What Is the Incidence of COVID-19 in Patients With IBD in Western Countries?

Dear Editors:

We read with interest the article by Gubatan et al¹ reporting that, among 168 patients with inflammatory bowel disease (IBD) tested in Northern California (Stanford University School of Medicine), the prevalence of coronavirus disease 2019 (COVID-19) was 3.0%, comparable with the population-weighted prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive serology in Santa Clara County at 2.8%. The authors concluded that their results provided much-needed epidemiologic data and reassurance that COVID-19 rates in patients IBD may be comparable with that in the general population.

Data on COVID-19 incidence in IBD have been contradictory. Initial evidence from China suggested that patients with IBD even had a decreased risk of COVID-19 compared with the general population, because no patients with IBD were reported to be infected with SARS-CoV-2 in the IBD Elite Union, which covers the 7 largest IBD referral centers in China, or in the 3 largest tertiary IBD centers in Wuhan.² Subsequently, a study reported that, among 522 patients with IBD followed in a tertiary center at Bergamo, the Italian province with one of the highest rates of infection anywhere in the world, no case of COVID-19 was diagnosed.³

We recently evaluated the risk of COVID-19 and associated mortality among 1918 patients followed at an IBD Unit in the Madrid region (Hospital Clínico San Carlos), one of the most affected regions in Spain, and compared it with the general population.⁴ Through April 8, 2020, we detected 12 COVID-19 cases, giving a crude cumulative incidence of 6.2 cases per 1000 patients with IBD. Because we do not follow pediatric patients in our unit, the mean age of 50 years in our patients with IBD (0.15% of patients <20 years) was significantly higher than the mean age of 42 years in the general population in Madrid (20.2% of individuals under 20 years; P < .001, unpublished data, May 10, 2020). After adjusting for age we obtained an age-standardized rate of 4.9 COVID-19 cases per 1000 patients with IBD, which was slightly lower than the rate in the general population. Given the low number of COVID-19 cases in our series, any missed diagnoses would, however, have a high impact on the reported incidence rate. We also reported an age-adjusted COVID-19 associated mortality rate of 0.82 per 1000 patients with IBD, similar to that of the general population.

A third study assessed the incidence of COVID-19 among a cohort of patients with IBD from France (Nancy University Hospital; 2000 patients) and Italy (Humanitas, Milan; 4000 patients).⁵ They identified 15 COVID-19 cases, corresponding with a crude cumulative incidence of 2.5 cases per 1000 patients with IBD, which was considered broadly similar to that observed in the general population (the cumulative incidence in France and Italy was 1.7 cases per 1000 at the time of the study). The incidence was not adjusted by age, and we do not know if the mean age of the IBD cohort was higher than that of the general population. If this were so, it would be expected that the age-standardized rate of COVID-19 in IBD would be less than that reported. We believe this study could also be affected by underreporting of COVID-19 among the IBD population, while all positive viral reverse transcriptase polymerase chain reaction were counted for the general population.

Although available evidence is limited, it seems that patients with IBD are not at a greater risk of acquiring COVID-19. This finding is noteworthy because approximately 37% of patients with IBD in the Northern California cohort and our cohort in Madrid were receiving immunosuppressants and/or biologics.^{1 , 5} The impact of these drugs on SARS-CoV-2 infection acquisition or progression needs to be further investigated. Although thiopurines⁶ and anti–tumor necrosis factor agents⁷ have been associated with serious viral infections, some authors believe that patients with IBD might be protected against severe disease because the viral-induced “cytokine release storm” sometimes reported in COVID-19 could potentially be attenuated by the potent anti-inflammatory drugs commonly used to treat IBD. As a result, COVID-19 may be milder in these patients and so infection may not be confirmed by testing. In agreement, a recent study of patients included in the SECURE-IBD registry reported that tumor necrosis factor antagonist monotherapy was not associated with and even may have a protective effect against severe COVID-19.⁸ We also believe that rigorous adherence of patients with IBD to protective measures, encouraged by routine advice from IBD nurses and IBD staff, may further help contain SARS-CoV-2 dissemination in this population.

In conclusion, we agree with Gubatan et al¹ that the available data indicate that COVID-19 is not more prevalent in patients with IBD than in the general population.