Frontiers in Immunology (Nov 2022)

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

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

DOI
https://doi.org/10.3389/fimmu.2022.1004023
Journal volume & issue
Vol. 13

Abstract

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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.

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