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      Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study

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          Abstract

          Background

          There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants.

          Methods

          This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models.

          Findings

          Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78–3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50–4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68–3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47–2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02–3.28), Sjögren's syndrome (aHR:2.62, 95% CI:2.29–3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26–4.36), Behçet's disease (aHR:2.32, 95% CI:1.38–3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36–3.57), vasculitis (aHR:1.96, 95% CI:1.74–2.20), psoriasis (aHR:2.91, 95% CI:2.67–3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72–1.84), celiac disease (aHR:2.68, 95% CI:2.51–2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51–2.85) and mortality (aHR:1.20, 95% CI:1.16–1.24).

          Interpretation

          COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms.

          Funding

          doi 10.13039/501100011913, Kaohsiung Veterans General Hospital; (KSVGH111-113).

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          Dysregulation of immune response in patients with COVID-19 in Wuhan, China

          Chuan Qin, Luoqi Zhou, Ziwei Hu … (2020)
          Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. Methods Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The data of laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between severe and non-severe patients. Results Of the 452 patients with COVID-19 recruited, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough and myalgia. Severe cases tend to have lower lymphocytes counts, higher leukocytes counts and neutrophil-lymphocyte-ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels, and lower level of helper T cells in severe group. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 also have lower level of regulatory T cells, and more obviously damaged in severe cases. Conclusions The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.
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            Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

            I Hamming, W Timens, MLC Bulthuis … (2004)
            Abstract Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS‐CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin‐converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS‐CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS‐CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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              Is Open Access

              The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement

              Eric Benchimol, Liam Smeeth, Astrid Guttmann … (2015)
              Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting.
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                Author and article information

                Journal
                Journal ID (nlm-ta): eClinicalMedicine
                Journal ID (iso-abbrev): EClinicalMedicine
                Title: eClinicalMedicine
                Publisher: The Authors. Published by Elsevier Ltd.
                ISSN (Electronic): 2589-5370
                Publication date PMC-release: 10 January 2023
                Publication date (Print): February 2023
                Publication date (Electronic): 10 January 2023
                Volume: 56
                Page: 101783
                Affiliations
                [a ]Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
                [b ]Department of Recreation and Sports Management, Tajen University, Pintung, Taiwan
                [c ]Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
                [d ]Harvard T.H. Chan School of Public Health, Boston, MA, USA
                [e ]Department of Medical Research and Education, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
                [f ]Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
                [g ]Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital Taitung Branch, Taiwan
                [h ]College of Science and Engineering, National Taitung University, Taitung, Taiwan
                [i ]College of Health and Nursing, Meiho University, Pingtung, Taiwan
                [j ]Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
                [k ]Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
                [l ]Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
                Author notes
                [∗ ]Corresponding author. No. 1000, Gengsheng Rd., Taitung City, Taitung County, Taiwan.
                [∗∗ ]Corresponding author. No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, Taiwan.
                [m]

                Contributed equally as first authors.

                Article
                Publisher Item ID: S2589-5370(22)00512-0 Publisher ID: 101783
                DOI: 10.1016/j.eclinm.2022.101783
                PMC ID: 9830133
                PubMed ID: 36643619
                SO-VID: 53a01cca-5ab0-48c7-91b3-fe1b359601a7
                Copyright © © 2022 The Authors
                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 : 26 July 2022
                Date revision received : 14 November 2022
                Date accepted : 28 November 2022
                Categories
                Subject: Articles

                Keywords: covid-19,sars-cov-2 infection,autoimmune disease,electronic health records,cohort study
                Data availability:
                Keywords: covid-19, sars-cov-2 infection, autoimmune disease, electronic health records, cohort study

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