# Extracellular vesicles isolated from the plasma of COVID-19 and sepsis patients: characterisation and association with clinical outcomes

## TL;DR

This study examines extracellular vesicles in the blood of ICU patients with COVID-19 and sepsis, finding higher concentrations and viral components, which may help explain disease progression.

## Contribution

The study identifies EVs as potential carriers of SARS-CoV-2 and links CD81 expression to mortality in patients.

## Key findings

- EVs from ICU patients showed higher concentrations of microparticles compared to healthy individuals.
- EVs carried SARS-CoV-2 components, including the Gamma variant, and were mainly from T cells and platelets.
- EVs from deceased patients had elevated CD81 expression, suggesting a link to poor clinical outcomes.

## Abstract

Extracellular vesicles (EVs) are involved in the pathogenesis of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection.

We analysed the concentration, size, cellular origin, and capacity for carrying viral components in plasma samples from patients with Coronavirus disease 2019 (COVID-19) and sepsis.

Plasma samples from COVID-19 patients admitted to the intensive care unit (ICU) with sepsis (N = 42) and healthy individuals (N = 19) were analysed. EVs were characterised by size and concentration using nanoparticle tracking analysis (NTA), polymerase chain reaction (RT-qPCR) for SARS-CoV-2 components, and flow cytometry for immunophenotyping. EVs were marked with phosphatidylserine and tetraspanins. Cellular origin markers were used for neutrophils, endothelial cells, T lymphocytes and platelets. Cryo-EM was used to assess EV size and integrity.

NTA showed an increased concentration of microparticles in patients. RT-qPCR analysis of EVs detected the virus in 14 samples, two of which were consistent with the Gamma variant. EVs predominantly derived from T cells and platelets and demonstrated an increased expression of CD81 in individuals who died. Cryo-EM revealed EVs with an average size of 200 nm.

Our findings suggest that patients’ EVs likely harboured viral components, suggesting their potential role as carriers of SARS-CoV-2. In addition, EVs from deceased patients demonstrated elevated levels of CD81 expression.