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      Prevention of COVID-19 in patients with inflammatory bowel disease in Wuhan, China

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          Abstract

          As recently outlined by Ren Mao and colleagues 1 in The Lancet Gastroenterology & Hepatology, patients with inflammatory bowel disease (IBD) are at increased risk of opportunistic infections. Particular attention is therefore required for these patients during the ongoing coronavirus disease 2019 (COVID-19) pandemic. 318 patients with IBD (114 with Crohn's disease, 204 with ulcerative colitis) were registered in a prospective database at the Regional Medical IBD Center of China, Renmin Hospital of Wuhan University, Wuhan, China, between Jan 1, 2000, and Dec 8, 2019. Patients' clinical characteristics and their location relative to the COVID-19 outbreak are shown in the appendix (pp 2–4). Median age was 39·2 years (IQR 15–79); 33 (10%) were older than 60 years. 49 (15%) patients (22 [19%] of those patients with Crohn's disease, 27 [13%] of those with ulcerative colitis) had other chronic medical conditions (appendix p 2). 35 (31%) of the patients with Crohn's disease and 93 (46%) of those with ulcerative colitis had active IBD. More than two-thirds (246 [77%]) lived and worked near Huanan seafood supermarket (≤30 km), the suspected location from which SARS-CoV-2 emerged (appendix p 4). We recorded the times and frequency of received alerts and information from our team, self-prevention measures, and confirmed or suspected diagnosis of COVID-19 between Dec 8, 2019, and March 30, 2020. Between Jan 3 and March 30, 2020, five (2%) patients had been hospitalised for severe active IBD during the COVID-19 outbreak, including one with Crohn's disease, who underwent emergency surgery for intestinal perforation, and one pregnant patient with Crohn's disease in whom preterm delivery was induced (appendix pp 2–3). Before the outbreak, 40 (13%) patients had been treated with corticosteroids, 35 (11%) with azathioprine, 37 (12%) with thalidomide, and 20 (6%) with infliximab; nine (3%) patients were enrolled in clinical trials (appendix pp 2–3). Between Jan 31 and March 30, 20 (6%) patients required medical management of disease flare, which was treated preferentially with exclusive enteral nutrition for Crohn's disease (n=15) and steroids (n=18), with a median time to review of 1·3 days (IQR 1·0-2·3). On Jan 3, 2020, we temporarily ceased infliximab infusions and immunosuppressive treatment for all patients, in accordance with national Chinese Society of Gastroenterology guidelines, 2 altering treatment to 5-aminosalicylic acid (37 patients) or thalidomide (43 patients; with 25 patients receiving both medications) depending on the patients' condition. On Jan 3, we sent educational and instructional alerts and messages to the online IBD groups of our outpatients via WeChat, with all patients responding to our alerts (table ). Within 3 days, most patients reported that they maintained good hand hygiene, sought medical assistance online rather than in person, and kept track of fever and respiratory symptoms; all confirmed notification of our information for self-prevention and all patients kept up to date on official news on COVID-19 (table). Most patients decreased the time they spent outside the home, wore masks when outside, and purchased masks for storage; most patients were very satisfied with our team's work (table). Table Responses to WeChat alerts Alerts on Jan 3, 2020 (n=318) Upgraded alerts on Jan 13, 2020 (n=318) Time from alert to patient response (days; median [IQR]) 1·8 (1·0–3·4) 1·2 (1·0–2·3) Responded to our alert 318 (100%) 318 (100%) Overall service satisfaction Very satisfied 300 (94%) 318 (100%) Satisfied 18 (6%) 0 Not satisfied 0 0 Reduced time spent outside* 291 (92%) 318 (100%) Attended any social gathering 0 0 Wore masks when outside 284 (89%) 318 (100%) Purchased masks for storage 246 (77%) 318 (100%) Maintained hand hygiene† 296 (93%) 318 (100%) Route of care Sought medical care or contacted doctors and pharmacies online 289 (91%) 318 (100%) Sought medical care in person 27 (8%) 0 Did not seek care 2 (1%) 0 Noted educational and instructional information sent by mobile messages and WeChat 318 (100%) 318 (100%) Maintained awareness of COVID-19 symptoms‡ 318 (100%) 318 (100%) Monitored social news on COVID-19 318 (100%) 318 (100%) COVID-19=coronavirus disease 2019. * Patients who had to leave their homes were outside for the shortest time necessary. † Cleaning hands with soap and using an alcohol-based sanitiser, especially before meals, after toilet use, and immediately after returning home. ‡ Fever and