84 results on '"Carolina, Lucas"'
Search Results
2. Towards privacy-preserving digital marketing: an integrated framework for user modeling using deep learning on a data monetization platform.
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Qiwei Han, Carolina Lucas, Emila Aguiar, Patrícia Macedo, and Zhenze Wu
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- 2023
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3. Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein
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Sarah Lapidus, Feimei Liu, Arnau Casanovas-Massana, Yile Dai, John D. Huck, Carolina Lucas, Jon Klein, Renata B. Filler, Madison S. Strine, Mouhamad Sy, Awa B. Deme, Aida S. Badiane, Baba Dieye, Ibrahima Mbaye Ndiaye, Younous Diedhiou, Amadou Moctar Mbaye, Cheikh Tidiane Diagne, Inés Vigan-Womas, Alassane Mbengue, Bacary D. Sadio, Moussa M. Diagne, Adam J. Moore, Khadidiatou Mangou, Fatoumata Diallo, Seynabou D. Sene, Mariama N. Pouye, Rokhaya Faye, Babacar Diouf, Nivison Nery, Federico Costa, Mitermayer G. Reis, M. Catherine Muenker, Daniel Z. Hodson, Yannick Mbarga, Ben Z. Katz, Jason R. Andrews, Melissa Campbell, Ariktha Srivathsan, Kathy Kamath, Elisabeth Baum-Jones, Ousmane Faye, Amadou Alpha Sall, Juan Carlos Quintero Vélez, Michael Cappello, Michael Wilson, Choukri Ben-Mamoun, Richard Tedder, Myra McClure, Peter Cherepanov, Fabrice A. Somé, Roch K. Dabiré, Carole Else Eboumbou Moukoko, Jean Bosco Ouédraogo, Yap Boum, John Shon, Daouda Ndiaye, Adam Wisnewski, Sunil Parikh, Akiko Iwasaki, Craig B. Wilen, Albert I. Ko, Aaron M. Ring, and Amy K. Bei
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Medicine ,Science - Abstract
Abstract Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.
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- 2022
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4. Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5
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Zhenhao Fang, Valter S. Monteiro, Anne M. Hahn, Nathan D. Grubaugh, Carolina Lucas, and Sidi Chen
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Cytology ,QH573-671 - Published
- 2022
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5. Integration of Deep Learning and Collaborative Robot for Assembly Tasks
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Enrico Mendez, Oscar Ochoa, David Olivera-Guzman, Victor Hugo Soto-Herrera, José Alfredo Luna-Sánchez, Carolina Lucas-Dophe, Eloina Lugo-del-Real, Ivo Neftali Ayala-Garcia, Miriam Alvarado Perez, and Alejandro González
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cobots ,Deep Learning ,neural network ,collaborative robotics ,human–robot interaction ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Human–robot collaboration has gained attention in the field of manufacturing and assembly tasks, necessitating the development of adaptable and user-friendly forms of interaction. To address this demand, collaborative robots (cobots) have emerged as a viable solution. Deep Learning has played a pivotal role in enhancing robot capabilities and facilitating their perception and understanding of the environment. This study proposes the integration of cobots and Deep Learning to assist users in assembly tasks such as part handover and storage. The proposed system includes an object classification system to categorize and store assembly elements, a voice recognition system to classify user commands, and a hand-tracking system for close interaction. Tests were conducted for each isolated system and for the complete application as used by different individuals, yielding an average accuracy of 91.25%. The integration of Deep Learning into cobot applications has significant potential for transforming industries, including manufacturing, healthcare, and assistive technologies. This work serves as a proof of concept for the use of several neural networks and a cobot in a collaborative task, demonstrating communication between the systems and proposing an evaluation approach for individual and integrated systems.
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- 2024
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6. Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
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Zhenhao Fang, Lei Peng, Carolina Lucas, Qianqian Lin, Liqun Zhou, Luojia Yang, Yanzhi Feng, Ping Ren, Paul A. Renauer, Valter S. Monteiro, Anne M. Hahn, Jonathan J. Park, Xiaoyu Zhou, Yale SARS-CoV-2 Genomic Surveillance Initiative, Nathan D. Grubaugh, Craig B. Wilen, and Sidi Chen
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Cytology ,QH573-671 - Published
- 2022
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7. High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19
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Winston A. Haynes, Kathy Kamath, Joel Bozekowski, Elisabeth Baum-Jones, Melissa Campbell, Arnau Casanovas-Massana, Patrick S. Daugherty, Charles S. Dela Cruz, Abhilash Dhal, Shelli F. Farhadian, Lynn Fitzgibbons, John Fournier, Michael Jhatro, Gregory Jordan, Jon Klein, Carolina Lucas, Debra Kessler, Larry L. Luchsinger, Brian Martinez, M. Catherine Muenker, Lauren Pischel, Jack Reifert, Jaymie R. Sawyer, Rebecca Waitz, Elsio A. Wunder, Minlu Zhang, Yale IMPACT Team, Akiko Iwasaki, Albert Ko, and John C. Shon
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Biology (General) ,QH301-705.5 - Abstract
Using a high throughput, random bacterial peptide display approach applied to patient serum samples, Haynes, Kamath, Bozekowski et al identify the antigens and epitopes that elicit a SARS-CoV-2 humoral response. They identify differences depending on disease severity and further in silico analysis suggests decreased epitope signal for Q677P but not for D614G mutant SARSCoV-2 strains.
