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Published in: BMC Gastroenterology 1/2023

Open Access 01-12-2023 | COVID-19 | Research

The risk for celiac disease after Covid-19 infection

Authors: Jesper Lexner, Ylva Lindroth, Klas Sjöberg

Published in: BMC Gastroenterology | Issue 1/2023

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Abstract

Background

Celiac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD.

Patients and methods

All patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016–2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden.

Results

During the Covid-19 pandemic (March 2020 – December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 – February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 – -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD − 1.3, 95% CI -8.5–5.9, p = 0.75).

Conclusions

Our results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.
Literature
2.
go back to reference Lohi S, Mustalahti K, Kaukinen K, Laurila K, Collin P, Rissanen H, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther. 2007;26(9):1217–25.CrossRefPubMed Lohi S, Mustalahti K, Kaukinen K, Laurila K, Collin P, Rissanen H, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther. 2007;26(9):1217–25.CrossRefPubMed
3.
go back to reference Rubio-Tapia A, Kyle RA, Kaplan EL, Johnson DR, Page W, Erdtmann F, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology. 2009;137(1):88–93.CrossRefPubMed Rubio-Tapia A, Kyle RA, Kaplan EL, Johnson DR, Page W, Erdtmann F, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology. 2009;137(1):88–93.CrossRefPubMed
4.
go back to reference Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, et al. Global prevalence of Celiac Disease: systematic review and Meta-analysis. Clin Gastroenterol Hepatol. 2018;16(6):823–36e2.CrossRefPubMed Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, et al. Global prevalence of Celiac Disease: systematic review and Meta-analysis. Clin Gastroenterol Hepatol. 2018;16(6):823–36e2.CrossRefPubMed
5.
go back to reference Ivarsson A, Myléus A, Norström F, van der Pals M, Rosén A, Högberg L, et al. Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics. 2013;131(3):e687–94.CrossRefPubMed Ivarsson A, Myléus A, Norström F, van der Pals M, Rosén A, Högberg L, et al. Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics. 2013;131(3):e687–94.CrossRefPubMed
6.
go back to reference Sandström O, Rosén A, Lagerqvist C, Carlsson A, Hernell O, Högberg L, et al. Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in sequential testing. J Pediatr Gastroenterol Nutr. 2013;57(4):472–6.CrossRefPubMed Sandström O, Rosén A, Lagerqvist C, Carlsson A, Hernell O, Högberg L, et al. Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in sequential testing. J Pediatr Gastroenterol Nutr. 2013;57(4):472–6.CrossRefPubMed
7.
go back to reference Kurppa K, Laitinen A, Agardh D. Coeliac disease in children with type 1 diabetes. Lancet Child Adolesc Health. 2018;2(2):133–43.CrossRefPubMed Kurppa K, Laitinen A, Agardh D. Coeliac disease in children with type 1 diabetes. Lancet Child Adolesc Health. 2018;2(2):133–43.CrossRefPubMed
8.
go back to reference Andrén Aronsson C, Lee HS, Koletzko S, Uusitalo U, Yang J, Virtanen SM, et al. Effects of Gluten Intake on Risk of Celiac Disease: a case-control study on a swedish birth cohort. Clin Gastroenterol Hepatol. 2016;14(3):403–9e3.CrossRefPubMed Andrén Aronsson C, Lee HS, Koletzko S, Uusitalo U, Yang J, Virtanen SM, et al. Effects of Gluten Intake on Risk of Celiac Disease: a case-control study on a swedish birth cohort. Clin Gastroenterol Hepatol. 2016;14(3):403–9e3.CrossRefPubMed
9.
go back to reference Canova C, Zabeo V, Pitter G, Romor P, Baldovin T, Zanotti R, et al. Association of maternal education, early infections, and antibiotic use with celiac disease: a population-based birth cohort study in northeastern Italy. Am J Epidemiol. 2014;180(1):76–85.CrossRefPubMed Canova C, Zabeo V, Pitter G, Romor P, Baldovin T, Zanotti R, et al. Association of maternal education, early infections, and antibiotic use with celiac disease: a population-based birth cohort study in northeastern Italy. Am J Epidemiol. 2014;180(1):76–85.CrossRefPubMed
