Implications of COVID-19 for patients with pre-existing digestive diseases
Authors: Ren Mao, Jie Liang, Jun Shen, Subrata Ghosh, Liang-Ru Zhu, Hong Yang, Kai-Chun Wu, Min-Hu Chen
Journal: The Lancet. Gastroenterology & hepatology (2020)

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,1Holshue ML DeBolt C Lindquist S et al.First case of 2019 novel coronavirus in the United States.N Engl J Med. 2020; (published online March 5.)DOI:10.1056/NEJMoa2001191Crossref PubMed Scopus (4278) Google Scholar much attention has been paid to the study and reporting of gastrointestinal tract infection of SARS-CoV-2. According to a study2Guan W Ni Z Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; (published online Feb 28.)DOI:10.1056/NEJMoa2002032Crossref Google Scholar 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 report3Liu Q Wang R Qu G et al.Macroscopic autopsy findings in a patient with COVID-19.J Forensic Med. 2020; 36 (in Chinese).: 1-3Google Scholar 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 study2Guan W Ni Z Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; (published online Feb 28.)DOI:10.1056/NEJMoa2002032Crossref Google Scholar 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,2Guan W Ni Z Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; (published online Feb 28.)DOI:10.1056/NEJMoa2002032Crossref Google Scholar 23 (2·1%) patients had hepatitis B infection; chronic hepatitis B infection did not seem to be associated with a severe course of COVID-19.2Guan W Ni Z Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; (published online Feb 28.)DOI:10.1056/NEJMoa2002032Crossref Google Scholar Abnormal liver function tests, including elevated aspartate aminotransferase, alanine aminotransferase, and total bilirubin were noted.2Guan W Ni Z Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; (published online Feb 28.)DOI:10.1056/NEJMoa2002032Crossref Google Scholar 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.4Zhang C Shi L Wang FS Liver injury in COVID-19: management and challenges.Lancet Gastroenterol Hepatol. 2020; (published online March 4)https://doi.org/10.1016/S2468-1253(20)30057-1Summary Full Text Full Text PDF Scopus (1321) Google Scholar Data suggest that liver injury is more prevalent in severe cases than in mild cases of COVID-19.4Zhang C Shi L Wang FS Liver injury in COVID-19: management and challenges.Lancet Gastroenterol Hepatol. 2020; (published online March 4)https://doi.org/10.1016/S2468-1253(20)30057-1Summary Full Text Full Text PDF Scopus (1321) Google Scholar 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.5Kumar D Tellier R Draker R Levy G Humar A Severe Acute Respiratory Syndrome (SARS) in a liver transplant recipient and guidelines for donor SARS screening.Am J Transplant. 2003; 3: 977-981Crossref PubMed Scopus (122) Google Scholar Although many patients had comorbidities in the reported series,2Guan W Ni Z Hu Y et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; (published online Feb 28.)DOI:10.1056/NEJMoa2002032Crossref Google Scholar none had been a transplant recipient. Transplant clinicians are encouraged to follow guidance issued by The Transplantation Society,6The Transplantation SocietyGuidance on coronavirus disease 2019 (COVID-19) for transplant clinicians.https://tts.org/23-tid/tid-news/657-tid-update-and-guidance-on-2019-novel-coronavirus-2019-ncov-for-transplant-id-cliniciansGoogle Scholar 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,7Liang W Guan W Chen R et al.Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China.Lancet Oncol. 2020; (published online Feb 14.)DOI:10.1016/S1470-2045(20)30096-6Summary Full Text Full Text PDF PubMed Scopus (3273) Google Scholar 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).7Liang W Guan W Chen R et al.Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China.Lancet Oncol. 2020; (published online Feb 14.)DOI:10.1016/S1470-2045(20)30096-6Summary Full Text Full Text PDF PubMed Scopus (3273) Google Scholar 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.7Liang W Guan W Chen R et al.Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China.Lancet Oncol. 2020; (published online Feb 14.)DOI:10.1016/S1470-2045(20)30096-6Summary Full Text Full Text PDF PubMed Scopus (3273) Google Scholar 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.8Mao R Chen MH Networked Clinical study collaboration on inflammatory bowel disease in China.Am J Gastroenterol. 2018; 113: 1266Crossref PubMed Scopus (8) Google Scholar 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 2020.9Chinse Society of IBD Managing IBD patients during the outbreak of COVID-19.Chin J Dig. 2020; 40: E001Google Scholar 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.10Crohn's Colitis FoundationWhat IBD patients should know about the 2019 novel coronavirus (COVID-19).https://www.crohnscolitisfoundation.org/what-ibd-patients-should-know-about-2019-novel-coronavirus-covid-19Google Scholar, 11Crohn's & Colitis UK Novel coronavirus (COVID-19) advice.https://www.crohnsandcolitis.org.uk/news/updated-wuhan-novel-coronavirus-adviceGoogle Scholar Such guidance and advice should be delivered urgently to health-care workers as well as patients with IBD.PanelKey recommendations for managing patients with IBD during the COVID-19 epidemicPotential 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 pregnantMedication 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 alternativesSurgery 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 surgeryPatients with IBD and fever *Fever is the most common reported symptom in COVID-19. •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 outCOVID-19=coronavirus disease 2019. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. 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 *Fever is the most common reported symptom in COVID-19. •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 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 This online publication has been corrected. The corrected version first appeared at thelancet.com/gastrohep on May 8, 2020 This online publication has been corrected. The corrected version first appeared at thelancet.com/gastrohep on May 8, 2020 We declare no competing interests. We thank the members of Chinese IBD Elite Union, Chinese Society of IBD and Chinese IBD Quality Care Evaluation Center Committee (IBDQCC) for their collaboration. RM and JL contributed equally. Download .pdf (.53 MB) Help with pdf files Chinese translation of the full text Correction to Lancet Gastroenterol Hepatol 2020; 5: 425–27Mao R, Liang J, Shen J, et al. Implications of COVID-19 for patients with pre-existing digestive diseases. Lancet Gastroenterol Hepatol 2020; 5: 425–27—The fourth sentence of the third paragraph of this Comment should read "In this study,2 23 (2·1%) patients had hepatitis B infection; chronic hepatitis B infection did not seem to be associated with a severe course of COVID-19.2" This correction has been made to the online version as of May 8, 2020. Full-Text PDF Prevention of COVID-19 in patients with inflammatory bowel disease in Wuhan, ChinaAs recently outlined by Ren Mao and colleagues1 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. Full-Text PDF