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      Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic

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          Abstract

          The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

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          Virological assessment of hospitalized patients with COVID-2019

          Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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            SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

            To the Editor: The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, and has been declared a public health emergency of international concern by the World Health Organization, may progress to a pandemic associated with substantial morbidity and mortality. SARS-CoV-2 is genetically related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries in 2002–2003. 1 The epidemic of SARS-CoV was successfully contained through public health interventions, including case detection and isolation. Transmission of SARS-CoV occurred mainly after days of illness 2 and was associated with modest viral loads in the respiratory tract early in the illness, with viral loads peaking approximately 10 days after symptom onset. 3 We monitored SARS-CoV-2 viral loads in upper respiratory specimens obtained from 18 patients (9 men and 9 women; median age, 59 years; range, 26 to 76) in Zhuhai, Guangdong, China, including 4 patients with secondary infections (1 of whom never had symptoms) within two family clusters (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The patient who never had symptoms was a close contact of a patient with a known case and was therefore monitored. A total of 72 nasal swabs (sampled from the mid-turbinate and nasopharynx) (Figure 1A) and 72 throat swabs (Figure 1B) were analyzed, with 1 to 9 sequential samples obtained from each patient. Polyester flock swabs were used for all the patients. From January 7 through January 26, 2020, a total of 14 patients who had recently returned from Wuhan and had fever (≥37.3°C) received a diagnosis of Covid-19 (the illness caused by SARS-CoV-2) by means of reverse-transcriptase–polymerase-chain-reaction assay with primers and probes targeting the N and Orf1b genes of SARS-CoV-2; the assay was developed by the Chinese Center for Disease Control and Prevention. Samples were tested at the Guangdong Provincial Center for Disease Control and Prevention. Thirteen of 14 patients with imported cases had evidence of pneumonia on computed tomography (CT). None of them had visited the Huanan Seafood Wholesale Market in Wuhan within 14 days before symptom onset. Patients E, I, and P required admission to intensive care units, whereas the others had mild-to-moderate illness. Secondary infections were detected in close contacts of Patients E, I, and P. Patient E worked in Wuhan and visited his wife (Patient L), mother (Patient D), and a friend (Patient Z) in Zhuhai on January 17. Symptoms developed in Patients L and D on January 20 and January 22, respectively, with viral RNA detected in their nasal and throat swabs soon after symptom onset. Patient Z reported no clinical symptoms, but his nasal swabs (cycle threshold [Ct] values, 22 to 28) and throat swabs (Ct values, 30 to 32) tested positive on days 7, 10, and 11 after contact. A CT scan of Patient Z that was obtained on February 6 was unremarkable. Patients I and P lived in Wuhan and visited their daughter (Patient H) in Zhuhai on January 11 when their symptoms first developed. Fever developed in Patient H on January 17, with viral RNA detected in nasal and throat swabs on day 1 after symptom onset. We analyzed the viral load in nasal and throat swabs obtained from the 17 symptomatic patients in relation to day of onset of any symptoms (Figure 1C). Higher viral loads (inversely related to Ct value) were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza 4 and appears different from that seen in patients infected with SARS-CoV. 3 The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection 5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV. How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.
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              Detection of SARS-CoV-2 in Different Types of Clinical Specimens

              This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.
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                Author and article information

                Journal
                Gut
                Gut
                gutjnl
                gut
                Gut
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0017-5749
                1468-3288
                September 2020
                3 July 2020
                3 July 2020
                : 69
                : 9
                : 1555-1563
                Affiliations
                [1 ] departmentDigestive Disease Center , Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore , Rome, Italy
                [2 ] departmentDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction , Faculty of Medicine, Imperial College London , London, UK
                [3 ] departmentDivision of Gastroenterology , Alpert Medical School of Brown University , Providence, Rhode Island, USA
                [4 ] Finch Therapeutics Group , Somerville, Massachusetts, USA
                [5 ] departmentCenter for Microbiota Analysis and Therapy, Department of Medical Microbiology , Leiden University Medical Centre , Leiden, The Netherlands
                [6 ] departmentNetherlands Donor Feces Bank , Leiden University Medical Center , Leiden, The Netherlands
                [7 ] departmentCenter for Gut Microbiota Research, Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences , Chinese University of Hong Kong , Hong Kong, Hong Kong
                [8 ] departmentMicrobiome Treatment Centre , University of Birmingham , Birmingham, UK
                [9 ] departmentDepartment of Gastroenterology , University Hospitals Birmingham NHS Foundation Trust , Birmingham, UK
                [10 ] departmentGastroenterology , Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts, USA
                [11 ] departmentService de Gastroenterologie; French Group of Fecal Microbiota Transplantation , Hôpital Saint Antoine, Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine , Paris, France
                [12 ] departmentINRA, UMR1319 Micalis , AgroParisTech , Jouy-en-Josas, France
                [13 ] departmentMedical Center for Digestive Diseases , the Second Affiliated Hospital of Nanjing Medical University , Nanjing, China
                [14 ] departmentDepartment of Medicine , Indiana University , Indianapolis, Indiana, USA
                [15 ] departmentDepartment of Gastroenterology , The Queen Elizabeth Hospital, University of Adelaide , Woodville, South Australia, Australia
                [16 ] departmentDepartment of Gastroenterology , Haaglanden Medical Center , The Hague, The Netherlands
                [17 ] departmentInstitute of Microbiology , Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore , Roma, Italy
                [18 ] departmentDepartment of Gastroenterology , St Mark's Hospital , Harrow, UK
                [19 ] departmentDivision of Gastroenterology, Department of Medicine , University of Alberta , Edmonton, Alberta, Canada
                [20 ] departmentHuman Microbiome Research Program , Faculty of Medicine, University of Helsinki , Helsinki, Finland
                [21 ] departmentDepartment of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism , Innsbruck Medical University , Innsbruck, Austria
                Author notes
                [Correspondence to ] Professor Giovanni Cammarota, Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy; giovanni.cammarota@ 123456unicatt.it
                Author information
                http://orcid.org/0000-0002-8318-0515
                http://orcid.org/0000-0001-6300-3100
                http://orcid.org/0000-0002-6850-4454
                http://orcid.org/0000-0003-2338-8397
                http://orcid.org/0000-0002-9668-0316
                http://orcid.org/0000-0002-4235-2579
                http://orcid.org/0000-0002-3626-6148
                Article
                gutjnl-2020-321829
                10.1136/gutjnl-2020-321829
                7456726
                32620549
                e8843843-ec74-408e-9a46-b92dfa9b1175
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 14 May 2020
                : 23 June 2020
                : 24 June 2020
                Funding
                Funded by: The project was in part funded by the Catholic University of Rome, Line D-1 research funding.;
                Award ID: Catholic University of Rome, Italy
                Categories
                Guidelines
                1506
                2474
                2312
                Custom metadata
                unlocked

                Gastroenterology & Hepatology
                colonic microflora,diarrhoeal disease
                Gastroenterology & Hepatology
                colonic microflora, diarrhoeal disease

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