LUANA DE MENDONCA OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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- Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants(2024) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; ALBERCA, Ricardo Wesley; SOUSA, Emanuella Sarmento Alho de; LEITE, Bruno Henrique de Sousa; ADAN, Wenny Camilla dos Santos; DUARTE, Alberto Jose da Silva; LINS, Roberto Dias; SATO, Maria Notomi; VIANA, Isabelle Freire TabosaZika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_Delta STP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_Delta STP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-Delta STP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_Delta STP+Alum protected adult mice upon viral challenge. Collectively, the ZK_Delta STP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.
- Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients(2022) GOZZI-SILVA, Sarah Cristina; OLIVEIRA, Luana de Mendonca; ALBERCA, Ricardo Wesley; PEREIRA, Natalli Zanete; YOSHIKAWA, Fabio Seiti; PIETROBON, Anna Julia; YENDO, Tatiana Mina; ANDRADE, Milena Mary de Souza; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves; OLIVEIRA, Emily Araujo; BESERRA, Danielle Rosa; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-alpha. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.
- COVID-19 Disease Course in Former Smokers, Smokers and COPD Patients(2021) ALBERCA, Ricardo Wesley; LIMA, Julia Cataldo; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; ANDRADE, Milena Mary de Souza; BESERRA, Danielle Rosa; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; TEIXEIRA, Franciane Mouradian Emidio; FERNANDES, Iara Grigoletto; DUARTE, Alberto Jose da Silva; BENARD, Gil; SATO, Maria NotomiThe severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the COVID-19 pandemic presents a huge social and health challenge worldwide. Many different risk factors are associated with disease severity, such as systemic arterial hypertension, diabetes mellitus, obesity, older age, and other co-infections. Other respiratory diseases such as chronic obstructive pulmonary disease (COPD) and smoking are common comorbidities worldwide. Previous investigations have identified among COVID-19 patients smokers and COPD patients, but recent investigations have questioned the higher risk among these populations. Nevertheless, previous reports failed to isolate smokers and COPD patients without other comorbidities. We performed a longitudinal evaluation of the disease course of smokers, former smokers, and COPD patients with COVID-19 without other comorbidities, from hospitalization to hospital discharge. Although no difference between groups was observed during hospital admission, smokers and COPD patients presented an increase in COVID-19-associated inflammatory markers during the disease course in comparison to non-smokers and former smokers. Our results demonstrated that smoking and COPD are risk factors for severe COVID-19 with possible implications for the ongoing pandemic.
- SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report(2021) GOZZI-SILVA, Sarah Cristina; BENARD, Gil; ALBERCA, Ricardo Wesley; YENDO, Tatiana Mina; TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BESERRA, Danielle Rosa; PIETROBON, Anna Julia; OLIVEIRA, Emily Araujo de; BRANCO, Anna Claudia Calvielli Castelo; ANDRADE, Milena Mary de Souza; FERNANDES, Iara Grigoletto; PEREIRA, Natalli Zanete; RAMOS, Yasmim Alefe Leuzzi; LIMA, Julia Cataldo; PROVENCI, Bruna; MANGINI, Sandrigo; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.
- Platelet-Based Biomarkers for Diagnosis and Prognosis in COVID-19 Patients(2021) 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; OLIVEIRA, Emily Araujo de; AOKI, Valeria; ORFALI, Raquel Leao; BESERRA, Danielle Rosa; ANDRADE, Milena Mary de Souza; SATO, Maria NotomiCoronavirus disease 2019 (COVID-19) caused millions of deaths worldwide. COVID-19's clinical manifestations range from no symptoms to a severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. Severe COVID-19 patients develop pulmonary and extrapulmonary infections, with a hypercoagulable state. Several inflammatory or coagulatory biomarkers are currently used with predictive values for COVID-19 severity and prognosis. In this manuscript, we investigate if a combination of coagulatory and inflammatory biomarkers could provide a better biomarker with predictive value for COVID-19 patients, being able to distinguish between patients that would develop a moderate or severe COVID-19 and predict the disease outcome. We investigated 306 patients with COVID-19, confirmed by severe acute respiratory syndrome coronavirus 2 RNA detected in the nasopharyngeal swab, and retrospectively analyzed the laboratory data from the first day of hospitalization. In our cohort, biomarkers such as neutrophil count and neutrophil-to-lymphocyte ratio from the day of hospitalization could predict if the patient would need to be transferred to the intensive care unit but failed to identify the patients & PRIME; outcomes. The ratio between platelets and inflammatory markers such as creatinine, C-reactive protein, and urea levels is associated with patient outcomes. Finally, the platelet/neutrophil-to-lymphocyte ratio on the first day of hospitalization can be used with predictive value as a novel severity and lethality biomarker in COVID-19. These new biomarkers with predictive value could be used routinely to stratify the risk in COVID-19 patients since the first day of hospitalization.
- Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity(2022) BESERRA, Danielle Rosa; ALBERCA, Ricardo Wesley; BRANCO, Anna Claudia Calvielli Castelo; OLIVEIRA, Luana de Mendonca; ANDRADE, Milena Mary de Souza; GOZZI-SILVA, Sarah Cristina; TEIXEIRA, Franciane Mouradian Emidio; YENDO, Tatiana Mina; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCOVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+ lymphocytes were verified in severe/critical COVID-19 patients. In addition, we found a decreased frequency of total monocytes with an increased PD-1 expression on CD14+ monocytes in severe/critical patients in association with the time of infection. Moreover, we observed an increase in sPD-L1 circulant levels associated with the severity of the disease. Overall, these data indicate an important role of the PD-1/PDL-1 axis in COVID-19 and may provide a severity-associated biomarker and therapeutic target during SARS-CoV-2 infection.
- Resveratrol Downmodulates Neutrophil Extracellular Trap (NET) Generation by Neutrophils in Patients with Severe COVID-19(2022) ANDRADE, Milena M. de Souza; LEAL, Vinicius N. C.; FERNANDES, Iara G.; GOZZI-SILVA, Sarah C.; BESERRA, Danielle R.; OLIVEIRA, Emily A.; TEIXEIRA, Franciane M. E.; YENDO, Tatiana M.; SOUSA, Maria da Gloria T.; TEODORO, Walcy R.; OLIVEIRA, Luana de M.; ALBERCA, Ricardo W.; AOKI, Valeria; DUARTE, Alberto J. S.; SATO, Maria N.The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clinicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.
- Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients(2022) PIETROBON, Anna Julia; ANDREJEW, Roberta; CUSTODIO, Ricardo Wesley Alberca; OLIVEIRA, Luana de Mendonca; SCHOLL, Juliete Nathali; TEIXEIRA, Franciane Mouradian Emidio; BRITO, Cyro Alves de; GLASER, Talita; KAZMIERSKI, Julia; GOFFINET, Christine; TURDO, Anna Claudia; YENDO, Tatiana; AOKI, Valeria; FIGUEIRO, Fabricio; BATTASTINI, Ana Maria; ULRICH, Henning; BENARD, Gill; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiEctonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients' cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.
- 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(2020) ALBERCA, Ricardo Wesley; ANDRADE, Milena Mary de Souza; BRANCO, Anna Claudia Calvielli Castelo; PIETROBON, Anna Julia; PEREIRA, Natalli Zanete; FERNANDES, Iara Grigoletto; OLIVEIRA, Luana de Mendonca; TEIXEIRA, Franciane Mouradian Emidio; BESERRA, Danielle Rosa; OLIVEIRA, Emily Araujo de; GOZZI-SILVA, Sarah Cristina; RAMOS, Yasmim Alefe Leuzzi; BRITO, Cyro Alves de; ARNONE, Marcelo; ORFALI, Raquel Leao; AOKI, Valeria; DUARTE, Alberto Jose da Silva; SATO, Maria NotomiCommon clinical features of patients with Coronavirus disease-2019 (COVID-19) vary from fever, to acute severe respiratory distress syndrome. Several laboratory parameters are reported as indicators of COVID-19 severity. We hereby describe the possible novel severity biomarkers for COVID-19, CD11b+CD33+HLA-DR-CD14+ cells and CD11b+CD33+HLA-DR-CD66b+ cells.
- Case Report: COVID-19 and Chagas Disease in Two Coinfected Patients(2020) ALBERCA, Ricardo; YENDO, Tatiana; RAMOS, Yasmim Leuzzi; FERNANDES, Iara; OLIVEIRA, Luana; TEIXEIRA, Franciane Emidio; BESERRA, Danielle; OLIVEIRA, Emily de; GOZZI-SILVA, Sarah; ANDRADE, Milena de Souza; BRANCO, Anna Castelo; PIETROBON, Anna; PEREIRA, Natalli; BRITO, Cyro de; ORFALI, Raquel; AOKI, Valeria; DUARTE, Alberto da Silva; BENARD, Gil; SATO, MariaAmerican trypanosomiasis, also named Chagas disease (CD), is an anthropozoonosis caused by the protozoan parasite Trypanosoma cruzi. The disease affects millions of people worldwide, leading yearly to approximately 50,000 deaths. COVID-19, generated by SARS-CoV-2, can lead to lymphopenia and death. We hereby describe the first report of two patients with CD and COVID-19 coinfection, from hospitalization until patients' death.