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- 2021
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8. No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
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Alice Lu-Culligan, Alexandra Tabachnikova, Eddy Pérez-Then, Maria Tokuyama, Hannah J. Lee, Carolina Lucas, Valter Silva Monteiro, Marija Miric, Vivian Brache, Leila Cochon, M. Catherine Muenker, Subhasis Mohanty, Jiefang Huang, Insoo Kang, Charles Dela Cruz, Shelli Farhadian, Melissa Campbell, Inci Yildirim, Albert C. Shaw, Shuangge Ma, Sten H. Vermund, Albert I. Ko, Saad B. Omer, and Akiko Iwasaki
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Biology (General) ,QH301-705.5 - Abstract
The impact of Coronavirus Disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated 2 of the most widely propagated claims to determine (1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities; and (2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from these murine pregnancies vaccinated prior to the formation of the definitive placenta exhibit high circulating levels of anti-spike and anti-receptor-binding domain (anti-RBD) antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) consistent with maternal antibody status, indicating transplacental transfer in the later stages of pregnancy after early immunization. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes. The impact of COVID-19 mRNA vaccination on pregnancy and fertility has become a major topic of public interest. This study shows that after inoculation of pregnant mice with COVID mRNA vaccines, no birth defects or growth restrictions were found, and no induction of anti-syncytin-1 antibodies was detected in a longitudinal human cohort compared to unvaccinated volunteers.
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- 2022
9. Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses.
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Adam V Wisnewski, Jian Liu, Carolina Lucas, Jon Klein, Akiko Iwasaki, Linda Cantley, Louis Fazen, Julian Campillo Luna, Martin Slade, and Carrie A Redlich
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Medicine ,Science - Abstract
BackgroundTests for SARS-CoV-2 immunity are needed to help assess responses to vaccination, which can be heterogeneous and may wane over time. The plaque reduction neutralization test (PRNT) is considered the gold standard for measuring serum neutralizing antibodies but requires high level biosafety, live viral cultures and days to complete. We hypothesized that competitive enzyme linked immunoassays (ELISAs) based on SARS-CoV-2 spike protein's receptor binding domain (RBD) attachment to its host receptor, the angiotensin converting enzyme 2 receptor (ACE2r), would correlate with PRNT, given the central role of RBD-ACE2r interactions in infection and published studies to date, and enable evaluation of vaccine responses.Methods and resultsConfiguration and development of a competitive ELISA with plate-bound RBD and soluble biotinylated ACE2r was accomplished using pairs of pre/post vaccine serum. When the competitive ELISA was used to evaluate N = 32 samples from COVID-19 patients previously tested by PRNT, excellent correlation in IC50 results were observed (rs = .83, p < 0.0001). When the competitive ELISA was used to evaluate N = 42 vaccinated individuals and an additional N = 13 unvaccinated recovered COVID-19 patients, significant differences in RBD-ACE2r inhibitory activity were associated with prior history of COVID-19 and type of vaccine received. In longitudinal analyses pre and up to 200 days post vaccine, surrogate neutralizing activity increased markedly after primary and booster vaccine doses, but fell substantially, up to ConclusionsA competitive ELISA based on inhibition of RBD-ACE2r attachment correlates well with PRNT, quantifies significantly higher activity among vaccine recipients with prior COVID (vs. those without), and highlights marked declines in surrogate neutralizing activity over a 6 month period post vaccination. The findings raise concern about the duration of vaccine responses and potential need for booster shots.
