The available data regarding the clinical attributes and outcomes within the cohort of COVID-19 patients, considering the presence or absence of IBD, are notably limited. The precise extent of infection risk among individuals with IBD remains unclear and is potentially influenced by variables such as age or genetic predisposition. Throughout the pandemic, there has been a heightened focus on the management and prognosis of IBD patients who have contracted the infection. In the initial stages of the pandemic, a handful of studies suggested that individuals with IBD might be at a lower risk of contracting COVID-19 than the broader population. Notably, investigations conducted by Ren Mao et al. in China [10] and Carlos Taxonera et al. in Italy [11] reported no COVID-19 cases within the IBD populations they examined. This finding was corroborated by a meta-analysis undertaken by Aziz et al. in 2020 [12], which synthesized findings from six studies encompassing a collective IBD patient sample of 9177 individuals. The meta-analysis demonstrated an aggregate incidence of 0.3% COVID-19 in the IBD patient population, a figure falling within the lower spectrum of the general population's incidence range (0.2–4.0%). Notably, the enhanced adherence of IBD patients to hygienic and preventive measures might confound the relationship between the two diseases, warranting cautious interpretation.
According to the CDC [13], 3.1 million (1.3%) adults in the USA are diagnosed with IBD, which includes both Crohn’s disease and ulcerative colitis. Given the dearth of comprehensive guidelines and available data pertaining to the interaction between COVID-19 and this specific patient demographic, we undertook a study aimed at scrutinizing IBD patients who were also diagnosed with COVID-19. This study entailed a comparative evaluation, contrasting IBD patients with their non-IBD counterparts across multiple dimensions, including sociodemographic attributes, clinical manifestations of COVID-19, concurrent comorbidities, duration of hospitalization, and mortality rates.
A retrospective cohort study conducted in the United States to assess the risk and outcomes of COVID-19 in IBD patients revealed a detrimental impact of steroid use on patient outcomes. Notably, this study reported a lower incidence of COVID-19 in the IBD patient population than in the non-IBD patient population [14]. However, within the COVID-19-affected IBD cohort, a heightened likelihood of hospitalization and critical care was observed, potentially attributed to some patients experiencing an IBD flare at the 3-month follow-up [14]. This may explain the larger bed size observed in our data among the IBD cohort than among the non-IBD cohort. Given the susceptibility of IBD patients to complications, whether attributed to advanced age, underlying conditions, or the use of biological agents, vigilant postdischarge monitoring is warranted. This observation may also explain the greater reliance on home health care (HCC) for IBD patients in our dataset than for their non-IBD counterparts. Using nationwide patient sample (NIS) data, Nguyen et al. analyzed US hospitals for the presence of methicillin-resistant Staphylococcus aureus (MRSA) infection in IBD patients [15]. The study demonstrated an augmented MRSA risk in IBD patients, correlated with a heightened fatality rate [15]. Alongside the consideration of the presence of COVID-19 among IBD patients, prudent measures against nosocomial infections within this patient demographic population have become imperative.
Our data revealed that there was a greater percentage of females in the IBD cohort. It is well known that female sex is a risk factor for the development of IBD; however, the complex pathogenesis of IBD also involves genetic susceptibility and external environmental triggers such as medication use and dietary changes [16]. A study conducted in the USA over the span of five years revealed a greater incidence of IBD among females than among males [16]. However, a large-scale analysis in 2019 of 11 Asian-Pacific countries revealed a significantly greater incidence of IBD among the male population [17]. This suggests that sex-based differences may be correlated with environmental and geographical factors in disease epidemiology. A male predominance was also observed in an IBD meta-analysis conducted in China, and the articles included in this meta-analysis mainly consisted of patients with low-grade severity when compared to the IBD cohorts from Belgium and France [18]. This could suggest that the incidence and prevalence of sex-based differences are correlated with disease severity. According to several large-scale studies, a female predominance has been observed in patients with inflammatory bowel disease in Western countries [19, 20, 21]. Hence, this may explain the greater number of females observed in our cohort of COVID-19 patients with IBD. Apart from the genetic, sex, environmental, and geographical factors that have been examined, the greater occurrence of IBD in females might also be associated with the use of oral contraceptives [22]. In a substantial cohort study conducted in the United States involving more than 200,000 women, a connection was established between the use of oral contraceptives and increased susceptibility to IBD [22]. Similarly, a separate case‒control study utilizing the United Kingdom General Practice Research Database also indicated a heightened risk of IBD linked to the utilization of oral contraceptives [23]. Moreover, within the limits of the limited available data, gender disparities have been noted in terms of COVID-19 hospitalization and mortality. An analysis encompassing data provided by the CDC revealed that more than a million COVID-19 cases in the United States indicated a greater frequency of ICU admissions and elevated fatality rates among males compared to females [24]. The mechanism underlying this sex-specific susceptibility to COVID-19 is potentially linked to ACE2 and transmembrane protease serine 2 (TMPRSS2) [25]. As previously discussed, given the correlation between increased ACE2 expression and increased COVID-19 susceptibility, research has revealed increased ACE2 expression among males [25, 26]. Furthermore, the expression of TMPRSS2, a significant player in COVID-19 cell entry, is increased in males due to the presence of androgen receptors [27]. These mechanisms may explain the male predominance observed in our non-IBD cohort, where the presence of COVID-19 and comorbidities were sufficient to increase the mortality rate to a rate similar to that of the IBD cohort. While ACE2 is also expressed in females, the inhibitory impact of estrogen on ACE2 may confer some level of defense against COVID-19 [28]. However, a study conducted on IBD patients with a history of COVID-19 infection reported that the prevalence of long COVID-19 was greater among female patients [25, 29]. Another study on long COVID-19 in IBD patients also reported the same findings [30, 31]. Due to the difference in immune response based on sex, it seems that females may have a continued systemic inflammatory reaction for long COVID-19 symptoms to develop. Thus, continuous monitoring is crucial for the early identification of complications in these patients. Further research is essential to determine the influence of long COVID-19 on the clinical progression of IBD patients.
