1. Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in China at the end of 2019, is a beta coronavirus that is transmitted by airway droplets from human to human [
1] and that caused the coronavirus disease 2019 (COVID-19) outbreak [
2,
3]. SARS-CoV-2 expresses surface spike proteins that bind to various receptors of human cells (CD26, CD147, and CD209), with the type 2 angiotensin-converting enzyme (ACE2) as the main target. ACE2 is highly expressed in respiratory and gastrointestinal systems, particularly in the oesophageal epithelium, glandular gastric mucosa, enterocytes, colonocytes [
4], and endothelial cells [
1]. Most patients have gastrointestinal symptoms, such as nausea, vomiting, anorexia, abdominal pain, and diarrhoea, while some patients only show gastrointestinal symptoms [
4,
5].
Data on the association between COVID-19 and ulcerative colitis (UC) are limited. The risk factors for a more severe COVID-19 disease in patients with inflammatory bowel disease (IBD) are an active disease and UC—a chronic, idiopathic, immune-mediated inflammatory disorder of the digestive tract [
2]. In general, IBD affects nearly 3 million people in the United States and 2.5–3 million people in Europe, with a direct healthcare cost of EUR 4.6–5.6 billion annually in Europe, mostly due to hospitalisations and surgeries [
6,
7]. The annual incidence of UC is estimated at 5–15 new cases per 100,000 people [
8]. The treatment of IBD is aimed at controlling an overactive immune response, which may involve the use of immune-modifying therapies, including immunomodulators or biologic drugs. Many of these treatments are associated with a known increased risk of infection, including an increased risk of a SARS-CoV-2 infection [
6,
9]. One of the big issues for IBD patients is therapeutic adherence, which has been reduced for COVID-19 with all the potential derivative implications. In addition, the vaccination rates against SARS-CoV-2 are affected by a fear of worsening the course of IBD or experiencing major side effects from the vaccine [
10]. The published data suggest that the use of vitamins and dietary supplements also increases in patients exhibiting COVID-related anxiety, with the most popular supplements being vitamin D, vitamin C, and multivitamin products [
11]. This study aims to bridge the gap in understanding the specific impact of COVID-19 on patients with UC, particularly focusing on lifestyle factors.
4. Discussion
In this cross-sectional study, we analysed the different characteristics of outpatients with UC—anthropometric data, the use of IBD medications and dietary supplements, and lifestyle habits and UC treatment—and their possible association with SARS-CoV-2 infections. We also evaluated the symptoms and severity of COVID-19 infections in patients who were positive for SARS-CoV-2.
Regarding the anthropometric data, reports in the literature show patients with UC being slightly shorter and leaner (with a smaller BMI) than healthy controls [
12,
13], with a median BMI in the healthy weight range [
12,
14]. Male patients with UC were taller than females and had a higher weight. Compared to other studies, the differences in height in late adolescence were not statistically significant compared to healthy controls [
12]. In this study, patients in the COVID-19-positive group had a higher BMI than those in the COVID-19-negative group. There were no overweight patients with UC in our study. The age of UC onset was similar to that reported in the literature, predominantly between 30 and 40 years of age in adult patients [
7,
12].
The mean duration of COVID-19 symptoms was seven days in our study. The clinical spectrum of COVID-19 is variable. Epidemiological studies have reported that the vast majority (80%) of patients infected with SARS-CoV-2 are asymptomatic or show mild symptoms; approximately 20% progress to a severe disease, of which 5% develop acute respiratory distress syndrome, septic shock, or multi-organ failure with a high mortality risk. The most frequent symptoms are a fever (up to 50–60%), a cough (40%), and anosmia/ageusia (40%). Diarrhoea is seen in approximately 18% of patients [
15]. The natural history of COVID-19 and the evolution of the SARS-CoV-2 infection were conditioned by cell tropism and the host immune response [
16,
17]. In our study, no patients had severe disease and the most common symptoms related to COVID-19 were similar to those reported in the literature [
18,
19,
20].
Depending on the extent and severity of IBD, patients may receive treatment with 5-ASA, biologics, corticosteroids, thiopurines, or molecular-targeting agents. One of the most widely used drug classes is 5-ASA, which corresponds to the findings in our study [
21,
22,
23,
24]. Reports have shown that a SARS-CoV-2 infection may contribute to UC flares [
25,
26].
