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      Anti-Phospholipid Antibodies in COVID-19 Are Different From Those Detectable in the Anti-Phospholipid Syndrome

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      1 , 2 , 1 , 3 , 4 , 5 , 1 , 6 , 1 , 1 , 7 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 5 , 9 , 9 , 7 , 6 , 10 , 7 , 1 , 7 , 1 , 11 , 1
      Frontiers in Immunology
      Frontiers Media S.A.
      anti-phospholipid antibodies, β2-glycoprotein I, prothrombin, autoimmunity, COVID-19, thrombosis

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          Abstract

          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-β 2GPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-β 2GPI 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-β 2GPI 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-β 2GPI 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 β 2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β 2GPI 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 β 2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.

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          Most cited references37

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          Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

          Abstract Background In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern. Objectives To describe the coagulation feature of patients with NCP. Methods Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed. Results The overall mortality was 11.5%, the non‐survivors revealed significantly higher D‐dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non‐survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay. Conclusions The present study shows that abnormal coagulation results, especially markedly elevated D‐dimer and FDP are common in deaths with NCP.
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            Incidence of thrombotic complications in critically ill ICU patients with COVID-19

            Introduction COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. Results We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.
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              Clinical and immunologic features in severe and moderate Coronavirus Disease 2019

              Journal of Clinical Investigation
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                15 October 2020
                2020
                15 October 2020
                : 11
                : 584241
                Affiliations
                [1] 1Immunorheumatology Research Laboratory, Istituto Auxologico Italiano, Istituto di Ricovero Cura a Carattere Scientifico (IRCCS) , Milan, Italy
                [2] 2Department of Clinical Sciences and Community Health, University of Milan , Milan, Italy
                [3] 3Rheumatology and Clinical Immunology Department, Faculty of Medicine, Alexandria University , Alexandria, Egypt
                [4] 4Department of Molecular and Translational Medicine, University of Brescia , Brescia, Italy
                [5] 5Department of Laboratory Diagnostics, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili , Brescia, Italy
                [6] 6Department of Chemical Chemistry, Istituto Auxologico Italiano, Istituto di Ricovero Cura a Carattere Scientifico (IRCCS) , Milan, Italy
                [7] 7Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, Istituto di Ricovero Cura a Carattere Scientifico (IRCCS), San Luca Hospital , Milan, Italy
                [8] 8Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili and University of Brescia , Brescia, Italy
                [9] 9Unità Operativa Complessa (UOC) 2° Medicina, Department of Clinical and Experimental Sciences, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili and University of Brescia , Brescia, Italy
                [10] 10Research and Development, Inova Diagnostics, Inc. , San Diego, CA, United States
                [11] 11Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine , St. Louis, MO, United States
                Author notes

                Edited by: Rolando Cimaz, University of Milan, Italy

                Reviewed by: Andras Perl, Upstate Medical University, United States; Tadej Avcin, University Medical Centre Ljubljana, Slovenia

                *Correspondence: Nicola Pozzi, nicola.pozzi@ 123456health.slu.edu ; Pier Luigi Meroni, pierluigi.meroni@ 123456unimi.it

                This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.584241
                7593765
                33178218
                2a2306e1-2cf0-4f83-be30-9a8d152930b0
                Copyright © 2020 Borghi, Beltagy, Garrafa, Curreli, Cecchini, Bodio, Grossi, Blengino, Tincani, Franceschini, Andreoli, Lazzaroni, Piantoni, Masneri, Crisafulli, Brugnoni, Muiesan, Salvetti, Parati, Torresani, Mahler, Heilbron, Pregnolato, Pengo, Tedesco, Pozzi and Meroni

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 July 2020
                : 25 September 2020
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 38, Pages: 7, Words: 2824
                Categories
                Immunology
                Original Research

                Immunology
                anti-phospholipid antibodies,β2-glycoprotein i,prothrombin,autoimmunity,covid-19,thrombosis

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