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Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients.

ABSTRACT: Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. While antibodies to glycans could recognize the virus and influence the clinical outcome, little is known about their roles. Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses.

SUBMITTER: Butler DL

PROVIDER: S-EPMC9291223 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients.

Butler Dorothy L DL Imberti Luisa L Quaresima Virginia V Fiorini Chiara C Gildersleeve Jeffrey C JC

PNAS nexus 20220617 3

Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. While antibodies to glycans could recognize the virus and influence the clinical outcome, little is known about their roles. Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. COVID-19 patients had numerous autoantibodies to self-glycans, including antigangliosid ...[more]

PMID: 35865361

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Project description:COVID-19 significantly impairs survival rates among hematological patients when compared to the general population. Our prospective multicentre project analyzed early administration of anti-SARS-CoV-2 spike protein neutralizing monoclonal antibodies (NmAbs) - bamlanivimab (72%) and casirivimab/imdevimab (28%) - efficacy among hematological patients with early-stage COVID-19. Mortality rate was compared to a control cohort of 575 SARS-CoV-2 positive hematological patients untreated with any specific anti-COVID-19 therapy. 88 hematological patients with lymphomas, acute leukemias, and myeloma as their most frequent underlying diagnoses (72%) were evaluated with a 97 days median follow-up after NmAb administration. One third of patients (32%) were treated with an anti-CD20 monoclonal antibody before COVID-19 diagnosis. Median time between first COVID-19 symptom and NmAb administration was 2 days. When administering NmAb, 29%, 57%, 11%, 2%, and 1% of our patients had asymptomatic, mild, moderate, severe, and critical degrees of COVID-19, respectively. 80% of baseline asymptomatic patients remained asymptomatic following NmAb administration. Median duration of COVID-19 symptoms after NmAb administration was 2.5 days. Progression to severe/critical COVID-19 occurred among a total of 17% (15/88) of our cases and numerically higher with bamlanivimab versus casirivimab/imdevimab (21% vs. 8%; p = 0.215), and myelomas (29%), lymphomas (17%) and acute leukemias (18%), respectively. During final follow-up, nine deaths (10%) were recorded - all after bamlanivimab (p = 0.056) with 8% attributed to COVID-19. Regarding "remdesivir/convalescent plasma naïve" patients, COVID-19 mortality rates were significantly lower in our NmAbs treated cohort compared to the control cohort of untreated SARS-CoV-2 positive hematological patients (6% vs. 16%, p = 0.020), respectively. Our study validated the safety and efficacy of NmAbs early use among hematological patients with newly diagnosed early-stage COVID-19 in terms of alleviating infection course and decreasing mortality. Results confirmed a more positive effect of a casirivimab/imdevimab combination versus bamlanivimab monotherapy.

Dataset Information

Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients.

Publications

Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients.

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