Incidence and Patterns of COVID-19 Among Inflammatory Bowel Disease Patients From the Nancy and Milan Cohorts
Authors: Mariangela Allocca, Gionata Fiorino, Camille Zallot, Federica Furfaro, Daniela Gilardi, Simona Radice, Silvio Danese, Laurent Peyrin-Biroulet
Journal: Clinical Gastroenterology and Hepatology (2020)

The first cases of COVID-19 infection were reported in December, 2019, in Wuhan, China. Italy (in particular Lombardy) and France (in particular Northeast) have been gravely hit. Both physicians and inflammatory bowel disease (IBD) patients are deeply concerned that immunosuppressants or biologics may increase the risk of COVID-19 infection. International Organization For the Study of Inflammatory Bowel Disease has put in place an international registry, Surveillance Epidemiology of Coronavirus Under Research Exclusion, for tracking all the cases with IBDs infected by COVID-19 (Surveillance Epidemiology of Coronavirus Under Research Exclusion registry: http://www.covidibd.org). It will describe the outcomes of infected patients and the association between IBD-related medications and these outcomes. Immune-mediated inflammatory disorders, including IBD, are known to be associated with changes in host defense. Hence, one could speculate that patients with immune-mediated inflammatory disorders may be more susceptible to COVID-19 infection. However, reports from areas exposed to a high risk of COVID-19 infection interestingly have not reported cases of IBD patients with COVID-19.1Norsa L. et al.Gastroenterology. 2020; (Epub ahead of print)PubMed Google Scholar Ongoing registries cannot address this issue because of the lack of accurate denominator data. In a large cohort of IBD patients from France (Nancy University Hospital, 2000 patients) and Italy (Humanitas, Milan, 4000 patients), all consecutive IBD patients infected by COVID-19 were included since the beginning of the pandemic. COVID-19 cases were identified via regular telemedicine visits and infusion center visits. Diagnosis of COVID-19 was made by routinely used polymerase chain reaction nasopharyngeal swab testing for all patients. The cumulative incidence was calculated. The denominator was based on prospectively maintained databases used to identify patients eligible for clinical trials at both centers. The characteristics of these 15 COVID-19–positive IBD patients are reported in Table 1. Nine patients have Crohn's disease, 3 patients had an active disease, and all but 1 were treated with biological therapy and/or immunosuppressive therapy at the time of the COVID-19 infection diagnosis. Four patients are male, and all but 1 are younger than age 60 years, and 2 patients have comorbidities, including obesity and hypertension, that are considered risk factors for a worse outcome of COVID-19 infection.2Yang J. et al.Int J Infect Dis. 2020; (Epub ahead of print)Google Scholar Five of 15 patients were hospitalized, but none of them required intensive care and no deaths were reported.Table 1Characteristics of IBD Patients With Infection by COVID-19PatientCountryAge, ySexDiagnosisComorbidityDisease activityTherapyHospitalizationIntensive careDeath1France37FCDRenal transplantationRemissionSteroid (5 mg/d), tacrolimus,everolimus, infliximabYesNoNo2France34MCDPrimary sclerosing cholangitisRemissionInfliximabNoNoNo3France33FCDChronic paranoid psychosisActiveInfliximabYesNoNo4France46FCDNoRemissionInfliximabNoNoNo5Italy61FUCArthrosis, muscular dystrophiaRemissionInfliximabNoNoNo6Italy46FUCHypertension, obesityRemissionVedolizumabYesNoNo7Italy49FCDArthritisRemissionUstekinumabNoNoNo8Italy39FCDNoRemissionAdalimumabNoNoNo9Italy26MCDNoRemissionUstekinumabNoNoNo10Italy53FUCObesityActiveSteroid (15 mg/d)YesNoNo11Italy28FCDNoRemissionClinical trial (guselkumab vs ustekinumab vs placebo)NoNoNo12Italy42FCDAnkylosing spondylitisRemissionAdalimumabNoNoNo13Italy26FUCNoRemissionMesalamineNoNoNo14Italy28MUCNoActiveAzathioprineYesNoNo15Italy38MUCMitral prolapseRemissionInfliximab, azathioprineNoNoNoNOTE. Active disease was determined by a partial Mayo score greater than 2, Harvey-bradshaw index greater than 4 and/or a Mayo score greater than 1, Simple endoscopic score for Crohn's disease greater than 2.CD, Crohn's disease; F, female; M, male; UC, ulcerative colitis. Open table in a new tab NOTE. Active disease was determined by a partial Mayo score greater than 2, Harvey-bradshaw index greater than 4 and/or a Mayo score greater than 1, Simple endoscopic score for Crohn's disease greater than 2. CD, Crohn's disease; F, female; M, male; UC, ulcerative colitis. The cumulative incidence of COVID-19–positive IBD patients in our cohort is 0.0025, which is broadly similar to that observed in the general population (current cumulative incidence in France and Italy, 0.0017). By contrast, the mortality rate (13%) and need for intensive care support (6%) are much higher in the general population than in our combined cohort (no cases). A key feature of COVID-19–related acute respiratory distress syndrome is the activation of the immune system characterized by a cytokine storm.3Xu Z. et al.Lancet Respiratory Med. 2020; 8: 420-422Abstract Full Text Full Text PDF PubMed Scopus (6406) Google Scholar IBD patients might be protected by the use of potent anti-inflammatory drugs such as anti–tumor necrosis factor therapy and present milder disease or be asymptomatic more frequently than in the general population. Anti–tumor necrosis factor therapy has been associated with a low risk of opportunistic viral infections in a large French administrative database.4Kirchgesner J. et al.Gastroenterology. 2018; 155: 337-346 e10Abstract Full Text Full Text PDF PubMed Scopus (398) Google Scholar Interestingly, no fatalities have been reported in patients undergoing transplantation treated with chemotherapy or other immunosuppressive treatments during Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus outbreaks.5Hui D.S. et al.Lancet Infect Dis. 2018; 18: E217-E227Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar A similar trend recently was reported during the recent COVID-19 pandemic.6Liang W. et al.Lancet Oncol. 2020; 21: 335-337Abstract Full Text Full Text PDF PubMed Scopus (3303) Google Scholar,7D'Antiga L. Liver Transplant. 2020; (Epub ahead of print)Google Scholar Other hypotheses cannot be excluded. The young age of the IBD population and the low rate of comorbidities, including diabetes, heart disease, and lung disease, known to be associated with a poor outcome during COVID-19 infection,2Yang J. et al.Int J Infect Dis. 2020; (Epub ahead of print)Google Scholar also may play a role. The European Crohn's and Colitis Organization guidelines recommend vaccination against some viruses, including influenza virus. It has been hypothesized that vaccination may protect against viral infections in general. In conclusion, we found that IBD patients do not have an increased risk of developing COVID-19 infection and develop less severe forms when infected in a large cohort of 6000 IBD patients treated in referral centers from high-incidence areas. Keeping on the High Quality of Health Care in Greek Inflammatory Bowel Disease Patients in the SARS-CoV-2 EraClinical Gastroenterology and HepatologyVol. 18Issue 10PreviewIt was with great interest that we read the article by Allocca et al1 describing the management strategy, amid COVID-19 pandemic, by 1 of the largest tertiary referral inflammatory bowel disease (IBD) centers in Europe. This report is of even greatest importance considering the high burden of COVID-19 in Italy. Full-Text PDF