RENATA APARECIDA DE ALMEIDA MONTEIRO
Projetos de Pesquisa
Unidades Organizacionais
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Ultrasound assessment of pulmonary fibroproliferative changes in severe COVID-19: a quantitative correlation study with histopathological findings(2021) MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SILVA, Luiz Fernando Ferraz da; OLIVEIRA, Ellen Pierre de; NASCIMENTO, Ellen Caroline Toledo do; MAUAD, Thais; SALDIVA, Paulo Hilario do Nascimento; DOLHNIKOFF, MarisaPurpose This study was designed to evaluate the usefulness of lung ultrasound (LUS) imaging to characterize the progression and severity of lung damage in cases of COVID-19. Methods We employed a set of combined ultrasound parameters and histopathological images obtained simultaneously in 28 patients (15 women, 0.6-83 years) with fatal COVID-19 submitted to minimally invasive autopsies, with different times of disease evolution from initial symptoms to death (3-37 days, median 18 days). For each patient, we analysed eight post-mortem LUS parameters and the proportion of three histological patterns (normal lung, exudative diffuse alveolar damage [DAD] and fibroproliferative DAD) in eight different lung regions. The relationship between histopathological and post-mortem ultrasonographic findings was assessed using various statistical approaches. Results Statistically significant positive correlations were observed between fibroproliferative DAD and peripheral consolidation (coefficient 0.43, p = 0.02) and pulmonary consolidation (coefficient 0.51, p = 0.005). A model combining age, time of evolution, sex and ultrasound score predicted reasonably well (r = 0.66) the proportion of pulmonary parenchyma with fibroproliferative DAD. Conclusion The present study adds information to previous studies related to the use of LUS as a tool to assess the severity of acute pulmonary damage. We provide a histological background that supports the concept that LUS can be used to characterize the progression and severity of lung damage in severe COVID-19.
- Testicular pathology in fatal COVID-19: A descriptive autopsy study(2022) DUARTE-NETO, Amaro N.; TEIXEIRA, Thiago A.; CALDINI, Elia G.; KANAMURA, Cristina T.; GOMES-GOUVEA, Michele S.; SANTOS, Angela B. G. dos; MONTEIRO, Renata A. A.; PINHO, Joao R. R.; MAUAD, Thais; SILVA, Luiz F. F. da; SALDIVA, Paulo H. N.; DOLHNIKOFF, Marisa; LEITE, Katia R. M.; HALLAK, JorgeBackground Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. Objective To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets. Materials and methods Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed. Results Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases. Discussion and conclusion The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.
- Tracking the time course of pathological patterns of lung injury in severe COVID-19(2021) MAUAD, Thais; DUARTE-NETO, Amaro Nunes; SILVA, Luiz Fernando Ferraz da; OLIVEIRA, Ellen Pierre de; BRITO, Jose Mara de; NASCIMENTO, Ellen Caroline Toledo do; MONTEIRO, Renata Aparecida de Almeida; FERREIRA, Juliana Carvalho; CARVALHO, Carlos Roberto Ribeiro de; SALDIVA, Paulo Hilario do Nascimento; DOLHNIKOFF, MarisaBackground: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. Methods: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. Results: Patient ' s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. Conclusion: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.
- Salivary glands are a target for SARS-CoV-2: a source for saliva contamination(2021) MATUCK, Bruno Fernandes; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro Nunes; MAIA, Gilvan; GOMES, Sara Costa; SENDYK, Daniel Isaac; ZARPELLON, Amanda; ANDRADE, Nathalia Paiva de; MONTEIRO, Renata Aparecida; PINHO, Joao Renato Rebello; GOMES-GOUVEA, Michele Soares; SOUZA, Suzana C. O. M.; KANAMURA, Cristina; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; BRAZ-SILVA, Paulo H.; CALDINI, Elia Garcia; SILVA, Luiz Fernando Ferraz daThe ability of the new coronavirus SARS-CoV-2 to spread and contaminate is one of the determinants of the COVID-19 pandemic status. SARS-CoV-2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound-guided postmortem biopsies in COVID-19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT-qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS-CoV-2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12 years (range 8-83 years). RT-qPCR for SARS-CoV-2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70-100 nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti-SARS-CoV-2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS-CoV-2 by immunohistochemistry. Salivary glands are a reservoir for SARS-CoV-2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID-19 and highlight this biological fluid's role in spreading the disease. (C) 2021 The Pathological Society of Great Britain and Ireland.
