Analysis of natural killer memory cells and the antiviral response of CD8 + T cells in SARS-CoV-2 infection

• Grant number: 19/22448-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2020
• End date: October 17, 2021
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Sarah Cristina Gozzi e Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

COVID-19, an infectious respiratory disease caused by SARS-CoV-2, has spread on an epidemic scale, infecting more than 62 million people worldwide to date. Virus infection can progress asymptomatically or generate more severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of the symptom is recurrent, including a decrease in the frequency of NKs cells (Natural Killers). However, the functional profile regarding the expression of antiviral factors in CD8 T cells and polyfunctionality have not yet been elucidated. Likewise, the presence of NK memory cells that are expanded with cytomegalovirus (CMV) infection, and its evidence in the skin tissue. We emphasize that studies on the evidence of immune cells in the skin tissue of autopsies of patients who died by COVID-19 are scarce. The purpose of this study is to evaluate the phenotypic profile regarding the polyfunctionality of CD8 + T lymphocytes and NKs cell subtypes in patients with moderate and severe COVID-19. In addition, the profile of the transcriptional expression of antiviral factors in peripheral blood TCD8 + lymphocytes will be evaluated by PCR-array of 84 antiviral genes and presence in the skin tissue of NK memory cells and CD8 + T from skin autopsy of individuals by SARS-CoV -two. Correlations between laboratory data and symptoms and comorbidities will be analyzed. In this pandemic period, we started the study related to phenotypic analysis of NK cell subtypes, in a cohort of 48 patients confirmed with SARS-CoV-2 (22 moderates coming from the ward and 26 severe ones admitted to the ICU, under mechanical ventilation) coming from the HC-FMUSP. We have observed so far in this cohort that the prevalence of death is 13.64% in moderate cases and 42.31% in critically ill patients. The most prevalent comorbidities were systemic arterial hypertension and cardiac disorders. In phenotypic analyzes of NKs cells in peripheral blood, we observed a percentage decrease in total NK cells, and in the NK subtypes CD16 + CD56dim and CD16 + CD56bright in critically ill patients. In contrast, there was an expansion of NK memory cells, NKG2C + and CD57 + cells, both in moderate and severe patients. Considering that the expansion of this population is related to infection and reactivation of the CVM, serology for CMV in these patients will be evaluated. Sampling of skin tissue from autopsies is being carried out in collaboration with the Department of Dermatology and Pathology at FMUSP. Together, the understanding of phenotypic and functional changes in CD8 + T cells and NKs in COVID-19 + patients, may contribute to strategies to enhance the response and the understanding of its relationship with the severity of COVID-19. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALBERCA, RICARDO WESLEY; DE SOUZA ANDRADE, MILENA MARY; CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; PIETROBON, ANNA JULIA; PEREIRA, NATALLI ZANETE; FERNANDES, IARA GRIGOLETTO; OLIVEIRA, LUANA DE MENDONCA; EMIDIO TEIXEIRA, FRANCIANE MOURADIAN; BESERRA, DANIELLE ROSA; DE OLIVEIRA, EMILY ARAUJO; et al. Frequencies of CD33+CD11b+HLA-DR-CD14-CD66b+and CD33+CD11b+HLA-DR-CD14+CD66b-Cells in Peripheral Blood as Severity Immune Biomarkers in COVID-19. FRONTIERS IN MEDICINE, v. 7, OCT 14 2020. (19/02679-7, 17/18199-9, 19/26928-6, 18/18230-6, 19/22448-0)

GOZZI-SILVA, SARAH CRISTINA; OLIVEIRA, LUANA DE MENDONCA; ALBERCA, RICARDO WESLEY; PEREIRA, NATALLI ZANETE; YOSHIKAWA, FABIO SEITI; PIETROBON, ANNA JULIA; YENDO, TATIANA MINA; DE SOUZA ANDRADE, MILENA MARY; LEUZZI RAMOS, YASMIM ALEFE; BRITO, CYRO ALVES; et al. Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients. CELLS, v. 11, n. 21, p. 18-pg., 2022-11-01. (19/25119-7, 19/22448-0)

ALBERCA, RICARDO WESLEY; PEREIRA, NATALLI ZANETE; OLIVEIRA, LUANDA MARA DA SILVA; GOZZI-SILVA, SARAH CRISTINA; SATO, MARIA NOTOMI. Pregnancy, Viral Infection, and COVID-19. FRONTIERS IN IMMUNOLOGY, v. 11, JUL 7 2020. (19/22448-0, 19/02679-7, 19/07976-0)

ALBERCA, RICARDO WESLEY; SOLIS-CASTRO, ROSA LILIANA; SOLIS-CASTRO, MARIA EDITH; CARDOSO, FERNANDA; DUARTE, ALBERTO JOSE DA SILVA; OLIVEIRA, LUANA DE MENDONCA; PEREIRA, NATALLI ZANETE; GOZZI-SILVA, SARAH CRISTINA; DE OLIVEIRA, EMILY ARAUJO; AOKI, VALERIA; et al. Platelet-Based Biomarkers for Diagnosis and Prognosis in COVID-19 Patients. LIFE-BASEL, v. 11, n. 10, OCT 2021. (19/02679-7, 20/13148-0, 19/22448-0, 17/18199-9)

GOZZI-SILVA, SARAH CRISTINA; BENARD, GIL; ALBERCA, RICARDO WESLEY; YENDO, TATIANA MINA; EMIDIO TEIXEIRA, FRANCIANE MOURADIAN; OLIVEIRA, LUANA DE MENDONCA; BESERRA, DANIELLE ROSA; PIETROBON, ANNA JULIA; DE OLIVEIRA, EMILY ARAUJO; CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; et al. SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report. TROPICAL MEDICINE AND INFECTIOUS DISEASE, v. 6, n. 1, MAR 2021. (18/18230-6, 17/18199-9, 19/02679-7, 19/26928-6, 19/22448-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Sarah Cristina Gozzi e. Analysis of Natural Killer memory cells and the antiviral response of CD8+ T cells in SARS-CoV-2 infection. 2022. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.