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- 2022
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10. EFEITO DA FREQUÊNCIA ALIMENTAR NA SOBREVIVÊNCIA E NO DESENVOLVIMENTO DE LARVAS DE JUNDIÁ (RHAMDIA QUELEN) EM CONDIÇÕES EXPERIMENTAIS
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Gomes, Ana Carolina Lucas, primary, Fosse, Paulo José, additional, Rodrigues, Mateus Fossi, additional, Lengruber, Elion Loureiro da Silva, additional, and Amaral, Atanásio Alves do, additional
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- 2021
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11. Fundamentos e Práticas Pediátricas e Neonatais - Volume 2
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Pena, Ângela Gil Patrus, primary, Silva, Ana Luiza Gonçalves, additional, Bacha, Fernanda Vaz de Melo, additional, Gomez, Fernanda Lustosa Cabral, additional, Chiari, Júlia Barroso, additional, Padrão, Lorena Ribeiro, additional, OLIVEIRA, ANA CAROLINA PRIOSTE DE, additional, GRILLO, ANA LUIZA YAEKASHI, additional, PAULA, DAVI SALOMÃO DE, additional, GALLATE, GLAUCO HERNANDES, additional, BORGES, GUSTAVO MIRANDA RAMOS, additional, HIRATA, HEITOR BUENO, additional, ROCHA, HIAGGO FILMIANO, additional, SOARES, ISABELLA ELIAS, additional, SILVA, JOÃO PEDRO NAVARRO, additional, BASÍLIO, JÚLIO CÉSAR CIPRIANO, additional, CAMILO, LUANA PERRONE, additional, OLIVEIRA, JONAS MUNCK DE, additional, BORDIM, GIOVANA MOREIRA, additional, GONÇALVES, LARYSSA DE SÁ BRAGANÇA, additional, SOARES, LAURA CUNHA, additional, MACHADO, MARIA JÚLIA MARTINS, additional, MONTEIRO, THIAGO LOPES, additional, SARKIS, DIEGO JUNQUEIRA, additional, FONSECA, LUIZA SOARES, additional, Souza, Érika de Lima, additional, FONSECA, ISABEL GOULART, additional, DIAS, LAVÍNIA DA SILVA, additional, COELHO, MARINA GUERRA MAIA, additional, SOARES, ARIANNY HELLEN DE OLIVEIRA, additional, TEIXEIRA, BEATRIZ PESSANHA DIAS, additional, FERREIRA, BRENDA DE SOUZA, additional, GALDINO, CARLA MENEGHETTI, additional, NEVES, GABRIELA CARNEIRO, additional, NETTO, GABRIELA DE PAULA FAGUNDES, additional, CASTRO, HUGO DUARTE MASCARENHAS DE, additional, PAULA, IGOR CRUZ DE, additional, ALÍPIO, ISABELLA GUIMARÃES SILVA, additional, OLIVEIRA, Jonas Munck de, additional, RIBEIRO, LAILA SOUZA, additional, MAIA, LAIS RODRIGUES, additional, CERQUEIRA, LARISSA VALDIER, additional, JABOUR, LETÍCIA GIANCOLI, additional, CAMPOS, MARIANA, additional, ARAUJO, MATHEUS FRANCO, additional, BARBEITOS, RAFAEL BATITUCCI, additional, CUNHA, VICTOR DOS REIS, additional, REIS, MARIA CLARA LARA, additional, REIS, ARMANDO, additional, BENITES, ANA LAURA CAMPOS RITTER, additional, SOUZA, ANDREZA ALMEIDA FERREIRA DE, additional, MACHADO, MELISSA ÁVILA, additional, Pereira, Gabriela Saldes Campos, additional, MONESI, ANDRESSA DE CÁSSIA COUTINHO, additional, SPINELLI, ISADORA, additional, RAMOS, FLAVIA FRUGOLI, additional, TAWIL, THAIS REAIDI EL, additional, DIAS, MARIA CAROLINA LUCAS, additional, NADER, SILVANA SALGADO, additional, BREIGEIRON, MÁRCIA KOJA, additional, GERHARDT, LUIZA MARIA, additional, WEGNER, WILIAM, additional, MAGALHÃES, CAROLINE DA CUNHA CAMPOS, additional, CASTRO, SIMONE BAGGIO DE, additional, AZEVEDO, BRENDA VELLUMA SOARES DE, additional, MARTINS, CAMILA MARQUES DE ARAUJO, additional, LEITE, MANUELLA FERNANDES, additional, NERI, WAGNER JOSÉ RAIA, additional, SILVA, PAULO ROBERTO DA, additional, COSTA, JESSIKA DOS SANTOS, additional, PEREIRA, LETÍCIA CAROLINA MALAQUIAS, additional, MENDES, JOÃO VICTOR BRAGA, additional, BARREIRO, ELISA