respiratory symptoms. On Jan 8, 2020, the first confirmed case of COVID-19 was diagnosed at our hospital, in the pulmonology department. On Jan 12, a second patient was diagnosed, in our gastroenterology department (appendix p 5). On Jan 13, we updated our alerts (table) and actions and implemented an updated model of care. All inpatients with IBD were placed in single-occupancy rooms. We sent daily alerts to outpatients with IBD with recommendations to stay at home if possible, encourage use of N95 masks for those with recent treatment with biologics and immunosuppressants, and to keep in daily contact with our IBD team. For patients with low health literacy and education, we remained in contact via phone calls. We mailed trial drugs to those in clinical trials who lived further from our hospital (>1 h driving distance), to reduce exposure to hospital facilities. By Jan 13, most patients with IBD in our hospital were discharged, IBD clinics were closed, and routine, non-urgent medical care was moved online. We published online recommended guidelines and precautions for prevention of COVID-19 in the IBD population. 2 On Jan 22, we sent alerts to outpatients to be aware of atypical COVID-19 (ie, confirmed COVID-19 with only gastrointestinal symptoms and no fever) and to maintain self-isolation, and sent alerts via public news media (major newspapers and periodicals) on Jan 24, when the shutdown of Wuhan was announced and domestic social lockdown and quarantine controls were instituted. With the escalation of our alerts, all of our patients reported within 2 days that they wore masks when outside, purchased masks for storage, decreased time spent outside, and were very satisfied with our information and service (table). Throughout this period (Jan 3 to March 30), a weekly multidisciplinary meeting with surgical, medical, and radiological teams was maintained to discuss hospitalised patients in critical or severe condition and formulate management plans. We sent a questionnaire to our patients on Feb 10, regarding their exposure history (ie, contact with confirmed or suspected cases of COVID-19), potential risk factors for exposure (eg, populated places and contact with health-care workers), telehealth outpatient visits, and recent symptoms (including fever and respiratory and gastrointestinal symptoms). In response, 24 (8%) patients reported risk factors for exposure to SARS-CoV-2, including one patient who reported contact with an individual with confirmed COVID-19 (appendix p 2). As of March 30, none of our registered patients with IBD had reported concern over respiratory symptoms and none had confirmed or suspected COVID-19. COVID-19 was excluded in 29 patients, including 20 patients with disease flare and six active cases, by diagnostic chest CT scans and virological testing. Patients with IBD are susceptible to frequent and severe infections. IBD treatment teams need to put emphasis on risk assessment, prevention strategies, patient education, and effective therapies. 2 Mass awareness of important prevention and protection strategies is paramount and might go beyond what is currently recommended in some guidelines. 3 Despite such guidelines, cases of COVID-19 have been reported in patients with IBD in many countries, including France, Italy, Spain, and the USA.4, 5 Our recommendations extend beyond the so-called shielding procedures described in other guidelines and resulted in no cases of COVID-19 being reported among our patients. At the height of a pandemic, assuming mass community spread is vital and implementation of strict criteria for patients on immunosuppression is crucial. We believe that our long-term relationships with our patients and understanding of their individual risk factors, along with routine emphasis on patient education, contributed to their adherence to our recommendations. Another crucial component is having a method of communication between patients and their IBD teams that allows concerns to be addressed in a timely fashion; our median times to response were within 1 day. We further discuss and evaluate our approach in the appendix (pp 6–9). Of note, given high rates of community transmission and the large number of confirmed COVID-19 cases in China, the Chinese Society of Gastroenterology recommended withholding immunosuppressive therapies, on the basis of potential increased risk of infection and worsening of COVID-19 disease course, especially in high-risk areas such as Wuhan. 2 However, local guidelines and isolation measures should be dictated by the background rate of COVID-19 in the community. Nonetheless, we believe our experiences could provide a model of care to prevent COVID-19 in patients with IBD.

