ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent pathogen responsible for the coronavirus disease 2019 (COVID-19). Since its emergence, the novel coronavirus has rapidly achieved pandemic proportions causing remarkably increased morbidity and mortality around the world. A hypercoagulability state has been reported as a major pathologic event in COVID-19, and thromboembolic complications listed among life-threatening complications of the disease. Platelets are chief effector cells of hemostasis and pathological thrombosis. However, the participation of platelets in the pathogenesis of COVID-19 remains elusive. This report demonstrates that increased platelet activation and platelet-monocyte aggregate formation are observed in severe COVID-19 patients, but not in patients presenting mild COVID-19 syndrome. In addition, exposure to plasma from severe COVID-19 patients increased the activation of control platelets ex vivo. In our cohort of COVID-19 patients admitted to the intensive care unit, platelet-monocyte interaction was strongly associated with tissue factor (TF) expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation exacerbation as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients who evolved with in-hospital mortality. Finally, platelets from severe COVID-19 patients were able to induce TF expression ex vivo in monocytes from healthy volunteers, a phenomenon that was inhibited by platelet P-selectin neutralization or integrin αIIb/ß3 blocking with the aggregation inhibitor abciximab. Altogether, these data shed light on new pathological mechanisms involving platelet activation and platelet-dependent monocyte TF expression, which were associated with COVID-19 severity and mortality.
Subject(s)
Betacoronavirus/immunology , Blood Coagulation Disorders/pathology , Blood Platelets/pathology , Coronavirus Infections/complications , Monocytes/pathology , Pneumonia, Viral/complications , Thromboplastin/metabolism , Adult , Biomarkers/metabolism , Blood Coagulation Disorders/immunology , Blood Coagulation Disorders/metabolism , Blood Coagulation Disorders/virology , Blood Platelets/metabolism , Blood Platelets/virology , COVID-19 , Case-Control Studies , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Monocytes/metabolism , Monocytes/virology , P-Selectin/metabolism , Pandemics , Platelet Activation , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Prognosis , Prospective Studies , SARS-CoV-2 , Survival RateABSTRACT
Desse modo, foi possível honrar o diálogo académico e democrático e sustentar o debate e a pesquisa em conjuntura nao apenas de sofrimento de diversas ordens, mas de ataque a cultura e a ciencia, reunindo centenas de pessoas de toda parte do país e de vários países: uma afirmaçâo de vida em meio a muitas mortes. Freud pensava que a condiçâo psicopatológica fundamental humana poderia ser explicada, em grande medida, pela neotínea: nascemos aparentemente antes do tempo (Freud, 1920/1996). Nascer prematuramente permite ao humano um desenho intelectual, social e cultural sem paralelo no mundo animal. Cada crise posterior - desmame, Édipo, adolescencia, saída da família, vida social e política, envelhecimento e morte - diz a psicopatologia fundamental, exige a instauraçâo de novo marco que permita o restabelecimento de um equivalente ao relacionamento primitivo mâe-bebe.