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

Frontiers in Immunology

Flávio Guimarães da Fonseca¹  Fernanda Mesquita de Souza²  Thais Fernanda de Campos Fraga-Silva²  Vânia Luiza Deperon Bonato²  Lorena de Almeida Teixeira³  Linziane Lopes Ferreira³  Henrique Retes de Moraes³  Daisymara Priscila de Almeida Marques³  Jordana Grazziela Coelho-dos-Reis³  Samille Henriques Pereira³  Patrícia de Melo Oliveira³  Adriana Alves Oliveira Paim³  Ariel E. S. Couto⁴  Christiane Becari⁴  Carolina D`Avila-Mesquita⁴  Ligia C. B. Campos⁴  Maria Auxiliadora-Martins⁵  Amanda Alves Silva Mazzoni⁵  Denise Ferro⁶  Mayra Gonçalves Menegueti⁶  Geovane Marques Ferreira⁷  Iara Antunes Batista⁷  Alice Aparecida Lourenço⁷  Ágata Lopes Ribeiro⁷  Camila Pacheco Silveira Martins da Mata⁷  Vanessa Egídio Silveira Almeida⁷  Ana Carolina Campi-Azevedo⁸  Vanessa Peruhype-Magalhães⁸  Márcio Sobreira Silva Araújo⁸  Juan Jonathan Gonçalves⁸  Olindo Assis Martins-Filho⁸  Andréa Teixeira-Carvalho⁸  Joaquim Pedro Brito-de-Sousa⁸ 

[1] Centro de Tecnologia em Vacinas da Universidade Federal de Minas Gerais (UFMG), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil;Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Divisão de Cirurgia Vascular, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil;Divisão de Medicina Intensiva, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil;Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil;Hospital Risoleta Tolentino Neves, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil;

关键词: COVID;    cytokines;    chemokines;    growth factors;    prognostic biomarkers;    systemic;   

DOI  :  10.3389/fimmu.2022.903903

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown