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      Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review

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          Abstract

          Introduction

          The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of gut microbiota in COVID-19 patients compared with healthy individuals may have potential value as a diagnostic and/or prognostic biomarker for the disease. Also, therapeutic interventions affecting gut microbial flora may open new horizons in the treatment of COVID-19 patients and accelerating their recovery.

          Methods

          A systematic search was conducted for relevant studies published from December 2019 to December 2021 using Pubmed/Medline, Embase, and Scopus. Articles containing the following keywords in titles or abstracts were selected: “SARS-CoV-2” or “COVID-19” or “Coronavirus Disease 19” and “gastrointestinal microbes” or “dysbiosis” or “gut microbiota” or “gut bacteria” or “gut microbes” or “gastrointestinal microbiota”.

          Results

          Out of 1,668 studies, 22 articles fulfilled the inclusion criteria and a total of 1,255 confirmed COVID-19 patients were examined. All included studies showed a significant association between COVID-19 and gut microbiota dysbiosis. The most alteration in bacterial composition of COVID-19 patients was depletion in genera Ruminococcus, Alistipes, Eubacterium, Bifidobacterium, Faecalibacterium, Roseburia, Fusicathenibacter, and Blautia and enrichment of Eggerthella, Bacteroides, Actinomyces, Clostridium, Streptococcus, Rothia, and Collinsella. Also, some gut microbiome alterations were associated with COVID-19 severity and poor prognosis including the increment of Bacteroides, Parabacteroides, Clostridium, Bifidobacterium, Ruminococcus, Campylobacter, Rothia, Corynebacterium, Megasphaera, Enterococcus, and Aspergillus spp. and the decrement of Roseburia, Eubacterium, Lachnospira, Faecalibacterium, and the Firmicutes/Bacteroidetes ratio.

          Conclusion

          Our study showed a significant change of gut microbiome composition in COVID-19 patients compared with healthy individuals. This great extent of impact has proposed the gut microbiota as a potential diagnostic, prognostic, and therapeutic strategy for COVID-19. There is much evidence about this issue, and it is expected to be increased in near future.

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          Most cited references143

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            A pneumonia outbreak associated with a new coronavirus of probable bat origin

            Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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              Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                04 March 2022
                2022
                04 March 2022
                : 12
                : 804644
                Affiliations
                [1] 1 Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [2] 2 Department of Biomedical Sciences, University of Sassari , Sassari, Italy
                [3] 3 Struttura Complessa (SC), Microbiologia e Virologia, Azienda Ospedaliera Universitaria , Sassari, Italy
                [4] 4 Clinician Scientist of Dental Materials and Restorative Dentistry, School of Dentistry, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [5] 5 Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [6] 6 Division of Pulmonary and Critical Care, College of Medicine-Jacksonville, University of Florida , Jacksonville, FL, United States
                Author notes

                Edited by: Yongqun Oliver He, University of Michigan, United States

                Reviewed by: Almagul Kushugulova, Nazarbayev University, Kazakhstan; Haihe Wang, Harbin Medical University at Daqing, China

                *Correspondence: Mehdi Mirsaeidi, m.mirsaeidi@ 123456ufl.edu ; Parnian Jamshidi, P.jamshidi@ 123456sbmu.ac.ir ; Mohammad Javad Nasiri, mj.nasiri@ 123456hotmail.com

                †These authors share first authorship

                This article was submitted to Microbiome in Health and Disease, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2022.804644
                8930898
                35310853
                344944b5-a45f-4bb4-9a6f-3bb1bd062c9b
                Copyright © 2022 Farsi, Tahvildari, Arbabi, Vazife, Sechi, Shahidi Bonjar, Jamshidi, Nasiri and Mirsaeidi

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 October 2021
                : 07 February 2022
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 144, Pages: 14, Words: 7283
                Categories
                Cellular and Infection Microbiology
                Review

                Infectious disease & Microbiology
                covid-19,sars-cov-2,gastrointestinal microbiome,dysbiosis,prognosis,diagnosis,gut microbiota,therapeutic

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