Evidence of SARS-CoV-2 infection in postmortem lung, kidney, and liver samples, revealing cellular targets involved in COVID-19 pathogenesis

Pathogenesis Coronavirus
DOI: 10.1007/s00705-023-05711-y Publication Date: 2023-02-26T11:02:30Z
ABSTRACT
There is an urgent need to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions involved in virus spread and pathogenesis, which might contribute the identification of new therapeutic targets. In this study, we investigated presence SARS-CoV-2 postmortem lung, kidney, liver samples patients who died with disease (COVID-19) its relationship host factors using microscopy-based methods. The cases analyzed showed advanced stages diffuse alveolar damage fibrosis. We identified nucleocapsid (NC) a variety cells, colocalizing mitochondrial proteins, lipid droplets (LDs), key proteins that have been implicated inflammation, tissue repair, life cycle (vimentin, NLRP3, fibronectin, LC3B, DDX3X, PPARγ), pointing vimentin LDs as platforms not only viral but also inflammation pathogenesis. isolated from patient´s nasal swab was grown cell culture used infect hamsters. Target cells human included lung epithelial endothelial cells; lipogenic fibroblast-like (FLCs) showing features lipofibroblasts such activated PPARγ signaling LDs; FLCs expressing fibronectin macrophages, both evidence NLRP3- IL1β-induced responses; regulatory immune-checkpoint repair responses contributing inflammatory lung; CD34+ hepatocytes vimentin; renal interstitial juxtaglomerular apparatus. This suggests may directly interfere critical renal, functions COVID-19-pathogenesis.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (123)
CITATIONS (8)