# Platelet-derived mediators in hospitalized COVID-19 patients and associations to respiratory failure, ICU admittance and 60-day mortality

## TL;DR

This study explores how platelet-derived mediators are linked to severe outcomes in hospitalized COVID-19 patients, including ICU admission and death.

## Contribution

The study identifies specific platelet-derived mediators associated with adverse outcomes and persistent platelet activation in COVID-19 patients.

## Key findings

- High P-selectin levels correlate with ICU/respiratory failure, while low PF4/CXCL4, ENA-78/CXCL5, and NAP-2/CXCL7 levels correlate with 60-day mortality.
- sCD40L, ENA-78/CXCL7, and VEGF-A remain elevated for up to 12 months post-hospitalization compared to healthy controls.
- In vitro, inactivated SARS-CoV-2 induces a dose-dependent release of several platelet-derived mediators.

## Abstract

Platelet activation is documented in COVID-19, but data on platelet-derived mediators are scarce.

To examine the levels of various platelet-derived mediators in relation to adverse outcomes defined as the need for treatment at intensive care unit (ICU) and/or respiratory failure (RF) and 60-day total mortality in hospitalized COVID-19 patients.

Plasma levels of RANTES/CCL5, PF4/CXCL4, ENA78/CXCL5, NAP-2/CXCL7, SDF-1/CXCL12, P-selectin, soluble CD40 ligand (sCD40L) and vascular endothelial cell growth factor A (VEGF-A) were measured in 245 hospitalized COVID-19 patients and in a subpopulation of the patients, also at three, six and 12 months after hospitalization.

Our main findings were: (i) High levels of P-selectin was associated with ICU/RF, while low levels of PF4/CXCL4, ENA-78/CXCL5 and NAP-2/CXCL7 were associated with 60-days mortality. (ii) Most of the mediators were normalized after hospitalization, but plasma levels of sCD40L, ENA-78/CXCL7 and VEGF-A were markedly elevated compared to healthy controls for up to 12 months after hospitalization. (iii) In vitro, inactivated SARS-CoV-2 induced a dose-dependent release of NAP-2, P-selectin, RANTES, sCD40L and VEGF-A from isolated platelets.

Our findings underscore the role of platelet-derived inflammatory mediators in the pathogenesis of COVID-19, potentially involving direct effects of SARS-CoV-2. The study also points to a persistent platelet activation following hospitalization.