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MeSH Disease

Human Phenotype

Transmission

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Seroprevalence
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    Severe COVID-19 is associated with elevated serum SERO IgA and antiphospholipid IgA- antibodies SERO

    Authors: Omar Hasan Ali; David Bomze; Lorenz Risch; Silvio D Brugger; Matthias Paprotny; Myriam Weber; Sarah Thiel; Lukas Kern; Werner C Albrich; Philipp Kohler; Christian R Kahlert; Pietro Vernazza; Philipp K Buehler; Reto A Schuepbach; Alejandro Gomez-Mejia; Alexandra M Popa; Andreas Bergthaler; Josef M Penninger; Lukas Flatz

    doi:10.1101/2020.07.21.20159244 Date: 2020-07-24 Source: medRxiv

    Background: While the pathogenesis of coronavirus disease MESHD 2019 (COVID-19) is becoming increasingly clear, there is little data on IgA response, the first line of bronchial immune defense. Objective: To determine, whether COVID-19 is associated with a vigorous total IgA response and whether IgA autoantibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome MESHD (APS), our approach focused on antiphospholipid antibodies SERO (aPL). Materials and methods: In this retrospective cohort study we compared clinical data and aPL from 64 patients with COVID-19 from three independent centers (two in Switzerland, one in Liechtenstein). Samples were collected from April 9, 2020 to May 1, 2020. Total IgA and aPL were measured with FDA-approved commercially available clinical diagnostic kits. Results: Clinical records of the 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID, n=26 [41%]), a discovery cohort with severe illness (sdCOVD, n=14 [22%]) and a confirmation cohort with severe illness (scCOVID, n=24 [38%]). Severe illness was significantly associated with increased total IgA (sdCOVID, P=0.01; scCOVID, P<0.001). Total IgG levels were similar in both cohorts. Among aPL, both cohorts with severe illness significantly correlated with elevated anti-Cardiolipin IgA (sdCOVID and scCOVID, P<0.001), anti-Cardiolipin IgM (sdCOVID, P=0.003; scCOVID, P<0.001), and anti-Beta2 Glycoprotein-1 IgA (sdCOVID and scCOVID, P<0.001). Systemic lupus erythematosus MESHD Systemic lupus erythematosus HP was excluded from all patients as a potential confounder of APS. Conclusions: Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA-response triggered in the bronchial mucosa induces systemic autoimmunity HP.

    Prevalence SERO, specificity, and clinical association of anti-phospholipid antibodies SERO in COVID-19 patients: are the antibodies SERO really guilty?

    Authors: Maria Orietta Borghi; Asmaa Beltagy; Emirena Garrafa; Daniele Curreli; Germana Cecchini; Caterina Bodio; Claudia Grossi; Simonetta Blengino; Angela Tincani; Franco Franceschini; Laura Andreoli; Maria Grazia Lazzaroni; Silvia Piantoni; Stefania Masneri; Francesca Crisafulli; Dulio Brugnoni; Maria Lorenza Muiesan; Massimo Salvetti; Gianfranco Parati; Erminio Torresani; Michael Mahler; Francesca Heilbron; Francesca Pregnolato; Martino Pengo; Francesco Tedesco; Nicola Pozzi; Pier Luigi Meroni

    doi:10.1101/2020.06.17.20134114 Date: 2020-06-19 Source: medRxiv

    Background. Critically ill patients with coronavirus disease MESHD 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death MESHD. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies SERO (aPL) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant HP) 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-{beta}2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies SERO was not investigated systematically. Epitope specificity of anti-{beta}2GPI antibodies SERO was not reported. Objective. To evaluate the prevalence SERO and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-{beta}2GPI antibodies SERO. Methods. ELISA SERO 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-{beta}2GPI IgG/IgA/IgM were the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM were detected in 5.7/6.6% by ELISA SERO. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA SERO. No association between thrombosis MESHD and aPL was found. Reactivity against domain 1 and 4-5 of {beta}2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-{beta}2GPI nor with thrombosis MESHD. Conclusions. aPL show a low prevalence SERO in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against {beta}2GPI but display an epitope specificity different from antibodies SERO in antiphospholipid syndrome MESHD.

    Prothrombotic antiphospholipid antibodies SERO in COVID-19

    Authors: Yu Zuo; Shanea K. Estes; Alex A. Gandhi; Srilakshmi Yalavarthi; Ramadan A. Ali; Hui Shi; Gautam Sule; Kelsey Gockman; Jacqueline A. Madison; Melanie Zuo; Wrenn Woodard; Sean P. Lezak; Njira L. Lugogo; Yogendra Kanthi; Jason S. Knight