GIANNINI, additional, VALENTINI, JULIANA, additional, RAMOS, GABRIEL NASCIMENTO, additional, SILVA, LARISSA VERISSIMO RAMOS, additional, GAZZI, LETÍCIA AZEVEDO, additional, VALÉRIO, RIANNE SOARES, additional, SILVA, SALETE PEREIRA DA, additional, MACHADO, ALYNE COUTO CARVALHO DA FONSECA, additional, COUTO, ELITON EDMILSON DO, additional, SALES, GUSTAVO FINAMOR, additional, SILVA, INGRED STEPHANY DOMINGUES DA, additional, SPENAZATO, VALDECIR BOENO, additional, BARBOSA, ARELLY BETHÂNIA FONSECA, additional, SILVEIRA, LYVI MAIRA, additional, PEREIRA, MARIA EDUARDA SIRINA, additional, DELLORTO, ZEFERINO CAMPOS, additional, FARIA, CAROLINA PENNA DE, additional, MARCARINI, GUSTAVO ALEXANDRE RIBONDI, additional, CUNHA, ISABELA FERNANDES COELHO, additional, BARROS, ISRAEL FELIPE DOMINGOS DE, additional, ARAÚJO, MARIANNA PAULA NUNES, additional, ESPESCHIT, ISIS DE FREITAS, additional, BARRETO, AMANDA BATISTA, additional, MARINS, GIOVANNA SHERLY DE SÁ GUEDES, additional, PEREIRA, MYLENA MARIA FERRAZ, additional, Gonçalves, Marcos Reis, additional, Santos, Caroline Nascimento, additional, DAUD, MIRELLA DE FREITAS, additional, SANZOVO, GIULIA DALESSANDRO, additional, FUMAGALLI, HELEN FIGUEIREDO, additional, ALMEIDA, RAFAEL MACEDO DE, additional, HARADA, MARCELA BERTOLDO, additional, PENHA, PAULA VIEIRA, additional, BRAGA, LUIZA DE CASTRO CANÇADO, additional, CANDOLATO, GABRIELA DE ARAÚJO, additional, GODOY, LUÍSA RIBEIRO DIAS, additional, MAGALHÃES, CLARA CABRAL DE, additional, LOPES, JÚLIA PEREIRA, additional, Lima, Carine Carvalho Vaz de, additional, BERNARDES, VINÍCIUS FONSECA, additional, Polo, Mateus Gomes, additional, Machado, Lucas Henrique de Carvalho, additional, BARBOSA, MARIANA MAGNO, additional, Chagas, Julia De Oliveira, additional, LIMA, CARINE CARVAHO VAZ DE, additional, Magalhães, Eugênio F, additional, SILVA, ISABELA BRAGA DA, additional, SIMÕES, ISABELLA STEPHANIE, additional, SACHI, JULIA RIBEIRO, additional, VILELA, MARIA LUÍZA COBRA, additional, PESCI, MARINA RODRIGES, additional, GUSMÃO, REBECA RIBEIRO DE, additional, LINO, FLÁVIA ELISA FIRMINO, additional, RÊGO, LEONARDO GURGEL, additional, EZEQUIEL, LUÍSA DE SOUZA, additional, FILHA, MARIA GORETH DE ANDRADE MORENO, additional, SOUZA, ANNA JÚLIA ARRAES ALVES DE, additional, GALDINO, NAYARA DA SILVA, additional, OLIVEIRA, MAYRA LOURES DE, additional, CAMPOS, LARISSA GONÇALVES, additional, PEREIRA, LARISSA REZENDE LIMA, additional, TEIXEIRA, RAMON FELIPE ALVES, additional, ROCHA, ANA KELLY TEIXEIRA, additional, MACHADO, DANIEL SOUSA, additional, LINHARES, GUSTAVO COELHO PEREIRA, additional, QUEIROZ, JORGE LACERDA DE, additional, MIRANDA, LAÍS TRIGO, additional, GARCIA, SAMILA ALVES, additional, CRUZ, SARA EDUARDA OLIVEIRA DA, additional, PEREIRA, TATIANE COSTA, additional, Peixoto, Stefany Monteiro, additional, RODRIGUES, MARIA CLARA CASTILHO, additional, SANTOS, AMANDA VILELA, additional, VIEIRA, RODRIGO AUGUSTO SILVA, additional, FARIA, MATHEUS CAMELO FERREIRA, additional, CARNEIRO, GUSTAVO NETTO DO CARMO, additional, PEREIRA, MIRIAN GABRIELA MARTINS, additional, TEIXEIRA, THULIO CESAR, additional, AZEVEDO, DANYELLY RODRIGUES MACHADO, additional, TEIXEIRA, THULIO CÉSAR, additional, Santos, Amanda Vilela, additional, PEIXOTO, STEFANY MONTEIRO, additional, MACHADO, LUCAS HENRIQUE DE CARVALHO, additional, DIAS, MARIANA NUNES LIMA, additional, MARTINS, JOÃO HENRIQUE SANTOS, additional, Tavares, Ricardo Henrique Freitas, additional, OLIVEIRA, ANA CAROLINA AMORIM, additional, OLIVEIRA, ANA PAULA AMORIM, additional, QUEIROZ, ANA PAULA MACEDO PRUDENTE DE, additional, BARRETO, DANIELLE