Microbiome research in patients with post COVID syndrome and gastrointestinal lesions to improve health and reduce the duration of rehabilitation

Microbiome research in patients with post COVID syndrome and gastrointestinal lesions to improve health and reduce the duration of rehabilitation  

IRN AP09563198

Relevance: In connection with the relevance of the issue under study and the direct influence of the composition of the intestinal microbiome on the course of COVID-19 disease, diagnosis of coronavirus infection in the gastrointestinal tract and the high role of the microbiome in enhancing immunity, a detailed study of the main genetic characteristics of the intestinal microbiome in coronavirus infection and systemic damage to the body is necessary. a patient after suffering COVID-19 (post Covid syndrome, manifested by complications of the respiratory, cardiovascular, digestive and excretory systems of organs during SARS-CoV-2 viral infection).

The results obtained will improve the clinical protocols for the management of patients with previous coronavirus infection and will make it possible to correct the state of the body after systemic damage and shorten the rehabilitation period. Thus, to reduce the prevalence of post Covid syndrome and reduce the workload of the domestic health care system during the global pandemic for coronavirus infection COVID-19 (SARS-CoV-2).

Objective of the project: A comprehensive study of various indicators of the gastrointestinal tract microbiome and predictors of assessing the health of patients after a coronavirus infection to improve rehabilitation.

Expected results

As a result, solving the set goal and objectives, the following results will be obtained:

1) A retrospective, epidemiological analysis of cases of infection with coronavirus infection will be carried out, and an assessment of the prevalence of symptoms associated with disorders of the digestive system;

2) The main genetic characteristics of the intestinal microbiome in coronavirus infection and systemic damage to the patient's body after suffering from COVID-19 (postcoid syndrome, manifested by complications of the respiratory, cardiovascular, digestive and excretory systems of organs during SARS-CoV-2 viral infection) will be studied;

3) Recommendations will be presented to improve clinical protocols for the management of patients and revise the terms of rehabilitation of patients with a history of CVI based on the results obtained during the study of the intestinal microbiome.

Also, according to the research results, 1 (one) article will be published, accepted for publication or submitted to a peer-reviewed scientific publication included in the Science Citation Index Expanded or Social Science Citation Index in the Web of Science database and (or) having a CiteScore percentile in the Scopus database not less than 35 (thirty five).

Achieved results: As part of a retrospective, epidemiological analysis of cases of coronavirus infection, and an assessment of the prevalence of symptoms associated with disorders of the digestive system, the following results were obtained: It has now been established that the initial stage of infection is the penetration of the SARS-CoV-2 virus into cells -targets by attaching type II angiotensin converting enzyme (ACE2) receptors in the epithelial cells of the upper respiratory tract. The upper esophagus, epithelial cells of the stomach, duodenum, ileum, and colon also contain a large number of ACE2 receptors, which may indicate the possibility of the SARS-CoV-2 virus affecting the cells of the gastrointestinal tract (GIT). In our study, among all recruited patients, the most frequent were patients with pneumonia - 82% of cases, with obesity of 1-3 degrees and diseases of the circulatory system (BSC) - 52%, with disorders of the gastrointestinal tract (GIT) - 37%, sugar diabetes of the 2nd degree - 20%. In biotopes of the small and large intestine obtained during colonoscopy / autopsy, the virus was also detected, and in stool samples it was present for more than 70 days after the onset of the first symptoms of the disease. The main symptom of the Indian strain of coronavirus is gastrointestinal upset. Disorders of the gastrointestinal tract, manifested in the form of - diarrhea, nausea, abdominal pain, vomiting. The incidence of COVID-19 gastrointestinal symptoms varies widely, ranging from about 2-10% to 20%. According to other sources, approximately 3.34-11.4% of patients with COVID-19 may experience gastrointestinal symptoms. In patients with diarrhea against the background of COVID-19, an increased level of fecal calprotectin was detected, which indicates the presence of inflammatory changes in the intestine against the background of SARS-CoV-2 infection.

