Adverse Outcome in COVID-19 Is Associated With an Aggravating Hypo-Responsive Platelet Phenotype

Abstract

Thromboembolic complications are frequently observed in Coronavirus disease 2019 (COVID-19). While COVID-19 is linked to platelet dysregulation, the association between disease outcome and platelet function is less clear. We prospectively monitored platelet activation and reactivity in 97 patients during the first week of hospitalization and determined plasma markers of platelet degranulation and inflammation. Adverse outcome in COVID-19 was associated with increased basal platelet activation and diminished platelet responses, which aggravated over time. Especially GPIIb/IIIa responses were abrogated, pointing toward impeded platelet aggregation. Moreover, platelet-leukocyte aggregate formation was diminished, pointing toward abrogated platelet-mediated immune responses in COVID-19. No general increase in plasma levels of platelet-derived granule components could be detected, arguing against platelet exhaustion. However, studies on platelets from healthy donors showed that plasma components in COVID-19 patients with unfavorable outcome were at least partly responsible for diminished platelet responses.Taken together this study shows that unfavorable outcome in COVID-19 is associated with a hypo-responsive platelet phenotype that aggravates with disease progression and may impact platelet-mediated immunoregulation.

A versatile and interoperable computational framework for the analysis and modeling of COVID-19 disease mechanisms

“…On the other hand, the presence of glycoproteins, such as GPVI and vWF, is involved in thromboembolism and thromboinflammation, and other coagulopathies (23). However, recent studies have shown that platelets are indeed hyperactivated in COVID-19 but show reduced glycoprotein VI (GPVI) reactivity in COVID-19 patients (24), which is consistent with our results.…”

Chronic Immune Platelet Activation Is Followed by Platelet Refractoriness and Impaired Contractility

“…Irrespective of the underlying mechanism(s), continuously activated platelets become exhausted, refractory, and have diversely impaired functionality. As a matter of fact, our findings are in agreement with an array of papers that describe the connection of platelet activation and subsequent dysfunction revealed in other pathological conditions, including a relatively new pathological condition known as vaccine-inducted thrombotic thrombocytopenia (VITT) [46][47][48][49][50][51][52][53].…”

Increased plasma level of soluble P-selectin in non-hospitalized COVID-19 convalescent donors

“…Higher levels of PLA compared to healthy controls were found in the acute phase of COVID-19 [9] , [12] , [17] . Interestingly, COVID-19 patients with fatal outcome had significantly lower PLA levels compared to patients with uncomplicated disease [18] . It is, however, not clear whether increased PLA levels persist in COVID-19 convalescent.…”