Análise sérica de citocinas e anafilotoxinas em pacientes com covid-19

Abstract

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fastly spread, resulting in the pandemic coronavirus disease 2019 (COVID-19). The pathogenesis of COVID-19 is associated with an inadequate or exaggerated immune response that can result in significantly elevated levels of cytokines, increased thrombosis, lung injury, acute myocarditis and multiple organs failure. Although several data have been published, knowledge gaps still exist and prognostic markers are needed. As such, our aim was to evaluate the cytokines and anaphylotoxins profile in patients with COVID-19 in Alagoas, Brazil to find prognostic markers. Methodology: A cross-sectional observational study, with 76 participants, of which 56 had COVID-19 with diagnosis confirmed by qRT-PCR, while 20 were donors without COVID-19. The study was approved by the human ethical committee (30732120.1.0000.5013). Control participants were age, sex and comorbidities-matched to the COVID-19 group. Blood samples were obtained as soon as patients arrived in the HUPAA/UFAL and their plasma were quantified for cytokines (IL-1β, IL-6, IL-8, IL-10, IL12p70, IFN-α2, IFN-β, IFN-λ1, IFN-λ2/3, IFN-γ, TNF-α, IP-10, GM-CSF, IL-2, IL-4, IL-6 and IL-17A) and anaphylotoxins (C3a, C4a and C5a) by flow cytometry bead-based assays. Results: COVID-19 patients had reduced levels of GM-CSF, and increased levels of C3a and C4a, which were also found as markers of severity. We also found increased levels of IL-10 and IL-12p70 in COVID-19 diceased patients in comparison to those hospital discharged. Elderly with COVID-19 had increased IFN-λ1, C3a and C4a in comparison to elderly controls. Sex comparison of COVID-19 patients showed that women had increased levels of IFN-α2, IFN-λ2/3, IFN-γ and GM-CSF. In comparison to control of the same sex, COVID-19 women had increased IFN-γ, C3a and C4a, while men had reduced IL-1β, IL-12p70 and GM-CSF, and increased C3a and C4a. Lastly, the ROC curve of C3a+C4a measures had high specificity (100%) and sensitivity (85%). Conclusion: Age, sex and comorbidities change specific cytokines that could be markers for them, while IL-10 and IL-12p70 increase could indicate a bad prognosis. C3a and C4a were remarkably increased in COVID-19 patients and could be markers of COVID-19 severity, indicating with high accuracy patients that would require ICU admission.