On the potential role of exosomes in the COVID-19 reinfection/reactivation opportunity

Abstract

We propose here that one of the potential mechanisms for the relapse of the COVID-19 infection could be a cellular transport pathway associated with the release of the SARS-CoV-2-loaded exosomes and other extracellular vesicles. It is possible that this "Trojan horse" strategy represents possible explanation for the reappearance of the viral RNA in the recovered COVID-19 patients 7-14 day post discharge, suggesting that viral material was hidden within such exosomes or extracellular vesicles during this "silence" time period and then started to re-spread again.

SARS-CoV-2 Infection Reaches the Human Nervous System: How?

“…Many viruses have been shown to enter the extracellular double-membrane vesicle (EDMV) or exosome avenues during intra-host spreading and synthesis [199]. As previously reviewed in detail, all positive-sense single-stranded RNA viruses (including SARS-CoV and MERS-CoV) use, redirect, and rearrange host cell membranes as part of the viral genome transcription and replication tactic, harnessing their non-structural protein apparatus nsp1-16 [200]. This tactic allows them to produce double-membrane vesicles of different size and configuration, carrying different levels of viral particle structures, from dsRNA to full mature viral particles, which would be released as extracellular double-membrane vesicles (EDMV) or exosomes during the release from the host cells, or as a result of the post cell-host rapture.…”

“…Of note, SARS-CoV-2 could infect almost all human body organs and tissues [189,153,200]. The infected cells shedding the exosomes (EDMVs).…”

“…The infected cells shedding the exosomes (EDMVs). Furthermore, apoptotic or the diffuse damage of infected cells can lead to the release of their contents in a form of different types of EDMVs containing different viral structures (ranging from viral dsRNA to mature viral particles), to infected the adjacent new cells/tissues and expanded to circulate systemically and disseminate to reaching distant tissues [200]. This hypothesis is supported by [102,189,155], where viral particles were detected in endothelial cells of lungs, kidneys, skin chilblains, and central nervous system of vascular system and organs-crosstalk via the vascular system.…”

“…Data sharing not applicable to this article as no datasets were generated or analysed during the current study [200]). From her the viral and/or its components can spread from renal anastomosis into CNS via nerve supply.…”

New Insights on the Mobility of Viral and Host Non-Coding RNAs Reveal Extracellular Vesicles as Intriguing Candidate Antiviral Targets

“…Moreover, cells infected with coronaviruses may produce exosomes that can transfer angiotensin converting enzyme 2 (ACE2), the receptor for the SARS-Cov-2 entry, to other cells and thereby make them susceptible to virus docking [20]. Finally, it has been suggested that exosomes may play an important role in the COVID-19 reinfection [21]. An in vitro study on SARS-CoV-1 cultured in AT2 cells revealed that the virions can be seen within the double membrane vesicles [22].…”