Our study revealed comparable mortality rates between the IBD and non-IBD patient groups. A US cohort study utilizing federal health data also reported no difference in mortality between these groups in the presence of COVID-19 [32]. During the pandemic, it is possible that only the most critical patients were admitted and that the increase in SARS-CoV-2 infection had no effect on patient outcomes. With SARS-CoV-2 detected in stool samples and ACE2 upregulation, one might assume that IBD patients are at a greater risk of infection [33]. However, according to the literature, there is no correlation between these factors and the infectivity rate or severity of COVID-19 in IBD patients. The use of immune-mediated therapies in IBD patients might increase the risk of infection; however, it is hypothesized that these same therapies could also provide protection against the cytokine storm or inflammatory response associated with severe COVID-19 [34]. According to the data released by the three largest tertiary IBD centers in Wuhan, China, no cases of COVID-19 were reported at these centers [34]. Another set of data was also released by a tertiary center located in northern Italy, which had one of the highest COVID-19 rates early in the pandemic. Based on the data, 522 IBD patients admitted to this center during that time reported no cases of COVID-19 for the remainder of their stay at the hospital [35]. It is quite possible that immunosuppressive treatment might have offered protection against COVID-19 in these IBD patients. This may explain the similar mortality rates observed in our data among IBD and non-IBD patients.
Our data demonstrated that the majority of COVID-19 patients with IBD were admitted to urban teaching hospitals, particularly in the southern and midwestern regions. A meta-analysis from China on IBD highlighted a sudden increase in cases in southeastern areas following the adoption of a westernized lifestyle [36]. This sudden rise suggests that environmental triggers underpin the disease, encompassing factors such as socioeconomic status, sanitation, infections, medications, and lifestyle practices [37]. Multiple studies, mirroring our findings, affirm that IBD is more prevalent in urban than in rural settings [38, 39]. The discussed environmental risk factors for IBD are more commonly found in urban regions of western nations, elevating the risk of IBD development among residents. A study conducted in Sweden reported an increased risk of IBD among families with low socioeconomic status [40]. In our study, there was no significant correlation between the median income of families and IBD, which suggests that factors other than socioeconomic status influenced the development of the disease in these patients. However, it is quite possible that a portion of the patients analyzed in our study who did not have proper access to healthcare during the pandemic due to financial constraints may have had a higher fatality rate in both cohorts. Our data revealed that more than half of the patients in both cohorts were treated with Medicare, and the remaining patients were treated with Medicaid and private insurance. A study was conducted using the State Inpatient Database, where the prevalence of fragmentation in patient care was reported to be among one in four IBD patients and was associated with poor visit outcomes [41]. Fragmentation has been linked to certain factors, such as Medicaid recipients, preexisting neurological conditions, substance misuse, and urgent readmissions [41]. Our study aligns with this, as we connected neurological comorbidities and immune disorders to in-hospital mortality among IBD patients. Substance abuse showed no correlation in our dataset; however, a subset of IBD patients had Medicaid ties, warranting vigilant monitoring and tailored interventions for enhanced outcomes among vulnerable groups.
Our retrospective study represents the most comprehensive assessment to date of the COVID-19 patient population with IBD, evaluating both epidemiology and outcomes. To date, our study is the first to thoroughly analyze COVID-19 hospitalizations with and without IBD to identify factors associated with high-risk individuals. Our analysis integrated comorbidities, predictors of mortality, and clinical characteristics to assess patient outcomes. Given the restricted accessibility of centralized patient databases, population-based studies on COVID-19 hospitalizations for IBD patients within the United States have been limited. Our research thus contributes pivotal insights to healthcare authorities concerning the factors governing IBD incidence and prevalence amid COVID-19 hospitalizations. A significant strength of our study lies in its comprehensive comparison of COVID-19 hospitalizations with and without IBD, facilitating a nuanced comprehension of mortality influencers in both cohorts. Nonetheless, we recognize certain limitations inherent to this study. When utilizing extensive databases such as the NIS, potential distortion could arise from errors within the ICD-10 diagnostic coding system. Additionally, inpatient discharge data may solely represent participating hospitals within the Healthcare Cost and Utilization Project (HCUP) [42]. Moreover, the NIS database lacks information regarding disease severity or treatment details. The geographical distribution of patients revealed variations in terms of underlying comorbidities, genetic predispositions, and IBD medications, potentially impacting COVID-19 risk. Furthermore, given that COVID-19 can exacerbate gastrointestinal symptoms in non-IBD patients, distinguishing between IBD patients and non-IBD patients could be challenging [43].