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          Implications of COVID-19 for patients with pre-existing digestive diseases

          The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first reported in China, in December, 2019, now affects the whole world. As of March 8, 2020, more than 105 000 laboratory-confirmed cases and more than 3500 deaths in over 100 countries had been reported. Since SARS-CoV-2 RNA was first detected in a stool specimen of the first reported COVID-19 case in the USA, 1 much attention has been paid to the study and reporting of gastrointestinal tract infection of SARS-CoV-2. According to a study 2 including 1099 patients with laboratory-confirmed COVID-19 from 552 hospitals in China as of Jan 29, 2020, nausea or vomiting, or both, and diarrhoea were reported in 55 (5·6%) and 42 (3·8%) patients. Autopsy studies are crucial to help understand the involvement of COVID-19 in the digestive system; however, to date, there has been only one autopsy report 3 for a man aged 85 years with COVID-19, which showed segmental dilatation and stenosis in the small intestine. Whether this finding is secondary to COVID-19 or a pre-existing gastrointestinal comorbidity is unknown. COVID-19 has implications for the management of patients with pre-existing digestive diseases. Indeed, the presence and number of comorbidities is associated with poorer clinical outcome in patients with COVID-19. In the study 2 of 1099 patients with laboratory-confirmed COVID-19, 261 (23·7%) patients with COVID-19 reported having at least one comorbidity, with hypertension, diabetes, and coronary heart disease being the most common. In this study, 2 23 (2·1%) patients had hepatitis B infection. Severe cases were more likely to have hepatitis B infection (2·4% vs 0·6%) than non-severe cases. Abnormal liver function tests, including elevated aspartate aminotransferase, alanine aminotransferase, and total bilirubin were noted. 2 Liver abnormalities in patients with COVID-19 might be due to viral infection in liver cells but could also be due to other causes such as drug toxicity and systemic inflammation. 4 Data suggest that liver injury is more prevalent in severe cases than in mild cases of COVID-19. 4 However, data about other underlying chronic liver conditions such as non-alcoholic fatty liver disease, alcohol-related liver disease, and autoimmune hepatitis, and their effect on prognosis of COVID-19 needs to be further evaluated. Liver transplantation might involve a risk of transmission of viral infection from donor to recipient, as shown in the previous SARS outbreak, and therefore donor screening and testing is crucial. 5 Although many patients had comorbidities in the reported series, 2 none had been a transplant recipient. Transplant clinicians are encouraged to follow guidance issued by The Transplantation Society, 6 as well as local health department guidelines for isolating, quarantining, testing, and monitoring returned travellers from endemic areas. Patients with cancer in general are more susceptible to infection due to their immunocompromised status caused by the malignancy and anticancer treatments. However, whether patients with gastrointestinal cancers are more likely to be infected with SARS-CoV-2 than healthy individuals remains unknown. In a recent nationwide analysis from China, 7 18 (1%) of 1590 COVID-19 cases had a history of cancer. Among these 18 cases, three had a history of colorectal cancer (one colonic tubular adenocarcinoma, one rectal carcinoma, and one colorectal carcinoma). 7 Patients with COVID-19 and cancer were observed to have a higher risk of severe events; several strategies have been proposed, such as intentional postponing of adjuvant chemotherapy or elective surgery on a patient-by-patient basis, stronger personal protection provisions, and more intensive surveillance or treatment. 7 Given the use of biologics and immunosuppressive agents, whether patients with inflammatory bowel disease (IBD) are more susceptible to SARS-CoV-2 infection has raised great concern. Currently no patients with IBD have been reported to be infected with SARS-CoV-2 in the IBD Elite Union, which incorporates the seven largest IBD referral centres in China with more than 20 000 patients with IBD. 8 Furthermore, no patients with IBD with SARS-CoV-2 infection have been reported from the three largest tertiary IBD centres in Wuhan (Tongji Hospital, Union Hospital, and Zhongnan Hospital) at the time that this manuscript was prepared (March 8, 2020). Several strategies have been implemented in China to minimise the potential risk of SARS-CoV-2 infection in patients with IBD since the outbreak of COVID-19. First, the Chinese IBD Society issued official guidelines for managing patients with IBD in early February 2020. 