COVID-19 Outcomes Among Racial and Ethnic Minority Individuals With Inflammatory Bowel Disease in the United States
Authors: Manasi Agrawal, Erica J. Brenner, Joyce Wing Yan Mak, Xian Zhang, Gilaad G. Kaplan, Siew C. Ng, Walter Reinisch, Flavio Steinwurz, James D. Lewis, Michele Kissous-Hunt, Irene Modesto, Ryan C. Ungaro, Jean-Frederic Colombel, Michael D. Kappelman
Journal: Clinical Gastroenterology and Hepatology (2021)

The coronavirus disease 2019 (COVID-19) has affected more than 29 million people and led to more than 542,000 deaths in the United States.1Johns Hopkins University and Medicine CRCCOVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins University & Medicine, Baltimore, MD2020Google Scholar Older age, comorbidities, and racial and ethnic minority status are associated with severe COVID-19.2Kirby T. Evidence mounts on the disproportionate effect of COVID-19 on ethnic minorities.Lancet Respir Med. 2020; 8: 547-548Abstract Full Text Full Text PDF PubMed Scopus (352) Google Scholar Among patients with inflammatory bowel disease (IBD), racial and ethnic minorities have worse outcomes, mediated in part by inequitable health care access.3Barnes E.L. Loftus Jr., E.V. Kappelman M.D. Effects of race and ethnicity on diagnosis and management of inflammatory bowel diseases.Gastroenterology. 2021; 160: 677-689Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar Racial and ethnic minority patients with IBD and COVID-19 may be an especially vulnerable population. The purpose of this study was to evaluate racial and ethnic disparities in COVID-19 outcomes among IBD patients and the impact of non-IBD comorbidities on observed disparities. The Surveillance of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database was established in March 2020 to determine the impact of COVID-19 on patients with IBD and evaluate factors affecting COVID-19 outcomes. Details of the data collection and quality control have been described in a previous publication.4Brenner E.J. Ungaro R.C. Gearry R.B. et al.Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry.Gastroenterology. 2020; 159: 481-491.e3Abstract Full Text Full Text PDF PubMed Scopus (565) Google Scholar Details of statistical analyses are provided in the Supplementary Methods section. We evaluated 2019 US cases reported to SECURE-IBD, of which 161 (8.0%) were Hispanic, 211 (10.5%) were non-Hispanic black, 1502 (74.4%) were non-Hispanic white, and 145 (7.2%) were reported as unknown or another race/ethnicity. In the entire cohort, the mean age was 35.7 years, 52.1% were female, and 23.4% were obese. Other baseline characteristics are described in Supplementary Table 1. Across race/ethnicity categories, minority groups had a higher prevalence of obesity, active IBD, and comorbid conditions including diabetes, hypertension, and lung disease. There was no difference across race/ethnicity categories in the proportion of patients on each IBD medication type. Hospitalization occurred in 12.4% of Hispanic, 7.1% of non-Hispanic white, and 20.4% of non-Hispanic black individuals (P < .001) (Supplementary Table 2). No reported deaths occurred outside of the hospital. Severe COVID-19 occurred in 3.1% of Hispanic, 1.6% of non-Hispanic white, and 7.6% of non-Hispanic black individuals (P < .001). In the first set of models, compared with non-Hispanic white individuals, Hispanic individuals had an increased risk of hospitalization (adjusted odds ratio [aOR], 2.70; 95% CI, 1.56–4.66; P = .0004) and severe COVID-19 (aOR, 3.04; 95% CI, 1.09–8.49; P = .03) (Figure 1). After additional adjustment for comorbidities, region, and IBD medications, the effect estimates were attenuated slightly compared with the initial analyses (hospitalization: aOR, 2.45; 95% CI, 1.35–4.44; P = .003; severe COVID-19: aOR, 2.74; 95% CI, 0.84–9.01; P = .096) (Figure 1). Similarly, in the first set of models, compared with non-Hispanic white individuals, non-Hispanic black individuals had higher odds of hospitalization (aOR, 3.58; 95% CI, 2.34–5.47; P < .0001) and severe COVID-19 (aOR, 5.43; 95% CI, 2.72–10.83; P < .0001). After further adjustment for comorbidities, region, and IBD medications, the aOR for hospitalization was 3.62 (95% CI, 2.27–5.77; P < .0001), and for severe COVID-19 the aOR was 4.96 (95% CI, 2.28–10.88; P < .0001). Effect estimates were similar without adjustment for IBD medications in otherwise identical models. We report that Hispanic and black individuals had higher odds of hospitalization and severe COVID-19 compared with non-Hispanic white individuals. Upon adjusting for comorbid conditions, region, and IBD medications, the effect estimates, although slightly attenuated, remained significant for hospitalization in both groups, and for severe COVID-19 among black individuals. Underlying comorbid conditions in both groups partially explain these findings, and are consistent with previous data. In a study of 3626 patients in Louisiana, the