ALVES, additional, ARAGÃO, DOUGLAS NORTON SANTOS, additional, SILVA, FERNANDA PRISCILLA BARBOSA, additional, BARROS, ISABELLA TATYANE MENEZES, additional, SANTANA, MYLLA BÁRBARA GOIS, additional, SANTOS, TATIANE DE OLIVEIRA, additional, Oliveira, Halley Ferraro, additional, Filardi, Maria Fernanda de Oliveira, additional, Filardi, Ana Carolina de Oliveira, additional, Tavares, Ana Tereza Teixeira, additional, Oliveira, Antônio Mascarenhas, additional, Borja, Bruno Mialarett, additional, Gripp, Fernanda Jardim, additional, Silva, Henrique Figueiredo, additional, Gomes, Julia Pimenta, additional, Pires, Laila Mameri, additional, Mendonça, Letícia Pereira, additional, Melo, Leonardo Ferreira, additional, Rodrigues, Priscila Nogueira, additional, Souza, Sofia Silva e, additional, HERCULANO, GABRIELLA SILVEIRA, additional, XAVIER, CAMILA DUARTE, additional, MARTINS, GIOVANA VERUSSA, additional, ARES, ROBERTA PEREIRA, additional, BAU, MATHEUS WINTONIAK, additional, PEREIRA, DANIELA MARIA, additional, SIMÕES, HENRIQUE RIVERA, additional, NISTAL, LETÍCIA, additional, LEITE, TIFFANY SOARES, additional, CAMARGO, ANA LUÍSA DE, additional, Bittencourt, Anna Lillian Canuto, additional, SALES, VINÍCIUS BARBOSA DOS SANTOS, additional, MACIEL, ELISA BENETTI DE PAIVA, additional, CASTRO, ROBERTA ESTEVES VIEIRA DE, additional, FUKUDA, MICHELLE KAORI MENEZES, additional, ARRUDA, TAINÁ BATISTA, additional, GIRON, PAULA GUIRÃO, additional, MOYSÉS, GIOVANNA, additional, BAPTISTA, KARINA MARTINS, additional, NASCIMENTO, MARIA LUIZA RODRIGUES, additional, NISTAL, LETICIA, additional, NUNES, PAULO HENRIQUE, additional, FIGUEIRA, MARIANA, additional, CURSI, PRISCILA PRATA, additional, BITTENCOURT, ANNA LILLIAN CANUTO, additional, GUIMARÃES, ALINE BRITO OLIVEIRA, additional, JESUS, ANA MOZER VIEIRA DE, additional, ANDRADE, ANDREANE MENESES, additional, CAMPOS, EDUARDA MEDEIROS, additional, Lamonica, Gabriela Guilhoto Cabral, additional, REIS, FERNANDA FONTES PRADO, additional, LAMONICA, GABRIELA GUILHOTO CABRAL, additional, BARBOSA, JULIA NATALINE OLIVEIRA, additional, OLIVEIRA, JULIA SILVA ALMEIDA DE, additional, RODRIGUES, LETYCIA SANTOS, additional, CARVALHO, LORENA RODRIGUES DE, additional, FARINA, LUANA ASANO, additional, ANDRADE, NAYSA GABRIELLY ALVES DE, additional, ANDRADE, RAFAELLA ROSA LOBO DE, additional, SOUSA, THAYSER NAYARAH ESTANISLAU, additional, CORRÊA, ANA PAULA EMERICK, additional, CORRÊA, CAMILA VIDOTTI CASTRO, additional, FERREIRA, MAÍRA LUCÍLIA MONTEIRO, additional, MOROZINI, ANDREA BIANCARDI, additional, PIRES, CATARINA AMORIM BACCARINI, additional, CASTRALLI, HELOÍSA AUGUSTA, additional, VIEIRA, MARIANA SOARES, additional, MACHADO, NATAN MARTINS, additional, SILVA, PAULA JANÓLIO CARDOSO, additional, Leal, Iane Brito, additional, MEIRA, PEDRO REGES PEREIRA, additional, SOARES, BEATRIZ LUDUVICE, additional, DINIZ, JÚLIA SOUZA, additional, SOUZA, LUANA ROCHA DE, additional, ÁVILA, MILENA PEREIRA DE, additional, FIGUEIREDO, MATEUS BEZERRA DE, additional, Nóbrega, Ana Cecília de Menêzes, additional, LIMA, JOÃO VINÍCIUS SANTOS, additional, COSTA, LUMA CAROLYNE ARAÚJO, additional, CHAGAS, MARIANA DO SACRAMENTO, additional, MENEZES, MARÍLIA ALVES, additional, CARVALHO, MATHEUS ALVES NUNES DE, additional, OLIVEIRA, HALLEY FERRARO, additional, NÓBREGA, ANA CECÍLIA DE MENÊZES, additional, MARTINS, EDSON ELOI, additional, ROCHA, LAURA COELHO PIRES, additional, FERREIRA, LÍCIA BRANT MOREIRA, additional, GUIMARÃES, VICTÓRIA MOREIRA HANNAS, additional, CARVALHO, BRUNA LATIF RODRIGUES, additional, LAGE, THALITA