9 The guidelines include practical recommendations on the use of immunosuppressive agents and biologics, diet, and intentional postponement of elective surgery and endoscopy, as well as personal protection provisions; these are outlined in the panel . Second, the China Crohn's & Colitis Foundation has organised a group of volunteer gastroenterologists that specialise in IBD to offer online consultancy to patients with IBD since Jan 29, 2020. Third, an online virtual IBD visit programme has been initiated in some IBD centres, which provides convenient and cost-effective care, and could potentially reduce the risk of SARS-CoV-2 infection by avoiding close contact with infected patients in public areas. With the increasing concern from patients with IBD globally, helpful online resources about COVID-19 have been provided by international non-profit organisations such as Crohn's Colitis of Foundation America and Crohn's & Colitis UK.10, 11 Such guidance and advice should be delivered urgently to health-care workers as well as patients with IBD. Panel Key recommendations for managing patients with IBD during the COVID-19 epidemic Potential risk factors for SARS-CoV-2 infection • Patients with inflammatory bowel disease (IBD) on immunosuppressive agents • Patients with active-stage IBD with malnutrition • Elderly patients with IBD • Patients with IBD frequently visiting medical clinic • Patients with IBD with underlying health conditions, such as hypertension and diabetes • Patients with IBD who are pregnant Medication for patients with IBD • Continue current treatment if disease is stable, and contact your doctor for suitable medicine if disease has flared • Use of mesalamine should be continued and should not increase the risk of infection • Corticosteroid use can be continued, but be cautious of possible side-effects • A new prescription of immunosuppressant or increase in dose of an ongoing immunosuppressant is not recommended in epidemic areas. • Use of biologics such as the anti-TNFs infliximab or adalimumab should be continued • If infliximab infusion is not accessible, switching to adalimumab injection at home is encouraged • Vedolizumab use can be continued due to the specificity of the drug for the intestine • Ustekinumab use can be continued, but starting ustekinumab requires infusion centre visits and therefore is not encouraged • Enteral nutrition might be used if biologics are not accessible • Tofacitinib should not be newly prescribed in epidemic areas unless there are no other alternatives Surgery and endoscopy • Postpone elective surgery and endoscopy • Screening for COVID-19 (complete blood count, IgM or IgG, nucleic acid detection, and chest CT) before emergency surgery Patients with IBD and fever * • Contact your IBD doctor about potential option to visit fever outpatient clinic with personal protection provisions if temperature continues over 38°C • Suspend the use of immunosuppressant and biological agents after consultation with your IBD doctor, and follow appropriate local guidance for suspected COVID-19 if COVID-19 cannot be ruled out COVID-19=coronavirus disease 2019. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. The comorbidity spectrum of digestive conditions and its impact on treatment and outcome of COVID-19 remains largely unknown. Further data need to be analysed from the COVID-19 cohort established by the National Health Commission of the People's Republic of China, which would help to more precisely ascertain the risk of SARS-CoV-2 infection in patients with digestive comorbidities such as IBD. These data and experience with guidance on how to manage patients with underlining comorbidities in China could facilitate integrated care for patients globally. For WHO Coronavirus Disease 2019 (COVID-19) Situation Report 48 see https://www.who.int/docs/default-source/coronaviruse/situationreports/20200308-sitrep-48-covid-19.pdf?sfvrsn=16f7ccef_4
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            Management of patients with inflammatory bowel disease during epidemic of 2019 novel coronavirus pneumonia

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              Author and article information

              Contributors
              Journal
              Lancet Gastroenterol Hepatol
              Lancet Gastroenterol Hepatol
              The Lancet. Gastroenterology & Hepatology
              Elsevier Ltd.
              2468-1253
              17 April 2020
              17 April 2020
              Affiliations
              [a ]Department of Gastroenterology, Key Laboratory of Hubei Province for Digestive System Disease, and Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China
              [b ]Department of Respiratory Medicine, Renmin Hospital of Wuhan University, Wuhan, China
              [c ]Infection Control Department, Renmin Hospital of Wuhan University, Wuhan, China
              [d ]Department of Gastroenterology, St Vincent's Hospital Melbourne, University of Melbourne, Australia
              Article
              S2468-1253(20)30121-7
              10.1016/S2468-1253(20)30121-7
              7164865
              31981518
              ec61eb33-252a-469d-860f-05c11133821c
              © 2020 Elsevier Ltd. All rights reserved.

              Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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