Extracellular vesicles in COVID-19 prognosis, treatment, and vaccination: an update

Abstract

The lethality of the COVID 19 pandemic became the trigger for one of the most meteoric races on record in the search for strategies of disease control. Those include development of rapid and sensitive diagnostic methods, therapies to treat severe cases, and development of anti-SARS-CoV-2 vaccines, the latter responsible for the current relative control of the disease. However, the commercially available vaccines are still far from conferring protection against acquiring the infection, so the development of more efficient vaccines that can cut the transmission of the variants of concerns that currently predominate and those that will emerge is a prevailing need. On the other hand, considering that COVID 19 is here to stay, the development of new diagnosis and treatment strategies is also desirable. In this sense, there has recently been a great interest in taking advantage of the benefits offered by extracellular vesicles (EVs), membrane structures of nanoscale size that carry information between cells participating in this manner in many physiological homeostatic and pathological processes. The interest has been focused on the fact that EVs are relatively easy to obtain and manipulate, allowing the design of natural nanocarriers that deliver molecules of interest, as well as the information about the pathogens, which can be exploited for the aforementioned purposes. Studies have shown that infection with SARS-CoV-2 induces the release of EVs from different sources, including platelets, and that their increase in blood, as well as some of their markers, could be used as a prognosis of disease severity. Likewise, EVs from different sources are being used as the ideal carriers for delivering active molecules and drugs to treat the disease, as well as vaccine antigens. In this review, we describe the progress that has been made in these three years of pandemic regarding the use of EVs for diagnosis, treatment, and vaccination against SARS-CoV-2 infection. KEY POINTS: • Covid-19 still requires more effective and specific treatments and vaccines. • The use of extracellular vesicles is emerging as an option with multiple advantages. • Association of EVs with COVID 19 and engineered EVs for its control are presented.

Keywords: COVID-19; Extracellular vesicles; Prognosis; SARS-CoV-2; Treatment; Vaccination.

Fig. 1

Summary of EV-based strategies proposed to control COVID-19 infection. A Use of EVs displaying the ACE2 receptor on their surface to neutralize SARS-CoV-2. B Use of ASTEX (activated specialized tissue effector EVs) to modulate the inflammatory response associated with the disease. C Use of mesenchymal stem cell-derived EVs (MSC-EVs) for the intranasal treatment of patients in order to attenuate the clinical signs of the disease

Fig. 2

Summary of proposed EV-based strategies of vaccination against COVID-19. A Vaccination with DNA coding for SARS-CoV-2 structural proteins that are coupled to the EVs released by muscle cells. These EVs are captured by antigen presenting cells (APC) and the virus proteins presented to activate specific CD8 + T cells responses. B Vaccination with EVs displaying a SpyCatcher that captures the RBD of protein S (S-RBD) through a SpyTag. Inoculation with these EVs is intended to induce strong humoral responses that neutralize the virus. C Intranasal nebulization vaccination with EVs derived from lung spheroids showing the S-RBD coupled to DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethy lene-glycol)-N-hydroxysuccinimide) to induce neutralizing mucosal antibody responses. D Intramuscular vaccination with mRNA coding for Spike or nucleocapsid proteins loaded into exosomes. Inoculation induces humoral response and cellular immunity mediated by CD4 and CD8 lymphocytes