SARS-CoV-2 and extracellular vesicles: An intricate interplay in pathogenesis, diagnosis and treatment

Abstract

Extracellular vesicles (EVs) are widely recognized as intercellular communication mediators. Among the different biological processes, EVs play a role in viral infections, supporting virus entrance and spread into host cells and immune response evasion. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an urgent public health issue with significant morbidity and mortality worldwide, being responsible for the current COVID-19 pandemic. Since EVs are implicated in SARS-CoV-2 infection in a morphological and functional level, they have gained growing interest for a better understanding of SARS-CoV-2 pathogenesis and represent possible diagnostic tools to track the disease progression. Furthermore, thanks to their biocompatibility and efficient immune activation, the use of EVs may also represent a promising strategy for the development of new therapeutic strategies against COVID-19. In this review, we explore the role of EVs in viral infections with a focus on SARS-CoV-2 biology and pathogenesis, considering recent morphometric studies. The common biogenesis aspects and structural similarities between EVs and SARS-CoV-2 will be examined, offering a panoramic of their multifaceted interplay and presenting EVs as a machinery supporting the viral cycle. On the other hand, EVs may be exploited as early diagnostic biomarkers and efficient carriers for drug delivery and vaccination, and ongoing studies will be reviewed to highlight EVs as potential alternative therapeutic strategies against SARS-CoV-2 infection.

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

“…Extracellular vesicles (EV) are found in various biofluids and serve as carriers that transfer biomolecules to target cells all over the body. EV secretion is a known pathway aiding in the transmission and spread of several RNA viruses using exosomes, the smallest EV subclass; however, the mechanisms that viruses use to accomplish this is still up for debate [105][106][107]. One model proposes that the autophagic pathway is involved as LC3-labeled "autophagosome-like" organelles selectively capture a cluster of viral particles and release them non-cytolytically from an infected cell [108][109][110].…”

“…An additional proposed mechanism states viral proteins, RNA, or entire virions may be directed into exosomes that are then expelled from the infected cell via exocytosis into the extracellular space [107,111]. Exosomes then bind to target cells and induce susceptibility for viral infection within these healthy cells using membrane receptors, such as ACE2 and CD9, while fusing to the target cell membrane and unloading viral cargo [105,111,112]. It is thought that EVs play an important role in the transformation of COVID-19 infection from a local to a systemic infection contributing to the development of systemic inflammatory response syndrome [113].…”

Genomic communication via circulating extracellular vesicles and long-term health consequences of COVID-19

“…EVs are released from all cell types including SARS-CoV-2 infected cells, and both EVs and the virus share similarities in terms of size, cellular pathways of biogenesis/infection, cellular release, and uptake by target cells [ 44 , 45 ]. Many viruses hijack the exosome biogenesis pathway for viral assembly, maturation, trafficking and release, and EVs released from virus infected cells are enriched in viral proteins and nucleic acids [ 46 – 49 ].…”