HAC (Russian)
RSCI (Russian)
Ulrichsweb (Ulrich’s Periodicals Directory)
Scientific Indexing Services

Significance of indicators of intestinal permeability, the state of the microbiota in the development of gastroenterological manifestations in the treatment of patients with a new coronavirus infection (COVID-19)

DOI: https://doi.org/10.29296/25877305-2022-01-14

A. Ratnikova(1, 4); Professor V. Grinevich(2), MD; Professor V. Ratnikov(1, 3), MD; Professor
K. Kozlov(2), MD; V. Gorelov(1), Candidate of Medical Sciences; Professor Yu. Kravchuk(2), MD (1)L.G.
Sokolov North-West District Scientific and Clinical Center Federal Medical and Biological Agency, Saint
Petersburg (2)S.M. Kirov Military Medical Academy, Saint Petersburg (3)Saint Petersburg State University,
Saint Petersburg 4«Pervaya Liniya», Health Care Resort, Saint Petersburg

The effectiveness of combating the pandemic of a new coronavirus infection (COVID-19) is based on a detailed analysis of the pathogenetic features of the course of SARS-CoV-2 infection, including an assessment of the state of the microbiota and intestinal permeability during the treatment of COVID-19 patients. Purpose: To study the dynamics of intestinal permeability, qualitative and quantitative composition of microbiota in the treatment of COVID-19 patients. Material and methods: The study was performed in 80 patients with COVID-19, whose average age was 45 years, 19 of them had mild and 61 had moderate severity of the disease. The scope of the examination included traditional clinical, clinical and laboratory, biochemical, instrumental and radiation studies, as well as original methods for studying intestinal permeability and microbiota. Rebamipid was used as an element of complex pathogenetic therapy in the treatment of 41 patients (51.3%). Results and conclusions: The clinical, laboratory and radiation semiotics of COVID-19 were studied, the interdependence of manifestations of systemic inflammation, changes in the intestinal microbiome in patients with mild and moderate severity was revealed. The characteristic dynamics of the concentration levels of proinflammatory cytokines, insulin, fecal calprotectin and zonulin, reflecting the peculiarities of changes in intestinal permeability during COVID-19 treatment, has been established. The necessity of correction of intestinal permeability in the treatment of COVID-19 patients has been proved, the effectiveness of rebamipid when used at the inpatient stage of treatment and with further use in the process of outpatient rehabilitation has been confirmed.

infectious diseases
new coronavirus infection
gastrointestinal tract (gastrointestinal tract)
intestinal permeability
fecal calprotectin

