Frontiers in Immunology (Jun 2022)

Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients

  • Juan Jonathan Gonçalves,
  • Camila Pacheco Silveira Martins da Mata,
  • Camila Pacheco Silveira Martins da Mata,
  • Alice Aparecida Lourenço,
  • Ágata Lopes Ribeiro,
  • Geovane Marques Ferreira,
  • Thais Fernanda de Campos Fraga-Silva,
  • Fernanda Mesquita de Souza,
  • Vanessa Egídio Silveira Almeida,
  • Iara Antunes Batista,
  • Carolina D`Avila-Mesquita,
  • Ariel E. S. Couto,
  • Ligia C. B. Campos,
  • Adriana Alves Oliveira Paim,
  • Linziane Lopes Ferreira,
  • Patrícia de Melo Oliveira,
  • Lorena de Almeida Teixeira,
  • Daisymara Priscila de Almeida Marques,
  • Henrique Retes de Moraes,
  • Samille Henriques Pereira,
  • Joaquim Pedro Brito-de-Sousa,
  • Ana Carolina Campi-Azevedo,
  • Vanessa Peruhype-Magalhães,
  • Márcio Sobreira Silva Araújo,
  • Andréa Teixeira-Carvalho,
  • Flávio Guimarães da Fonseca,
  • Flávio Guimarães da Fonseca,
  • Vânia Luiza Deperon Bonato,
  • Christiane Becari,
  • Christiane Becari,
  • Denise Ferro,
  • Mayra Gonçalves Menegueti,
  • Amanda Alves Silva Mazzoni,
  • Maria Auxiliadora-Martins,
  • Jordana Grazziela Coelho-dos-Reis,
  • Olindo Assis Martins-Filho

DOI
https://doi.org/10.3389/fimmu.2022.903903
Journal volume & issue
Vol. 13

Abstract

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In the present study, the levels of serum and airway soluble chemokines, pro-inflammatory/regulatory cytokines, and growth factors were quantified in critically ill COVID-19 patients (total n=286) at distinct time points (D0, D2-6, D7, D8-13 and D>14-36) upon Intensive Care Unit (ICU) admission. Augmented levels of soluble mediators were observed in serum from COVID-19 patients who progress to death. An opposite profile was observed in tracheal aspirate samples, indicating that systemic and airway microenvironment diverge in their inflammatory milieu. While a bimodal distribution was observed in the serum samples, a unimodal peak around D7 was found for most soluble mediators in tracheal aspirate samples. Systems biology tools further demonstrated that COVID-19 display distinct eccentric soluble mediator networks as compared to controls, with opposite profiles in serum and tracheal aspirates. Regardless the systemic-compartmentalized microenvironment, networks from patients progressing to death were linked to a pro-inflammatory/growth factor-rich, highly integrated center. Conversely, patients evolving to discharge exhibited networks of weak central architecture, with lower number of neighborhood connections and clusters of pro-inflammatory and regulatory cytokines. All in all, this investigation with robust sample size landed a comprehensive snapshot of the systemic and local divergencies composed of distinct immune responses driven by SARS-CoV-2 early on severe COVID-19.

Keywords