MARTINS, additional, CUPERTINO, VALÉRIA LOPES, additional, BARROS, NATÁLIA QUINTÃO, additional, SANTOS, ANA FLÁVIA ANDRADE EMERY, additional, ABREU, ISABELLA ALVARENGA, additional, SILVA, ANA BEATRIZ GOMES, additional, SANTOS, MÁRCIA ELENA ANDRADE, additional, VALADÃO, ANALINA FURTADO, additional, OLIVEIRA, BÁRBARA MARTINS MELLO DE, additional, FREITAS, PEDRO HENRIQUE AQUINO GIL DE, additional, HOHL, LUISA TEIXEIRA, additional, BARBOSA, NATÁLIA NICHELE, additional, COELHO, RACHEL MOCELIN DIAS, additional, SILVEIRA, JOÃO PEDRO DA, additional, LOPES, GABRIEL DANTAS, additional, Lopes, Gabriel Dantas, additional, Sobral, Larissa Dantas, additional, Moura, Maria Alice Menezes, additional, SOBRA, LARISSA DANTAS, additional, MOURA, MARIA ALICE MENEZES, additional, CARVALHO, PEDRO SADDI DE, additional, ANDRADE, CLARICE MARQUES MOTTA, additional, BARREIROS, DANIELA TEIXEIRA, additional, ANTUNES, HELOISA DE MATOS, additional, MOURÃO, MARCELO DOS SANTOS, additional, VIDAL, MARIA LUIZA MOTA, additional, SANTOS, ISAAC PÊGO, additional, SALEH, NAHIMAN ASSAD FERREIRA, additional, GARCIA, JULIANA FERNANDES SAAR, additional, BARRETO, NATÁLIA ARAÚJO, additional, MATOS, JAIRA VANESSA DE CARVALHO, additional, BISPO, ANA JOVINA BARRETO, additional, GLEITZMANN, HANNAH BRYSKIER, additional, MENDES, NAIANE CRISTINA FERREIRA, additional, CISNEIROS, MIRELLY GRACE RAMOS, additional, Castro, Mayara Raquel de Jesus, additional, TAVARES, ÍRIS GABRIELA SANTOS, additional, SOBRAL, LARISSA DANTAS, additional, BARBOSA, RAFAELLA RANGEL, additional, MONTEIRO, VITÓRIA REZENDE ROCHA, additional, COELHO, NICOLLE FRAGA, additional, ASSIS, ANNA LUISA LUPI VENTURA DE, additional, SANTIAGO, LUIZA GABRIELA NORONHA, additional, ALVES, LETÍCIA THAIS DE OLIVEIRA, additional, COUTO, LETÍCIA MACHADO, additional, FERREIRA, MARIA EDUARDA RODRIGUES, additional, DIAS, MARIA EDUARDA LIMA, additional, GUEDES, LARISSA CAMARGOS, additional, MELO, LENILSON DO NASCIMENTO, additional, AGUIAR, MARIA RIKELLY FROTA, additional, COSTA, DANIELE ALCOFORADO, additional, SANTOS, JAIANE CRUZ DOS, additional, COELHO, LEONARA MARIA ALVES, additional, SANTOS, NATHANAEL ALVES DOS, additional, SALES, ANA CLARA SILVA, additional, SOUSA, DAIANE CARVALHO DE, additional, CARVALHO, NATANIEL FRANÇA, additional, COSTA, DACYLLA SAMPAIO, additional, PEREIRA, BRUNA MARIA DE CARVALHO, additional, PRADO, EDUARDO DE MELO, additional, Canalle, Renata, additional, MARQUES, CAMYLLA MACHADO, additional, NASCIMENTO, LUANA, additional, ARRUDA, EVILANNA LIMA, additional, NASCIMENTO, LUCILA CASTANHEIRA, additional, LEITE, ANA CAROLINA ANDRADE BIAGGI, additional, ALVARENGA, WILLYANE DE ANDRADE, additional, BANCA, REBECCA ORTIZ LA, additional, NERIS, RHYQUELLE RHIBNA, additional, NUNES, MICHELLE DAREZZO RODRIGUES, additional, ANDRADE, ROSYAN CARVALHO DE, additional, SANTOS, LOUISE BITTENCOURT PAES ABREU DOS, additional, ESPER, MARCOS VENICIO, additional, MARQUES, ESTEFÂNIA ANDRÉIA, additional, POLITA, NAIARA BARROS, additional, SILVA-RODRIGUES, FERNANDA MACHADO, additional, PINHO, RAFAELA TONHOLLI, additional, PIRES, BÁRBARA CALDEIRA, additional, LOPES, JOICE RIBEIRO, additional, NOGUEIRA, GABRIELA GUIMARÃES, additional, Soares, Ana Carolina De Souza, additional, RIBEIRO, GERALDO DE BARROS, additional, CASTRO, BEATRIZ GOMES DE, additional, CARVALHO, BRUNA DOS SANTOS DE, additional, BRAGHETTA, GIOVANA JUNQUEIRA FRANCHI, additional, BRAGHETTA, GIULIA JUNQUEIRA FRANCHI, additional, BRITO, LUANA PIMENTEL, additional, GRAÇAS, THALLITA VASCONCELOS DAS, additional, RODRIGUES, AMANDHA VICTÓRIA DE PINHO