LUCY SANTOS VILAS BOAS
Projetos de Pesquisa
Unidades Organizacionais
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
8 resultados
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- Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease(2013) WEG, Cornelia A. M. van de; PANNUTI, Claudio S.; ARAUJO, Evaldo S. A. de; HAM, Henk-Jan van den; ANDEWEG, Arno C.; BOAS, Lucy S. V.; FELIX, Alvina C.; CARVALHO, Karina I.; MATOS, Andreia M. de; LEVI, Jose E.; ROMANO, Camila M.; CENTRONE, Cristiane C.; RODRIGUES, Celia L. de Lima; LUNA, Expedito; GORP, Eric C. M. van; OSTERHAUS, Albert D. M. E.; MARTINA, Byron E. E.; KALLAS, Esper G.Background: Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection. Methods: Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of Sao Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles. Results: Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease. Conclusions: The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.
- First case report of monkeypox in Brazil: clinical manifestations and differential diagnosis with sexually transmitted infections(2022) LIMA, Evelyn Lepka de; BARRA, Luiz Alberto Costa; BORGES, Luciana Marques Sansao; MEDEIROS, Lucas Alberto; TOMISHIGE, Marcia Y. S.; SANTOS, Lucas de Souza Loureiro Abbud; SILVA, Anderson Jose Dias da; RODRIGUES, Camila Cristina Martini; AZEVEDO, Luiz Cesar Fernandes de; VILLAS-BOAS, Lucy Santos; SILVA, Camila Alves Maia da; COLETTI, Thais Moura; MANULI, Erika R.; CLARO, Ingra Morales; ROMANO, Camila Malta; RAMUNDO, Mariana Severo; MOUTINHO, Tomas; SABINO, Ester Cerdeira; LINDOSO, Jose Angelo Lauletta; FIGUEIREDO-MELLO, ClaudiaIn 2022, an outbreak of monkeypox is being reported in non-endemic areas, with unusual clinical manifestations. The detailed clinical description of the first patient that received the diagnosis of monkeypox in Brazil is reported here, whose clinical manifestations can easily lead to misdiagnosis of sexually transmitted infections. A 41 years old male presented to an emergency room with a vesicular rash with eight days of evolution. He had traveled to Portugal and Spain and reported non-penetrative sexual involvement with three different male individuals. On the third day of symptoms, he sought medical care and received empirical treatment directed to sexually transmitted infections. As the symptoms did not improve, he sought medical attention at an infectious disease referral center presenting, on admission, an ulcerated penile lesion with central necrotic crusts, a disseminated pleomorphic skin rash and an oropharyngeal ulcer. The monkeypox diagnosis was suspected due to the characteristics of the lesions and the history of intimate contact with casual partners, and it was later confirmed by sequencing the almost complete monkeypox genome. The patient was hospitalized for pain control, which required opiate administration. He developed a secondary bacterial infection on the penile lesions, which were treated with oral antibiotics. He was discharged after 14 days, with lesions in process of re-epithelialization. Given the current outbreak, we must consider the possibility of monkeypox in patients with suggestive lesions, anywhere on the body (including the genitals), added to an epidemiological link or history of intimate contact with strangers or casual partners.
- Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak(2013) ROMANO, Camila Malta; LAUCK, Michael; SALVADOR, Felipe S.; LIMA, Celia Rodrigues; VILLAS-BOAS, Lucy S.; ARAUJO, Evaldo Stanislau A.; LEVI, Jose Eduardo; PANNUTI, Claudio Sergio; O'CONNOR, David; KALLAS, Esper GeorgesBackground: High genetic diversity at both inter-and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. Methods and Principal Findings: We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. Conclusions and Significance: Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.
- SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains(2023) MENDES-CORREA, Maria Cassia; SALOMAO, Matias Chiarastelli; GHILARDI, Fabio; TOZETTO-MENDOZA, Tania Regina; VILLAS-BOAS, Lucy Santos; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; COSTA, Antonio Charlys da; LEAL, Fabio E.; FERRAZ, Andrea de Barros Coscelli; SALES, Flavia C. S.; CLARO, Ingra M.; FERREIRA, Noely E.; PEREIRA, Geovana M.; JR, Almir Ribeiro da Silva; FREIRE, Wilton; ESPINOZA, Evelyn Patricia Sanchez; MANULI, Erika R.; ROMANO, Camila M.; JESUS, Jaqueline G. de; SABINO, Ester C.; WITKIN, Steven S.Introduction-The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods-We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results-A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.
- Prolonged presence of replication-competent SARS-CoV-2 in mildly symptomatic individuals: A report of two cases(2021) CORREA, Maria C. Mendes; LEAL, Fabio E.; BOAS, Lucy S. Villas; WITKIN, Steven S.; PAULA, Anderson de; MENDONZA, Tania R. Tozetto; FERREIRA, Noely E.; CURTY, Gislaine; CARVALHO, Pedro S. de; BUSS, Lewis F.; COSTA, Silvia F.; CARVALHO, Flavia M. da Cunha; KAWAKAMI, Joyce; TANIWAKI, Noemi N.; PAIAO, Heuder; BIZARIO, Joao C. da Silva; JESUS, Jaqueline G. de; SABINO, Ester C.; ROMANO, Camila M.; GREPAN, Regina M. Z.; SESSO, AntonioIt has been estimated that individuals with COVID-19 can shed replication-competent virus up to a maximum of 20 days after initiation of symptoms. The majority of studies that addressed this situation involved hospitalized individuals and those with severe disease. Studies to address the possible presence of SARS-CoV-2 during the different phases of COVID-19 disease in mildly infected individuals, and utilization of viral culture techniques to identify replication-competent viruses, have been limited. This report describes two patients with mild forms of the disease who shed replication-competent virus for 24 and 37 days, respectively, after symptom onset.