As part of the study of the main genetic characteristics of the intestinal microbiome in coronavirus infection and systemic damage to the patient's body after suffering COVID-19 (post-coccygeal syndrome, manifested by complications of the respiratory, cardiovascular, digestive and excretory systems of organs during SARS-CoV-2 viral infection), the following were obtained Results: In the course of the analysis of the compositional composition of the intestinal microbiota of the study participants using 16S rRNA as a marker, more than 35 species of bacteria were identified, most of which belong to four types: Firmicutes, Actinobacteria, Bacteroides and Proteobacteria, which, according to literature data, corresponds to information on intestinal microflora of a conditionally healthy adult. Representatives of other phyla have also been identified, including Fusobacteria, Elusimicrobia, Synergistetes, Spirochaetes, and Verrucomicrobia. Strains of Streptophyta (Eukaryota) have also been found. Violations of the intestinal microbiota composition are possible in many diseases of both the gastrointestinal tract and other organs and systems (for example, obesity, diabetes mellitus, cardiovascular, autoimmune, mental illnesses, etc.). It was found that the intestinal microbiota of patients with COVID-19, who did not take any antibacterial drugs until hospitalization, was characterized by a higher prevalence of pathogenic and opportunistic bacteria, such as Clostridium hathewayi, Bacteroides nordii, Actinomyces viscosus. The intestinal microbiota of patients with a severe course of COVID-19 was distinguished by an initially higher representation of such strains as Clostridium hathewayi, Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii. Firmicuts contain the class Clostridia and Bacillus. It was also found that the presence of bacteria of the phylum Firmicutes, especially Clostridium ramosum and Clostridium hathewayi, correlated with the severity of COVID-19 infection. In contrast, the abundance of bacteria Alistipes onderdonkii and Faecalibacterium prausnitzii was inversely correlated with the severity of the COVID-19 infection. Bacteroides can be potentially protective against the SARS-CoV-2 virus. A positive correlation was found between the presence of the bacterium Erysipelotrichaceae bacterium and the level of SARS-CoV-2 viral load in the fecal microbiota. Some studies have shown that bacteria from the genus Erysipelotrichaceae may be involved in inflammatory bowel disease.

As part of the task of improving clinical protocols for managing patients and revising the timing of rehabilitation of patients with CVI, based on the results obtained during the study of the intestinal microbiome, the following results were obtained: The most significant in the era of the COVID-19 pandemic were the protective and immunomodulatory functions of the microbiota. The anti-inflammatory and immunomodulatory properties of some probiotic strains can improve the functioning of the intestinal-lung axis and, possibly, prevent the development, mitigate the course of COVID-19, and increase the effectiveness of vaccination against SARS-CoV-2. The intake of probiotic strains, the effectiveness and safety of which is confirmed by evidence-based medicine data in the treatment and prevention of ARVI / diarrhea (L. rhamnosus, L. plantarum, L. acidophilus, B. bifidum, S. boulardii, Streptococcus thermophilus), can be recommended for patients from the group risk, as well as for patients with COVID-19, respectively, as a prophylactic and / or adjuvant agent. Bacteriotherapy using probiotic strains Streptococcus thermophilus, L. acidophilus, L. helveticus, L. paracasei, L. plantarum, L. brevis, B. lactis, B. lactis contributed to the relief of diarrhea, remission of other symptoms in almost all patients taking probiotics, compared with patients who did not receive these drugs. In addition, the risk of developing respiratory failure was eight times lower in patients receiving oral bacteriotherapy. The prevalence of respiratory failure and the mortality rate of patients transferred to the intensive care unit and who did not receive oral probiotics were significantly higher than those in patients who took beneficial bacteria. Based on the findings, the researchers believe that probiotics can significantly improve the clinical condition of patients infected with SARS-CoV-2.

Research group:

Publications under the project in 2021:

As part of the implementation of the project task, it took part in international conferences, teleconferences and seminars regarding the research topic:

- participation in the work of the online teleconference "Euro-Asian teleconference" COVID-19 - about the important ", January 21, 2021, Kiev, Ukraine;

- participation in the seminar "The first year of the COVID-19 pandemic in Russia (April 2020-March 2021)" June 3, 2021, Higher School of Economics, National Research University, Moscow, Russian Federation;

- participation in the online teleconference "New wave of COVID-19: the Delta strain is another threat", July 23, 2021, Center for the Development of Professional Qualifications of Medical Workers at the Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan;

- Online course on research methods of the European Academy of Science and Research, August 5, 2021, Hamburg, Germany;

- participation in the work of the online teleconference “Euro-Asian teleconference. Delta strain. Experience of international experts ", September 16, 2021, Center for the Development of Professional Qualifications of Medical Workers at the Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan;

- participation in the International online conference "Topical issues of biological safety in modern conditions", September 22-23, 2021, Nur-Sultan, Kazakhstan (International online conference "Topical issues of biological safety in modern conditions", September 22-23, 2021, Nur-Sultan, Kazakhstan);

- participation in the II Kazakhstan Congress of Infectious Diseases "Infectious Diseases in the Context of Globalization: Challenges and Solutions", October 7-8, 2021, Nur-Sultan, Kazakhstan.