Serum‐derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID‐19 patients

Abstract

COVID-19 is characterized by a wide spectrum of disease severity, whose indicators and underlying mechanisms need to be identified. The role of extracellular vesicles (EVs) in COVID-19 and their biomarker potential, however, remains largely unknown. Aiming to identify specific EV signatures of patients with mild compared to severe COVID-19, we characterized the EV composition of 20 mild and 26 severe COVID-19 patients along with 16 sex and age-matched healthy donors with a panel of eight different antibodies by imaging flow cytometry (IFCM). We correlated the obtained data with 37 clinical, prerecorded biochemical and immunological parameters. Severe patients' sera contained increased amounts of CD13 + and CD82 + EVs, which positively correlated with IL-6-producing and circulating myeloid-derived suppressor cells (MDSCs) and with the serum concentration of proinflammatory cytokines, respectively. Sera of mild COVID-19 patients contained more HLA-ABC + EVs than sera of the healthy donors and more CD24 + EVs than severe COVID-19 patients. Their increased abundance negatively correlated with disease severity and accumulation of MDSCs, being considered as key drivers of immunopathogenesis in COVID-19. Altogether, our results support the potential of serum EVs as powerful biomarkers for COVID-19 severity and pave the way for future investigations aiming to unravel the role of EVs in COVID-19 progression.

Isolation of native EVs from primary biofluids—Free‐flow electrophoresis as a novel approach to purify ascites‐derived EVs

“…Extracellular vesicles (EVs) are biological nanoparticles that are secreted by virtually every cell into the extracellular environment and can be found in all tissues and biofluids. These vesicles, especially the endosomal-derived exosomes and plasma-membrane origin ectosomes or microvesicles, play important roles in physiological and pathophysiological intercellular communication and act as transmitters of various cargoes such as nucleic acids, proteins, lipids, and metabolites (for review see van Niel et al, 2018) Being assembled in cell-type-specific manners, EVs are considered as a promising class of novel biomarkers for various diseases including tumours and proinflammatory diseases such as COVID-19 Tertel et al, 2022).…”

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

“…In the vaccine field, the interest in EV-mediated antigen delivery is growing based on the observation that mammalian cells infected with viral pathogens release EVs containing viral constituents able to trigger an immune response [ 37 ]. Moreover, EVs carrying S protein have been detected in infected patients, and their potential role in inducing a humoral specific immune response has been suggested [ 38 , 39 ].…”

Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus

“…CD24 is a marker of several B cell subtypes including regulatory B cells and the presence of these cells has been associated with the duration of COVID-19 symptoms [9] , [10] . On the other hand, CD82+ EVs correlated with the frequency of circulating IL-6-producing myeloid-derived suppressor cells [8] . Importantly, the quantification of CD82+ and CD24+ EVs displayed better performance by linear discriminant effect size (LEfSe) analysis as indicators for severe COVID-19, as compared to previously known biomarkers such as the number of circulating neutrophils and myeloid-derived suppressor cells (MDSCs) or the concentration of various pro-inflammatory markers (e.g., C-reactive protein, D-dimer, interleukin IL-8) in the blood [8] .…”

“…Extracellular vesicles (EVs) are key players in intercellular and interorgan communication in both normal physiology and disease pathogenesis. In COVID-19, several studies suggest that EVs play a role in the pathogenesis of SARS-CoV-2 infection and severity of COVID-19 [3] , [4] , [5] , [6] , [7] , [8] . Platelet-derived EVs, for example, were found to be elevated in multiple cohorts [4] , [5] .…”

“…In hospitalized COVID-19 patients, alterations in these proteins may contribute to severe disease [7] . More recently, using state-of-the-art imaging flow cytometry, Tertel and colleague found that CD24+ EV subpopulations were enriched in people with mild symptoms, while CD82+ EVs were enriched in people with severe symptoms [8] . CD24 is a marker of several B cell subtypes including regulatory B cells and the presence of these cells has been associated with the duration of COVID-19 symptoms [9] , [10] .…”