New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19

Renata Moll-Bernardes; Juliana R Ferreira; Eduardo B Schaustz; Andréa S Sousa; João D Mattos; Mariana B Tortelly; Adriana L Pimentel; Ana Cristina B S Figueiredo; Marcia M Noya-Rabelo; Sergio Fortier; Flavia A Matos E Silva; Narendra Vera; Luciana Conde; Mauro Jorge Cabral-Castro; Denilson C Albuquerque; Paulo Henrique Rosado-de-Castro; Gabriel C Camargo; Martha V T Pinheiro; Daniele O L Freitas; Ana M Pittella; José Afonso M Araújo; André C Marques; Elias P Gouvêa; Flavia V O Terzi; Cleverson N Zukowski; Ronaldo A O C Gismondi; Bruno S Bandeira; Renée S Oliveira; Barbara E J Abufaiad; Jacqueline S S Miranda; Luiz Guilherme Miranda; Olga F Souza; Fernando A Bozza; Ronir R Luiz; Emiliano Medei

doi:10.1007/s10875-023-01523-6

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19

J Clin Immunol. 2023 Oct;43(7):1496-1505. doi: 10.1007/s10875-023-01523-6. Epub 2023 Jun 9.

Authors

Renata Moll-Bernardes¹, Juliana R Ferreira^{1

2}, Eduardo B Schaustz¹, Andréa S Sousa^{1

3}, João D Mattos¹, Mariana B Tortelly^{1

2}, Adriana L Pimentel^{1

2}, Ana Cristina B S Figueiredo^{1

2}, Marcia M Noya-Rabelo^{1

2

4}, Sergio Fortier¹, Flavia A Matos E Silva¹, Narendra Vera⁵, Luciana Conde⁵, Mauro Jorge Cabral-Castro^{6

7}, Denilson C Albuquerque^{1

8}, Paulo Henrique Rosado-de-Castro¹, Gabriel C Camargo¹, Martha V T Pinheiro¹, Daniele O L Freitas¹, Ana M Pittella¹, José Afonso M Araújo^{1

2}, André C Marques^{1

2}, Elias P Gouvêa^{1

2}, Flavia V O Terzi^{1

2}, Cleverson N Zukowski^{1

2}, Ronaldo A O C Gismondi^{1

2}, Bruno S Bandeira^{1

2}, Renée S Oliveira^{1

2

9}, Barbara E J Abufaiad^{1

2}, Jacqueline S S Miranda^{1

2}, Luiz Guilherme Miranda^{1

2}, Olga F Souza^{1

2}, Fernando A Bozza^{1

3}, Ronir R Luiz^{1

10}, Emiliano Medei^{11

12

13}

Affiliations

¹ D'Or Institute for Research and Education, Rua Diniz Cordeiro, 30, 22281100, Rio de Janeiro, Brazil.
² Cardiology and Internal Medicine Department, Rede D'Or São Luiz, Brazil.
³ Evandro Chagas National Institute of Infectious Disease, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
⁴ Bahia School of Medicine and Public Health, Bahia, Brazil.
⁵ Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
⁶ Institute of Microbiology Paulo de Góes, UFRJ, Rio de Janeiro, Brazil.
⁷ Department of Pathology, Faculty of Medicine, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.
⁸ Cardiology Department, Rio de Janeiro State University, Rio de Janeiro, Brazil.
⁹ Internal Medicine Department, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.
¹⁰ Institute for Studies in Public Health-IESC, UFRJ, Rio de Janeiro, Brazil.
¹¹ D'Or Institute for Research and Education, Rua Diniz Cordeiro, 30, 22281100, Rio de Janeiro, Brazil. emedei70@biof.ufrj.br.
¹² Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. emedei70@biof.ufrj.br.
¹³ National Center for Structural Biology and Bioimaging, UFRJ, Rio de Janeiro, Brazil. emedei70@biof.ufrj.br.

Abstract

Purpose: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated.

Methods: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury.

Results: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8⁺CD38⁺ mean fluorescence intensity (MFI), and percentage of CD8⁺ human leukocyte antigen DR isotope (HLA-DR)⁺ CD38^-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)⁺ MFI, percentage of CD8⁺CD38⁺cells, CD8⁺HLA-DR⁺MFI, CD8⁺NKG2A⁺MFI, and percentage of CD8⁺HLA-DR^-CD38⁺cells. On multivariate regression, the CD8⁺HLA-DR⁺MFI, CD8⁺CD38⁺MFI, and total lymphocyte count were associated significantly with myocardial injury.

Conclusion: Our findings suggest that lymphopenia, CD8⁺CD38⁺MFI, and CD8⁺HLA-DR⁺MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Keywords: COVID-19; Troponin; hypertension; immune system; myocardial injury.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

ADP-ribosyl Cyclase 1
Adult
Biomarkers
CD8-Positive T-Lymphocytes*
COVID-19* / complications
HLA-DR Antigens
Humans
Lymphocyte Activation

Substances

ADP-ribosyl Cyclase 1
HLA-DR Antigens
Biomarkers

Grants and funding

1/CX/CSRD VA/United States