Clinical investigation of intestinal fatty acid-binding protein (I-FABP) as a biomarker of SARS-CoV-2 infection

Abstract

Objectives SARS-CoV-2 exhibits tropism for the gastrointestinal tract, however lesions in enterocytes and their correlation with disease severity and patient prognosis are still unknown. Methods SARS-CoV-2 patients were enrolled in five medical centres in the São Paulo State, Brazil. Clinical characteristics and laboratory findings of patients were recorded. At admission, 7 th and 14 th day of hospitalisation, plasma and urine samples were collected. The levels of cytokines (IFN-γ, IL-6 and TNF-α) and the biomarker intestinal fatty acid-binding protein (I-FABP) were measured. Results COVID-19 patients displayed ≈48-, 74- and 125-fold increased urinary I-FABP levels at admission ( n= 283; p <0.001), 7 th ( n =142; p <0.01) and 14 th day ( n =75; p <0.01) of hospitalisation, respectively. Critically ill patients and nonsurvivors showed higher I-FABP concentrations compared to those in the infirmary and survivors, respectively, within the same hospital stay periods. At admission, infected patients demonstrated enhanced production of plasma IFN-γ and IL-6. The ROC curve suggested I-FABP as a biomarker for disease severity of COVID-19 at admission ( p <0.0001; Youden index=6.89; AUC=0.699). Patients with I-FABP≥6.89 showed higher IL-6 and C-reactive protein levels ( p <0.001) at admission, as well as prolonged length of hospital stay. Conclusions Our findings revealed damage to enterocytes in SARS-CoV-2 infection, which is associated to illness severity, poor prognosis and exacerbated inflammatory response.

Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome

“…We also observed clear differences in the systemic levels of host factors, such as I-FABP and IL-10, indicating the loss in intestinal homeostasis in post-COVID subjects compared to controls. Indeed, I-FABP has been shown to be a relevant biomarker for COVID-19 disease prognostic [44].…”

“…ELISA for measurements of Intestinal fatty acid-binding protein (I-FABP) and cytokines ELISA techniques were used to quantify the concentrations of I-FABP as described before [44]. IL-10, TNFa and IL-1b concentrations were determined using IL-10 ELISA kits (R&D Systems, USA) according to the manufacturer's instructions.…”

Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms

“…We also observed apparent differences in the systemic levels of host factors, such as I-FABP, indicating loss of intestinal homeostasis in post-COVID subjects compared to controls. Indeed, I-FABP is a relevant prognostic biomarker that is positively correlated with a worse prognosis for COVID-19 (Saia et al, 2021). Thus, although no significant differences in α and β-diversity were observed in the gut microbiota of post-COVID and control subjects, functional changes were observed in both patients and mice.…”

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential

“…Importantly, serum markers of tight junction permeability and microbial translocation were significantly associated with circulating proinflammatory mediators such as IL-6, suggesting that systemic inflammation is triggered to some extent by gut barrier disruption. In addition, intestinal fatty acid binding protein (I-FABP), a protein synthesized by mature enterocytes responsible for fatty acid turnover and used as a biomarker of intestinal injury, was measured in the urine of 283 patients hospitalized for COVID-19 ( 8 , 9 ). Urinary I-FABP levels were significantly elevated compared with controls and remained high in patients’ samples two weeks after hospitalization; levels were even higher in patients with critical illness than in milder cases ( 8 ).…”

“…In addition, intestinal fatty acid binding protein (I-FABP), a protein synthesized by mature enterocytes responsible for fatty acid turnover and used as a biomarker of intestinal injury, was measured in the urine of 283 patients hospitalized for COVID-19 ( 8 , 9 ). Urinary I-FABP levels were significantly elevated compared with controls and remained high in patients’ samples two weeks after hospitalization; levels were even higher in patients with critical illness than in milder cases ( 8 ). Another study found that serum levels of zonula occludins-1 (ZO-1), a marker of structural and functional integrity of the paracellular barrier, were significantly elevated in patients with COVID-19 pneumonia but were not predictive of progression to severe respiratory failure ( 10 ).…”