Post-mortem tissue proteomics reveals the pathogenesis of multi-organ injuries of COVID-19.
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ABSTRACT:
SUBMITTER: Qiu Y
PROVIDER: S-EPMC8644997 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We review the microbiological aspects of COVID-19 infection and present the microbiological studies that should be performed in forensic cases. We describe the taxonomic characteristics of the virus, its relationship with the coronaviridae family and its genetic structure. We briefly present the clinical and pathological characteristics of COVID-19 infection, as well as the co-infections that could be associated with this virus. In the laboratory, PCR is a first-choice technique in the acute phase of the infection, together with antigen and serological studies. Finally, we describe the main objectives of microbiological studies in the deceased in relation to the COVID-19 pandemic, as well as the main post-mortem microbiological analysis to be carried out in the medico-legal context. The microbiological analysis should aim to detect both SARS-CoV-2 and coinfections, which may also contribute to the cause of death.
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Project description:Visualization of gene expression in lung tissue was performed using Visium spatial gene expression kits (10x Genomics) following the manufacturer`s protocol. The four capture areas in a 10x Genomics Visium Gene Expression slide consist of 5000 spots with DNA oligos for mRNA capture that have a unique spatial barcode and a unique Molecular Identifier (UMI). Each spot has 55 µm diameter and can therefore capture mRNA from 1 to 10 cells. We report the spatially resolved transcriptome of 3 control lung samples from non-COVID-19-related pneumonia donors and 9 COVID-19 lung samples analyzed with the 10x Visium platform.
2022-12-21 | GSE190732 | GEO
Project description:The persistence of SARS-CoV-2 after death of infected individuals is unclear. The aim of this study was to investigate the presence of SARS-CoV-2 RNA in different organs in correlation with tissue damage and post-mortem viral dynamics in COVID-19 deceased. Twenty-eight patients (17 males, 11 females; age 66-96 years; mean 82.9, median 82.5 years) diagnosed with COVID-19 were studied. Swabs were taken post-mortem during autopsy (N = 19) from the throat, both lungs, intestine, gallbladder, and brain or without autopsy (N = 9) only from the throat. Selective amplification of target nucleic acid from the samples was achieved by using primers for ORF1a/b non-structural region and the structural protein envelope E-gene of the virus. The results of 125 post-mortem and 47 ante-mortem swabs were presented as cycle threshold (Ct) values and categorized as strong, moderate, and weak. Viral RNA was detected more frequently in the lungs and throat than in the intestine. Blood, bile, and the brain were negative. Consecutive throat swabs were positive up to 128 h after death without significant increase of Ct values. All lungs showed diffuse alveolar damage, thrombosis, and infarction and less frequently bronchopneumonia irrespective of Ct values. In 30% the intestine revealed focal ischemic changes. Nucleocapsid protein of SARS-CoV-2 was detected by immunohistochemistry in bronchial and intestinal epithelium, bronchial glands, and pneumocytes. In conclusion, viral RNA is still present several days after death, most frequently in the respiratory tract and associated with severe and fatal organ damage. Potential infectivity cannot be ruled out post-mortem.
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| S-EPMC10258006 | biostudies-literature
Project description:Chinese hamster ovary (CHO) cells are the predominant production vehicle for biotherapeutics. Quantitative proteomics data were obtained from two CHO cell lines (CHO-S and CHO DG44) and compared with seven Chinese hamster (Cricetulus griseus) tissues (brain, heart, kidney, liver, lung, ovary and spleen) by tandem mass tag (TMT) labeling followed by mass spectrometry, providing a comprehensive hamster tissue and cell line proteomics atlas. Of the 8470 unique proteins identified, high similarity was observed between CHO-S and CHO DG44 and included increases in proteins involved in DNA replication, cell cycle, RNA processing, and chromosome processing. Alternatively, gene ontology and pathway analysis in tissues indicated increased protein intensities related to important tissue functionalities. Proteins enriched in the brain included those involved in acidic amino acid metabolism, Golgi apparatus, and ion and phospholipid transport. The lung showed enrichment in proteins involved in BCAA catabolism, ROS metabolism, vesicle trafficking, and lipid synthesis while the ovary exhibited enrichments in extracellular matrix and adhesion proteins. The heart proteome included vasoconstriction, complement activation, and lipoprotein metabolism enrichments. These detailed comparisons of CHO cell lines and hamster tissues will enhance understanding of the relationship between proteins and tissue function and pinpoint potential pathways of biotechnological relevance for future cell engineering.
| S-EPMC7522264 | biostudies-literature
Project description:The lungs are the main site that is affected in severe COVID-19, and post-mortem lung tissue provides crucial insights into the pathophysiology of severe disease. From basic histology to state-of-the-art multiparameter digital pathology technologies, post-mortem lung tissue provides snapshots of tissue architecture, and resident and inflammatory cell phenotypes and composition at the time of death. Contrary to early assumptions that COVID-19 in the lungs is a uniform disease, post-mortem findings have established a high degree of disease heterogeneity. Classic diffuse alveolar damage represents just one phenotype, with disease divisible by early and late progression as well as by pathophysiological process. A distinct lung tissue state occurs with secondary infection; extrapulmonary causes of death might also originate from a pathological process in the lungs linked to microthrombosis. This heterogeneity of COVID-19 lung disease must be recognised in the management of patients and in the development of novel treatment strategies.
| S-EPMC8641959 | biostudies-literature
Project description:BackgroundEpigenetic (including DNA and histone) modifications occur in a variety of neurological disorders. If epigenetic features of brain autopsy material are to be studied, it is critical to understand the post-mortem stability of the modifications.MethodsPig and mouse brain tissue were formalin-fixed and paraffin-embedded, or frozen after post-mortem delays of 0, 24, 48, and 72?h. Epigenetic modifications frequently reported in the literature were studied by DNA agarose gel electrophoresis, DNA methylation enzyme-linked immunosorbent assays, Western blotting, and immunohistochemistry. We constructed a tissue microarray of human neocortex samples with devitalization or death to fixation times ranging from <?60?min to 5?days.ResultsIn pig and mouse brain tissue, we found that DNA cytosine modifications (5mC, 5hmC, 5fC, and 5caC) were stable for ??72?h post-mortem. Histone methylation was generally stable for ??48?h (H3K9me2/K9me3, H3K27me2, H3K36me3) or ??72?h post-mortem (H3K4me3, H3K27me3). Histone acetylation was generally less stable. The levels of H3K9ac, H3K27ac, H4K5ac, H4K12ac, and H4K16ac declined as early as ??24?h post-mortem, while the levels of H3K14ac did not change at ??48?h. Immunohistochemistry showed that histone acetylation loss occurred primarily in the nuclei of large neurons, while immunoreactivity in glial cell nuclei was relatively unchanged. In the human brain tissue array, immunoreactivity for DNA cytosine modifications and histone methylation was stable, while subtle changes were apparent in histone acetylation at 4 to 5?days post-mortem.ConclusionWe conclude that global epigenetic studies on human post-mortem brain tissue are feasible, but great caution is needed for selection of post-mortem delay matched controls if histone acetylation is of interest.
| S-EPMC6330433 | biostudies-literature