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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.
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1 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)
2 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)
3 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)
4 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)
5 University of São Paulo, Virology Research Center, Ribeirão Preto Medical School, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)
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)