Inflammatory protein biomarkers elevated several years before ulcerative colitis diagnosis

17th August 2021

Patient blood samples several years before developing ulcerative colitis indicated elevated levels of inflammatory protein biomarkers.

Ulcerative colitis is a bowel disease characterised by inflammation in the large bowel and rectum. It is a chronic, relapsing, remitting disease with an estimated prevalence of 9 to 20 cases per 100,000 people per year and which causes diarrhoea, abdominal pain and rectal bleeding. While the underlying aetiology is uncertain, it is believed to arise from exposure to environmental triggers in susceptible individuals. Furthermore, it is widely accepted that treating the disease at an earlier stage is the preferred strategy, particularly as once the diagnosis is established, bowel damage is already present in the majority of patients highlighting the need to identify possible early disease markers. Though research has already identified several inflammatory protein biomarkers that are predictive of Crohn’s disease within 5 years, there are currently no known relevant protein biomarkers for ulcerative colitis.

In trying to identify any such relevant protein biomarkers, a team from the Department of Gastroenterology, Faculty of Medicine and Health, Orebro University, Sweden, performed a case-control study comparing pre-diagnostic plasma samples of those who later developed ulcerative colitis (cases) with those who remained free of the disease (controls). In an effort to determine the influence of genetics and environmental factors, the researchers also examined twin pairs and healthy controls. The team used principal component analysis to identify specific proteins that were elevated in either case or control patients.

Findings
The researchers focused on 92 different potential protein biomarkers and obtained pre-diagnostic plasma samples from 72 individuals who later developed ulcerative colitis and 140 matched healthy controls. The median age of both case and control cohorts was 50 years (47% male) and the median time from when the pre-diagnostic samples were taken before diagnosis was 4.8 years. Analysis of the protein biomarkers revealed a total of six specific proteins that differentiated between cases and controls (p < 0.05) and which remained significantly elevated (after adjustments for age, sex and smoking status). An analysis of the area under the receiver operating curves showed that these six proteins had a valve of 0.92. Among the of twin samples, only four of these six proteins were discriminatory for ulcerative colitis.

In a discussion of their findings, the authors highlighted the importance of identifying predictive signatures for ulcerative colitis and concluded that the up-regulation of these six protein biomarkers were highly predictive of the subsequent development of ulcerative colitis and concluded that this provided a novel means of identifying patients who were likely to develop the disease in the future.

Citation
Bergemalm D et al. Systemic inflammation in pre-clinical ulcerative colitis. Gastroenterology 2021

IBD patients develop new gastrointestinal symptoms with COVID-19

12th August 2021

New gastrointestinal symptoms in patients with irritable bowel disease is a feature of infection with COVID-19 rather than a disease flare.

The presence of gastrointestinal (GI) symptoms among those infected with COVID-19, occurs in around 17.6% of patients. Whether or not the presence of GI symptoms is prognostic for more severe disease, however, remains unclear except perhaps for abdominal pain. In contrast, other studies have indicated that the development of GI symptoms could even attenuate any COVID-19 associated inflammation. The term inflammatory bowel disease (IBD) is essential an umbrella term which covers both Crohn’s disease and ulcerative colitis although typically, both groups of patients will experience symptoms of diarrhoea, abdominal pain, fatigue, rectal bleeding and weight loss. Some evidence indicates that among those with IBD infected with COVID-19, there is a higher incidence of both diarrhoea and abdominal pain, compared to non-IBD patients. In fact, in a review of 1028 patients with IBD infected with COVID-19, 20% experienced diarrhoea. Given that infection with COVID-19 can lead to gastrointestinal symptoms in nearly a fifth of patients without IBD, researchers from the Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine, New York, US, decided to examine the extent of symptoms experienced by IBD patients using data held within a global disease registry. The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry, created to monitor the outcomes of COVID-19 in both adults and children with IBD. Clinicians are advised to the voluntarily report all cases of PCR-confirmed infections in all their IBD patients onto the registry to enable the capture of data related to those with IBD. Using this registry, the team sought to determine the association between any new GI symptoms with the odds of death due to COVID-19.

Findings
Data were available for 2917 IBD patients who had COVID-19, of whom, 26.4%, with a mean age of 43 years (55.5% female) developed new GI symptoms when infected with the virus. There was no significant difference in the incidence of new GI symptoms in those with Crohn’s disease or ulcerative colitis. Moreover, new gastrointestinal symptoms occurred more frequently in those with active disease compared to those in remission (29.4% vs 23.3%, p < 0.01). The pattern of symptoms however, was broadly similar apart from abdominal pain. For instance, diarrhoea occurred in 83% vs 76% (active disease vs remission) and nausea in 24% vs 25% (active disease vs remission). The greatest disparity was in abdominal pain (44% vs 26%, active disease vs remission). In addition, patients with IBD experiencing new GI symptoms were more likely to be hospitalised because of COVID-19 (31.4% vs 19.2%, p < 0.01) although the development of new symptoms was not associated with a higher risk of death.

The authors discussed how the development of new gastrointestinal symptoms were unlikely to represent a disease flare, because a large number of those in remission also experienced new symptoms after becoming infected. They concluded that the presence of new gastrointestinal symptoms in a patient with IBD should clinicians to consider infection with COVID-19 although the team also felt that further studies were needed to determine if infection could trigger an IBD flare or even alter the subsequent course of the disease.

Citation
Ungaro RC et al. New Gastrointestinal Symptoms Are Common in Inflammatory Bowel Disease Patients With COVID-19: Data from an International Registry. Inflamm Bowel Dis 2021

COVID-19 infection rates no higher among patients with immune-mediated inflammatory diseases

28th May 2021

A large European study has revealed that the risk of COVID-19 is no higher among immunosuppressed patients, provided systemic inflammation is controlled.

Disease severity in COVID-19 is known to be worse in those with associated co-morbidities such as hypertension and diabetes. Furthermore, concerns have been raised that the presence of a dysfunctional immune system as seen in patients with immune-mediated inflammatory diseases such as rheumatoid arthritis, also increases the risk of a poor prognosis. In fact, one meta-analysis has estimated that patients with autoimmune diseases have more than twice the risk of infection with COVID-19. Nevertheless, it has also been suggested that due to the systemic inflammatory response induced by COVID-19, patients prescribed treatments aimed at controlling the inflammatory response, may be protected against more severe disease. In an effort to understand more about how COVID-19 impacts upon those with immune-mediated inflammatory conditions, the Euro-COVIMID study was undertaken. This cross-sectional study, followed-up patients in six European countries with one of several immune-related inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus and Sjogren’s syndrome. Data was collected on demographics, co-morbidities, number of recent disease flares and the presence of COVID-19 in a questionnaire completed in consultation with a healthcare professional when the patient was seen at an outpatient clinic. The primary outcome of the study was the prevalence of serological and clinical COVID-19 and the authors examined whether there were any particular factors associated with the risk of infection.

Findings
A total of 3038 patients with a mean age of 58 years (73.9% female) were included in the analysis. The most common immune disease was rheumatoid arthritis (29.4%), axial spondylarthritis (22.1%) and systemic lupus erythematosus (20%). Nearly a third (32%) of patients were taking oral prednisolone and 35.9% were prescribed a biological or synthetic DMARD. Co-morbidities included hypertension (29.7%), dyslipidaemia (13.6%) and obesity (8.1%).

COVID-19 antibodies were detected in 5.5% of patients and symptomatic COVID-19 occurred in 122 (4%) of whom, 24 were hospitalised and 4 died. Factors significantly associated with symptomatic COVID-19 included higher plasma levels of C-reactive protein, CRP (odds ratio, OR = 1.18, 95% CL 1.05 – 1.33, p = 0.006) and a higher number of disease flares (OR = 1.27). In contrast, the use of biological therapy was associated with a reduced risk (OR = 0.51) of symptomatic COVID-19.

In their discussion, the authors noted that the prevalence of COVID-19 among those with immune-mediated inflammatory diseases was no higher than in the general population. They also speculated that the presence of elevated CRP levels, representing systemic inflammation, might contribute towards the development of COVID-19 and that biological therapy, which effectively dampened systemic inflammation, appeared to exert a protective effect. The authors concluded that adequate control of inflammatory activity in those immune-mediated diseases could be crucial during the COVID-19 pandemic.

Citation
Saasoun D et al. SARS-CoV-2 outbreak in immune-mediated inflammatory diseases: the Euro-COVIMID multi-centre cross-sectional study. Lancet Rheumatol 2021