key: cord-0924898-k2ijm3rc
authors: Grunert, P C; Reuken, P A; Stallhofer, J; Teich, N; Stallmach, A
title: Inflammatory Bowel Disease in the COVID-19 Pandemic – the Patients‘ Perspective
date: 2020-06-20
journal: J Crohns Colitis
DOI: 10.1093/ecco-jcc/jjaa126
sha: 3c0ea048775ff16bacea6f950e58d13b258f8175
doc_id: 924898
cord_uid: k2ijm3rc

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is affecting lives worldwide. The influence of inflammatory bowel disease (IBD) medication and IBD itself on COVID-19 is controversial. Additionally, IBD focused guidance is scarce. OBJECTIVE: To determine COVID-19 prevalence/exposure, perception and information sources, medication compliance, patient behaviour and physician contact among patients with IBD compared with non-IBD controls. METHODS: A cross-sectional anonymous survey of patients with IBD (N=415) at one university IBD clinic and one gastroenterology practice, matched 4:1 with control participants (N=116), was performed. RESULTS: Patients with IBD had high fear of infection. The fear was more pronounced in patients taking immunosuppressants and it extended to hospitals, private practices and public places, such as supermarkets. IBD patients reported leaving their homes less frequently than their peers without IBD. A total of 90% of patients with IBD reported washing their hands more frequently. Patients taking immunosuppressants were concerned about interactions between medication and COVID-19, whereas patients taking 5-aminosalicylates were not. Nonetheless, 96.4% of patients adhered to continuing their medication. Patients sought guidance primarily from television and internet news sites. Video consultations were found to be a suitable solution for a subset of patients who are young, have a high level of fear and leave their home less frequently than their peers, whereas overall acceptance of video consultations was limited. CONCLUSION: Patients with IBD are significantly more affected by the COVID-19 pandemic than their non-IBD peers, but they continue to adhere to their medication regimens. IBD focused COVID-19 information should be actively conveyed.

The coronavirus disease , a new form of severe acute respiratory syndrome (SARS), is caused by the novel coronavirus SARS-CoV-2. On 12 March 2020, after an unprecedented worldwide spread following its outbreak in China in December 2019, SARS-CoV-2 was announced as a global pandemic by the World Health Organization (WHO) 1 . It infected more than 5 million people in the subsequent weeks and has become a substantial threat to public health and society, worldwide. Governments around the world have responded with surges in new public policies, and one-third of the world's population has now been subjected to social restrictions ranging from bans of public assembly to complete lockdowns 2 .

Symptoms of COVID-19 comprise fever, aches, dry cough and shortness of breath; however life-threatening conditions, ranging from respiratory failure to multi-organ dysfunction, may also result. Increasing evidence indicates that older and immunocompromised patients, as well as patients with existing comorbidities, are at higher risk of more complicated or even lethal courses of COVID-19 3 .

Although there is no evidence to date of higher susceptibility of patients with IBD to COVID-19 4 , IBD medications may pose a threat. IBD treatments often rely on immunosuppressive therapy regimens to induce and maintain clinical remission. Opinions differ as to whether these medications should be continued or discontinued, owing to their potential to cause infectious complications 5 ; however, in cytokine storm driven inflammation immunosuppressive therapies might possibly have a protective effect 6 . Moreover, experimental evidence suggests that commonly used IBD treatments may have lung protective effects 7 .

WHO guidance for behaviour during the COVID-19 pandemic includes basic protective measures, such as frequent hand washing; social distancing; avoiding touching of the eyes, A c c e p t e d M a n u s c r i p t Manuscript Doi: 10.1093/ecco-jcc/jjaa126 nose and mouth; respiratory hygiene; seeking medical care early in the case of respiratory symptoms; and remaining informed 8 . However, IBD specific guidance for patients is lacking.

In our daily outpatient practice visits, there is notable uncertainty among patients with IBD regarding the influence of their disease and medication on COVID-19 disease. To date, there is a lack of data regarding how this uncertainty translates into the daily lives of our patients.

