High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients: A proof-of-concept study

doi:10.3748/wjg.v27.i22.3130

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World Journal of Gastroenterology

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World J Gastroenterol. Jun 14, 2021; 27(22): 3130-3137
Published online Jun 14, 2021. doi: 10.3748/wjg.v27.i22.3130

High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients: A proof-of-concept study

Verena Zerbato, Stefano Di Bella, Mauro Giuffrè, Anna Wladyslawa Jaracz, Ylenia Gobbo, Diego Luppino, Paolo Macor, Ludovica Segat, Raffaella Koncan, Pierlanfranco D'Agaro, Michael Valentini, Lory Saveria Crocé, Maurizio Ruscio, Roberto Luzzati

Verena Zerbato, Anna Wladyslawa Jaracz, Ylenia Gobbo, Diego Luppino, Michael Valentini, Infectious Diseases Unit, Trieste University Hospital (ASUGI), Trieste 34125, Italy

Stefano Di Bella, Roberto Luzzati, Infectious Diseases Unit, Clinical Department of Medical, Surgical and Health Sciences, Trieste University, Trieste 34123, Italy

Mauro Giuffrè, Lory Saveria Crocé, Liver Unit, Clinical Department of Medical, Surgical and Health Sciences, Trieste University, Trieste 34127, Italy

Paolo Macor, Department of Life Sciences, Trieste University, Trieste 34127, Italy

Ludovica Segat, Raffaella Koncan, Pierlanfranco D'Agaro, Department of Hygiene and Public Health Unit, Trieste University Hospital (ASUGI), Trieste 34125, Italy

Maurizio Ruscio, Division of Laboratory Medicine, Trieste University Hospital (ASUGI), Trieste 34125, Italy

Author contributions: Zerbato V and Di Bella S conceived/organized the study and wrote the manuscript; Giuffrè M performed the statistics; Zerbato V, Jaracz AW, Gobbo Y, Luppino D and Valentini M collected samples and provided help with conduction of the study; Segat L, Koncan R and D'Agaro P performed the virologic analysis; Macor P, Crocé LS, Ruscio M and Luzzati R reviewed the manuscript.

Institutional review board statement: This study was conducted according to the declaration of Helsinki and approved by the Ethics Committee (Unique Regional Ethical Committee, Friuli Venezia-Giulia 16 April 2020), No. CEUR 2020-OS-072.

Clinical trial registration statement: This study did not involve clinical trials.

Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.

Conflict-of-interest statement: The authors declare no conflicts of interest.

Data sharing statement: All study participants provided written consent prior to study enrollment.

CONSORT 2010 statement: CONSORT not applicable.

Corresponding author: Stefano Di Bella, MD, Doctor, Infectious Diseases Unit, Clinical Department of Medical, Surgical and Health Sciences, Trieste University, Trieste 34123, Italy. stefano932@gmail.com

Received: February 2, 2021
Peer-review started: February 7, 2021
First decision: February 27, 2021
Revised: March 12, 2021
Accepted: April 21, 2021
Article in press: April 21, 2021
Published online: June 14, 2021
Processing time: 125 Days and 17.7 Hours

Abstract

BACKGROUND

One third of coronavirus disease 2019 (COVID-19) patients have gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in stool samples of approximately 50% of COVID-19 individuals. Fecal calprotectin is a marker of gastrointestinal inflammation in the general population.

AIM

To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia.

METHODS

Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit (University Hospital of Trieste, Italy) from September to November 2020 were consecutively enrolled in the study. Fecal samples were collected and analyzed for quantification of fecal calprotectin (normal value < 50 mg/kg) and SARS-CoV-2 RNA presence by polymerase chain reaction (PCR). Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2.

RESULTS

We enrolled 51 adults (40 males) with SARS-CoV-2 pneumonia. Ten patients (20%) presented with diarrhea. Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients (76%), in all patients with diarrhea (100%) and in more than two thirds (29/41, 71%) of patients without diarrhea. Obesity was one of the most common comorbidities (13 patients, 25%); all obese patients (100%) (P = 0.021) tested positive for fecal SARS-CoV-2. Median fecal calprotectin levels were 60 mg/kg [interquartile range (IQR) 21; 108]; higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools (74 mg/kg, IQR 29; 132.5) compared to the group without SARS-CoV-2 (39 mg/kg, IQR 14; 71) (P < 0.001).

CONCLUSION

High fecal calprotectin levels among COVID-19 patients correlate with SARS-CoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the ‘leaky gut’ syndrome.

Keywords: COVID-19; SARS-CoV-2; Obesity; Fecal calprotectin; Gut; Viral shedding

Core Tip: In this prospective study of 51 hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, whether fecal calprotectin correlated with SARS-CoV-2 intestinal shedding was investigated. We found that high fecal calprotectin level is a common finding among hospitalized coronavirus disease 2019 (COVID-19) patients, especially those with SARS-CoV-2 fecal shedding. Obese COVID-19 patients showed high fecal viral shedding.