More than half of the patients in this study (51%) followed specific diets, most commonly the anti-inflammatory IBD diet. Most patients on the IBD diet were COVID-19-negative, though the result was not statistically significant, likely due to the small sample size. We did not find any studies on diet and COVID-19 in patients with IBD. Experts from the European Society for Clinical Nutrition and Metabolism (ESPEN) state that, beyond the dietary management of IBD, nutritional optimisation and the treatment of both malnutrition and obesity-related illnesses are important to best equip patients to face COVID-19 [
27]. Preserving the nutritional status and preventing or treating malnutrition have the potential to reduce complications and negative outcomes. As COVID-19 can be accompanied by nausea, vomiting, and diarrhoea, impairing food intake and absorption, a good nutritional status is an advantage for people at risk of severe COVID-19 [
27,
28].
Almost half of our patients used different kinds of food supplements, mostly magnesium, fish oil, and iron. Women used food supplements more often than men. In a cross-sectional study conducted in Greece to evaluate the use of dietary supplements and their association with other factors, particularly anxiety related to COVID-19, it was found that 62.6% of the participants used dietary supplements. The most popular supplements were vitamin D, followed by vitamin C, multivitamins, and mineral products. The researchers found that women, former smokers, and people exhibiting signs of COVID-19-related anxiety were approximately two times more likely to use dietary supplements of any kind [
11]. While it is important to prevent and treat micronutrient deficiencies, there is no established evidence that the routine, empirical use of a supraphysiological or supratherapeutic amount of micronutrients can prevent or improve the clinical outcomes in COVID-19 [
27]. In a prospective, randomised, double-blind, placebo-controlled, multicentre trial, oral zinc administration in COVID-19 patients reduced the 30-day mortality, the chance of admission to the intensive care unit, and the duration of the symptoms [
29]. In another randomised clinical trial of outpatients with COVID-19, high-dose zinc gluconate, ascorbic acid, or a combination of the two supplements did not significantly decrease the duration of the symptoms compared to the standard of care [
30].
Most of the patients in our study, in both the COVID-19-positive and the COVID-19-negative groups, did not use probiotics. As millions of people have been infected during the ongoing COVID-19 pandemic, the performed studies strongly suggest that gut microbiota modulation could facilitate a timely recovery from COVID-19 and reduce the risk of post-acute COVID-19 syndrome (PACS) [
31]. A variety of possible microbiota-based prophylaxes and therapies for COVID-19, including faecal microbiota transplantation, probiotics, and prebiotics, have been discussed. The China National Health Commission has recommended the administration of probiotics to patients with severe COVID-19 to restore and maintain the intestinal microflora balance and prevent secondary infections [
31]. Supplementation with microbiota-targeted substrates (prebiotics), such as specific dietary fibres and/or the direct transfer of one or several specific beneficial microbiota (probiotics), are promising approaches to COVID-19 treatment that modulate the gut microbiota [
32,
33]. For example, a Lactococcus lactis strain was engineered to express and secrete the anti-inflammatory cytokine IL-10 to treat colitis [
34].
In the COVID-19-positive group, most of the patients did not use vitamin D. In the COVID-19-negative group, more patients supplemented with vitamin D, but in both cases, the results were not statistically significant. We collected data on vitamin intake, but not the precise dosage. Active vitamin D (1,25(OH)2D3—calcitriol) exerts multiple biological properties (endocrine, paracrine, and intracrine) in the human body [
35]. The vitamin D receptor is almost ubiquitously expressed by the cells of the immune system, supporting the role of vitamin D in the regulation of acute and chronic inflammatory responses. Recently, a robust meta-analysis of more than 1500 articles on this topic identified vitamin D supplementation as a protective factor against acute airway infections, thanks to its immunomodulatory properties [
1,
36]. Low serum concentrations of 25(OH)D3, especially below 25 nmol/L, are a risk factor for susceptibility to viral respiratory infections [
36]. Various studies with vitamin D supplementation in COVID-19 patients have shown an accelerated recovery, a reduction in the need for intensive care, and a reduction in mortality with oral calcifediol and cholecalciferol [
37,
38]. Vitamin D supplementation seems to be effective in COVID-19 when administered for a medium or long term, while high and/or single doses were found to be ineffective [
1].
