Antemortem vs. postmortem histopathological and ultrastructural findings in paired transbronchial biopsies and lung autopsy samples from three patients with confirmed SARS-CoV-2 infection

Abstract

BackgroundAcute respiratory distress syndrome (ARDS) is the major cause of death in coronavirus disease 2019 (COVID-19). Multiple autopsy-based reports of COVID-19 lung pathology describe diffuse alveolar damage (DAD), organizing pneumonia (OP) and fibrotic change, but data on early pathological changes as well as during progression of the disease are rare.Research questionComparison of histopathological and ultrastructural findings in paired transbronchial biopsies (TBBs) and autopsy material from three patients with confirmed SARS-CoV-2-infection.MethodsWe prospectively enrolled 3 patients with confirmed SARS-CoV-2 infection. Full clinical evaluation was performed including high-resolution computed tomography (HR-CT). We took TBBs at different time points during the disease and autopsy tissue samples after the patients’ death.ResultsSARS-CoV-2 was detected by RT-PCR and/or FISH in all TBBs. Lung histology revealed pneumocyte hyperplasia and capillary congestion in one patient who died short after hospital admission with detectable virus in 1/2 autopsy samples from the lung. SARS-CoV-2 was detected in 2/2 autopsy samples from a patient with a fulminant course of the disease and very short latency between biopsy and autopsy, both showing widespread DAD. In a third patient with a prolonged course, i.e. five weeks of ICU treatment with ECMO, autopsy samples showed extensive interstitial fibrosis without detectable virus by RT-PCR and/or FISH.InterpretationWe report the course of COVID-19 in paired TBB and autopsy samples from three patients at an early stage, in rapidly progressive and in a prolonged disease course. Our findings illustrate vascular, organizing and fibrotic patterns of COVID-19-induced lung injury and suggest an early spread of SARS-CoV-2 from the upper airways to the lung periphery with diminishing viral load during disease.

Clinical, imaging, serological, and histopathological features of pulmonary post-acute sequelae after mild COVID-19 (PASC)

“…The copyright holder for this this version posted November 30, 2022. ; https://doi.org/10.1101/2022.11.29.22282913 doi: medRxiv preprint from the presence of virus [15]. With respect to autoantibodies, 33.3% of patients in the present study had detectable autoantibodies (ANA/ENA).…”

“…The proportion of CD163+ macrophage subpopulation in PASC lung tissue samples was higher than in a previously published control cohort, but this result was not statistically significant and the density of pro-fibrotic macrophages did not correlate with presence of fibrosis, clinical or imaging characteristics or the detection of autoantibodies. Still, we feel that pulmonary function should be monitored closely in PASC patients to allow for early detection and treatment of possible pulmonary fibrosis since it has been previously shown that SARS-CoV-2 has the ability to induce lung fibrosis [30,15].…”

“…Autopsy-derived tissue samples from deceased COVID-19 patients (Fig. 2 B, upper panel) served as positive controls [15]. For SARS-Cov-2 fluorescence in situ hybridization (FISH), paraformaldehyde-fixed, paraffin-embedded 1µm sections of transbronchial biopsies (TBBs) and lung autopsy material (positive controls) were deparaffinized followed by dehydration with 100% ethanol.…”

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

“…Post-mortem investigation, i.e., autopsy, provides a comprehensive insight into the pathophysiology of novel diseases such as COVID-19, allowing investigation of the multisystemic viral spread and effects on a tissue and cellular level [8]. Recent studies using in situ hybridization (ISH) have found SARS-CoV-2 tropism and replication in airways, i.e., trachea, lung, bronchi, or submucosal glands, within pneumocytes, alveolar and pulmonary lymph node macrophages, endothelium, and respiratory epithelium [9][10][11][12][13][14][15][16]. In the extra-respiratory organs, ISH demonstrated direct infection of vascular endothelium in the kidney (renal proximal and distal tubular epithelial cells) [14,[17][18][19], heart [15], liver [14], brain stem and leptomeninges [14] and placenta (syncytiotrophoblast and cytotrophoblast) [20].…”

Multisystemic cellular tropism of SARS-CoV-2 in autopsies of COVID-19 patients

“…Post-mortem investigation, i.e., autopsy, provides a comprehensive insight into the pathophysiology of novel diseases, such as COVID-19, allowing investigation of the multisystemic viral spread and effects on a tissue and cellular level 3 . Recent studies using in situ hybridization (ISH) have found SARS-CoV-2 tropism and replication in airways, i.e., trachea, lung, bronchi, or submucosal glands, within pneumocytes, alveolar and pulmonary lymph node macrophages, endothelium, and respiratory epithelium [4][5][6][7][8][9][10][11] . In extra-respiratory organs, ISH demonstrated direct infection of vascular endothelium in the kidney (renal proximal and distal tubular epithelial cells) 9,12-14 , heart 10 , liver 9 , brain stem and leptomeninges 9 and placenta (syncytiotrophoblast and cytotrophoblast) 15 .…”