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

Background: 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.

Methods: Patients with COVID-19 were stratified by platelet δ-granule content using the luciferin/luciferase assay into 2 groups: normal (COV_δ-norm) and low (COV_δ-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.

Results: A total of 75 patients with COVID-19 were enrolled; 57 presented normal levels of platelet δ-granule content (COV_δ-norm) and 18 had low levels of platelet δ-granules (COV_δ-low). Groups were comparable in terms of age, sex, comorbidities, and SARS-CoV-2 RNAemia levels. Patients in the COV_δ-low group showed significantly higher chemokine and cytokine levels compared to those in the COV_δ-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.

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