Can the Prognosis of COVID-19 Disease Be Determined by Fecal Markers and Cytokines?

The coronavirus disease 2019 (COVID-19) pandemic has affected the entire world, and has a variety of clinical presentations. The aim of this study is to determine the relationships of fecal cytokines and markers with the symptoms and prognosis of children with COVID-19 infection, and to identify noninvasive markers during follow-up. In a cohort of 40 COVID-19-positive children and 40 healthy controls, fecal cytokines and markers were examined in stool samples. A binary logistic model was used to assess the potential of cytokines as risk factors for hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. A P-value <0.05 was accepted as statistically significant. Levels of fecal lysozyme, myeloperoxidase, hemoglobin, and interleukin-5 (IL-5) (P < 0.05) were significantly higher among the patients than controls. In a logistic regression analysis, fecal IL-2 (OR = 3.83; 95% CI: 1.44-15.92), IL-4 (OR = 2.96; 95% CI: 1.09-12.93), IL-5 (OR = 4.56; 95% CI: 1.18-27.88), IL-10 (OR = 2.71 95% CI: 1.19-7.94), interferon-gamma (IFN-γ) (OR = 4.03; 95% CI: 1.44-15.73), IFN-α (OR = 3.02; 95% CI: 1.08-11.65), calcium-binding protein B S100 (S100 B) (OR = 4.78; 95% CI: 1.31-27.82), neutrophil elastase (NE) 2 (OR = 4.07; 95% CI: 1.17-19.69), and matrix metalloproteinase 1 (MMP-1) (OR = 3.67; 95% CI: 1.1-18.82) levels were significantly higher in hospitalized patients with COVID-19 infection than outpatients. We demonstrated that various fecal cytokines and markers were increased in patients who had COVID-19. Fecal IL-2, IL-4, IL-5, IL-10, IFN-γ, IFN-α, S100 B, NE, and MMP-1 levels were significantly elevated in hospitalized patients. We suggest that the fecal and serum levels of cytokines could be used to predict the prognosis of COVID-19 disease, although more studies are needed to confirm this.

Independent risk factors for resolution of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome within 4 years after the disease onset.

BACKGROUND/OBJECTIVE: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a polygenic disease with unknown etiology. In this retrospective cohort study, we aimed to evaluate the risk factors for the resolution of PFAPA syndrome within 4 years after the onset. METHODS: In total, 466 patients with PFAPA syndrome that are being followed up our department were included into the study. Between May 2020 and September 2020, medical charts of the patients were reviewed retrospectively. RESULTS: The median age of the patients at the time of the study and at disease onset were 8.6 (2.9-20.5; IQR 6.9-10.6) years and 18 (1-84; IQR 11-31) months. On univariate analysis age at disease onset (p = 0.003), positive family history of PFAPA syndrome (p = 0.04), absence of myalgia (p = 0.04), and absence of headache (p = 0.003) were all associated with the resolution of PFAPA syndrome within 4 years after the onset. Multivariate logistic regression analysis revealed that age at disease onset (OR 1.04, 95% CI 1.01-1.07, p = 0.002), positive family history of PFAPA syndrome (OR 2.69, 95% CI 1.12-6.48, p = 0.02), and absence of headache (OR 0.2, 95% CI 0.05-0.74, p = 0.01) were independent risk factors for the resolution of PFAPA syndrome within 4 years after the onset. CONCLUSION: We report later age of disease onset, positive family history of PFAPA syndrome, and absence of headache as independent risk factors for resolution of PFAPA syndrome within 4 years after the onset. KEY POINTS: • Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a multifactorial disease with unknown etiology. • Although, PFAPA syndrome usually resolves within 3-5 years after the disease onset, it can persist for years and even continue into adulthood. With our current knowledge, there is no clue to predict which patients will have a long disease course and which patients will not. • Later age of disease onset, positive family history of PFAPA syndrome and absence of headache as independent risk factors for resolution of PFAPA syndrome within 4 years after the onset.