GONZAGA, additional, FRAGA, BYANKA PORTO, additional, GUSMÃO, FERNANDA LUIZA BUARQUE DE, additional, RODRIGUES, LETÍCIA MARIA CARDOSO LIMA, additional, LEITE, REBECCA SCHUSTER DOREA, additional, ARGOLO, YSLLA SILVA, additional, CAMPOS, FELLIPE MATOS MELO, additional, DALLOGLIO, LAURA MARIA, additional, GALLON, MALU, additional, JULIANO, ISABELLA MALTAURO, additional, SUMIDA, ISABELA AKEMI GUIRAO, additional, DEINA, MARINA, additional, COLOMÉ, FERNANDA BONILLA, additional, Sousa, Carlyne Alves de, additional, DAMASCENO, GLÍCIA MARIA DE OLIVEIRA, additional, Lima, Edilany Aguiar, additional, CISNE, DÉBORA PINHEIRO, additional, Albuquerque, Rosalice Araújo de Sousa, additional, Campos, João Victor Reis, additional, POLO, MATEUS GOMES, additional, BOSCHI, JOSÉ CARLOS, additional, ZUCARELI, BIANCA, additional, MEDEIROS, IASMIM, additional, FILGUEIRA, AMANDA MARAN, additional, Antunes, Larychelle de P, additional, Filgueira, Amanda M, additional, Ninomiya, Felipe C M, additional, TALON, MAISA SANTOS VALDERRAMAS, additional, MARTINS, DÉBORA RODRIGUES, additional, CARVALHO, GABRIELA COSTA, additional, MAIA, LAÍS RODRIDUES, additional, LIMA, LUCAS MIZRAHY, additional, CÂNDIDO, VICTÓRIA MARQUES, additional, OLIVEIRA, VÍVIAN MARIA GOMES DE, additional, OLIVEIRA, WILLIANE CROLMAN DE, additional, NICÁCIO, BÁRBARA COSTA, additional, CÁRIA, NAYARA ZINATO, additional, FREITAS, LESLIÊ APARECIDA DE, additional, SÁ, CACILDA ANDRADE DE, additional, SOUZA, MÁRCIA HELENA FÁVERO DE, additional, NERY, JOSÉ ARIMATÉA DE OLIVEIRA, additional, BEZERRA, GABRIELA LEAL, additional, NUNES, RAFAELA ODÍSIO, additional, and Barroso, Guilherme, additional
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- 2020
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12. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
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Eric Song, Christopher M. Bartley, Ryan D. Chow, Thomas T. Ngo, Ruoyi Jiang, Colin R. Zamecnik, Ravi Dandekar, Rita P. Loudermilk, Yile Dai, Feimei Liu, Sara Sunshine, Jamin Liu, Wesley Wu, Isobel A. Hawes, Bonny D. Alvarenga, Trung Huynh, Lindsay McAlpine, Nur-Taz Rahman, Bertie Geng, Jennifer Chiarella, Benjamin Goldman-Israelow, Chantal B.F. Vogels, Nathan D. Grubaugh, Arnau Casanovas-Massana, Brett S. Phinney, Michelle Salemi, Jessa R. Alexander, Juan A. Gallego, Todd Lencz, Hannah Walsh, Anne E. Wapniarski, Subhasis Mohanty, Carolina Lucas, Jon Klein, Tianyang Mao, Jieun Oh, Aaron Ring, Serena Spudich, Albert I. Ko, Steven H. Kleinstein, John Pak, Joseph L. DeRisi, Akiko Iwasaki, Samuel J. Pleasure, Michael R. Wilson, and Shelli F. Farhadian
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COVID-19 ,neurological infection ,autoimmunity ,cerebrospinal fluid ,SARS-CoV-2 ,Medicine (General) ,R5-920 - Abstract
Summary: Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with COVID-19 with neurological symptoms, we find compartmentalized, CNS-specific T cell activation and B cell responses. All affected individuals had CSF anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are present only during brain infection and not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from an individual with COVID-19 and found that these monoclonal antibodies (mAbs) target antiviral and antineural antigens, including one mAb that reacted to spike protein and neural tissue. CSF immunoglobulin G (IgG) from 5 of 7 patients showed antineural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of individuals with COVID-19 and suggests a role of autoimmunity in neurologic sequelae of COVID-19.
