Pathological findings and morphologic correlation of the lungs of autopsied patients with SARS-CoV-2 infection in the Brazilian Amazon using transmission electron microscopy

Abstract

INTRODUCTION: Electron microscopy (EM) is a rapid and effective tool that can be used to create images of a whole spectrum of virus-host interactions and, as such, has long been used in the discovery and description of viral mechanisms. METHODS: Electron microscopy was used to evaluate the pulmonary pathologies of postmortem lung sections from three patients who died from infection with SARS-associated coronavirus 2 (SARS-CoV-2), a new member of the Coronaviridae family. RESULTS: Diffuse alveolar damage (DAD) was predominant in all three patients. The early exudative stage was characterized principally by edema and extravasation of red blood cells into the alveolar space with injury to the alveolar epithelial cells; this was followed by detachment, apoptosis, and necrosis of type I and II pneumocytes. The capillaries exhibited congestion, exposure of the basement membrane from denuded endothelial cells, platelet adhesion, fibrin thrombi, and rupture of the capillary walls. The proliferative stage was characterized by pronounced proliferation of type II alveolar pneumocytes and multinucleated giant cells. The cytopathic effect of SARS-CoV-2 was observed both in degenerated type II pneumocytes and freely circulating in the alveoli, with components from virions, macrophages, lymphocytes, and cellular debris. CONCLUSIONS: Viral particles consistent with the characteristics of SARS-CoV-2 were observed mainly in degenerated pneumocytes, in the endothelium, or freely circulating in the alveoli. In the final stage of illness, the alveolar spaces were replaced by fibrosis.

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

“…Analyses of down-regulated DEGs by Ingenuity Pathway Analysis (IPA) Diseases and Functions feature, remarkably provided the same top scoring annotation by z-score for all groups, Organismal death, with the exception of the Alfi organoid study where the top annotation was Perinatal death (Supplemental Table 5). Down-regulated DEGs would thus largely and consistently appear to arise from tissue damage, with cell death and injury in SARS-CoV-2 infected lungs induced via direct viral cytopathic effects (44) and via the cytokine storm (45). The comparable levels of virus infection seen in the mouse groups (Fig.…”

Detection and identification of coronaviruses in human tissues using electron microscopy

“…An increasing number of articles have included descriptions of ultrastructural changes in SARS‐CoV‐2 positive autopsy tissues (Ackermann et al, 2020 ; Akilesh, Nast, et al, 2021 ; Deinhardt‐Emmer, Böttcher, et al, 2021 ; Deinhardt‐Emmer, Wittschieber, et al, 2021 ; Duarte‐Neto et al, 2021 ; Lüke et al, 2020 ; Rizzo et al, 2021 ; Santana et al, 2021 ; Saraiva et al, 2021 ). These articles do not necessarily include EM images of viral particles but describe possible ultrastructural alterations due to infection.…”

“…Comparison of infected and healthy tissues is necessary, and correlation with results of other diagnostic techniques is always recommended. Respiratory system changes due to SARS‐CoV‐2 infection have been most thoroughly described (Ackermann et al, 2020 ; Martines et al, 2020 ; Santana et al, 2021 ; Saraiva et al, 2021 ). Type I pneumocyte degeneration, type II pneumocyte hyperplasia, and hyaline membrane formation were common ultrastructural features of SARS‐CoV‐2 infection (Martines et al, 2020 ; Santana et al, 2021 ).…”

“…A recent study of nasopharyngeal epithelial cells from SARS‐CoV‐2 infected individuals showed loss of microvilli and the primary cilium in squamous cells as well as an increase in the number of multivesicular bodies and autophagosomes when compared with specimens from SARS‐CoV‐2 negative individuals (Saraiva et al, 2021 ). Santana et al further noted disruption of the epithelial‐endothelial barrier, in addition to cellular debris and fibrin in the alveolar space and detachment of type II pneumocytes from the basement membrane (Santana et al, 2021 ). Observations of vessel barrier damage are in agreement with suggestions that these changes and increases in pro‐inflammatory cytokines contribute to the development of acute respiratory distress syndrome in COVID‐19 patients by mediating inflammatory cell infiltration in the lungs (Perico et al, 2021 ).…”

Ultrastructural examination of lung “cryobiopsies” from a series of fatal COVID-19 cases hardly revealed infected cells

“…These results coincide with data from many other studies and reveal a considerable similarity with histopathological data from other cases showing ARDS [ 6 , 8 , 25 ]. Few and still limited ultrastructural investigations on the ultrastructural changes of the lung in COVID-19 patients have been published so far (e.g., [ 7 , 26 ]). These studies underline the similarity between lung damage induced by COVID-19 and other cases of ARDS.…”