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

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.

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

“…Therefore, the lipid peroxidation trigger and 4-HNE mediated systemic vascular and oxidative stress could be associated with an uncontrolled (auto)immune stress response, which may lead to ARDS and MOF, as observed in our patients. The high importance of the malfunctioning immune system destroying vital organs, not only the lungs but even the brain, for severe/lethal SARC-CoV-2 infection is well known, even if the virus itself may not always be the [52][53][54], as is also the importance of uncontrolled oxidative stress [55,56]. Both of the supporting findings of our study suggest that lipid peroxidation, notably, 4-HNE, might be the link between these two vicious circles of lethal COVID-19.…”

Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19

“…Protein turnover is also increased in critical illness in the early stages of COVID-19, in response to massive proteolytic stimuli [10]. Suggested mechanisms include direct muscle invasion by ECoV particles and immune-mediated muscle injury, presenting as myositis, although satisfactory proof of the direct invasion of SARS-CoV-2 into muscle cells is still lacking [11]. Lastly, muscle deconditioning due to immobility and corticosteroid treatment has been associated with diffuse atrophy at muscle biopsy [12].…”

Integrated cell-free DNA and cytokine analysis uncovers distinct tissue injury and immune response patterns in solid organ transplant recipients with COVID-19

“…Although the lung is the primary target organ for SARS-CoV-2, multiple cells, tissue, or organ types can be involved due to broad SARS-CoV-2 cellular tropism 59 and subsequent inflammatory responses 48 . Our deconvolution results indicated that hematopoietic cells, including granulocytes, erythrocyte progenitors, monocytes, NK cells and B cells, are the predominant source of circulating cfDNA levels in SOTRs with COVID-19.…”