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      Latent Rheumatic, Thyroid and Phospholipid Autoimmunity in Hospitalized Patients with COVID-19

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          Abstract

          Autoimmune responses mediated by autoantibodies have been previously observed in SARS-CoV-2 infection. Herein, we evaluated the presence of rheumatic, thyroid and phospholipid autoantibodies in sera samples from 120 hospitalized patients with COVID-19 in comparison to pre-pandemic samples from 100 healthy individuals. In addition, to estimate the frequency of these autoantibodies in COVID-19, a meta-analysis of selected articles was conducted. Hospitalized patients with COVID-19 displayed latent autoimmunity mainly mediated by a high frequency of anti-thyroid peroxidase antibodies, rheumatoid factor (RF), anti-cyclic citrullinated peptide third generation antibodies, antinuclear antibodies (ANAs), IgM β2-glycoprotein I (β2GP1) and IgM anti-cardiolipin antibodies. The meta-analysis confirmed our results, being RF and ANAs the most common autoantibodies. In addition, cluster analysis revealed that those patients with high positivity for RF, IgM β2GP1 antibodies and ANAs had a longer hospital stay, required more vasopressors during hospitalization, and were more likely to develop critical disease. These data suggest that latent autoimmunity influences the severity of COVID-19, and support further post-COVID studies in order to evaluate the development of overt autoimmunity.

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          Autoantibodies against type I IFNs in patients with life-threatening COVID-19

          Paul Bastard, Lindsey B. Rosen, Qian Zhang … (2021)
          The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science, this issue p. eabd4570, p. eabd4585; see also p. 404
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            Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis

            Jonathan A. C. Sterne, Srinivas Murthy, Janet V. Diaz … (2021)
            Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support.
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              Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes

              Daniel E. Leisman, Lukas Ronner, Rachel Pinotti … (2020)
              The description of a so-called cytokine storm in patients with COVID-19 has prompted consideration of anti-cytokine therapies, particularly interleukin-6 antagonists. However, direct systematic comparisons of COVID-19 with other critical illnesses associated with elevated cytokine concentrations have not been reported. In this Rapid Review, we report the results of a systematic review and meta-analysis of COVID-19 studies published or posted as preprints between Nov 1, 2019, and April 14, 2020, in which interleukin-6 concentrations in patients with severe or critical disease were recorded. 25 COVID-19 studies (n=1245 patients) were ultimately included. Comparator groups included four trials each in sepsis (n=5320), cytokine release syndrome (n=72), and acute respiratory distress syndrome unrelated to COVID-19 (n=2767). In patients with severe or critical COVID-19, the pooled mean serum interleukin-6 concentration was 36·7 pg/mL (95% CI 21·6–62·3 pg/mL; I 2=57·7%). Mean interleukin-6 concentrations were nearly 100 times higher in patients with cytokine release syndrome (3110·5 pg/mL, 632·3–15 302·9 pg/mL; p<0·0001), 27 times higher in patients with sepsis (983·6 pg/mL, 550·1–1758·4 pg/mL; p<0·0001), and 12 times higher in patients with acute respiratory distress syndrome unrelated to COVID-19 (460 pg/mL, 216·3–978·7 pg/mL; p<0·0001). Our findings question the role of a cytokine storm in COVID-19-induced organ dysfunction. Many questions remain about the immune features of COVID-19 and the potential role of anti-cytokine and immune-modulating treatments in patients with the disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Transl Autoimmun
                Journal ID (iso-abbrev): J Transl Autoimmun
                Title: Journal of Translational Autoimmunity
                Publisher: The Author(s). Published by Elsevier B.V.
                ISSN (Electronic): 2589-9090
                Publication date PMC-release: 2 March 2021
                Publication date (Electronic): 2 March 2021
                Electronic Location Identifier: 100091
                Affiliations
                [a ]Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogota, Colombia
                [b ]Clínica Del Occidente, Bogota, Colombia
                [c ]Hospital Universitario Mayor – Méderi, Universidad Del Rosario, Bogota, Colombia
                [d ]School of Medicine and Health Sciences, Universidad Del Rosario, Bogota, Colombia
                Author notes
                [∗ ]Corresponding author. PhD Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Carrera 24 # 63c 69, 110010 Bogota, Colombia
                [1]

                Both authors contributed equally

                Article
                Publisher Item ID: S2589-9090(21)00011-3 Publisher ID: 100091
                DOI: 10.1016/j.jtauto.2021.100091
                PMC ID: 7920824
                PubMed ID: 33681751
                SO-VID: 1a916c20-9822-4def-bd38-c0e2764231e6
                Copyright © © 2021 The Author(s)
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 12 February 2021
                Date accepted : 21 February 2021
                Categories
                Subject: Article

                Keywords: covid-19,sars-cov-2,autoimmunity,latent autoimmunity,clusters
                Data availability:
                Keywords: covid-19, sars-cov-2, autoimmunity, latent autoimmunity, clusters

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