- Shotgun metagenomic sequencing of the first case of monkeypox virus in Brazil, 2022(2022) CLARO, Ingra Morales; ROMANO, Camila Malta; CANDIDO, Darlan da Silva; LIMA, Evelyn Lepka de; LINDOSO, Jose Angelo Lauletta; RAMUNDO, Mariana Severo; MOREIRA, Filipe Romero Rebello; BARRA, Luiz Alberto Costa; BORGES, Luciana Marques Sansao; MEDEIROS, Lucas Alberto; TOMISHIGE, Marcia Y. S.; MOUTINHO, Tomas; SILVA, Anderson Jose Dias da; RODRIGUES, Camila Cristina Martini; AZEVEDO, Luiz Cesar Fernandes de; VILLAS-BOAS, Lucy Santos; SILVA, Camila Alves Maia da; COLETTI, Thais Moura; MANULI, Erika R.; O'TOOLE, Aine; QUICK, Joshua; LOMAN, Nicholas; RAMBAUT, Andrew; FARIA, Nuno R.; FIGUEIREDO-MELLO, Claudia; SABINO, Ester CerdeiraMonkeypox virus (MPXV), a zoonotic virus endemic to the African continent, has been reported in 33 non-endemic countries since May 2022. We report an almost complete genome of the first confirmed case of MPXV in Brazil. Shotgun metagenomic sequencing was completed in 18 hours, from DNA extraction to consensus sequence generation.
- Low Sensitivity of NS1 Protein Tests Evidenced during a Dengue Type 2 Virus Outbreak in Santos, Brazil, in 2010(2012) FELIX, Alvina Clara; ROMANO, Camila Malta; CENTRONE, Cristiane de Campos; RODRIGUES, Celia Lima; VILLAS-BOAS, Lucy; ARAUJO, Evaldo Stanislau; MATOS, Andreia Manso de; CARVALHO, Karina Inacio; MARTELLI, Celina Maria Turchi; KALLAS, Esper Georges; PANNUTI, Claudio Sergio; LEVI, Jose EduardoIn 2010, a large outbreak of dengue occurred in Santos, Brazil. The detection of the NS1 antigen was used for diagnosis in addition to the detection of IgG, IgM, and RNA. A large number of NS1 false-negative results were obtained. A total of 379 RNA-positive samples were selected for thorough evaluation. NS1 was reactive in 37.7% of cases. Most of the cases were characterized as a secondary infection by dengue 2 virus. Sequencing of NS1 positive and negative isolates did not reveal any mutation that could justify the diagnostic failure. Use of existing NS1 tests in the Brazilian population may present a low negative predictive value, and they should be used with caution, preferentially after performing a validation with samples freshly obtained during the ongoing epidemic.
- Serum angiopoietin-2 and soluble VEGF receptor 2 are surrogate markers for plasma leakage in patients with acute dengue virus infection(2014) WEG, Cornella A. M. van de; PANNUTI, Claudio S.; HAM, Henk-Jan van den; ARAUJO, Evaldo S. A. de; BOAS, Lucy S. V.; FELIX, Alvina C.; CARVALHO, Karina I.; LEVI, Jose E.; ROMANO, Camila M.; CENTRONE, Cristiane C.; RODRIGUES, Celia L. de Lima; LUNA, Expedito; GORP, Eric C. M. van; OSTERHAUS, Albert D. M. E.; KALLAS, Esper G.; MARTINA, Byron E. E.Background: Endothelial cell dysfunction is believed to play an important role in the pathogenesis of plasma leakage in patients with acute dengue virus (DENV) infection. Several factors, produced by activated endothelial cells, have been associated with plasma leakage or severe disease in patients with infectious diseases. Objectives: The aim of this study was to investigate which of these markers could serve as a surrogate marker for the occurrence of plasma leakage in patients with acute DENV infection. Study design: A case-control study was performed in patients with acute DENV infection in Santos, Brazil. Plasma leakage was detected with X-ray and/or ultrasound examination at admission. Serum levels of soluble endoglin, endothelin-1, angiopoietin-2, VEGF, soluble VEGFR-2, MMP-2, MMP-9, TIMP-1 and TIMP2 were determined using commercially available ELISAs. Results: Increased levels of angiopoietin-2, endothelin-1 and MMP-2 and decreased levels of soluble VEGFR2 were significantly associated with the occurrence of plasma leakage. An unsupervised cluster analysis confirmed that angiopoietin-2 and soluble VEGFR-2 were strongly associated with clinical apparent vascular leakage. Conclusion: Angiopoietin-2 and soluble VEGFR-2 can serve as surrogate markers for the occurrence of plasma leakage in patients with acute DENV infection.