    doi:10.1101/2020.06.15.20131607 Date: 2020-06-17 Source: medRxiv

    Patients with coronavirus disease MESHD 19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions HP. At the same time, lung histopathology often reveals fibrin-based occlusion of small vessels in patients who succumb to the disease MESHD. Antiphospholipid syndrome MESHD (APS) is an acquired and potentially life-threatening thrombophilia MESHD in which patients develop pathogenic autoantibodies (aPL) targeting phospholipids and phospholipid-binding proteins. Small case series have recently detected aPL in patients with COVID-19. Here, we measured eight types of aPL (anticardiolipin IgG/IgM/IgA, anti-beta-2 glycoprotein I IgG/IgM/IgA, and anti- phosphatidylserine/prothrombin (PS/PT) IgG/IgM) in the sera of 172 patients hospitalized with COVID-19. We detected anticardiolipin IgM antibodies SERO in 23%, anti-PS/PT IgG in 24%, and anti-PS/PT IgM in 18%. Any aPL was present in 52% of patients using the manufacturer's threshold and in 30% using a more stringent cutoff (>40 units). Higher levels of aPL were associated with neutrophil hyperactivity HP (including the release of neutrophil extracellular traps/NETs), higher platelet count, more severe respiratory disease MESHD, and lower glomerular filtration rates. Similar to patients with known and longstanding APS, IgG fractions isolated from patients with COVID-19 promoted NET release from control neutrophils. Furthermore, injection of these COVID-19 IgG fractions into mice accelerated venous thrombosis MESHD venous thrombosis HP. Taken together, these studies suggest that a significant percentage of patients with COVID-19 become at least transiently positive for aPL and that these aPL are potentially pathogenic.

    Acutely Altered Mental Status as the Main Clinical Presentation of Multiple Strokes MESHD Strokes HP in Critically Ill Patients With COVID-19.

    Authors: Carolina Díaz-Pérez; Carmen Ramos; Alberto López-Cruz; José Muñoz Olmedo; Jimena Lázaro González; Enrique de Vega-Ríos; Carmen González-Ávila; Carlos Hervás; Santiago Trillo; José Vivancos

    doi:10.21203/rs.3.rs-31769/v1 Date: 2020-05-26 Source: ResearchSquare

    Background and aims: Cerebral infarction MESHD in COVID-19 patients might be associated with a hypercoagulable state related to a systemic inflammatory response. Its diagnosis might be challenging. We present two critically ill patients with COVID-19 who presented acutely altered mental status as the main manifestation of multiple strokes MESHD strokes HP.Methods:Clinical presentation and diagnostic work-up of the patients.Results:Two patients in their sixties were hospitalized with a bilateral pneumonia MESHD pneumonia HP COVID-19. They developed respiratory failure HP and were admitted to ICU for mechanical ventilation and intense medical treatment. They were started on low-molecular-weight heparin since admission. Their laboratory results showed lymphopenia MESHD lymphopenia HP and increased levels of C-reactive protein and D-dimer. Case 1 developed hypofibrinogenemia HP and presented several cutaneous lesions with biopsy features of thrombotic vasculopathy. Case 2 was performed a CT pulmonary angiogram at ICU showing a bilateral pulmonary embolism MESHD pulmonary embolism HP. When waking up, both patients were conscious but with a remarkable global altered mental status without focal neurological deficits. A brain MRI revealed multiple acute bilateral ischemic lesions with areas of hemorrhagic transformation in both patients (Case 1: affecting the left frontal and temporal lobes and both occipital lobes; Case 2: affecting both frontal and left occipital lobes). Cardioembolic source and acquired antiphospholipid syndrome MESHD were ruled out. COVID-19-associated coagulopathy was suspected as the possible main etiology of the strokes MESHD strokes HP.Conclusion:Acutely altered mental status might be the main manifestation of multiple brain infarctions MESHD in critically ill COVID-19 patients. It should be specially considered in those with suspected COVID-19-associated coagulopathy. Full-dose anticoagulation and clinical-radiological monitoring might reduce their neurological consequences.

    THE PATHOGENESIS OF THROMBOEMBOLIC DISEASE MESHD IN COVID-19 PATIENTS: COULD BE A CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME MESHD?

    Authors: Giulia Previtali; Michela Seghezzi; Valentina Moioli; Aurelio Sonzogni; Roberto Marozzi; Lorenzo Cerutti; Rudi Ravasio; Andrea Gianatti; Giovanni Guerra; Maria Grazia Alessio

    doi:10.1101/2020.04.30.20086397 Date: 2020-05-06 Source: medRxiv

    Background The most severely COVID-19 patients need intensive care and show increased risk of thromboembolic events. Although some patients meet the diagnostic criteria for the Disseminated Intravascular Coagulation MESHD Disseminated Intravascular Coagulation HP, the pathogenesis of the diffuse thrombotic status remains unclear. The aim of the present study is to evaluate the presence of antiphospholipid antibodies SERO (aPL) in sera of deceased patients with autoptic proven thrombotic microangiopathy MESHD to evaluate if some patients may have developed Catastrophic Antiphospholipid Syndrome MESHD (CAPS). Methods Thirty-five patients were enrolled. The available medical history, comorbidities, therapies, laboratory and autopsy findings were collected post-mortem from clinical records. IgA, IgG and IgM anti cardiolipin (ACA) and anti {beta}2 glycoprotein 1 ({beta}2GP1) antibodies, IgG and IgM SERO anti phosphatidylserine/prothrombin (PS/PT) antibodies were tested SERO for all the patients. Results 3/35 (8.6%) patients were slightly positive for aPL: one for ACA IgG and two for ACA IgM but values were low (< 3X the cut off). No patients tested positive for ACA IgA neither for {beta}2GP1 isotypes. 3/35 (8.6%) patients were positive for PS/PT, one for IgG and two for IgM, but values were less than 2X the cut off. No patients showed simultaneous positivity for ACA and PS/ PT. Conclusions It is difficult to categorize the vascular events into a conventional disease MESHD: we did not find significant association with anti-phospholipid antibodies SERO. It is most likely that several factors contribute to trigger the hypercoagulability HP status and the thromboembolism MESHD thromboembolism HP but, on the basis our results, CAPS is probably not involved into the pathogenesis of these phenomena.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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