- 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.
- Post-Mortem Diagnosis of Pediatric Dengue Using Minimally Invasive Autopsy during the COVID-19 Pandemic in Brazil(2022) MELO, Deborah N.; LIMA, Giovanna R. P.; FERNANDES, Carolina G.; TEIXEIRA, Andre C.; FILHO, Joel B.; ARAUJO, Fernanda M. C.; ARAUJO, Lia C.; SIQUEIRA, Andre M.; FARIAS, Luis A. B. G.; MONTEIRO, Renata A. A.; ORDI, Jaume; MARTINEZ, Miguel J.; SALDIVA, Paulo H. N.; CAVALCANTI, Luciano P. G.We report the first pediatric disease in which the use of minimally invasive autopsy (MIA) confirmed severe dengue as the cause of death. During the COVID-19 pandemic, a previously healthy 10-year-old girl living in north-eastern Brazil presented fever, headache, diffuse abdominal pain, diarrhoea, and vomiting. On the fourth day, the clinical symptoms worsened and the patient died. An MIA was performed, and cores of brain, lungs, heart, liver, kidneys, and spleen were collected with 14G biopsy needles. Microscopic examination showed diffuse oedema and congestion, pulmonary intra-alveolar haemorrhage, small foci of midzonal necrosis in the liver, and tubular cell necrosis in the kidneys. Dengue virus RNA and NS1 antigen were detected in blood and cerebrospinal fluid samples. Clinical, pathological, and laboratory findings, in combination with the absence of other lesions and microorganisms, allowed concluding that the patient had died from complications of severe dengue.
- Ultrasound-Guided Minimally Invasive Tissue Sampling: A Minimally Invasive Autopsy Strategy During the COVID-19 Pandemic in Brazil, 2020(2021) DUARTE-NETO, Amaro Nunes; SILVA, Luiz Fernando Ferraz da; MONTEIRO, Renata Aparecida de Almeida; FILHO, Jair Theodoro; LEITE, Thabata Larissa Luciano Ferreira; MOURA, Catia Sales de; GOMES-GOUVEA, Michele Soares; PINHO, Joao Renato Rebellho; KANAMURA, Cristina Takami; OLIVERIA, Ellen Pierre de; BISPO, Kely Cristina Soares; ARRUDA, Cassia; SANTOS, Aline Brito dos; AQUINO, Flavia Cristina Goncalves; CALDINI, Elia Garcia; MAUAD, Thais; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, MarisaBackground: Minimally invasive autopsies, also known as minimally invasive tissue sampling (MITS), have proven to be an alternative to complete diagnostic autopsies (CDAs) in places or situations where this procedure cannot be performed. During the coronavirus disease 2019 (COVID-19) pandemic, CDAs were suspended by March 2020 in Brazil to reduce biohazard. To contribute to the understanding of COVID-19 pathology, we have conducted ultrasound (US)-guided MITS as a strategy. Methods: This case series study includes 80 autopsies performed in patients with COVID-19 confirmed by laboratorial tests. Different organs were sampled using a standardized MITS protocol. Tissues were submitted to histopathological analysis as well as immunohistochemical and molecular analysis and electron microscopy in selected cases. Results: US-guided MITS proved to be a safe and highly accurate procedure; none of the personnel were infected, and accuracy ranged from 69.1% for kidney, up to 90.1% for lungs, and reaching 98.7% and 97.5% for liver and heart, respectively. US-guided MITS provided a systemic view of the disease, describing the most common pathological findings and identifying viral and other infectious agents using ancillary techniques, and also allowed COVID-19 diagnosis confirmation in 5% of the cases that were negative in premortem and postmortem nasopharyngeal/oropharyngeal swab real-time reverse-transcription polymerase chain reaction. Conclusions: Our data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases.
