fever, dyspnea, and dry cough, other symptoms indicate the involvement of other organ systems, e.g., diarrhea, vomiting, or anosmia. Patients develop acute respiratory distress syndrome (ARDS), pneumonia and systemic inflammation, heart diseases (e.g., elevated cardiac markers, acute heart failure) [2], and acute kidney injury (AKI). These data suggest that COVID-19 can be viewed as a multisystemic disease

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