COVID-19 and Extracellular Vesicles: An Intriguing Interplay

Abstract

<b><i>Background:</i></b> The outbreak of severe acute respiratory syndrome β-coronavirus 2 (SARS-CoV-2) has the potential to become a long-lasting global health crisis. The number of people infected with the novel coronavirus has surpassed 22 million globally, resulting in over 700,000 deaths with more than 15 million people having recovered (https://covid19.who.int). Enormous efforts are underway for rapid vaccine and treatment developments. Amongst the many ways of tackling the novel coronavirus disease 2019 (COVID-19) pandemic, extracellular vesicles (EVs) are emerging. <b><i>Summary:</i></b> EVs are lipid bilayer-enclosed structures secreted from all types of cells, including those lining the respiratory tract. They have established roles in lung immunity and are involved in the pathogenesis of various lung diseases, including viral infection. In this review, we point out the roles and possible contribution of EVs in viral infections, as well as ongoing EV-based approaches for the treatment of COVID-19, including clinical trials. <b><i>Key Messages:</i></b> EVs share structural similarities to viruses and recent findings demonstrate that viruses exploit EVs for cellular exit and EVs exploit viral entry mechanisms for cargo delivery. Moreover, EV-virus interplay could be exploited for future antiviral drug and vaccine development. EV-based therapies, especially the mesenchymal stem cell-derived EVs, are being intensively studied for the treatment of COVID-19.

A Role for Extracellular Vesicles in SARS-CoV-2 Therapeutics and Prevention

“…The immunogenic responses of exosomal S vaccine were boosted after the subsequent injection of AAV S vaccine (Kuate et al 2007). Based on this knowledge, exosomes from SARS-CoV-2 infected cells may induce similar immune responses (Elrashdy et al 2020b;Pocsfalvi et al 2020).…”

“…With these limitations in mind newer types of carriers have been devised. One at the forefront of development are extracellular vesicles (EVs) (O'Driscoll, 2020;Pocsfalvi et al 2020). They have gained considerable attention based on their natural biocompatibility and defined effectiveness as therapeutic and disease preventative agents in parallel microbial systems (Raposo and Stoorvogel, 2013;Pitt et al 2016).…”

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

“…Endothelium contributes significantly to the circulating EVs in blood and lymph, and it is conceivable to propose that endothelium-derived EVs could be responsible for the dissemination of pro-coagulant and pro-inflammatory molecules that can perpetuate the dysfunction initiated in infected cells. 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 ].…”

Therapeutic Potential of Mesenchymal Stem Cells and Their Products in Lung Diseases—Intravenous Administration versus Inhalation

“…The exchange of EVs between blood and lung can explain why intravenously administered EVs can influence lung physiology. Information on the mechanism of intercellular signaling by miRs and proteins contained in EVs are available in several reviews (e.g., [ 52 , 54 , 55 ]).…”