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

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.

Viral load and gastrointestinal inflammation in COVID-19 patients

“…This suggests the potential risk of fecal-oral transmission and raises the question of whether this prolonged delayed clearance in the gut system causes persistent gastrointestinal inflammation or becomes one of the long COVID-19 manifestations that needs further investigation. 27 There were several limitations of this study. The monocentric study with a small sample of this study might not be enough to represent the general population.…”

Calprotectin and SARS-CoV-2: A Brief-Report of the Current Literature

“…The authors did not detect any differences in FC concentrations between patients with and without diarrhea. However, the patients with SARS-CoV-2 RNA detected in fecal samples had higher FC (74 vs. 39 mg/kg, p < 0.001), lower neutrophil counts (5550 vs. 4390 cell/µL, p < 0.035), and higher D-Dimer (723 vs. 580 ng/mLFEU) [40]. On the contrary, Britton et al did not find any correlation or difference in FC concentrations between patients stratified by gastrointestinal symptoms or detection of fecal viral-RNA [38].…”

Calprotectin in spondyloarthritis and gut inflammation, is it clinically meaningful?

“…The downside of this strategy includes the disturbance of the fCAL level by several confounding factors. Approximately 20% of healthy participants, patients using non‐steroidal anti‐inflammatory drugs (NSAIDs), body mass index (BMI) >25 kg/m 2 and even in the groups with coronavirus disease 19 (COVID‐19) have statistically significantly higher fCAL levels 15,16 . The users of anti‐TNF antibodies, including infliximab, adalimumab, golimumab had significantly lower fCAL compared to patients without therapy 11 …”