IL-10 and IL-12 (P70) Levels Predict the Risk of Covid-19 Progression in Hypertensive Patients: Insights From the BRACE-CORONA Trial

Renata Moll-Bernardes; Andrea Silvestre de Sousa; Ariane V S Macedo; Renato D Lopes; Narendra Vera; Luciana C R Maia; André Feldman; Guilherme D A S Arruda; Mauro J C Castro; Pedro M Pimentel-Coelho; Denílson C de Albuquerque; Thiago Ceccatto de Paula; Thyago A B Furquim; Vitor A Loures; Karla G D Giusti; Nathália M de Oliveira; Fábio A De Luca; Marisol D M Kotsugai; Rafael A M Domiciano; Mayara Fraga Santos; Olga Ferreira de Souza; Fernando A Bozza; Ronir Raggio Luiz; Emiliano Medei

doi:10.3389/fcvm.2021.702507

IL-10 and IL-12 (P70) Levels Predict the Risk of Covid-19 Progression in Hypertensive Patients: Insights From the BRACE-CORONA Trial

Front Cardiovasc Med. 2021 Jul 27:8:702507. doi: 10.3389/fcvm.2021.702507. eCollection 2021.

Authors

Renata Moll-Bernardes¹, Andrea Silvestre de Sousa^{1

2}, Ariane V S Macedo^{1

3

4}, Renato D Lopes^{1

5

6}, Narendra Vera⁷, Luciana C R Maia⁷, André Feldman^{1

8}, Guilherme D A S Arruda⁹, Mauro J C Castro¹⁰, Pedro M Pimentel-Coelho⁷, Denílson C de Albuquerque^{1

11}, Thiago Ceccatto de Paula³, Thyago A B Furquim¹², Vitor A Loures⁸, Karla G D Giusti¹³, Nathália M de Oliveira¹³, Fábio A De Luca¹⁴, Marisol D M Kotsugai¹⁴, Rafael A M Domiciano⁸, Mayara Fraga Santos¹, Olga Ferreira de Souza^{1

15}, Fernando A Bozza^{1

2}, Ronir Raggio Luiz^{1

16}, Emiliano Medei^{1

7

17}

Affiliations

¹ D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
² Evandro Chagas National Institute of Infectious Disease, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
³ Hospital São Luiz Jabaquara, São Paulo, Brazil.
⁴ Santa Casa de São Paulo, São Paulo, Brazil.
⁵ Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, United States.
⁶ Brazilian Clinical Research Institute, São Paulo, Brazil.
⁷ Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁸ Hospital São Luiz Anália Franco, São Paulo, Brazil.
⁹ Hospital São Luiz São Caetano, São Caetano do Sul, Brazil.
¹⁰ Instituto de Microbiologia Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹¹ Cardiology Department, Rio de Janeiro State University, Rio de Janeiro, Brazil.
¹² Hospital Sino Brasileiro, Osasco, Brazil.
¹³ Hospital Villa Lobos, São Paulo, Brazil.
¹⁴ Hospital São Luiz Morumbi, São Paulo, Brazil.
¹⁵ Hospital Copa Star, Rio de Janeiro, Brazil.
¹⁶ Institute for Studies in Public Health-IESC, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹⁷ National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Background: Cardiovascular comorbidities such as hypertension and inflammatory response dysregulation are associated with worse COVID-19 prognoses. Different cytokines have been proposed to play vital pathophysiological roles in COVID-19 progression, but appropriate prognostic biomarkers remain lacking. We hypothesized that the combination of immunological and clinical variables at admission could predict the clinical progression of COVID-19 in hypertensive patients. Methods: The levels of biomarkers, including C-reactive protein, lymphocytes, monocytes, and a panel of 29 cytokines, were measured in blood samples from 167 hypertensive patients included in the BRACE-CORONA trial. The primary outcome was the highest score during hospitalization on the modified WHO Ordinal Scale for Clinical Improvement. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and biomarkers associated significantly with the primary outcome. Results: During hospitalization, 13 (7.8%) patients showed progression to more severe forms of COVID-19, including three deaths. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography examination, the C-reactive protein level, levels of 15 cytokines, and lymphopenia on admission were associated with progression to severe COVID-19. Elevated levels of interleukin-10 and interleukin-12 (p70) combined with two or three of the abovementioned clinical comorbidities were associated strongly with progression to severe COVID-19. The risk of progression to severe disease reached 97.5% in the presence of the five variables included in our model. Conclusions: This study demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19.

Keywords: COVID-19; biomarker; cytokine; hypertension; inflammation; prognosis.

Copyright © 2021 Moll-Bernardes, de Sousa, Macedo, Lopes, Vera, Maia, Feldman, Arruda, Castro, Pimentel-Coelho, de Albuquerque, de Paula, Furquim, Loures, Giusti, de Oliveira, De Luca, Kotsugai, Domiciano, Santos, de Souza, Bozza, Luiz and Medei.