10.
go back to reference Mårild K, Kahrs CR, Tapia G, Stene LC, Størdal K. Infections and risk of celiac disease in childhood: a prospective nationwide cohort study. Am J Gastroenterol. 2015;110(10):1475–84.CrossRefPubMed Mårild K, Kahrs CR, Tapia G, Stene LC, Størdal K. Infections and risk of celiac disease in childhood: a prospective nationwide cohort study. Am J Gastroenterol. 2015;110(10):1475–84.CrossRefPubMed
11.
go back to reference Myléus A, Hernell O, Gothefors L, Hammarström ML, Persson L, Stenlund H, et al. Early infections are associated with increased risk for celiac disease: an incident case-referent study. BMC Pediatr. 2012;12:194.CrossRefPubMedPubMedCentral Myléus A, Hernell O, Gothefors L, Hammarström ML, Persson L, Stenlund H, et al. Early infections are associated with increased risk for celiac disease: an incident case-referent study. BMC Pediatr. 2012;12:194.CrossRefPubMedPubMedCentral
12.
go back to reference Simre K, Uibo O, Peet A, Tillmann V, Kool P, Hämäläinen AM, et al. Exploring the risk factors for differences in the cumulative incidence of coeliac disease in two neighboring countries: the prospective DIABIMMUNE study. Dig Liver Dis. 2016;48(11):1296–301.CrossRefPubMed Simre K, Uibo O, Peet A, Tillmann V, Kool P, Hämäläinen AM, et al. Exploring the risk factors for differences in the cumulative incidence of coeliac disease in two neighboring countries: the prospective DIABIMMUNE study. Dig Liver Dis. 2016;48(11):1296–301.CrossRefPubMed
13.
go back to reference Kemppainen KM, Lynch KF, Liu E, Lönnrot M, Simell V, Briese T, et al. Factors that increase risk of Celiac Disease Autoimmunity after a gastrointestinal infection in early life. Clin Gastroenterol Hepatol. 2017;15(5):694–702e5.CrossRefPubMed Kemppainen KM, Lynch KF, Liu E, Lönnrot M, Simell V, Briese T, et al. Factors that increase risk of Celiac Disease Autoimmunity after a gastrointestinal infection in early life. Clin Gastroenterol Hepatol. 2017;15(5):694–702e5.CrossRefPubMed
14.
go back to reference Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, Emery L, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006;101(10):2333–40.CrossRefPubMed Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, Emery L, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006;101(10):2333–40.CrossRefPubMed
15.
go back to reference Kahrs CR, Chuda K, Tapia G, Stene LC, Mårild K, Rasmussen T, et al. Enterovirus as trigger of coeliac disease: nested case-control study within prospective birth cohort. BMJ. 2019;364:l231.CrossRefPubMedPubMedCentral Kahrs CR, Chuda K, Tapia G, Stene LC, Mårild K, Rasmussen T, et al. Enterovirus as trigger of coeliac disease: nested case-control study within prospective birth cohort. BMJ. 2019;364:l231.CrossRefPubMedPubMedCentral
16.
go back to reference Lindfors K, Lin J, Lee HS, Hyöty H, Nykter M, Kurppa K, et al. Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children: the TEDDY study. Gut. 2020;69(8):1416–22.CrossRefPubMed Lindfors K, Lin J, Lee HS, Hyöty H, Nykter M, Kurppa K, et al. Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children: the TEDDY study. Gut. 2020;69(8):1416–22.CrossRefPubMed
17.
go back to reference Oikarinen M, Puustinen L, Lehtonen J, Hakola L, Simell S, Toppari J, et al. Enterovirus Infections are Associated with the development of Celiac Disease in a birth cohort study. Front Immunol. 2020;11:604529.CrossRefPubMed Oikarinen M, Puustinen L, Lehtonen J, Hakola L, Simell S, Toppari J, et al. Enterovirus Infections are Associated with the development of Celiac Disease in a birth cohort study. Front Immunol. 2020;11:604529.CrossRefPubMed
18.
go back to reference Auricchio R, Cielo D, de Falco R, Galatola M, Bruno V, Malamisura B et al. Respiratory Infections and the Risk of Celiac Disease. Pediatrics. 2017;140(4). Auricchio R, Cielo D, de Falco R, Galatola M, Bruno V, Malamisura B et al. Respiratory Infections and the Risk of Celiac Disease. Pediatrics. 2017;140(4).
