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Possible Role of P-Selectin Adhesion in Long-COVID: A Comparative Analysis of a Long-COVID Case vs. an Asymptomatic Post-COVID Case

Michael Tarasev, Sabrina Mota, Xiufeng Gao, Marta Ferranti, Aliya U. Zaidi, Bryan Hannan, Patrick Hines

Background: Long-term outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized as an emerging public health challenge-a condition termed Long-COVID. The pathophysiology of Long-COVID remains to be established. Functional P-selectin activity, implicated in COVID-19 sequelae, was measured between two convalescent COVID-19 subjects, one with (Long-COVID subject) and another without Long-COVID symptoms.

Methods: Flow adhesion of whole blood or isolated white blood cells to P-selectin (FA-WB-Psel and FA-WBC-Psel) was measured using a standardized microfluidics clinical assay; impedance aggregometry with a collagen agonist was measured using model 590 Chrono-Log impedance aggregometer; standard laboratory assays were performed to evaluate changes in blood chemistries.

Results: For both subjects, hemoglobin, WBC, platelet counts, electrolytes and ferritin were within normal reference ranges, with FA-WB-Psel significantly elevated compared to healthy controls (p< 0.01). In vitro treatment of whole blood samples with crizanlizumab (anti-p-selectin monoclonal antibody) within the clinical dose range (10 μg/ml) inhibited FA-WB-Psel only in samples from asymptomatic Post-COVID subject, with the Long-COVID subject sample requiring close to 5-fold elevated dose to achieve a response. Pronounced inhibition of P-selectin adhesion of isolated leukocytes was observed for both subjects in autologous platelet-poor plasma and buffer. Impedance aggregometry showed greater baseline platelet aggregation to collagen in the Long-COVID sample, although both samples responded similarly to aspirin-induced platelet inhibition.

Conclusion: Presented results suggest that elevated platelet activation in Long-COVID subject may be associated with increased P-selectin activity. The results are discussed in terms of possible use of P-selectin inhibition therapies in treating Long-COVID.