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      Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis

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          Abstract

          Background

          Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients.

          Methods

          Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2 −∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6).

          Results

          While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group ( p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group ( p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls ( p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls ( p < 0.0001 for both of them).

          Conclusions

          Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

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          Most cited references54

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          Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

          Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+ T cells or CD4+ T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.
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            A Review of Coronavirus Disease-2019 (COVID-19)

            There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and 3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 d. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Diagnosis is by demonstration of the virus in respiratory secretions by special molecular tests. Common laboratory findings include normal/ low white cell counts with elevated C-reactive protein (CRP). The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The virus spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. The global impact of this new epidemic is yet uncertain.
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              IL-6 in inflammation, immunity, and disease.

              Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions. Although its expression is strictly controlled by transcriptional and posttranscriptional mechanisms, dysregulated continual synthesis of IL-6 plays a pathological effect on chronic inflammation and autoimmunity. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody was developed. Various clinical trials have since shown the exceptional efficacy of tocilizumab, which resulted in its approval for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Moreover, tocilizumab is expected to be effective for other intractable immune-mediated diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
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                Author and article information

                Contributors
                m.rostamii@gmail.com
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                11 December 2021
                11 December 2021
                2021
                : 21
                : 462
                Affiliations
                [1 ]GRID grid.411600.2, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                [2 ]GRID grid.411600.2, Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                [3 ]GRID grid.411600.2, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                [4 ]GRID grid.411600.2, Proteomics Research Center, Faculty of Paramedical Sciences, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran
                [5 ]Department of Gastroenterology, MidCentral DHB, Palmerston North, New Zealand
                [6 ]GRID grid.414125.7, ISNI 0000 0001 0727 6809, Research Laboratories, , Bambino Gesù Children’s Hospital-IRCCS, ; Rome, Italy
                Author information
                http://orcid.org/0000-0003-2495-1831
                Article
                2056
                10.1186/s12876-021-02056-1
                8665626
                34895167
                f5c5a28e-d8c4-4f0a-9ffd-de840967953a
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 14 August 2021
                : 7 December 2021
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Gastroenterology & Hepatology
                sars-cov-2,covid-19,celiac disease,gene expression,t-lymphocytes,regulatory,interleukin-6

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