19.
go back to reference Beyerlein A, Donnachie E, Ziegler AG. Infections in early life and development of Celiac Disease. Am J Epidemiol. 2017;186(11):1277–80.CrossRefPubMed Beyerlein A, Donnachie E, Ziegler AG. Infections in early life and development of Celiac Disease. Am J Epidemiol. 2017;186(11):1277–80.CrossRefPubMed
20.
go back to reference Tjernberg AR, Ludvigsson JF. Children with celiac disease are more likely to have attended hospital for prior respiratory syncytial virus infection. Dig Dis Sci. 2014;59(7):1502–8.CrossRefPubMed Tjernberg AR, Ludvigsson JF. Children with celiac disease are more likely to have attended hospital for prior respiratory syncytial virus infection. Dig Dis Sci. 2014;59(7):1502–8.CrossRefPubMed
21.
go back to reference Kårhus LL, Gunnes N, Størdal K, Bakken IJ, Tapia G, Stene LC, et al. Influenza and risk of later celiac disease: a cohort study of 2.6 million people. Scand J Gastroenterol. 2018;53(1):15–23.CrossRefPubMed Kårhus LL, Gunnes N, Størdal K, Bakken IJ, Tapia G, Stene LC, et al. Influenza and risk of later celiac disease: a cohort study of 2.6 million people. Scand J Gastroenterol. 2018;53(1):15–23.CrossRefPubMed
23.
go back to reference D’Amico F, Baumgart DC, Danese S, Peyrin-Biroulet L. Diarrhea during COVID-19 infection: Pathogenesis, Epidemiology, Prevention, and management. Clin Gastroenterol Hepatol. 2020;18(8):1663–72.CrossRefPubMedPubMedCentral D’Amico F, Baumgart DC, Danese S, Peyrin-Biroulet L. Diarrhea during COVID-19 infection: Pathogenesis, Epidemiology, Prevention, and management. Clin Gastroenterol Hepatol. 2020;18(8):1663–72.CrossRefPubMedPubMedCentral
24.
go back to reference Dotan A, Muller S, Kanduc D, David P, Halpert G, Shoenfeld Y. The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev. 2021;20(4):102792.CrossRefPubMedPubMedCentral Dotan A, Muller S, Kanduc D, David P, Halpert G, Shoenfeld Y. The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev. 2021;20(4):102792.CrossRefPubMedPubMedCentral
25.
go back to reference Liu Y, Sawalha AH, Lu Q. COVID-19 and autoimmune diseases. Curr Opin Rheumatol. 2021;33(2):155–62.CrossRefPubMed Liu Y, Sawalha AH, Lu Q. COVID-19 and autoimmune diseases. Curr Opin Rheumatol. 2021;33(2):155–62.CrossRefPubMed
26.
go back to reference Lai H, Yang M, Sun M, Pan B, Wang Q, Wang J, et al. Risk of incident diabetes after COVID-19 infection: a systematic review and meta-analysis. Metabolism. 2022;137:155330.CrossRefPubMedPubMedCentral Lai H, Yang M, Sun M, Pan B, Wang Q, Wang J, et al. Risk of incident diabetes after COVID-19 infection: a systematic review and meta-analysis. Metabolism. 2022;137:155330.CrossRefPubMedPubMedCentral
27.
go back to reference Trovato CM, Montuori M, Pietropaoli N, Oliva S. COVID-19 and celiac disease: a pathogenetic hypothesis for a celiac outbreak. Int J Clin Pract. 2021;75(9):e14452.CrossRefPubMed Trovato CM, Montuori M, Pietropaoli N, Oliva S. COVID-19 and celiac disease: a pathogenetic hypothesis for a celiac outbreak. Int J Clin Pract. 2021;75(9):e14452.CrossRefPubMed
29.
go back to reference Ludvigsson JF, Brandt L, Montgomery SM, Granath F, Ekbom A. Validation study of villous atrophy and small intestinal inflammation in swedish biopsy registers. BMC Gastroenterol. 2009;9:19.CrossRefPubMedPubMedCentral Ludvigsson JF, Brandt L, Montgomery SM, Granath F, Ekbom A. Validation study of villous atrophy and small intestinal inflammation in swedish biopsy registers. BMC Gastroenterol. 2009;9:19.CrossRefPubMedPubMedCentral
30.
go back to reference Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136–60.CrossRefPubMed Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136–60.CrossRefPubMed
32.
go back to reference Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3). Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3).
33.