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- 2021
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13. Abordagem Cultural: materiais didáticos em línguas estrangeiras
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Goulart, Ana Carolina Lucas Souza, primary, Vieira, Ana Paula Gabatteli, additional, Azevedo, Andreia Matias, additional, Virgulino, Camila Geyse da Conceição, additional, Flexa, Cinthia Schattevo de Morais, additional, Frech, Cristina, additional, Jozefiak, Daniela, additional, Soares, Débora Racy, additional, Santos, Eliani de Moraes, additional, Brandão, Lauana Vale de Mello, additional, Ribeiro, Luciana, additional, Sánchez, María Graciela, additional, Almeida, Mariana Eunice Alves de, additional, Oliveira, Mariana Muniz de, additional, Santos, Priscila Formiga dos, additional, Conrado, Rosana Salvini, additional, Oliveira, Selma Cristina Rosal, additional, Ferreira, Suzan de Mattos Leão, additional, and Costa, Vânia Lemos, additional
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- 2020
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14. Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens
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Zhenhao Fang, Valter S. Monteiro, Paul A. Renauer, Xingbo Shang, Kazushi Suzuki, Xinyu Ling, Meizhu Bai, Yan Xiang, Andre Levchenko, Carmen J. Booth, Carolina Lucas, and Sidi Chen
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Cell Biology ,Molecular Biology - Published
- 2023
15. Associations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel.
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Joseph Zell, Adam V Wisnewski, Jian Liu, Jon Klein, Carolina Lucas, Martin Slade, Akiko Iwasaki, and Carrie A Redlich
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Medicine ,Science - Abstract
BackgroundCountries across the globe have mobilized their armed forces in response to COVID-19, placing them at increased risk for viral exposure. Humoral responses to SARS-CoV-2 among military personnel serve as biomarkers of infection and provide a basis for disease surveillance and recognition of work-related risk factors.MethodsEnzyme-linked immunosorbent assays (ELISA) were used to measure SARS-CoV-2 spike antigen-specific IgG in serum obtained from N = 988 US National Guard soldiers between April-June 2020. Occupational information, e.g. military operating specialty (MOS) codes, and demographic data were obtained via questionnaire. Plaque assays with live SARS-CoV-2 were used to assess serum neutralizing capacity for limited subjects (N = 12).ResultsThe SARS-CoV-2 IgG seropositivity rate among the study population was 10.3% and significantly associated with occupation and demographics. Odds ratios were highest for those working in MOS 2T-Transportation (3.6; 95% CI 0.7-18) and 92F-Fuel specialist/ground and aircraft (6.8; 95% CI 1.5-30), as well as black race (2.2; 95% CI 1.2-4.1), household size ≥6 (2.5; 95% CI 1.3-4.6) and known COVID-19 exposure (2.0; 95% CI 1.2-3.3). Seropositivity tracked along major interstate highways and clustered near the international airport and the New York City border. SARS-CoV-2 spike IgG+ serum exhibited low to moderate SARS-CoV-2 neutralizing capacity with IC50s ranging from 1:15 to 1:280. In limited follow-up testing SARS-CoV-2 serum IgG levels remained elevated up to 7 months.ConclusionsThe data highlight increased SARS-CoV-2 seroprevalence among National Guard vs. the local civilian population in association with transportation-related occupations and specific demographics.
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- 2021
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16. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis
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Anis Barmada, Jon Klein, Anjali Ramaswamy, Nina N. Brodsky, Jillian R. Jaycox, Hassan Sheikha, Kate M. Jones, Victoria Habet, Melissa Campbell, Tomokazu S. Sumida, Amy Kontorovich, Dusan Bogunovic, Carlos R. Oliveira, Jeremy Steele, E. Kevin Hall, Mario Pena-Hernandez, Valter Monteiro, Carolina Lucas, Aaron M. Ring, Saad B. Omer, Akiko Iwasaki, Inci Yildirim, and Carrie L. Lucas
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Immunology ,General Medicine - