Elevated fecal and serum calprotectin in COVID-19 are not consistent with gastrointestinal symptoms

Abstract

Intestinal epithelial cell damage caused by SARS-CoV-2 infection was thought to be associated with gastrointestinal symptoms and decreased fecal consistency. The association of the gastrointestinal symptoms with the COVID-19-mediated inflammatory response triggered by the gastrointestinal immune system was investigated in this paper. Intestinal inflammation marker fecal calprotectin along with serum calprotectin and other inflammatory markers were measured in COVID-19 cases with and without GI manifestations as well as healthy individuals. Analyses were performed to compare COVID-19 patient subgroups and healthy controls and examine the relationship between fecal and serum calprotectin levels with gastrointestinal symptoms and disease severity. COVID-19 patients (n = 70) were found to have markedly elevated median levels of fecal (124.3 vs. 25.0 µg/g; P < 0/0001) and serum calprotectin (3500 vs. 1060 ng/mL; P < 0/0001) compared with uninfected controls. Fecal and serum calprotectin levels were not significantly different between COVID-19 patients who displayed GI symptoms and those who did not. Compared with other acute phase markers, both fecal and serum calprotectin were superior in identifying COVID-19 patients who progressed to severe illness. Although the progression of COVID-19 disease is marked by an elevation of fecal and serum calprotectin, gastrointestinal symptoms or diarrhea were not correlated with calprotectin increase level.

Figure 1

The proportion of patients based on GI symptoms. (A) The proportion of COVID-19 patients with or without GI symptoms. (B) Frequency of reported GI symptoms in both all patients and patients with GI symptoms.

Figure 2

Laboratory findings of COVID-19 and healthy individuals. Hematology and biochemistry markers in COVID-19 patients compared with control. Comparisons between patients with and without GI symptoms are also shown. The median and the interquartile ranges are represented on violin plots. Each point indicates a value of a patient. The P values calculated using the Mann–Whitney test and Welch t-test with significance defined as P < 0.05.

Figure 3

Concentrations of SC and FC in COVID-19 and healthy donors. Comparison of FC and SC concentrations based on COVID-19 infection as well as having GI symptoms (A,B). SC and FC levels based on the types of GI problems in patients with GI symptoms (C,D). SC and FC concentrations in COVID-19 patients based on the presence of diarrhea (E,H). The correlation of FC and SC with diarrhea severity (F,I). Comparison of FC and SC levels between two diarrhea conditions (G,J). Plots show median ± interquartile range, and P values are shown in the figures.

Figure 4

Correlation of FC with clinical laboratory studies. Data were examined by Pearson correlation and Spearman correlation for normal and non-normal data. Correlation coefficients and P values are shown in the figures.

Figure 5

FC and SC relation to COVID-19 severity. Comparison of SC and FC levels according to three classes of disease severity (A,B). The correlation of FC or SC with disease severity (C,D). The correlation of FC or SC with the duration of hospitalization (E). Receiver operating characteristic (ROC) curve evaluation of the performance of FC, SC and CRP risk score in diagnosis COVID-19 patients or distinguish severe cases (F,G). AUC: under the ROC curve. P values are shown in the figures.