Author:
de Lima Mikhael Haruo Fernandes,Machado Caio Cavalcante,Nascimento Daniele Carvalho,Silva Camila Meirelles S.,Toller-Kawahisa Juliana Escher,Rodrigues Tamara Silva,Veras Flavio Protassio,Pontelli Marjorie Cornejo,Castro Italo A.,Zamboni Dario Simões,Filho José-Carlos A.,Cunha Thiago M.,Arruda Eurico,da Cunha Larissa Dias,Oliveira Renê D. R.,Cunha Fernando Q.,Louzada-Junior Paulo
Abstract
AbstractThe 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.
Funder
Fundação de Amparo à Pesquisa do Estado de São Paulo
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Center for Research in Inflammatory Diseases (CRID), Brazil
Publisher
Springer Science and Business Media LLC