- Extended minimally invasive autopsy: Technical imp-rovements for the investigation of cardiopulmonary events in COVID-19(2021) THEODORO-FILHO, Jair; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, MarisaOBJECTIVES: Ultrasound-guided minimally invasive autopsies (MIA-US) are an alternative to conventional autopsies and have been used in our institution to investigate the pathophysiology of COVID-19 since the beginning of the pandemic. Owing to the limitations of post-mortem biopsies for evaluating cardiopulmonary events involving large vessels, we continuously improved the technique during this period. Objectives: To demonstrate the usefulness of an extended MIA-US technique (EMIA-US) for the study of thoracic involvement in COVID-19. METHOD: US-guided percutaneous tissue sampling was combined with a small thoracic incision (p5 cm), allowing for the sampling of larger tissue samples or even the entire organ (lungs and heart). RESULTS: EMIA-US was performed for eight patients who died of COVID-19 in 2021. We demonstrate cardiopulmonary events, mainly thromboembolism and myocardial infarction, that could be evaluated using EMIA-US. CONCLUSIONS: Minimally invasive image-guided post-mortem tissue sampling isa flexible and practical method to conduct post-mortem studies of human diseases, mainly in areas that do not have autopsy facilities or, alternatively, when autopsy is not possible owing to financial constraints, cultural and religious values, or for safety reasons, such as in the case of highly contagious infectious diseases. We present evidence that EMIA-US is feasible and can be used as an alternative to increase the accuracy of MIA-US in detecting cardiopulmonary events involving large vessels, which may not be assessed through post-mortem biopsies.
- COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review(2022) ALMAMLOUK, Raghed; KASHOUR, Tarek; OBEIDAT, Sawsan; BOIS, Melanie C.; MALESZEWSKI, Joseph J.; OMRANI, Osama A.; TLEYJEH, Rana; BERBARI, Elie; CHAKHACHIRO, Zaher; ZEIN-SABATTO, Bassel; GERBERI, Dana; TLEYJEH, Imad M.; MONDOLFI, Alberto E. Paniz; V, Aloke Finn; DUARTE-NETO, Amaro Nunes; V, Amy Rapkiewicz; FRUSTACI, Andrea; KERESZTESI, Arthur-Atilla; HANLEY, Brian; MAERKL, Bruno; LARDI, Christelle; BRYCE, Clare; LINDNER, Diana; AGUIAR, Diego; WESTERMANN, Dirk; STROBERG, Edana; DUVAL, Eric J.; YOUD, Esther; BULFAMANTE, Gaetano Pietro; SALMON, Isabelle; AUER, Johann; HIRSCHBUEHL, Klaus; ABSIL, Lara; BARTON, Lisa M.; SILVA, Luiz Fernando Ferraz da; MOORE, Luiza; DOLHNIKOFF, Marisa; LAMMENS, Martin; OSBORN, Michael; REMMELINK, Myriam; SALDIVA, Paulo Hilario Nascimento; JORENS, Philippe G.; CRAVER, Randall; MONTEIRO, Renata Aparecida de Almeida; SCENDONI, Roberto; MUKHOPADHYAY, Sanjay; SUZUKI, Tadaki; MAUAD, Thais; FRACASSO, Tony; GRIMES, ZacharyBackground: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. Objectives: The aim of this systematic review is to better understand the various aspects of the cardio-vascular complications of COVID-19 by pooling data from a large number of autopsy studies. Data sources: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published be-tween database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. Study eligibility criteria: Articles were considered eligible for inclusion if they reported human post-mortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. Participants: Confirmed COVID-19 patients with post-mortem cardiovascular findings. Interventions: None. Methods: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). Results: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-10 0%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median re-ported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). Conclusions: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in 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.