Abstract

The TIGIT+FOXP3+Treg subset (TIGIT+Tregs) exerts robust suppressive activity on cellular immunity and predisposes septic individuals to opportunistic infection. We hypothesized that TIGIT+Tregs could play an important role in intensifying the COVID-19 severity and hampering the defense against nosocomial infections during hospitalization. Herein we aimed to verify the association between the levels of the TIGIT+Tregs with the mechanical ventilation requirement, fatal outcome, and bacteremia during hospitalization. TIGIT+Tregs were immunophenotyped by flow cytometry from the peripheral blood of 72 unvaccinated hospitalized COVID-19 patients at admission from May 29th to August 6th, 2020. The patients were stratified during hospitalization according to their mechanical ventilation requirement and fatal outcome. COVID-19 resulted in a high prevalence of the TIGIT+Tregs at admission, which progressively increased in patients with mechanical ventilation needs and fatal outcomes. The prevalence of TIGIT+Tregs positively correlated with poor pulmonary function and higher plasma levels of LDH, HMGB1, FGL2, and TNF. The non-survivors presented higher plasma levels of IL-33, HMGB1, FGL2, IL-10, IL-6, and 5.54 times more bacteremia than survivors. Conclusions: The expansion of the TIGIT+Tregs in COVID-19 patients was associated with inflammation, lung dysfunction, bacteremia, and fatal outcome.

Details

Title
The TIGIT+ T regulatory cells subset associates with nosocomial infection and fatal outcome in COVID-19 patients under mechanical ventilation
Author
de Lima, Mikhael Haruo Fernandes 1 ; Machado, Caio Cavalcante 2 ; Nascimento, Daniele Carvalho 3 ; Silva, Camila Meirelles S. 3 ; Toller-Kawahisa, Juliana Escher 3 ; Rodrigues, Tamara Silva 4 ; Veras, Flavio Protassio 3 ; Pontelli, Marjorie Cornejo 5 ; Castro, Italo A. 5 ; Zamboni, Dario Simões 4 ; Filho, José-Carlos A. 3 ; Cunha, Thiago M. 3 ; Arruda, Eurico 5 ; da Cunha, Larissa Dias 4 ; Oliveira, Renê D. R. 2 ; Cunha, Fernando Q. 3 ; Louzada-Junior, Paulo 6 

 University of São Paulo, Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722); University of São Paulo, Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722); University of São Paulo, Departament of Pharmacology, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 University of São Paulo, Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 University of São Paulo, Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722); University of São Paulo, Departament of Pharmacology, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 University of São Paulo, Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722); University of São Paulo, Department of Cell and Molecular Biology, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 University of São Paulo, Virology Research Center, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 University of São Paulo, Divisions of Clinical Immunology, Emergency, Infectious Diseases and Intensive Care Unit, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722); University of São Paulo, Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
Pages
13599
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2854125632
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.