The Usefulness of Fecal Calprotectin in the era of the COVID-19 Pandemic

Dear Editors:

The coronavirus disease 2019 (COVID-19) pandemic has caused significant modifications in patient management, especially for chronically immunocompromised individuals. With approximately 3 million patients in the United States with inflammatory bowel disease (IBD) and the absence of substantial data in the era of coronavirus, this has become a complicated matter for gastroenterologists.^{1 , 2} We have encountered concerns among patients with IBD, given the nature of IBD therapies, requiring comprehensive discussions regarding the pros and cons of different management.

To protect patients and providers, American Gastroenterological Association published guidelines for endoscopic procedures and endorsed delaying elective procedures along with using a N95 and full personal protective equipment when performing essential procedures.³ Shortly thereafter, the American Gastroenterological Association published a practice update regarding the management of IBD.² This update is congruent with previous endoscopic guidelines, and it also has great recommendations about how to care for patients who are suspected or confirmed to be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with different clinical scenarios related to the severity of the underlying IBD and COVID-19 infection and a detailed discussion about the safety concerns regarding IBD therapies and how to modify them.^{2 , 3}

The practice update has also addressed options for disease assessment in these patients, given the need to avoid nonurgent procedures. Fecal calprotectin (FC) is a calcium-binding, primarily neutrophilic-specific protein and its concentration is proportional to the concentration of neutrophils in the colorectal mucosa. FC is useful for evaluation of gut inflammation in patients with gastrointestinal symptoms and can help us not only differentiate between irritable bowel syndrome and IBD, but also in assessment of disease activity of IBD.⁴ Currently, FC testing is underused, with most testing being done alongside endoscopic procedures; however, during this pandemic it may be a great diagnostic tool for the assessment of possible flares in patients with IBD.⁵

FC has been studied extensively in the setting of IBD and has demonstrated usefulness as a noninvasive marker for diagnosis and assessment of disease activity, given its correlation with intestinal inflammation.⁶ FC has a great sensitivity and specificity for the detection of histologic remission in patients with IBD with colitis, depending on the cut-off value being used. A sensitivity of 100%, specificity of 77%, negative predictive value of 100%, and positive predictive value of 81.2% has been reported with a cut off value of <100 μg/g.⁶ It may also help predict future flare. In patients who are in clinical remission, a FC of >150 μg/g has shown a 2-fold and 14-fold increased risk of relapse among patients with Crohn’s disease and ulcerative colitis, respectively.⁷

For the patient with irritable bowel syndrome symptoms, FC is more reliable than C-reactive protein and the erythrocyte sedimentation rate to screen for IBD. The 2018 guidelines endorsed incorporating the use of FC in the management of patients with IBD and, given the limitations that COVID-19 has caused on performing endoscopic procedures, it seems even more crucial to take advantage of this underused diagnostic tool.⁵

However, one should use caution in interpreting FC results in patients with COVID-19, because a positive FC may occur with both bacterial and viral colonic infections. Thus, the FC data elicited from COVID-19–positive patients should be analyzed judiciously; SARS-CoV-2 viral RNA has been noted in fecal samples with an unclear effect on intestinal inflammation, with 1 reported case of a patient with COVID-19 whose initial symptom was bloody diarrhea and was found to have hemorrhagic colitis.⁸

Inflammatory markers being used for the evaluation of symptomatic patients with IBD to confirm the presence of active flares may be elevated in those with COVID-19.² This issue may affect their usefulness for evaluation of IBD flare among those infected with SARS-CoV-2, because intestinal inflammation from any etiology may increase inflammatory markers. It is important to know that, although a high level of FC in an patient with IBD and COVID-19 with diarrhea may not be very helpful in distinguishing an active IBD flare from the effect of SARS-CoV-2 on the gastrointestinal tract, a FC level of <100 μg/g should be used to rule out the presence of active inflammation in patients with history of colitis based on its high sensitivity and negative predictive value for the detection of inflammation. This approach will minimize the unnecessary use of essential personal protective equipment and decrease disease transmission. Although FC testing cannot completely obviate the need for the endoscopic evaluation of patients with new symptoms, it may help many patients with IBD to postpone endoscopic evaluation until the end of this crisis and possibly even beyond this time.