Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Abstract

Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. 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. The study’s data are available via ProteomeXchange with the identifier PXD021144.

Proteomics of extracellular vesicles in plasma reveals the characteristics and residual traces of COVID-19 patients without underlying diseases after 3 months of recovery

“…Previous study focus on patients during the disease revealed DEPs between COVID-19 patients and healthy control. In that study, Elettra Barberis et al found that DEPs were mainly belonged to three functional enrichments, inflammatory, immune response, and coagulation, while we found the DEPs between recovered COVID-19 patients and healthy subjects mainly focus on lipid metabolic process, response to cellular, and response to stress oxygen-containing compound, suggesting that different biological characteristics also occurred between recovered COVID-19 patients and patients during the disease 15 . Through analyzing DEPs, we found that some acute phase associated proteins decreased in severe recovered patients such as apolipoprotein APOC4 and CPB1 protein, while the regulator of complement system CPN1 protein was elevated.…”

“…Through analyzing DEPs, we found that some acute phase associated proteins decreased in severe recovered patients such as apolipoprotein APOC4 and CPB1 protein, while the regulator of complement system CPN1 protein was elevated. In previous study, there is some acute phase associated proteins such as Alpha 1-antichymotrypsin and CRP protein increased in EVs from severe patients during the disease 15 . In other word, APOC4 and CPB1 proteins were damaged, which may be associated with the degree of infection.…”

“…The elevation of SERPINA6 was an indirect appearance of increased cortisol, which is common under the conditions of infections. In addiction, severe patients during the disease have a higher level of SERPINA6 than non-severe patients, while severe recovered patients have a lower level of SERPINA6 than non-severe patients, suggesting that SERPINA6 was consumed in severe recovered patients 15 . As an important protein, TGFBI was widely studied in malignant progression, which was suggested to play an important role both in immune response and tumor immune microenvironment 18 – 20 .…”

Endothelial Extracellular Vesicles: From Keepers of Health to Messengers of Disease

“…Indeed, proteomic analysis of the EV in plasma of patients with different degrees of COVID-19 severity showed distinct protein signatures that correlate with clinical manifestations of the disease [ 184 ]. In a separate study, Barberis et al found that the proteome of the circulating EVs contained a large number of immune, pro-inflammatory and pro-coagulant proteins, and identified SARS-Cov-2 RNA in the exosomal cargo [ 185 ]. In a recent study, human lung endothelial cells exposed to the plasma of patients with severe disease and the plasma of patients with mild disease showed a significant difference in caspase3/7 and decreased cell survival in the former [ 186 ].…”

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

“…Albeit pioneering studies have been focused on anti-cancer therapies, the attention has now shifted to viral disease. Of note, EVs are also used as biomarkers of several human diseases, including viral infections [121,122].…”