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pmid:33693030
Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection.
Elettra Barberis · Virginia V Vanella · Marco Falasca · Valeria Caneapero · Giuseppe Cappellano · Davide Raineri · Marco Ghirimoldi · Veronica De Giorgis · Chiara Puricelli · Rosanna Vaschetto · Pier Paolo Sainaghi · Stefania Bruno · Antonio Sica · Umberto Dianzani · Roberta Rolla · Annalisa Chiocchetti · Vincenzo Cantaluppi · Gianluca Baldanzi · Emilio Marengo · Marcello Manfredi
Frontiers in molecular biosciences · 2021 doi:10.3389/fmolb.2021.632290
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Complete file
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During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes' response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes' involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19-associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers-such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component-were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes' significant contribution to several processes-such as inflammation, coagulation, and immunomodulation-during SARS-CoV-2 infection. 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"Characteristics of the patients included in the validation phase study.", "structure": {"pmcid": "PMC7937875", "section_index": 13, "section_title": "4.1 Patients", "row_count": 33, "column_count": 9}, "table": {"label": "TABLE 3", "caption": "Characteristics of the patients included in the validation phase study.", "rows": [["Variables", "COVID-19", "Non-COVID-19"], ["Sex–no.", "Total (N=36)", "Non-Critical (N=23)", "Critical (N=13)", "Total (N=29)", "Non-Critical (N=8)", "Critical (N=6)", "Healthy Control (N=8)", "Healed (N=7)"], ["Male", "21", "13", "8", "12", "5", "3", "2", "2"], ["Female", "15", "10", "5", "17", "3", "3", "6", "5"], ["Age-year"], ["Mean ± SD", "65.6 ±17.6", "66.5 ± 20.6", "53.8 ± 10.7", "60.4 ± 17.0", "76 ± 12.9", "68.6 ± 8.9", "50.4 ± 5.4", "46.8 ± 17.6"], ["Range", "35.0 − 101.0", "35.0 − 101.0", "49.0 − 84.0", "30.0 − 96.0", "59.0 − 96.0", "56.0 − 82.0", "43.0 − 56.0", "30.0 − 72.0"], ["Time from Onset to Admission, Days"], ["Mean ± SD", "4.3 ± 4.5", "4.5 ± 5.0", "4 ± 3.6", "4.8 ± 6.1", "5.7 ± 7.0", "1.0 ± 0.0", "", ""], ["Range", "1.0 − 19.0", "1.0 − 19.0", "1.0 − 10.0", "1.0 − 21.0", "1.0 − 21.0", "1.0 − 1.0", "", ""], ["Time from Admission to Severe, Days"], ["Mean ± SD", "", "", "3.1 ± 2.8", "", "", "3.0 ± 4.9", "", ""], ["Range", "", "", "1.0 − 8.0", "", "", "1.0 − 13.0", "", ""], ["Symptoms–no."], ["Fever", "18", "11", "7", "3", "1", "2", "", ""], ["Cough", "16", "11", "5", "3", "0", "3", "", ""], ["Headache", "0", "0", "0", "2", "0", "2", "", ""], ["fatigue", "3", "2", "1", "3", "0", "3", "", ""], ["Dyspnea", "8", "6", "2", "5", "1", "4", "", ""], ["Diarrhea", "4", "2", "2", "0", "0", "0", "", ""], ["Chest pain", "1", "1", "0", "2", "0", "2", "", ""], ["Abdomial Pain", "2", "1", "1", "0", "0", "0", "", ""], ["vomit", "1", "1", "0", "1", "1", "0", "", ""], ["Comorbility–no."], ["Hypertension", "10", "5", "5", "6", "4", "2", "", ""], ["Diabetes", "8", "4", "4", "1", "0", "1", "", ""], ["Respiratory system", "4", "2", "2", "1", "1", "0", "", ""], ["Cardiovascolar system", "16", "8", "8", "1", "0", "1", "", ""], ["Other Endocrine system", "1", "0", "1", "8", "8", "0", "", ""], ["Chronic Kidney", "3", "1", "2", "1", "1", "0", "", ""], ["Oxygen saturation index–%"], ["Mean ± SD", "91.3 ± 7.4", "93.3 ± 5.2", "97.4 ± 9.6", "92.1 ± 5.6", "94.0 ± 4.1", "85.5 ± 6.4", "", ""], ["Range", "71.0 − 99.0", "81.0 − 99.0", "71.0 − 98.0", "81.0 − 99.0", "87.0 − 99.0", "81.0 − 90.0", "", ""]], "row_count": 33, "column_count": 9, "numeric_cells": 160, "header_rows": 2, "locator": "section[13]/table-wrap[2]#T3"}}], "gaps": ["asset:data:geo:PXD021144 not downloaded", "asset:data:geo:PXD021144 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 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