go back to reference Bergman D, King J, Lebwohl B, Clements MS, Roelstraete B, Kaplan GG, et al. Two waves of coeliac disease incidence in Sweden: a nationwide population-based cohort study from 1990 to 2015. Gut. 2022;71(6):1088–94.CrossRefPubMed Bergman D, King J, Lebwohl B, Clements MS, Roelstraete B, Kaplan GG, et al. Two waves of coeliac disease incidence in Sweden: a nationwide population-based cohort study from 1990 to 2015. Gut. 2022;71(6):1088–94.CrossRefPubMed
34.
go back to reference Lingel H, Meltendorf S, Billing U, Thurm C, Vogel K, Majer C, et al. Unique autoantibody prevalence in long-term recovered SARS-CoV-2-infected individuals. J Autoimmun. 2021;122:102682.CrossRefPubMedPubMedCentral Lingel H, Meltendorf S, Billing U, Thurm C, Vogel K, Majer C, et al. Unique autoantibody prevalence in long-term recovered SARS-CoV-2-infected individuals. J Autoimmun. 2021;122:102682.CrossRefPubMedPubMedCentral
35.
go back to reference Ferrara F, Quaglia S, Caputo I, Esposito C, Lepretti M, Pastore S, et al. Anti-transglutaminase antibodies in non-coeliac children suffering from infectious diseases. Clin Exp Immunol. 2010;159(2):217–23.CrossRefPubMedPubMedCentral Ferrara F, Quaglia S, Caputo I, Esposito C, Lepretti M, Pastore S, et al. Anti-transglutaminase antibodies in non-coeliac children suffering from infectious diseases. Clin Exp Immunol. 2010;159(2):217–23.CrossRefPubMedPubMedCentral
36.
go back to reference Crocco M, Calvi A, Canzoneri F, Malerba F, Zampatti N, Chiaro A et al. The Influence of SARS-CoV-2 Pandemic on the Diagnosis of Celiac Disease and Clinical Practice in Pediatric Gastroenterology. Nutrients. 2023;15(3). Crocco M, Calvi A, Canzoneri F, Malerba F, Zampatti N, Chiaro A et al. The Influence of SARS-CoV-2 Pandemic on the Diagnosis of Celiac Disease and Clinical Practice in Pediatric Gastroenterology. Nutrients. 2023;15(3).
38.
go back to reference Thurm C, Reinhold A, Borucki K, Kahlfuss S, Feist E, Schreiber J et al. Homologous and Heterologous Anti-COVID-19 Vaccination Does Not Induce New-Onset Formation of Autoantibodies Typically Accompanying Lupus Erythematodes, Rheumatoid Arthritis, Celiac Disease and Antiphospholipid Syndrome. Vaccines (Basel). 2022;10(2). Thurm C, Reinhold A, Borucki K, Kahlfuss S, Feist E, Schreiber J et al. Homologous and Heterologous Anti-COVID-19 Vaccination Does Not Induce New-Onset Formation of Autoantibodies Typically Accompanying Lupus Erythematodes, Rheumatoid Arthritis, Celiac Disease and Antiphospholipid Syndrome. Vaccines (Basel). 2022;10(2).
39.
go back to reference Hemming-Harlo M, Lähdeaho ML, Mäki M, Vesikari T. Rotavirus Vaccination does not increase type 1 diabetes and May decrease Celiac Disease in Children and Adolescents. Pediatr Infect Dis J. 2019;38(5):539–41.CrossRefPubMed Hemming-Harlo M, Lähdeaho ML, Mäki M, Vesikari T. Rotavirus Vaccination does not increase type 1 diabetes and May decrease Celiac Disease in Children and Adolescents. Pediatr Infect Dis J. 2019;38(5):539–41.CrossRefPubMed
40.
go back to reference Kamerlin SCL, Kasson PM. Managing Coronavirus Disease 2019 Spread with Voluntary Public Health Measures: Sweden as a case study for Pandemic Control. Clin Infect Dis. 2020;71(12):3174–81.CrossRefPubMedPubMedCentral Kamerlin SCL, Kasson PM. Managing Coronavirus Disease 2019 Spread with Voluntary Public Health Measures: Sweden as a case study for Pandemic Control. Clin Infect Dis. 2020;71(12):3174–81.CrossRefPubMedPubMedCentral
41.
go back to reference Fredriksson M, Hallberg A. COVID-19 testing in Sweden during 2020-Split Responsibilities and Multi-Level Challenges. Front Public Health. 2021;9:754861.CrossRefPubMedPubMedCentral Fredriksson M, Hallberg A. COVID-19 testing in Sweden during 2020-Split Responsibilities and Multi-Level Challenges. Front Public Health. 2021;9:754861.CrossRefPubMedPubMedCentral
Metadata
Title
The risk for celiac disease after Covid-19 infection
Authors
Jesper Lexner
Ylva Lindroth
Klas Sjöberg
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2023
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-023-02795-3

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