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Feng J, Chen J, Li X, Ren X, Chen J, Li Z, Wu Y, Zhang Z, Yang R, Li J, Lu Y, Liu Y. Mendelian randomization and Bayesian model averaging of autoimmune diseases and Long COVID. Front Genet 2024; 15:1383162. [PMID: 39005628 PMCID: PMC11240141 DOI: 10.3389/fgene.2024.1383162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 05/27/2024] [Indexed: 07/16/2024] Open
Abstract
Background Following COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated. Methods Summary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn's disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA). Results The evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00-1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01-1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03-1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD. Conclusion This MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.
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Affiliation(s)
- Jieni Feng
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiankun Chen
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, China
| | - Xiaoya Li
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaolei Ren
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Junxu Chen
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zuming Li
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuan Wu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhongde Zhang
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Rongyuan Yang
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, China
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiqiang Li
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, China
| | - Yue Lu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuntao Liu
- The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, China
- State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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Ruiz MA, Kaiser Junior RL, Piron-Ruiz L, Pinho TS, Castiglioni L, de Quadros LG. COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation. World J Hematol 2024; 11:89084. [DOI: 10.5315/wjh.v11.i1.89084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 01/11/2024] [Accepted: 03/26/2024] [Indexed: 04/29/2024] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019 (COVID-19), a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases. Crohn's disease (CD) is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota. Patients who underwent hematopoietic stem cell transplantation (HSCT) are considered at risk for COVID-19.
AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous, non-myeloablative HSCT.
METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19. For two patients there were reports of the occurrence of two infectious episodes. Parameters related to HSCT, such as time elapsed since the procedure, vaccination status, CD status before and after infection, and clinical manifestations resulting from COVID-19, were evaluated.
RESULTS Among the patients with COVID-19, three, who underwent Auto HSCT less than six months ago, relapsed and one, in addition to the CD symptoms, started to present thyroid impairment with positive anti-TPO. Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission. Nine patients reported late symptoms that may be related to COVID-19. There were no deaths, and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.
CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms, we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.
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Affiliation(s)
- Milton Artur Ruiz
- Department of Bone Marrow Transplantation, Associação Portuguesa de Beneficência, São José do Rio Preto SP 15090 470, Brazil
| | | | - Lilian Piron-Ruiz
- Department of Bone Marrow Transplantation, Beneficência Portuguesa Hospital, São José do Rio Preto 15090 470, São Paulo, Brazil
| | - Tainara Souza Pinho
- Department of Bone Marrow Transplantation, Beneficência Portuguesa Hospital, São José do Rio Preto 15090 470, São Paulo, Brazil
| | - Lilian Castiglioni
- FAMERP, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto 15090 000, São Paulo, Brazil
| | - Luiz Gustavo de Quadros
- Beneficência Portuguesa Hospital, ABC Medical School, São Bernardo 15015 110, São Paulo, Brazil
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Lim SH, Ju HJ, Han JH, Lee JH, Lee WS, Bae JM, Lee S. Autoimmune and Autoinflammatory Connective Tissue Disorders Following COVID-19. JAMA Netw Open 2023; 6:e2336120. [PMID: 37801317 PMCID: PMC10559181 DOI: 10.1001/jamanetworkopen.2023.36120] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/22/2023] [Indexed: 10/07/2023] Open
Abstract
Importance Multiple cases of autoimmune and autoinflammatory diseases after COVID-19 have been reported. However, their incidences and risks have rarely been quantified. Objective To investigate the incidences and risks of autoimmune and autoinflammatory connective tissue disorders after COVID-19. Design, Setting, and Participants This was a retrospective population-based study conducted between October 8, 2020, and December 31, 2021, that used nationwide data from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort and included individuals who received a diagnosis of COVID-19 via polymerase chain reaction testing and a control group with no evidence of COVID-19 identified from National Health Insurance Service of Korea cohort. Data analysis was conducted from September 2022 to August 2023. Exposures Receipt of diagnosis of COVID-19. Main Outcomes and Measures The primary outcomes were the incidence and risk of autoimmune and autoinflammatory connective tissue disorders following COVID-19. A total of 32 covariates, including demographics, socioeconomic statuses, lifestyle factors, and comorbidity profiles, were balanced through inverse probability weighting. The incidences and risks of autoimmune and autoinflammatory connective tissue disorders were compared between the groups using multivariable Cox proportional hazard analyses. Results A total of 354 527 individuals with COVID-19 (mean [SD] age, 52.24 [15.55] years; 179 041 women [50.50%]) and 6 134 940 controls (mean [SD] age, 52.05 [15.63] years; 3 074 573 women [50.12%]) were included. The risks of alopecia areata (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.05-1.19), alopecia totalis (aHR, 1.74; 95% CI, 1.39-2.17), antineutrophil cytoplasmic antibody-associated vasculitis (aHR, 2.76; 95% CI, 1.64-4.65), Crohn disease (aHR, 1.68; 95% CI, 1.31-2.15), and sarcoidosis (aHR, 1.59; 95% CI, 1.00-2.52) were higher in the COVID-19 group. The risks of alopecia totalis, psoriasis, vitiligo, vasculitis, Crohn disease, ulcerative colitis, rheumatoid arthritis, adult-onset Still disease, Sjögren syndrome, ankylosing spondylitis, and sarcoidosis were associated with the severity of COVID-19. Conclusions and Relevance In this retrospective cohort study, COVID-19 was associated with a substantial risk for autoimmune and autoinflammatory connective tissue disorders, indicating that long-term management of patients with COVID-19 should include evaluation for such disorders.