  1. Karim S.S.A., Karim Q.A. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet. 2021; 398 (10317): 2126–8. DOI: 10.1016/S0140-6736(21)02758-6
  2. Vremennye metodicheskie rekomendatsii. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infektsii (COVID-19). Versija 14 (27.12.2021). M., 2021; 233 s. [Temporary methodological recommendations. Prevention, diagnosis and treatment of a new coronavirus infection (COVID-19). Version 14 (27.12.2021). M., 2021; 233 p. (in Russ.)].
  3. Gudima G.O., Haitov R.M., Kudlaj D.A. i dr. Molekuljarno-immunologicheskie aspekty diagnostiki, profilaktiki i lechenija koronavirusnoj infektsii. Immunologija. 2021; 42 (3): 198–210 [Gudima G.O., Khaitov R.M., Kudlay D.A. et al. Molecular immunological aspects of diagnostics, prevention and treatment of coronavirus infection. Immunologiya. 2021; 42 (3): 198–210 (in Russ.)]. DOI: 10.33029/0206-4952-2021-42-3-198-210
  4. Ganesh B., Rajakumar T., Malathi M. et al. Epidemiology and pathobiology of SARS-CoV-2 (COVID-19) in comparison with SARS, MERS: An updated overview of current knowledge and future perspectives. Clin Epidemiol Glob Health. 2021; 10: 100694. DOI: 10.1016/j.cegh.2020.100694
  5. Huang C., Wang Y., Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497–506. DOI: 10.1016/S0140-6736(20)30183-5
  6. Ahlawat S., Asha, Sharma K.K. Immunological co-ordination between gut and lungs in SARS-CoV-2 infection. Virus Res. 2020; 286: 198103. DOI: 10.1016/j.virusres.2020.198103
  7. Caviglia G.P., Dughera F., Ribaldone D.G. et al. Serum zonulin in patients with inflammatory bowel disease: a pilot study. Minerva Med. 2019; 110 (2): 95–100. DOI: 10.23736/S0026-4806.18.05787-7
  8. Llorens S., Nava E., Muñoz-López M. et al. Neurological symptoms of COVID-19: the zonulin hypothesis. Front Immunol. 2021; 12: 665300. DOI: 10.3389/fimmu.2021.665300
  9. Di Micco S., Musella S., Sala M. et al. Peptide derivatives of the zonulin inhibitor larazotide (AT1001) as potential anti SARS-CoV-2: molecular modelling, synthesis and bioactivity evaluation. Int J Mol Sci. 2021; 22: 9427. DOI: 10.3390/ijms22179427
  10. Oliva A., Cammisotto V., Cangemi R. et al. Low-grade endotoxemia and thrombosis in COVID-19. Clin Transl Gastroenterol. 2021; 12 (6): e00348. DOI: 10.14309/ctg.0000000000000348
  11. Giron L.B., Dweep H., Yin X. et al. Severe COVID-19 is fueled by disrupted gut barrier integrity. medRxiv. 2020; 11 (9): 13.20231209. DOI: doi.org/10.1101/2020.11.13.20231209
  12. Zuo T., Zhang F., Lui G.C.Y. et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020; 159 (3): 944–55.e8. DOI: 10.1053/j.gastro.2020.05.048
  13. Yeoh Y.K., Zuo T., Lui G.C. et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021; 70 (4): 698–706. DOI: 10.1136/gutjnl-2020-323020
  14. Naito Y., Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol. 2010; 4 (3): 261–70. DOI: 10.1586/ egh.10.25
  15. Jaafar M.H., Safi S.Z., Tan M.P. et al. Efficacy of rebamipide in organic and functional dyspepsia: a systematic review and meta-analysis. Dig Dis Sci. 2018; 63 (5): 1250–60. DOI: 10.1007/s10620-017-4871-9
  16. Moroz E.V., Karateev A.E. Rebamipid: effektivnaja medikamentoznaja profilaktika NPVP-enteropatii vozmozhna. Sovremennaja revmatologija. 2016; 10 (4): 97–105 [Moroz E.V., Karateev A.E. Rebamipide: effective drug prevention of NSAID enteropathy is possible. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2016; 10 (4): 97–105 (in Russ.)]. DOI: 10.14412/1996-7012-2016-4-97-105
  17. Nagljadnaja meditsinskaja statistika: uchebnoe posobie. A. Petri, K. Sebin; per. s angl. pod red. V.P. Leonova. 3-e izd., pererab i dop. M.: GEOTAR-Media, 2019; 216 s. [Visual medical statistics: textbook. A.V. Petri, K. Sabin; transl. from English. Ed. V.P. Leonova. 3rd ed., revised and supplementary. M.: GEOTAR-Media, 2019; 216 p. (in Russ.)].
  18. Kljushin D.A., Petunin Ju.I. Dokazatel'naja meditsina. Primenenie statisticheskih metodov. M.: OOO «I.D. Vil'jams», 2017; 316 s. [Klyushin D.A., Petunin Yu.I. Evidence-based medicine. Application of statistical methods. M.: LLC «I.D. Williams», 2017; 316 p. (in Russ.)].
  19. Mamaev A.N., Kudlaj D.A. Statisticheskie metody v meditsine. M.: Prakticheskaja meditsina, 2021; 136 s. [Mamaev A.N., Kudlay D.A. Statisticheskie metody v meditsine. M.: Prakticheskaya meditsina, 2021; 136 s. (in Russ.)].
  20. Eastin C., Eastin T. Clinical characteristics of coronavirus disease 2019 in China. J Emerg Med. 2020; 58 (4): 711–2. DOI: 10.1016/ j.jemermed.2020.04.004
  21. Kim G.H., Lee H.L., Joo M.K. et al. Efficacy and safety of rebamipide versus its new formulation, AD-203, in patients with erosive gastritis: A randomized, double-blind, active control, noninferiority, multicenter, phase 3 study. Gut Liver. 2021; 15 (6): 841–50. DOI: 10.5009/gnl20338
  22. Lei P., Zhang L, Han P. et al. Liver injury in patients with COVID-19: clinical profiles, CT findings, the correlation of the severity with liver injury. Hepatol Int. 2020; 14 (5): 733–42. DOI: 10.1007/s12072-020-10087-1