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DOI: 10.1055/a-2180-9872
Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination
Abstract
Background and study aims Gut infection is common during acute COVID-19, and persistent SARS-CoV-2 gut infection has been reported months after the initial infection, potentially linked to long-COVID syndrome. This study tested the incidence of persistent gut infection in patients with a history of COVID-19 undergoing endoscopic examination.
Patients and methods Endoscopic biopsies were prospectively collected from patients with previous COVID-19 infection undergoing upper or lower gastrointestinal endoscopy (UGE or LGE). Immunohistochemistry was used to detect the presence of persistent SARS-CoV-2 nucleocapsid proteins.
Results A total of 166 UGEs and 83 LGE were analyzed. No significant differences were observed between patients with positive and negative immunostaining regarding the number of previous COVID-19 infections, time since the last infection, symptoms, or vaccination status. The incidence of positive immunostaining was significantly higher in UGE biopsies than in LGE biopsies (37.34% vs. 16.87%, P=0.002). Smokers showed a significantly higher incidence of positive immunostaining in the overall cohort and UGE and LGE subgroups (P <0.001). Diabetic patients exhibited a significantly higher incidence in the overall cohort (P=0.002) and UGE subgroup (P=0.022), with a similar trend observed in the LGE subgroup (P=0.055).
Conclusions Gut mucosal tissues can act as a long-term reservoir for SARS-CoV-2, retaining viral particles for months following the primary COVID-19 infection. Smokers and individuals with diabetes may be at an increased risk of persistent viral gut infection. These findings provide insights into the dynamics of SARS-CoV-2 infection in the gut and have implications for further research.
Publication History
Received: 17 July 2023
Accepted after revision: 21 September 2023
Accepted Manuscript online:
25 September 2023
Article published online:
05 January 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
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References
- 1 World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19. Accessed January 01, 2000 at: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19
- 2 World Health Organization. Weekly epidemiological update on COVID-19. Accessed January 01, 2000 at: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19
- 3 Vanella G, Capurso G, Burti C. et al. Gastrointestinal mucosal damage in patients with COVID-19 undergoing endoscopy: an international multicentre study. BMJ Open Gastroenterol 2021; 8: e000578
- 4 Brooks EF, Bhatt AS. The gut microbiome: a missing link in understanding the gastrointestinal manifestations of COVID-19?. Cold Spring Harb Mol Case Stud 2021; 7: a006031
- 5 Neuberger M, Jungbluth A, Irlbeck M. et al. Duodenal tropism of SARS-CoV-2 and clinical findings in critically ill COVID-19 patients. Infection 2022; 50: 1111-1120
- 6 Xiao F, Tang M, Zheng X. et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020; 158: 1831-1833.e3
- 7 Lin L, Jiang X, Zhang Z. et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut 2020; 69: 997-1001
- 8 Martin TA, Wan DW, Hajifathalian K. et al. Gastrointestinal bleeding in patients with coronavirus disease 2019: a matched case-control study. Am J Gastroenterol 2020; 115: 1609-1616
- 9 Cherne MD, Gentry AB, Nemudraia A. et al. Severe acute respiratory syndrome coronavirus 2 is detected in the gastrointestinal tract of asymptomatic endoscopy patients but is unlikely to pose a significant risk to healthcare personnel. Gastro Hep Advances 2022; 1: 844-852
- 10 Wu Y, Guo C, Tang L. et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol 2020; 5: 434-435
- 11 Britton GJ, Chen-Liaw A, Cossarini F. et al. Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19. Sci Rep 2021; 11: 13308
- 12 Zang R, Castro MFG, McCune BT. et al. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci Immunol 2020; 5: eabc3582
