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NKG2A EXPRESSION AMONG CD8 CELLS IS ASSOCIATED WITH COVID-19 PROGRESSION IN HYPERTENSIVE PATIENTS: INSIGHTS FROM THE BRACE CORONA RANDOMIZED TRIAL
Author
Moll-Bernardes, Renata
Fortier, Sérgio C.
Sousa, Andréa S.
Lopes, Renato D.
Vera, Narendra
Conde, Luciana
Feldman, André
Arruda, Guilherme
Cabral-Castro, Mauro
Albuquerque, Denílson C.
Paula, Thiago C.
Furquim, Thyago
Loures, Vitor A.
Giusti, Karla
Oliveira, Nathália
Macedo, Ariane
Silva, Pedro Barros E.
De Luca, Fábio
Kotsugai, Marisol
Domiciano, Rafael
Silva, Flávia A.
Santos, Mayara F.
Souza, Olga F.
Bozza, Fernando A.
Luiz, Ronir R.
Medei, Emiliano
Fortier, Sérgio C.
Sousa, Andréa S.
Lopes, Renato D.
Vera, Narendra
Conde, Luciana
Feldman, André
Arruda, Guilherme
Cabral-Castro, Mauro
Albuquerque, Denílson C.
Paula, Thiago C.
Furquim, Thyago
Loures, Vitor A.
Giusti, Karla
Oliveira, Nathália
Macedo, Ariane
Silva, Pedro Barros E.
De Luca, Fábio
Kotsugai, Marisol
Domiciano, Rafael
Silva, Flávia A.
Santos, Mayara F.
Souza, Olga F.
Bozza, Fernando A.
Luiz, Ronir R.
Medei, Emiliano
Affilliation
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Rede D'Or São Luiz. Pathological Anatomy Laboratory. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Duke University Medical Center. Duke Clinical Research Institute. Durham, NC, USA / Brazilian Clinical Research Institute. São Paulo, SP, Brazil.
Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Anália Franco Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz São Caetano Hospital. São Caetano do Sul, SP, Brazil.
Federal University of Rio de Janeiro. Institute of Microbiology Paulo de Góes. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Rio de Janeiro State University. Cardiology Department. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Jabaquara Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Sino Brasileiro Hospital. Osasco, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Anália Franco Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Villa Lobos Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Villa Lobos Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Jabaquara Hospital. São Paulo, SP, Brazil / Santa Casa of São Paulo. São Paulo, SP, Brazil.
Brazilian Clinical Research Institute. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Morumbi Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Morumbi Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Anália Franco Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Rede D'Or São Luiz. Pathological Anatomy Laboratory. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Copa Star Hospital. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Public Health Studies Institute. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. National Center for Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Rede D'Or São Luiz. Pathological Anatomy Laboratory. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Duke University Medical Center. Duke Clinical Research Institute. Durham, NC, USA / Brazilian Clinical Research Institute. São Paulo, SP, Brazil.
Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Anália Franco Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz São Caetano Hospital. São Caetano do Sul, SP, Brazil.
Federal University of Rio de Janeiro. Institute of Microbiology Paulo de Góes. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Rio de Janeiro State University. Cardiology Department. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Jabaquara Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Sino Brasileiro Hospital. Osasco, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Anália Franco Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Villa Lobos Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Villa Lobos Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Jabaquara Hospital. São Paulo, SP, Brazil / Santa Casa of São Paulo. São Paulo, SP, Brazil.
Brazilian Clinical Research Institute. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Morumbi Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Morumbi Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / São Luiz Anália Franco Hospital. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Rede D'Or São Luiz. Pathological Anatomy Laboratory. São Paulo, SP, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Copa Star Hospital. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Public Health Studies Institute. Rio de Janeiro, RJ, Brazil.
D'Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. National Center for Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil.
Abstract
Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.
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