Effects of the circulating environment of COVID-19 on platelet and neutrophil behavior
Alexander T Fields1, Elizabeth A Andraska2, Christof Kaltenmeier2
1Department of Surgery, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, CA, United States.
Insights
COVID-19 patient plasma affects platelet function, causing auto-aggregation. Platelet releasates from these patients also induce inflammatory responses in neutrophils, impacting their gene expression and extracellular trap formation.
Area of Science:
- Immunology
- Hematology
- Infectious Diseases
Background:
- Thromboinflammatory complications are common in Coronavirus Disease 2019 (COVID-19).
- The role of the circulating environment on platelet and neutrophil behavior in COVID-19 is not well understood.
Purpose of the Study:
- To investigate if plasma from COVID-19 patients induces a prothrombotic platelet phenotype.
- To determine if platelet releasates from COVID-19 patients induce a proinflammatory neutrophil phenotype.
Main Methods:
- Platelets were treated with plasma from COVID-19 patients and controls.
- Neutrophils were exposed to platelet releasates, and neutrophil extracellular trap formation was measured.
- RNA sequencing was performed on neutrophils exposed to platelet releasates.
Main Results:
- COVID-19 patient plasma promoted platelet auto-aggregation, reducing subsequent responsiveness.
- Platelet size was reduced in both COVID-19 patients and controls.
- COVID-19 patient platelet releasates increased neutrophil extracellular traps and altered neutrophil gene expression.
Conclusions:
- The circulating environment in COVID-19 influences platelet function.
- Platelet releasates contribute to neutrophil inflammation independently of direct cell contact.
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.
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