Impact of COVID-19 disease on platelet reactivity and association with inflammatory parameters

Abstract

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Aside from the pulmonary manifestations, COVID-19 is associated with increased risk of venous and arterial thrombotic complications. The actual impact of SARS-CoV-2 infection on platelet reactivity and whether this is mediated by a hyperinflammatory status has not been fully elucidated to date.ObjectiveTo evaluate platelet reactivity in COVID-19 patients compared to healthy subjects and to assess the association between platelet reactivity and levels of inflammatory biomarkers among COVID-19 patients.MethodsThis prospective observational investigation included COVID-19 patients admitted into a tertiary care hospital and adult healthy volunteers, all of them not receiving any antiplatelet therapy. Subjects were classified in three groups: 1) Healthy subjects (HS group); 2) COVID-19 patients in a pulmonary phase (viral pneumonia and bilateral infiltrates) but without meeting criteria for systemic hyperinflammation (C19-Pulm group); and 3) COVID-19 patients in a hyperinflammation phase (C19-Infl group) meeting at least 2 of the following criteria: CRP>100mg/l, D-dimer >1000mcg/l, LDH>400U/l, ferritin>1000ng/ml, IL-6>70ng/l. Blood samples for platelet function testing and quantification of inflammatory parkers were collected at a single visit. Platelet function was measured with multiple electrode aggregometry using ADP (MEA-ADP, primary endpoint), arachidonic acid (AA) and thrombin receptor activating peptide (TRAP) as stimuli. Unadjusted analyses are presented.ResultsA total of 60 patients were included in the present investigation (20 in each group). A significantly greater platelet reactivity, measured with MEA-ADP, was observed in both groups of COVID-patients compared to healthy subjects (HS: 634,9±53,5, C19-Pulm: 919,9±53,5 and C19-Infl: 931,6±53,5 AU*min; p for C19-Pulm vs. HS <0,001, p for C19-Infl vs. HS <0,001, p for C19-Pulm vs. C19-Infl 0,878; Figure 1). Parallel findings were found when using AA as stimulus for platelet aggregation showing greater platelet aggregation in COVID-19 patients compared to healthy subjects, but numerical differences were not statistically significant when using TRAP. Among COVID-19 patients, when stratified by IL-6 levels splitted into tertiles, greater platelet reactivity was observed in patients with higher IL-6 concentrations (mid and upper tertile together) compared to those with values in the lower tertile, as assessed with MEA-ADP (lower tertile: 829,0±75,8, mid and upper tertile: 1028,7±56,2; p=0,043); a similar trend was observed with AA and TRAP as stimuli.ConclusionPatients with severe COVID-19 disease have greater platelet reactivity than healthy subjects. Increased IL-6 levels might be associated with the observed heightened platelet reactivity among COVID-19 patients.Funding AcknowledgementType of funding sources: None. Figure 1