학술논문
Timeline Kinetics of Systemic and Airway Immune Mediator Storm for Comprehensive Analysis of Disease Outcome in Critically Ill COVID-19 Patients
Document Type
article
Author
Juan Jonathan Gonçalves; 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; Vânia Luiza Deperon Bonato; Christiane Becari; Denise Ferro; Mayra Gonçalves Menegueti; Amanda Alves Silva Mazzoni; Maria Auxiliadora-Martins; Jordana Grazziela Coelho-dos-Reis; Olindo Assis Martins-Filho
Source
Frontiers in Immunology, Vol 13 (2022)
Subject
Language
English
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.