- 13 Hany M, Zidan A, Gaballa M. et al. Lingering SARS-CoV-2 in gastric and gallbladder tissues of patients with previous COVID-19 infection undergoing bariatric surgery. Obes Surg 2023; 33: 139-148
- 14 Cheruiyot I, Sehmi P, Ngure B. et al. Laparoscopic surgery during the COVID-19 pandemic: detection of SARS-COV-2 in abdominal tissues, fluids, and surgical smoke. Langenbecks Arch Surg 2021; 406: 1007-1014
- 15 Meringer H, Mehandru S. Gastrointestinal post-acute COVID-19 syndrome. Nat Rev Gastroenterol Hepatol 2022; 19: 345-346
- 16 Zollner A, Koch R, Jukic A. et al. Postacute COVID-19 is characterized by gut viral antigen persistence in inflammatory bowel diseases. Gastroenterology 2022; 163: 495-506.e8
- 17 Arostegui D, Castro K, Schwarz S. et al. Persistent SARS-CoV-2 nucleocapsid protein presence in the intestinal epithelium of a pediatric patient 3 months after acute infection. JPGN Reports 2022; 3: e152
- 18 Mehandru S, Merad M. Pathological sequelae of long-haul COVID. Nat Immunol 2022; 23: 194-202
- 19 Cheung CCL, Goh D, Lim X. et al. Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues from five recovered patients with COVID-19. Gut 2022; 71: 226-229
- 20 Sandal S, Tanas Ö, Karabulut Ş. et al. A histopathological view at the long-term effects of covid-19 on the gastrointestinal system in children: a single center experience. Turk J Pediatr 2023; 65: 416
- 21 Nguyen NN, Mutnal MB, Gomez RR. et al. Correlation of ELISA method with three other automated serological tests for the detection of anti-SARS-CoV-2 antibodies. PLoS One 2020; 15: e0240076
- 22 Gralnek IM, Hassan C, Beilenhoff U. et al. ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemic. Endoscopy 2020; 52: 483-490
- 23 Mauro A, De Grazia F, Lenti MV. et al. Upper gastrointestinal bleeding in COVID-19 inpatients: Incidence and management in a multicenter experience from Northern Italy. Clin Res Hepatol Gastroenterol 2021; 45: 101521
- 24 Massironi S, Viganò C, Dioscoridi L. et al. Endoscopic findings in patients infected with 2019 novel coronavirus in Lombardy, Italy. Clin Gastroenterol Hepatol 2020; 18: 2375-2377
- 25 Zhou P, Yang X-L, Wang X-G. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579: 270-273
- 26 Hoffmann M, Kleine-Weber H, Schroeder S. et al. SARS-CoV-2 cell entry depends on ace2 and tmprss2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271-280.e8
- 27 Lamers MM, Beumer J, Van Der Vaart J. et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020; 369: 50-54
- 28 Zuo T, Zhang F, Lui GCY. et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020; 159: 944-955.e8
- 29 Budden KF, Gellatly SL, Wood DLA. et al. Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol 2017; 15: 55-63
- 30 Mehta P, McAuley DF, Brown M. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033-1034
- 31 Carfì A, Bernabei R, Landi F. et al. Persistent symptoms in patients after acute COVID-19. JAMA 2020; 324: 603-605
- 32 Raveendran AV, Misra A. Post COVID-19 syndrome (“Long COVID”) and diabetes: challenges in diagnosis and management: diabetes & metabolic syndrome. Clin Res Rev 2021; 15: 102235
- 33 Fändriks L. The angiotensin II type 2 receptor and the gastrointestinal tract. J Renin Angiotensin Aldosterone Syst 2010; 11: 43-48
- 34 Lee S, Yoon GY, Myoung J. et al. Robust and persistent SARS-CoV-2 infection in the human intestinal brush border expressing cells. Emerg Microbe Infect 2020; 9: 2169-2179
- 35 Jacobs JJL. Persistent SARS-2 infections contribute to long COVID-19. Medical Hypotheses 2021; 149: 110538
- 36 Bai F, Tomasoni D, Falcinella C. et al. Female gender is associated with long COVID syndrome: a prospective cohort study. Clin Microbiol Infect 2022; 28: 611.e9-611.e16
- 37 Barthélémy H, Mougenot E, Duracinsky M. et al. Smoking increases the risk of post-acute COVID-19syndrome: Results from a French community-based survey. Tob Induc Dis 2022; 20: 1-10
- 38 Su Y, Yuan D, Chen DG. et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell 2022; 185: 881-895.e20
- 39 Masiá M, Fernández-González M, Telenti G. et al. Durable antibody response one year after hospitalization for COVID-19: A longitudinal cohort study. J Autoimmunity 2021; 123: 102703