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Affiliation(s)
- Sung Ha Lim
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Hyun Jeong Ju
- Department of Dermatology, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Ju Hee Han
- Department of Dermatology, Seoul St Mary’s Hospital College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji Hae Lee
- Department of Dermatology, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Won-Soo Lee
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Jung Min Bae
- Department of Dermatology, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Solam Lee
- Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- Department of Preventive Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
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Morita A, Imagawa K, Tagawa M, Sakamoto N, Takada H. Case report: Immunological characteristics of de novo ulcerative colitis in a child post COVID-19. Front Immunol 2023; 14:1107808. [PMID: 36875135 PMCID: PMC9978098 DOI: 10.3389/fimmu.2023.1107808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 02/07/2023] [Indexed: 02/18/2023] Open
Abstract
The pathological mechanisms of de novo inflammatory bowel disease (IBD) following SARS-CoV-2 infection are unknown. However, cases of coexisting IBD and multisystem inflammatory syndrome in children (MIS-C), which occurs 2-6 weeks after SARS-CoV-2 infection, have been reported, suggesting a shared underlying dysfunction of immune responses. Herein, we conducted the immunological analyses of a Japanese patient with de novo ulcerative colitis following SARS-CoV-2 infection based on the pathological hypothesis of MIS-C. Her serum level of lipopolysaccharide-binding protein, a microbial translocation marker, was elevated with T cell activation and skewed T cell receptor repertoire. The dynamics of activated CD8+ T cells, including T cells expressing the gut-homing marker α4β7, and serum anti-SARS-CoV-2 spike IgG antibody titer reflected her clinical symptoms. These findings suggest that SARS-CoV-2 infection may trigger the de novo occurrence of ulcerative colitis by impairing intestinal barrier function, T cell activation with a skewed T cell receptor repertoire, and increasing levels of anti-SARS-CoV-2 spike IgG antibodies. Further research is needed to clarify the association between the functional role of the SARS-CoV-2 spike protein as a superantigen and ulcerative colitis.
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Affiliation(s)
- Atsushi Morita
- Department of Pediatrics, University of Tsukuba Hospital, Tsukuba, Japan
| | - Kazuo Imagawa
- Department of Pediatrics, University of Tsukuba Hospital, Tsukuba, Japan.,Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Manabu Tagawa
- Department of Pediatrics, University of Tsukuba Hospital, Tsukuba, Japan.,Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Noriaki Sakamoto
- Department of Diagnostic Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Hidetoshi Takada
- Department of Pediatrics, University of Tsukuba Hospital, Tsukuba, Japan.,Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
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Tong CW, Jiwane A. A complicated case of terminal ileitis post-COVID-19 infection requiring bowel resection. J Surg Case Rep 2022; 2022:rjac457. [PMID: 36348639 PMCID: PMC9629472 DOI: 10.1093/jscr/rjac457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 09/07/2022] [Indexed: 11/06/2022] Open
Abstract
Since the beginning of the COVID-19 pandemic, there have been reports of children developing systemic hyperinflammatory response to COVID-19 infection, known as Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS). Here we would like to discuss a case of a 15-year-old male with PIMS-TS presenting as complicated terminal ileitis, requiring ileocaecal resection. Histopathologic findings of the ileocaecal specimen revealed thickened bowel mucosa, with features of granulomatous inflammation similar to Crohn’s disease, without features of intestinal vasculitis or viral particles. His post-operative course was complicated by fresh rectal bleeding, requiring urgent blood transfusion and endoscopy. Source of bleeding was not identified and his bleeding self-resolved. Gut biopsies of the remaining bowel taken during endoscopy were normal. Although this case suggests that the inflammatory process is focal to the terminal ileum with a good short-term prognosis, further follow-up is required to assess for long-term effects and risks of bowel disease.
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Affiliation(s)
- Chai Wei Tong
- Department of Paediatric Surgery, Sydney Children’s Hospital , Randwick, New South Wales , Australia
| | - Ashish Jiwane
- Department of Paediatric Surgery, Sydney Children’s Hospital , Randwick, New South Wales , Australia
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Tursi A, Lopetuso LR, Vetrone LM, Gasbarrini A, Papa A. SARS-CoV-2 infection as a potential trigger factor for de novo occurrence of inflammatory bowel disease. Eur J Gastroenterol Hepatol 2022; 34:883-884. [PMID: 35802531 PMCID: PMC9245529 DOI: 10.1097/meg.0000000000002379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 03/20/2022] [Indexed: 12/10/2022]
Affiliation(s)
- Antonio Tursi
- Territorial Gastroenterology Service, ASL BAT, Andria
- Department of Medicine and Surgery, Post-Graduate School of Digestive Disease, Catholic University, Rome
| | - Loris Riccardo Lopetuso
- Department of Medicine and Ageing Sciences, “G. d’Annunzio” University of Chieti- Pescara
- Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, Chieti
- CEMAD, Digestive Disease Center, Fondazione Policlinico A. Gemelli, IRCCS
| | | | - Antonio Gasbarrini
- CEMAD, Digestive Disease Center, Fondazione Policlinico A. Gemelli, IRCCS
- Department of Medicine and Surgery, Catholic University, Rome, Italy
| | - Alfredo Papa
- CEMAD, Digestive Disease Center, Fondazione Policlinico A. Gemelli, IRCCS
- Department of Medicine and Surgery, Catholic University, Rome, Italy
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