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

• Published in: Frontiers in immunology Vol. 13; p. 903903
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 03-06-2022
• Subjects: chemokines; COVID; cytokines; growth factors; Immunology; prognostic biomarkers; systemic
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.903903

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.