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Front Immunol ; 11: 584241, 2020.
Article in English | MEDLINE | ID: covidwho-908875


Background: Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-ß2GPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-ß2GPI antibodies was not reported. Objective: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-ß2GPI antibodies. Methods: ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events. Results: Anti-ß2GPI IgG/IgA/IgM was the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM was detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of ß2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-ß2GPI nor with thrombosis. Conclusions: aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against ß2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.

Antibodies, Anticardiolipin/immunology , Antiphospholipid Syndrome/immunology , COVID-19/immunology , SARS-CoV-2 , Aged , Aged, 80 and over , Antibodies, Anticardiolipin/blood , Antiphospholipid Syndrome/blood , COVID-19/blood , COVID-19/virology , Critical Illness , Enzyme-Linked Immunosorbent Assay , Epitopes/immunology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Luminescent Measurements , Male , Middle Aged , Phosphatidylserines/immunology , Prothrombin/immunology , Thrombosis/immunology , beta 2-Glycoprotein I/immunology
Blood Rev ; 46: 100745, 2021 03.
Article in English | MEDLINE | ID: covidwho-726418


COVID-19 is a new pandemic, caused by Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-Cov2) infection and characterized by a broad spectrum of clinical manifestations. Inflammation and the innate immune system have been recently recognized as pivotal players in the most severe forms, characterized by significantly elevated levels of pro-inflammatory cytokines. In this setting, several studies have also reported the presence of abnormalities in coagulation parameters and platelets count, possibly identifying a subgroup of patients with poor prognosis. Some reports of full-blown thromboembolic events are emerging. Among the possible mechanisms underlying coagulation dysfunction, the so-called "cytokine storm" seems to play a pivotal role. Other candidate factors include virus-specific mechanisms, related to the virus interaction with renin angiotensin system (RAS) and the fibrinolytic pathway, but also comorbidities affecting these patients. Coagulation dysfunction is therefore a candidate risk factor for adverse outcomes in COVID-19 and should be carefully addressed in clinical practice.

Blood Coagulation Disorders/virology , COVID-19/blood , Aged , Blood Coagulation , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/immunology , COVID-19/immunology , Female , Humans , Immune System , Inflammation/blood , Inflammation/immunology , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Virus Diseases/blood , Virus Diseases/immunology