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Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients

2022; Frontiers Media; Volume: 13; Linguagem: Inglês

10.3389/fimmu.2022.1004023

1664-3224

Gabriela Profírio Jardim-Santos, Heidi Luise Schulte, Patrícia Shu Kurizky, Ciro Martins Gomes, Otávio Tolêdo Nóbrega, Eliana Teles de Gois, Maíra Rocha Machado de Carvalho, Francielle Pulcinelli Martins, André Moraes Nicola, Cleandro Pires de Albuquerque, Laila Salmen Espíndola, Luciana Ansaneli Naves, Alexandre Anderson de Sousa Munhoz Soares, Patrícia Albuquerque, Wagner Fontes, Laurence Rodrigues do Amaral, Matheus de Souza Gomes, Pedro Luiz Lima Bertarini, Joaquim Pedro Brito‐de‐Sousa, Ana Carolina Campi‐Azevedo, Vanessa Peruhype-Magalhães, Andréa Teixeira−Carvalho, Valéria Valim, Olindo Assis Martins‐Filho, Lícia Maria Henrique da Mota,

Long-Term Effects of COVID-19

The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls - HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs "CCL3 and G-CSF" and "CXCL10 and IL-6" were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.