We assessed the COVID-19 prevalence/exposure, perception and information sources, patient behaviour, physician contact and medication compliance among patients with IBD in April 2020, by using a cross-sectional anonymous survey, and we compared the results with those from a non-IBD control cohort.

Patients from the IBD outpatient clinic of Jena University Hospital (Jena, Germany) and an IBD-specialized gastroenterology practice in Leipzig, Germany were identified. A total of 715 patients with IBD were asked to complete the survey. Recruitment occurred between 2 April 2020 and 17 April 2020. To compare opinions, concerns and behaviour, mostly healthy non-IBD participants were asked to complete a similar survey (control group). This group consisted of healthy family members of patients with IBD (n=75) and relatives/acquaintances of health care workers (n=41).

The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee (2020-1733-Reg). All participants provided written informed consent before inclusion into the study.

Statistical analysis was performed in SPSS 23 (IBM Inc, Armonk, NY) and PRISM 6 (GraphPad Software, La Jolla, CA). Statistical differences between groups were analysed with non-parametric Mann-Whitney U-test for continuous data or Fisher's exact test for discrete data. To analyse correlations between variables, Spearman's correlation was used.

Results with P < 0.05 in two-sided tests were considered statistically significant.

A c c e p t e d M a n u s c r i p t 25.9% in the control group) ( Table 1) .

Patients with IBD had more comorbidities than participants in the control group.

Approximately half of the surveyed IBD population had at least one comorbidity (n=207 (49.9%)), in contrast to only 37% of the controls (n=43 (37.1%)).

The participants in the IBD group showed a nearly even distribution between Crohn's disease (51.8%) and ulcerative colitis (46.3%). Five patients (1.2%) had IBD unclassified (IBDU), and the disease type was not further specified by three patients ( A c c e p t e d M a n u s c r i p t Manuscript Doi: 10.1093/ecco-jcc/jjaa126

The most common medication was 5-aminosalicylates, which were taken by one-third of the patients with IBD (34.5%), and this was followed by anti-tumor necrosis factor alpha (anti-TNF) therapy (25.5%). However, biologic agents together composed the largest group of IBD medication (46.8%). Combination treatment with more than one immunosuppressant was used in 13% of the patients with IBD. Only 15.3% of patients in the IBD cohort were not taking any IBD therapy ( Table 2) .

Patients with IBD were more afraid of being infected with SARS-CoV-2 (question 1 (Q1)) than participants in the control group ("agree" vs. "neutral", statistically significant, p=0.009) (Supplementary Table 1 ). This fear was more pronounced in patients taking immunosuppressants (Figure 1 ). Patients with IBD were afraid of contracting SARS-CoV-2 in three different external environments: hospitals (Q3), private practice (Q4) and supermarkets (Q5) (all median "agree"). In contrast, the control group did not fear these environments as much: they rated their fear of private practices (p=0.062) or supermarkets as "neutral" (p=0.65) and they "disagreed" with being afraid of being infected in hospitals (p=0.03).

Participants in both groups "agreed" that they "leave the house less frequently than before the coronavirus pandemic" (Q7). However, the control group leaned more towards a "neutral" sentiment (statistically significant, p=0.037). Moreover, 38.2% of patients with IBD A c c e p t e d M a n u s c r i p t Manuscript Doi: 10.1093/ecco-jcc/jjaa126

(controls 23%) indicated that they leave the house less frequently than their partners/flatmates (Q8) (statistically significant, p<0.001).

Patients with IBD were more concerned about the negative effects of their medication on COVID-19 disease than controls (Q2). A subgroup analysis of Q2 for medication type showed that patients taking biological agents or Janus kinase inhibitors, combination therapy (anti-TNF and thiopurines) or corticosteroids were more afraid of their medications' effects ( Figure 1) . A total of 44.1% of patients taking one, and 57.7% taking two, immunosuppressants agreed or strongly agreed with fearing a negative effect (data not shown), whereas the concern among patients with IBD taking 5-aminosalicylates or no medication was statistically not different from that of the control group (both "strongly disagree").

