VERONICA PORTO CARREIRO DE VASCONCELLOS COELHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape(2023) OLIVEIRA, Jamille Ramos; RUIZ, Cesar Manuel Remuzgo; MACHADO, Rafael Rahal Guaragna; MAGAWA, Jhosiene Yukari; DAHER, Isabela Pazotti; URBANSKI, Alysson Henrique; SCHMITZ, Gabriela Justamante Haendel; ARCURI, Helen Andrade; FERREIRA, Marcelo Alves; SASAHARA, Greyce Luri; MEDEIROS, Giuliana Xavier de; JR, Roberto Carlos Vieira Silva; DURIGON, Edison Luiz; BOSCARDIN, Silvia Beatriz; ROSA, Daniela Santoro; SCHECHTMAN, Deborah; NAKAYA, Helder. I. I.; CUNHA-NETO, Edecio; GADERMAIER, Gabriele; KALIL, Jorge; COELHO, Veronica; SANTOS, Keity SouzaIntroductionConsidering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information. MethodsWe used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. ResultsWe found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity. DiscussionThis peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
- Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19(2023) GARDINASSI, Luiz Gustavo; SERVIAN, Carolina do Prado; LIMA, Gesiane da Silva; ANJOS, Deborah Carolina Carvalho dos; JR, Antonio Roberto Gomes; GUILARDE, Adriana Oliveira; BORGES, Moara Alves Santa Barbara; SANTOS, Gabriel Franco dos; MORAES, Brenda Grazielli Nogueira; SILVA, Joao Marcos Maia; MASSON, Leticia Carrijo; SOUZA, Flavia Pereira de; SILVA, Rodolfo Rodrigues da; ARAUJO, Giovanna Lopes de; RODRIGUES, Marcella Ferreira; SILVA, Lidya Cardozo da; MEIRA, Sueli; FIACCADORI, Fabiola Souza; SOUZA, Menira; ROMAO, Pedro Roosevelt Torres; FERREIRA, Monica Spadafora; COELHO, Veronica; CHAVES, Andrea Rodrigues; SIMAS, Rosineide Costa; VAZ, Boniek Gontijo; FONSECA, Simone GoncalvesCOVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19.IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.
conferenceObject Low-volume direct strip multiplex PCR of intraocular fluid in uveitis(2023) YAMAMOTO, Joyce H.; ODA, Eduardo Ferracioli; TANAKA, Tatiana; GOUVEA, Michele Soares Gomes; PINHO, Joao Renato Rebello; COELHO, Veronica; BISPO, Paulo J. M.; HIRATA, Carlos EduardoconferenceObject Cytokines profile in ocular fluid of individuals with uveitis: preliminary result(2023) ODA, Eduardo Ferracioli; COELHO, Veronica; ANTONANGELO, Leila; HIRATA, Carlos Eduardo; YAMAMOTO, Joyce H.- Distinct anti-NP, anti-RBD and anti-Spike antibody profiles discriminate death from survival in COVID-19(2023) SERVIAN, Carolina do Prado; SPADAFORA-FERREIRA, Monica; ANJOS, Deborah Carolina Carvalho dos; GUILARDE, Adriana Oliveira; GOMES-JUNIOR, Antonio Roberto; BORGES, Moara Alves Santa Barbara; MASSON, Leticia Carrijo; SILVA, Joao Marcos Maia; LIMA, Matheus Henrique Assis de; MORAES, Brenda Grazielli Nogueira; SOUZA, Sueli Meira; XAVIER, Luiz Eterno; OLIVEIRA, Denise Cristina Andre de; BATALHA-CARVALHO, Joao Victor; MORO, Ana Maria; BOCCA, Anamelia Lorenzetti; PFRIMER, Irmtraut Araci Hoffmann; COSTA, Nadia Lago; FERES, Valeria Christina de Rezende; FIACCADORI, Fabiola Souza; SOUZA, Menira; GARDINASSI, Luiz Gustavo; DURIGON, Edison Luiz; ROMAO, Pedro Roosevelt Torres; JORGE, Soraia Attie Calil; COELHO, Veronica; BOTOSSO, Viviane Fongaro; FONSECA, Simone GoncalvesIntroductionInfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces rapid production of IgM, IgA, and IgG antibodies directed to multiple viral antigens that may have impact diverse clinical outcomes.MethodsWe evaluated IgM, IgA, and IgG antibodies directed to the nucleocapsid (NP), IgA and IgG to the Spike protein and to the receptor-binding domain (RBD), and the presence of neutralizing antibodies (nAb), in a cohort of unvaccinated SARS-CoV-2 infected individuals, in the first 30 days of post-symptom onset (PSO) (T1).ResultsThis study included 193 coronavirus disease 2019 (COVID-19) participants classified as mild, moderate, severe, critical, and fatal and 27 uninfected controls. In T1, we identified differential antibody profiles associated with distinct clinical presentation. The mild group presented lower levels of anti-NP IgG, and IgA (vs moderate and severe), anti-NP IgM (vs severe, critical and fatal), anti-Spike IgA (vs severe and fatal), and anti-RBD IgG (vs severe). The moderate group presented higher levels of anti-RBD IgA, comparing with severe group. The severe group presented higher levels of anti-NP IgA (vs mild and fatal) and anti-RBD IgG (vs mild and moderate). The fatal group presented higher levels of anti-NP IgM and anti-Spike IgA (vs mild), but lower levels of anti-NP IgA (vs severe). The levels of nAb was lower just in mild group compared to severe, critical, and fatal groups, moreover, no difference was observed among the more severe groups. In addition, we studied 82 convalescent individuals, between 31 days to 6 months (T2) or more than 6 months (T3), PSO, those: 12 mild, 26 moderate, and 46 severe plus critical. The longitudinal analyzes, for the severe plus critical group showed lower levels of anti-NP IgG, IgA and IgM, anti-Spike IgA in relation T3. The follow-up in the fatal group, reveals that the levels of anti-spike IgG increased, while anti-NP IgM levels was decreased along the time in severe/critical and fatal as well as anti-NP IgG and IgA in several/critical groups.DiscussionIn summary, the anti-NP IgA and IgG lower levels and the higher levels of anti-RBD and anti-Spike IgA in fatal compared to survival group of individuals admitted to the intensive care unit (ICU). Collectively, our data discriminate death from survival, suggesting that anti-RBD IgA and anti-Spike IgA may play some deleterious effect, in contrast with the potentially protective effect of anti-NP IgA and IgG in the survival group.