Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.
Наблюдательное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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, do Amaral Laurence Rodrigues, 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
Аннотация
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.