AUTHOR=Fields Alexander T. , Andraska Elizabeth A. , Kaltenmeier Christof , Matthay Zachary A. , Herrera Kimberly , Nuñez-Garcia Brenda , Jones Chayse M. , Wick Katherine D. , Liu Silvia , Luo Jian-Hua , Yu Yan-Ping , Matthay Michael A. , Hendrickson Carolyn M. , Bainton Roland J. , Barrett Tessa J. , Berger Jeffrey S. , Neal Matthew D. , Kornblith Lucy Z. , the COVID-19 Associated Coagulopathy Inflammation and Thrombosis (Co-ACIT) Study Group , Ambachew; Biniam , Cary; Sarah , Chalwell; Lauren , Colwell; Christopher , Josephy; Clayton , Lee; Deanna , LeGrand; Matthieu , Montoy; Juan Carlos , Kornblith; Aaron E. , Kurien; Philip , Nunez-Garcia; Brenda , Nguyen; Viet , Park; John J. , Prakash; Arun , Robinson; Brittany , Shelley India TITLE=Effects of the circulating environment of COVID-19 on platelet and neutrophil behavior JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1130288 DOI=10.3389/fimmu.2023.1130288 ISSN=1664-3224 ABSTRACT=Introduction

Thromboinflammatory complications are well described sequalae of Coronavirus Disease 2019 (COVID-19), and there is evidence of both hyperreactive platelet and inflammatory neutrophil biology that contributes to the thromoinflammatory milieu. It has been demonstrated in other thromboinflammatory diseases that the circulating environment may affect cellular behavior, but what role this environment exerts on platelets and neutrophils in COVID-19 remains unknown. We tested the hypotheses that 1) plasma from COVID-19 patients can induce a prothrombotic platelet functional phenotype, and 2) contents released from platelets (platelet releasate) from COVID-19 patients can induce a proinflammatory neutrophil phenotype.

Methods

We treated platelets with COVID-19 patient and disease control plasma, and measured their aggregation response to collagen and adhesion in a microfluidic parallel plate flow chamber coated with collagen and thromboplastin. We exposed healthy neutrophils to platelet releasate from COVID-19 patients and disease controls and measured neutrophil extracellular trap formation and performed RNA sequencing.

Results

We found that COVID-19 patient plasma promoted auto-aggregation, thereby reducing response to further stimulation ex-vivo. Neither disease condition increased the number of platelets adhered to a collagen and thromboplastin coated parallel plate flow chamber, but both markedly reduced platelet size. COVID-19 patient platelet releasate increased myeloperoxidasedeoxyribonucleic acid complexes and induced changes to neutrophil gene expression.

Discussion

Together these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.