Severe COVID-19 infection is associated with increased antibody-mediated platelet apoptosis

Abstract

The pathophysiology of COVID-19 associated thrombosis seems to be multifactorial, involving interplay between cellular and plasmatic elements of the hemostasis. We hypothesized that COVID-19 is accompanied by platelet apoptosis with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca2+) concentration, and phosphatidylserine (PS) externalization by flow cytometry. Platelets from intensive care unit (ICU) COVID-19 patients (n=21) showed higher ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization, compared to healthy controls (n=18) and COVID-19 non-ICU patients (n=4). Moreover significant higher cytosolic Ca2+ concentration and PS was observed compared to septic ICU control group (ICU control). In ICU control group (n=5; non-COVID-19 ICU) cytosolic Ca2+ concentration and PS externalization was comparable to healthy control, with an increase in ΔΨm depolarization. Sera from ICU COVID-19 patients induced significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization) compared to healthy volunteer and septic ICU control. Interestingly, immunoglobulin G (IgG) fractions from COVID-19 patients induced an Fc gamma receptor IIA dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca2+ concentration and PS externalization). Enhanced PS externalization in platelets from ICU COVID-19 patients was associated with increased sequential organ failure assessment (SOFA) score (r=0.5635) and D-Dimer (r=0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared to those without. The strong correlations between apoptosis markers and increased D-Dimer levels as well as the incidence of thrombosis may indicate that antibody-mediated platelet apoptosis potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients.

Platelet Activation and Plasma Levels of Furin Are Associated With Prognosis of Patients With Coronary Artery Disease and COVID-19

“… 75 In critically affected patients, nonsurvivors showed a trend towards a drop in platelet count and leukocytosis. 76 Recently, in critical COVID-19 ICU patients an enhanced platelet apoptosis has been described 77 and excessive platelet and neutrophil activation. 38 , 39 Our data confirm and extent the published findings and show that platelet activation not only is evident in progressive SARS-CoV-2 associated infection but substantially is present at an early disease stage as soon as SARS-CoV-2 infection was verified by reverse transcriptase polymerase chain reaction.…”

Alarmins, COVID-19 and comorbidities

“…Cellular processes, such as autophagy [ 17 ], cytokine storm activation [ 18 ], cellular damage [ 19 ] and apoptosis [ 20 ] induced by SARS-CoV-2 virus seem strictly associated with the production and release of alarmins.…”

Alterações Hematológicas Em Gestantes Com Covid-19

“…A CAC engloba alterações laboratoriais de coagulação, trombose e sangramento (IBA et al, 2021). Tem sido proposto que a CAC pode estar relacionada a superestimulação da cascata inflamatória, levando à ativação endotelial e plaquetária semelhante à observada na coagulação intravascular disseminada (GOSHUA et al, 2020;IBA et al, 2021;NAZY et al, 2021;ALTHAUS et al, 2020).…”