Vitamin C was used by 14% of the UC patients in our study. The antioxidant properties of vitamin C have led to a hypothesis about its neuroprotective properties [
39]. It is difficult to find unambiguous results that indicate such an effect in vivo [
40]. Stimulating the immune system with high doses of vitamin C may paradoxically reduce immunity [
41]. A meta-analysis showed that the use of vitamin C in randomised trials was associated with a significant reduction in the in-hospital mortality for patients with COVID-19, compared to patients who did not receive vitamin C [
42]. In one study, the use of vitamin C with other supplements (including zinc and vitamin D) did not reduce the in-hospital mortality, possibly due to multicomponent supplementation being used in patients with more severe disease [
43].
In general, low levels of vitamins A, E, B6, B12, zinc, and selenium have been associated with adverse clinical outcomes during viral infections. An assessment of vitamin levels, the intake of Ω-3 polyunsaturated fatty acids, and the selenium, zinc, and iron levels should be considered in patients with COVID-19 [
27,
44]. We suggest that the provision of daily allowances for vitamins and trace elements be ensured for malnourished patients at risk for or with COVID-19, aiming to maximise the general nutritional defence against infection [
27].
In 2020, 22.3% of the world’s population used tobacco: 36.7% of men and 7.8% of women [
45]. Smoking is associated with an increased expression of angiotensin-converting enzyme (ACE), which is the main receptor that allows the penetration of SARS-CoV-2 into human cells [
18]. In our study, there were more non-smokers in the COVID-19-negative group, though the results were not statistically significant. Studies have shown a negative association between smoking and COVID-19 infections [
46,
47]. Current smokers have an excess risk of 34% for developing a severe course of COVID-19 (based on 124 studies) and an excess risk of 32% for mortality (based on 119 studies) [
48].
The results of a large study that evaluated alcohol use during the COVID-19 pandemic in the United Kingdom suggested that being older is associated with increased alcohol consumption [
49]. In our study, the COVID-19-positive group had more alcohol users, though this was not statistically significant. Although many studies have emphasised the increase in the consumption of alcoholic beverages during the pandemic [
50,
51,
52,
53], most of our study participants did not use alcohol as often, mostly 1–2 times a week.
In the COVID-19-positive group, only a few patients self-reported high stress levels in the last month before the interview; most people in both groups admitted less stress in the last month. In some studies on the stress levels in patients with IBD during the COVID-19 pandemic, the patients showed depression, anxiety, and fear associated with COVID-19, including a fear of being diagnosed with the infection [
54,
55,
56]. Furthermore, the lockdowns imposed by COVID-19 had a negative effect on the lifestyle and psychological stress of patients with IBD [
22]. Half of our study patients remained physically active by participating in sports activities. Most participants engaged in physical exercise 1–3 times a week. Patients who were physically active were less likely to contract COVID-19, although without statistical significance. In a study by Yu et al., one of the self-reported factors that influenced IBD symptoms in patients during the COVID-19 pandemic was a “reduction of exercise”. The results showed that the decrease in physical activity was a risk factor for a worsening disease [
23], although the relationship between exercise and IBD activity is not clear. Another study showed that the proportion of patients who were stressed due to COVID-19 rendering them unable to exercise and who stayed indoors increased significantly during lockdown [
57]. In a 2023 study of physical activity in IBD patients, almost half (42%) of the participants were not sufficiently active. Furthermore, most of the physically inactive patients believed that physical exercise might worsen their IBD symptoms [
14]. The advice of ESPEN experts to increase physical activity during lockdown included walking in the house and to the store, lifting and carrying groceries, alternating leg lunges, climbing stairs, and performing stand-to-sit and sit-to-stand exercises, chair squats, sit-ups, and push-ups. The use of eHealth and exercise videos, which focus on encouraging and delivering physical activity through the Internet, mobile technologies, and television, are other options to maintain physical function and mental health. Everyday physical activity for more than 30 min (or every other day for more than 1 h) is recommended to maintain fitness, mental health, muscle mass, and thus, energy expenditure and body composition [
27].