RESUMO
Different biomarkers for SARS-CoV-2 have been linked to detection, diagnosis, treatment, disease progression, and development of new drugs and vaccines. The objective of this research was to evaluate various hematological, biochemicals, immunological, radiological and spirometric parameters in 20 adult patients convalescing from COVID-19 and their possible relationship with the clinical course of the disease. The frequencies of categorical variables were compared using the chi-square and Fisher's exact test. The levels of statistical significance were denoted in each figure legend. Two-dimensional clustering analysis was performed using MeV software from TIGR. The tests with P value of ≤ 0.05 were considered statistically significant. Most of the patients studied presented alterations in dissimilar laboratory, radiological and spirometric parameters, which were related to the clinical evolution of the disease. The results obtained show that certain hematological, biochemical, immunological and radiological parameters can be considered as biomarkers of sequela in adult COVID-19 patients, which allows their stratification, according to the degree of involvement or sequela, into three groups: I (mild degree of involvement or sequela), without lung lesions on computerized axial tomography (CT scan) and high values of IgG, C3 and hemoglobin, II (moderate degree of involvement or sequel), without lung lesions on CT scan, characterized by high levels of CD3+/CD4+ T lymphocytes and the rest of the variables with low values and III (severe degree of involvement or sequela), with lung lesions on CT scan and high values of erythrocyte sedimentation rate, monocytes and neutrophils, associated with lymphopenia and decreased concentrations of IgG and C3.
RESUMO
BACKGROUND: Pro-inflammatory cytokines are directly implicated in the pathogenesis of Rheumatoid arthritis (RA). Variable clinical response to cytokine targeted therapies as TNFalpha and IL-6, strongly highlights the heterogeneity of inflammatory process in RA. Another cytokine, IL-15 has also been related to the inflammatory process in RA. Recently we described for the first time, the presence of its specific receptor, IL-15Ralpha, in synovial fluid (SF). The aim of this work was to compare the expression profile of IL-15Ralpha, its ligand IL-15, TNFalpha and IL-6 and how these cytokines are correlated in SF from RA patients taking as a reference Osteoarthritis (OA), an articular but not autoimmune disease. METHODS: Synovial fluids were obtained from the knee joints of 60 patients, 30 with confirmed diagnosis of RA and 30 with OA diagnosis. The levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha were measured by ELISA. A statistical analysis was performed with GraphPad Prism v5.0 using the Mann-Whitney U test and Spearman's rank correlation. A cluster analysis was run in MeV software v4.9.0 and differences across clusters were evaluated by an ANOVA including post-test analysis. RESULTS: We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group. Additionally, a high inter-individual variability in the levels of these 4 cytokines was observed in RA, although we identified 4 patients' subgroups by cluster analysis of cytokines concentration in SF. We also found a positive correlation between IL-15Ralpha-IL-6 and IL-15Ralpha-IL-15, but not for other pairs of cytokines in RA. In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28. CONCLUSIONS: In our current work we found a high inter-individual variability in the levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha in SF of RA patients and were identified four principal clusters of cytokines concentration in SF, suggesting the importance of identifying disease subset of patients for personalized treatment. Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.