odds of hospitalization and death were higher among black individuals compared with white individuals, the latter explained by comorbid conditions and social determinants of health.5Price-Haywood E.G. Burton J. Fort D. et al.Hospitalization and mortality among black patients and white patients with covid-19.N Engl J Med. 2020; 382: 2534-2543Crossref PubMed Scopus (1220) Google Scholar Limited access to health care, economic and educational disadvantages, and disparities in social determinants of health contributed directly to worse COVID-19 outcomes, and indirectly through a higher prevalence of comorbid conditions.6Webb Hooper M. Nápoles A.M. Pérez-Stable E.J. COVID-19 and racial/ethnic disparities.JAMA. 2020; 323: 2466-2467Crossref PubMed Scopus (1578) Google Scholar The role of a biological basis for differences in COVID-19 outcomes by race/ethnicity is less clear.7Zeberg H. Paabo S. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals.Nature. 2020; 587: 610-612Crossref PubMed Scopus (353) Google Scholar,8Bunyavanich S. Grant C. Vicencio A. Racial/ethnic variation in nasal gene expression of transmembrane serine protease 2 (TMPRSS2).JAMA. 2020; 324: 1567-1568Crossref PubMed Scopus (40) Google Scholar Our study had several strengths. In this large collaborative registry, we have data on COVID-19 in IBD patients from most US states for more than 1 year. Limitations included the risk of unmeasured confounding, reporting bias with potential under-representation of vulnerable groups, missing data (although <4% for all variables except ethnicity), and lack of data on social determinants of health. In summary, we highlight disparities in COVID-19 outcomes in IBD patients based on race and ethnicity, mediated in part by comorbid conditions. These findings underscore the clinical importance of considering social determinants of health and higher risk in minority groups. Ultimately, health policies are needed to bridge these gaps and improve health care access and outcomes for all. The authors thank other members of the Surveillance of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) Advisory Committee including Richard B. Gearry, MBChB, PhD, FRACP, FRCPC, and Jean-Francois Rahier, MD, PhD. The authors thank Fox E. Underwood, MSc, for the design and implementation of the SECURE-IBD interactive map. The authors acknowledge the physicians and other health care providers worldwide who have reported cases to the SECURE-IBD database and the organizations who supported or promoted the SECURE-IBD database (reporter names are available at www.covidibd.org/reporter-acknowledgment, and organization names are available at www.covidibd.org/our-partners). We included US cases reported to the registry between March 2020 and March 2021. We used descriptive statistics to summarize demographic and disease characteristics. The outcomes were as follows: adverse COVID-19 outcomes, a composite of hospitalization or death from COVID-19; and severe COVID-19, a composite of intensive care unit stay, mechanical ventilation, and/or death. We categorized race/ethnicity into Hispanic, non-Hispanic black, non-Hispanic white, and other. We excluded individuals with missing race/ethnicity data and those in the other category (n = 4 and 149, respectively). We used multivariable logistic regression to analyze the impact of race/ethnicity on outcomes. In the first set of models, we included race/ethnicity, age, sex, and IBD activity by physician global assessment. Because IBD medications were not associated with race/ethnicity on bivariate analysis except for a heterogeneous other IBD medications category, we did not include this variable in the models. For each outcome variable, we conducted a second analysis. In these models, we included race/ethnicity, age, sex, IBD activity, obesity (body mass index, ≥30 kg/m2), systemic corticosteroids (vs not), tumor necrosis factor antagonists (vs not), 6-mercaptopurine/azathioprine (vs not), and mesalamine/sulfasalazine (vs not) a priori. We then used backward selection of all variables associated with each outcome (P ≤ .10 on bivariate analysis), including comorbid conditions, US Census regions (Northeast, Midwest, South and West), interleukin 12/23 inhibitor (vs not), anti-integrin agent (vs not), and Janus kinase inhibitor (vs not). Medications included in the model a priori were the most commonly used IBD medications, while less common medications were subject to backward selection. We additionally performed otherwise identical models without adjustment for IBD medications. SAS version 9.4 (SAS Institute, Cary, NC) was used for data preparation and analyses.Supplementary Table 1Baseline Demographic and Clinical Characteristics for US Cases Reported to SECURE-IBD: Overall and Stratified by Race/EthnicityaUnless otherwise specified, percentages do not include missing values or unknown values. For all characteristics, less than 4% of data was missing and