AUTHOR=Jardim-Santos Gabriela Profírio , Schulte Heidi Luise , Kurizky Patricia Shu , Gomes Ciro Martins , Nóbrega Otávio Tolêdo , de Gois Eliana Teles , de Carvalho Maíra Rocha Machado , Martins Francielle Pulccinelli , Nicola André Moraes , de Albuquerque Cleandro Pires , Espindola Laila Salmen , Naves Luciana Ansaneli , Soares Alexandre Anderson de Sousa Munhoz , Albuquerque Patrícia , Fontes Wagner , Amaral Laurence Rodrigues do , Gomes Matheus de Souza , Bertarini Pedro Luiz Lima , Brito-de-Sousa Joaquim Pedro , Campi-Azevedo Ana Carolina , Peruhype-Magalhães Vanessa , Teixeira-Carvalho Andrea , Valim Valéria , Martins-Filho Olindo Assis , da Mota Licia Maria Henrique TITLE=Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1004023 DOI=10.3389/fimmu.2022.1004023 ISSN=1664-3224 ABSTRACT=

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.