# Investigating the Interplay of SARS-CoV-2 RNAemia and Peripheral Inflammation in Platelet Dysfunction During Acute SARS-CoV-2 Infection

## TL;DR

This study explores how inflammation, not the presence of SARS-CoV-2 RNA in blood, is linked to platelet dysfunction in patients with acute COVID-19.

## Contribution

The study identifies peripheral inflammation as a key driver of platelet dysfunction during acute SARS-CoV-2 infection, distinct from RNAemia levels.

## Key findings

- Patients with low platelet δ-granule content had higher levels of chemokines and cytokines.
- IL-6 and GM-CSF were strongly correlated with platelet degranulation parameters.
- Peripheral inflammation, not SARS-CoV-2 RNAemia, is associated with platelet dysfunction in acute infection.

## Abstract

Circulating degranulated platelets have been described during acute SARS-CoV-2 infection and associated with COVID-19 complications. This study investigated the relationship between the presence of plasma SARS-CoV-2 RNA (ie, SARS-CoV-2 RNAemia), systemic inflammation, and platelet dysfunction in a group of patients with COVID-19. Unlike our previous publication, which focused on platelet characterization, this work explores potential determinants of platelet activation, based on a distinct subset of patients with available stored samples.

Patients with COVID-19 were stratified by platelet δ-granule content using the luciferin/luciferase assay into 2 groups: normal (COVδ-norm) and low (COVδ-low). Plasma SARS-CoV-2 RNAemia (RT-qPCR), cytokines, and chemokines (Cytometric Bead Array) were quantified on plasma samples. Markers of platelet activation were measured by flow cytometry in whole blood.

A total of 75 patients with COVID-19 were enrolled; 57 presented normal levels of platelet δ-granule content (COVδ-norm) and 18 had low levels of platelet δ-granules (COVδ-low). Groups were comparable in terms of age, sex, comorbidities, and SARS-CoV-2 RNAemia levels. Patients in the COVδ-low group showed significantly higher chemokine and cytokine levels compared to those in the COVδ-norm group, with strong correlations between IL-6, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF), with platelet degranulation parameters. A similar trend, albeit less pronounced, was observed when patients were stratified based on their platelet activation phenotype.

These findings suggest that peripheral inflammation, rather than SARS-CoV-2 RNAemia, is associated with platelet dysfunction during acute SARS-CoV-2 infection.