unknown, respectively, for each category. Percentages and numbers from each subcategory may not add up to the exact number of total reported cases owing to missing values and/or non–mutually exclusive variables.CharacteristicAll patientsHispanicNon-Hispanic blackNon-Hispanic white (reference)P valuebP values include Hispanic, non-Hispanic white, and non-Hispanic black. They do not include other/unknown.Other/unknownN%N%N%N%N%Total patients, n2019100.01618.021110.5150274.41457.2Age (mean, SD)35.717.8730.015.0636.619.0736.317.95.12134.917.20Female sex105152.17546.612659.778452.26645.5US Census region<.001 Midwest63831.61911.86430.351134.04430.3 Northeast52125.84930.43818.038625.74833.1 South56828.14226.19645.540226.82819.3 West23011.44628.673.315310.22416.6 Other or missing623.153.162.8503.310.7BMI<.001 <30135967.310766.511655.0104069.29666.2 ≥3047323.43723.07937.432921.92819.3 Missing1879.31710.6167.61338.92114.5Disease type.038 Crohn's disease129764.28854.714066.498265.48760.0 Ulcerative colitis65832.66641.06832.247731.84732.4 IBD-unspecified522.674.331.4332.296.2IBD disease activitycBy physician global assessment at time of COVID-19 infection..002 Remission114556.78049.711454.088458.96746.2 Mild39619.63421.14822.727318.24128.3 Moderate26313.02716.83014.218612.42013.8 Severe623.195.6125.7322.196.2 Unknown1195.9106.262.8976.564.1IBD medicationdAt time of COVID-19 infection. Medication categories are not mutually exclusive unless otherwise noted. Any medication190594.415193.819692.9142995.1.32812989.0 Sulfasalazine/mesalamine30215.03219.92612.321714.4.1072718.6 Budesonide673.353.194.3473.1.68064.1 Oral/parenteral steroids944.7116.894.3694.6.42053.4 6MP/AZAeMonotherapy indicates no concomitant TNF antagonist, anti-integrin, anti-interleukin 12/23, or JAK inhibitor.804.095.673.3553.7.44396.2 MethotrexateeMonotherapy indicates no concomitant TNF antagonist, anti-integrin, anti-interleukin 12/23, or JAK inhibitor.120.600.020.990.6.49010.7 Anti-TNFfMonotherapy.80740.06842.28741.260640.3.8814631.7 Anti-TNF + IMM1788.8169.9178.11338.9.819128.3 Anti-integrin27213.51710.62813.321314.2.437149.7 IL12/23 inhibitor28714.22113.02612.321714.4.6542315.9 JAK inhibitor412.053.131.4302.0.51232.1 Other IBD medication623.185.083.8402.7.20264.1Comorbid conditions Any condition59429.45332.99042.741027.3<.0014128.3 Cardiovascular disease934.663.7136.2684.5.48564.1 Diabetes783.9106.2157.1463.1.00474.8 Lung disease1839.1148.73315.61298.6.00474.8Hypertension1929.5159.33717.51298.6<.001117.6Cancer251.200.031.4201.3.33321.4History of stroke120.610.641.970.5.05100.0Chronic renal disease402.031.962.8302.0.70810.7Chronic liver disease552.774.383.8362.4.21042.8Other1979.81911.82712.81308.7.0852114.5Current smoker512.531.9115.2342.3.03332.1AZA, azathioprine; BMI, body mass index; COVID-19, coronavirus disease 2019; IL, interleukin; IMM, immunomodulator (includes 6-mercaptopurine, azathioprine, methotrexate); JAK, Janus kinase; SECURE-IBD, Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease; 6MP, 6-mercaptopurine; TNF, tumor necrosis factor.a Unless otherwise specified, percentages do not include missing values or unknown values. For all characteristics, less than 4% of data was missing and unknown, respectively, for each category. Percentages and numbers from each subcategory may not add up to the exact number of total reported cases owing to missing values and/or non–mutually exclusive variables.b P values include Hispanic, non-Hispanic white, and non-Hispanic black. They do not include other/unknown.c By physician global assessment at time of COVID-19 infection.d At time of COVID-19 infection. Medication categories are not mutually exclusive unless otherwise noted.e Monotherapy indicates no concomitant TNF antagonist, anti-integrin, anti-interleukin 12/23, or JAK inhibitor.f Monotherapy. Open table in a new tab Supplementary Table 2COVID-19 Outcomes for US Cases Reported to SECURE-IBD, Overall and Stratified by Race/EthnicityAll patientsHispanicNon-Hispanic blackNon-Hispanic white (reference)P valueaP values include Hispanic, non-Hispanic white, and non-Hispanic black. They do not include other/unknown.Other/unknownN%N%N%N%N%Hospitalization1879.32012.44320.41067.1<.0011812.4ICU/ventilator/death472.353.1167.6241.6<.00121.4COVID-19, Coronavirus Disease 2019; ICU, intensive care unit; SECURE-IBD, Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease.a P values include Hispanic, non-Hispanic white, and non-Hispanic black. They do not include other/unknown. Open table in a new tab AZA, azathioprine; BMI, body mass index; COVID-19, coronavirus disease 2019; IL, interleukin; IMM, immunomodulator (includes 6-mercaptopurine, azathioprine, methotrexate); JAK, Janus kinase; SECURE-IBD, Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease; 6MP, 6-mercaptopurine; TNF, tumor necrosis factor. COVID-19, Coronavirus Disease 2019; ICU, intensive care unit; SECURE-IBD, Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease.