key: cord-350466-z5yvfo22
authors: Jena, Anuraag; Kumar-M, Praveen; Singh, Anupam Kumar; Sharma, Vishal
title: Fecal calprotectin levels in COVID-19: Lessons from a systematic review on its use in inflammatory bowel disease during the pandemic
date: 2020-10-19
journal: Dig Liver Dis
DOI: 10.1016/j.dld.2020.10.021
sha: 
doc_id: 350466
cord_uid: z5yvfo22

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Fecal calprotectin measurement is often used for discriminating inflammatory bowel disease (IBD) from irritable bowel syndrome, distinguishing active IBD from remission and in management of Crohn's disease using a tight control approach. 1 Use of fecal calprotectin, especially home-based testing, has been suggested as a tool for remote monitoring during the COVID pandemic. Point of care calprotectin tests can help in evaluating disease activity in IBD patients. 2 Their use can help tide over the delays in diagnostic endoscopy which are frequent in the COVID era. 3 Recent reports, including one published in the journal, about elevations of fecal calprotectin in COVID-19 raise concerns about this strategy of home based monitoring using fecal calprotectin. 4-7 SARS-CoV2 RNA has been isolated in stool specimens. The interaction of SARS-CoV2 with the angiotensin converting enzyme-2 (ACE-2) receptors on gut epithelium could lead to myriad of gastrointestinal manifestations. 8 We therefore performed a systematic review to study the elevations of fecal calprotectin in COVID-19 and if these elevations were different in patients with or without gastrointestinal symptoms .

We searched the databases on PubMed and Embase on 27 September 2020 using the keywords "coronavirus, COVID-19, SARS-COV-2, nCOV, coronaviridae infection, coronavirus disease 2019"with 'AND' "Calprotectin or Calgranulin" (Supplementary Table 1 ). After removing the duplicates, we screened for the original studies reporting about fecal calprotectin in COVID-19 patients. We excluded the studies which reported the use of serum calprotectin in COVID-19. Relevant data were extracted and used for analysis. We identified 52 titles, of which 12 duplicates were removed (Supplementary Figure 1) . Out of the remaining 40 articles, 8 articles were assessed for full text screening. Data from 4 articles were used in the systematic review and other 4 studies were excluded (Supplementary Table 2 ). These four studies reported about fecal calprotectin levels in 174 patients with COVID-19 ( Table 1) . The rates of elevated fecal calprotectin were variable amongst the studies but all studies had significant number of patients with elevated levels (29.3-75%). The elevations of fecal calprotectin were more frequent in those patients who had gastrointestinal symptoms in all the three studies which provided this information (Figure 1 ).

Our analysis showed that fecal calprotectin levels were elevated in a significant proportion of patients with COVID-19. The elevation of calprotectin could be related to gastrointestinal inflammation resulting from SARS-CoV-2 infection. This could be due to direct viral injury to the gastrointestinal epithelium. [8] [9] Therefore, COVID-19 could cause elevated fecal calprotectin levels especially in the presence of GI symptoms. This could make the differentiation of COVID-19 infection difficult from a disease flares in IBD. So the evaluation of IBD flares solely with fecal calprotectin may not be sufficient. Further, as patients of IBD with elevated fecal calprotectin levels could be immunocompromised, it would be better to exclude COVID-19 infection prior to increasing immunosuppression. Our study addresses an important area of ambiguity but comes with certain limitations. First, the included studies only analyzed the data of hospitalized COVID-19 patients. Also, there are no direct studies of fecal calprotectin in IBD patients infected with COVID-19. This limits the generalizability of our findings to patients having underlying IBD. Future prospective studies could throw more light on this issue.

To conclude, routine testing for COVID-19 should be done in all patients of IBD with elevated fecal calprotectin in COVID-19. Relying merely on fecal calprotectin for differentiating IBD flare from diarrhea due to COVID-19 is questionable.

The authors declare that they have no conflicts of interest 

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Home-based fecal calprotectin test is expected to play an important role in patients with inflammatory bowel diseases

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