CAROLINE SILVERIO FARIA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
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- Dynamics and Heterogeneity of the Lung Immunopathology in Severe COVID-19(2022) ERJEFALT, J.; COSTA, N. De Souza Xavier; JONSSON, J.; COZZOLINO, O.; DANTAS, K.; CLAUSSON, C.; SIDDHURAJ, P.; LINDO, C.; LOMBARDI, S. Ferreira Spina; MENDRONI JUNIOR, A.; ANTONANGELO, L.; FARIA, C. Silverio; DUARTE NETO, A. Nunes; MONTEIRO, R. De Almeida; PINHO, J. Rebello; GOMES-GOUVEA, M. Soares; PEREIRA, R. Verciano; MONTEIRO, J. Sirino; SETUBAL, J.; OLIVEIRA, E. Pierre De; THEODORO FILHO, J.; SANDEN, C.; ORENGO, J.; SLEEMAN, M.; SILVA, L. Ferraz Da; SALDIVA, P. Nascimento; DOLHNIKOFF, M.; MAUAD, T.
- Differentially expressed genes in Diffuse Alveolar Damage (DAD) patterns of COVID-19.(2022) COSTA, N. de Souza Xavier; MONTEIRO, J. Sirino; ERJEFALT, J.; JONSSON, J.; COZZOLINO, O.; DANTAS, K.; CLAUSSON, C.; SIDDHURAJ, P.; LINDO, C.; LOMBARDI, S. Ferreira Spina; MENDRONI JUNIOR, A.; ANTONANGELO, L.; FARIA, C. Silverio; DUARTE NETO, A. Nunes; MONTEIRO, R. Almeida; PINHO, J. R. Rebello; GOMES-GOUVEA, M. Soares; PEREIRA, R. Verciano; OLIVEIRA, E. Pierre De; THEODORO FILHO, J.; SANDEN, C.; ORENGO, J.; SLEEMAN, M.; SILVA, L. F. Ferraz Da; SALDIVA, P. Nascimento; DOLHNIKOFF, M.; MAUAD, T.; SETUBAL, J. C.
- Understanding yellow fever-associated myocardial injury: an autopsy study(2023) GIUGNI, Fernando Rabioglio; DEMARCHIAIELLO, Vera; FARIA, Caroline Silverio; POUR, Shahab Zaki; CUNHA, Marielton dos Passos; GIUGNI, Melina Valdo; PINESI, Henrique Trombini; LEDESMA, Felipe Lourenco; MORAIS, Carolina Esteves; HO, Yeh-Li; SZTAJNBOK, Jaques; FERNEZLIAN, Sandra de Morais; SILVA, Luiz Fernando Ferraz da; MAUAD, Thais; ALVES, Venancio Avancini Ferreira; SALDIVA, Paulo Hilario do Nascimento; ANTONANGELO, Leila; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro NunesBackground Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF.Methods This retrospective autopsy study included cases from the Sao Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers.Findings Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test.Interpretation Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10.
- COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Caroline Toledo do; BRITO, Jose Mara de; ANTONANGELO, Leila; FARIA, Caroline Silverio; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; SEELAENDER, Marilia; CASTRO, Gabriela Salim de; LIMA, Joanna D. C. C.; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz da; DOLHNIKOFF, Marisa; MAUAD, ThaisBackgroundLung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS.MethodsWe have quantified different ECM elements and TGF-beta expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile.ResultsWe observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-beta, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-beta was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course.ConclusionsFatal COVID-19 is associated with an early TGF-beta expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
- Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19(2022) ERJEFALT, Jonas S.; COSTA, Natalia de Souza Xavier; JONSSON, Jimmie; COZZOLINO, Olga; DANTAS, Katia Cristina; CLAUSSON, Carl-Magnus; SIDDHURAJ, Premkumar; LINDO, Caroline; ALYAMANI, Manar; LOMBARDI, Suzete Cleusa Ferreira Spina; MENDRONI JUNIOR, Alfredo; ANTONANGELO, Leila; FARIA, Caroline Silverio; DUARTE-NETO, Amaro Nunes; MONTEIRO, Renata Aparecida de Almeida; PINHO, Joao Renato Rebello; GOMES-GOUVEA, Michele Soares; PEREIRA, Roberta Verciano; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; OLIVEIRA, Ellen Pierre de; THEODORO FILHO, Jair; SANDEN, Caroline; ORENGO, Jamie M.; SLEEMAN, Matthew A.; SILVA, Luiz Fernando Ferraz da; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; MAUAD, ThaisBackground Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed. Findings Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with dis-ease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Interpretation Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments.
- Correlation between lung inflammatory cells, viral load and cytokines in fatal COVID-19(2022) COSTA, N. de Souza Xavier; ERJEFALT, J.; JONSSON, J.; COZZOLINO, O.; DANTAS, K.; CLAUSSON, C.; SIDDHURAJ, P.; LINDO, C.; LOMBARDI, S. Ferreira Spina; MENDRONI JUNIOR, A.; ANTONANGELO, L.; FARIA, C. Silverio; DUARTE NETO, A. Nunes; MONTEIRO, R. Almeida; PINHO, J. R. Rebello; GOMES-GOUVEA, M. Soares; PEREIRA, R. Verciano; MONTEIRO, J. Sirino; SETUBAL, J. C.; OLIVEIRA, E. Pierre De; THEODORO FILHO, J.; SANDEN, C.; ORENGO, J.; SLEEMAN, M.; SILVA, L. F. Ferraz Da; SALDIVA, P. Nascimento; DOLHNIKOFF, M.; MAUAD, T.