AUTHOR=Gonçalves Juan Jonathan , da Mata Camila Pacheco Silveira Martins , Lourenço Alice Aparecida , Ribeiro Ágata Lopes , Ferreira Geovane Marques , Fraga-Silva Thais Fernanda de Campos , de Souza Fernanda Mesquita , Almeida Vanessa Egídio Silveira , Batista Iara Antunes , D`Avila-Mesquita Carolina , Couto Ariel E. S. , Campos Ligia C. B. , Paim Adriana Alves Oliveira , Ferreira Linziane Lopes , de Melo Oliveira Patrícia , de Almeida Teixeira Lorena , Priscila de Almeida Marques Daisymara , Retes de Moraes Henrique , Pereira Samille Henriques , Brito-de-Sousa Joaquim Pedro , Campi-Azevedo Ana Carolina , Peruhype-Magalhães Vanessa , Araújo Márcio Sobreira Silva , Teixeira-Carvalho Andréa , da Fonseca Flávio Guimarães , Bonato Vânia Luiza Deperon , Becari Christiane , Ferro Denise , Menegueti Mayra Gonçalves , Mazzoni Amanda Alves Silva , Auxiliadora-Martins Maria , Coelho-dos-Reis Jordana Grazziela , Martins-Filho Olindo Assis TITLE=Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.903903 DOI=10.3389/fimmu.2022.903903 ISSN=1664-3224 ABSTRACT=

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.