Early SARS-CoV-2 infection: Platelet-neutrophil complexes and platelet function

Marina Rieder; Niklas Baldus; Daniela Stallmann; Maren Jeserich; Isabella Goller; Luisa Wirth; Luisa Pollmeier; Maike Hofmann; Christoph Bode; Hans-Joerg Busch; Bonaventura Schmid; Nadine Gauchel; Rüdiger E Scharf; Daniel Duerschmied; Achim Lother; Krystin Krauel

doi:10.1016/j.rpth.2022.100025

Early SARS-CoV-2 infection: Platelet-neutrophil complexes and platelet function

Res Pract Thromb Haemost. 2023 Jan;7(1):100025. doi: 10.1016/j.rpth.2022.100025. Epub 2022 Dec 23.

Authors

Marina Rieder^{1

2}, Niklas Baldus^{1

2}, Daniela Stallmann², Maren Jeserich^{1

2}, Isabella Goller^{1

2}, Luisa Wirth³, Luisa Pollmeier³, Maike Hofmann⁴, Christoph Bode², Hans-Joerg Busch⁵, Bonaventura Schmid⁵, Nadine Gauchel^{1

2}, Rüdiger E Scharf^{6

7

8}, Daniel Duerschmied^{1

2

8

9}, Achim Lother^{1

3}, Krystin Krauel^{2

8}

Affiliations

¹ Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.
³ Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Medicine II, University Hospital Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁵ Department of Emergency Medicine, University Hospital of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁶ Division of Experimental and Clinical Hemostasis, Hemotherapy, and Transfusion Medicine, Institute of Transplantation Diagnostics and Cell Therapy, Heinrich Heine University Medical Center, Düsseldorf, Germany.
⁷ Hemophilia Comprehensive Care Center, Institute of Transplantation Diagnostics and Cell Therapy, Heinrich Heine University Medical Center, Düsseldorf, Germany.
⁸ Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁹ European Center for AngioScience and German Center for Cardiovascular Research partner site Heidelberg/Mannheim, Mannheim, Germany.

Abstract

Background: Conflicting results have been reported on platelet activity ex vivo and responsiveness in vitro among patients with COVID-19 with or without thromboembolic complications.

Objectives: To assess platelet reactivity in patients with moderate disease at early stages of COVID-19.

Methods: We performed a prospective, descriptive analysis of 100 consecutive patients presenting with suspected SARS-CoV-2 infection at University Medical Center Freiburg during the first or second wave of the pandemic. Following polymerase chain reaction testing and compliance with study inclusion criteria, 20 SARS-CoV-2-positive and 55 SARS-CoV-2-negative patients (serving as patient controls) were enrolled. In addition, 15 healthy subjects were included. Platelet reactivity was assessed using whole-blood impedance aggregometry and flow cytometry in response to various agonists.

Results: Platelet aggregation was significantly impaired in the patients with COVID-19 compared with that in the patient controls or healthy subjects. The reduced platelet responsiveness in the patients with COVID-19 was associated with impaired activation of GPIIb/IIIa (α_IIbβ₃). In contrast, low expression of P-selectin at baseline and intact secretion upon stimulation in vitro suggest that no preactivation in vivo, leading to "exhausted" platelets, had occurred. The proportion of circulating platelet-neutrophil complexes was significantly higher in the patients with COVID-19 (mean ± SD, 41% ± 13%) than in the patient controls (18% ± 7%; 95% CI, 11.1-34.1; P = .0002) or healthy subjects (17% ± 4%; 95% CI, 13.8-33.8; P < .0001). An analysis of neutrophil adhesion receptors revealed upregulation of CD11b (α-subunit of α_Mβ₂) and CD66b (CEACAM8) but not of CD162 (PSGL-1) in the patients with COVID-19.

Conclusion: Despite reduced platelet responsiveness, platelet-neutrophil complexes are increased at early stages of moderate disease. Thus, this cellular interaction may occur during COVID-19 without preceding platelet activation.

Keywords: COVID-19; SARS-CoV-2; neutrophils; platelet aggregation; platelets.