When patients with IBD were asked whether they would prefer a video consultation over an in-person consultation (Q6), the median response was "disagree". (1.7%) in the IBD group (statistically significant, p<0.001)) ( A c c e p t e d M a n u s c r i p t Manuscript Doi: 10.1093/ecco-jcc/jjaa126

The most important source of information to guide behaviour during the COVID-19 pandemic among patients with IBD was the public media (Supplementary Table 2 

In this survey of more than 400 patients with IBD, we found that the fear of infection by SARS-CoV-2 was high and exceeded that in the non-IBD participants. The fear extended to hospitals and private practices as well as public places such as supermarkets. Therefore, the question arose as to whether the daily lives of patients with IBD might be influenced.

Patients with IBD reported leaving their homes less frequently than they used to before the COVID-19 pandemic. This result was expected; however, this group of participants left the house even less frequently than their partners/flatmates in the same household. A total of 90% of participants said that they washed their hands more often than they did before and, therefore, followed the WHO recommendations. Paradoxically, this cautious behaviour did not translate into greater use of personal protective equipment, such as surgical masks, when leaving the home. This finding may be explained by the rapidly changing governmental Normally patients with IBD do ask medical professionals for information regarding IBD diagnosis and medical therapy and ask their peers online for advice regarding daily problems and coping strategies 16, 17 . However, in the COVID-19 pandemic, we observed that patients with IBD primarily consulted television and internet news for guidance, whereas IBD support groups and physicians were of far lesser importance. We therefore recommend actively reaching out to patients with IBD (e.g., sending informative letters, e-mails and suggestions of reliable information sources) to provide IBD relevant information and advice concerning the COVID-19 pandemic. IBD organisations do provide expert based guidance for physicians regarding COVID-19 10 . We should grant patients access to these sources by providing a patient focused version.

Medical systems worldwide have been transformed to treat patients with COVID-19. Regular testing are not sufficiently feasible with current video consultation techniques, thus resulting in reduced acceptance 22 .

Despite the large sample size of IBD patients, high response rate and comparison to a non-IBD cohort, there are some limitations to this study. Over 100 control participants were surveyed, still, the ratio of IBD to non-IBD subjects was about 4:1. Even though this ratio is also being used for similar quantities of subjects in clinical trials 23 , it does limit comparison of the two groups.

The control group had a similar demographic distribution (age, sex, education), but two thirds of the participants were living in the same household as IBD patients. This could bias the results to a more cautious behaviour or attitude because of their more vulnerable IBDhousehold member. Nevertheless, attitude and behaviour towards COVID-19 differed significantly between the control group and IBD patients. Furthermore, similar significant differences were also seen in a survey comparing liver transplant recipients with their household members during the COVID-19 pandemic 24 .

In our survey, the prevalence of exposure to infected individuals in the IBD group was 1.7%

and no SARS-CoV-2 infection was reported in this group. The true prevalence of SARS-CoV-2 may be underestimated, given the report-based data acquisition and the possible underdiagnosis of COVID-19 due to asymptomatic patients or atypical symptoms such as smell/taste disorders or muscle aches, which were not recommended for testing in the early phase of the COVID-19 pandemic.

Most participants were from the state of Thuringia and Saxony, where the cumulative SARS-CoV-2 incidence is as low as 90/100,000 and 106/100,000, respectively (as of 23 April 2020) 25 . This geographic range might be a limitation of our study. Although the actual number of infections is lower than that in some other countries, media coverage regarding A c c e p t e d M a n u s c r i p t Manuscript Doi: 10.1093/ecco-jcc/jjaa126

Funding No funding was sourced for this project.

No potential conflict of interest was reported by the authors.

We thank Cornelia Nageler for survey data input. A c c e p t e d M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t 

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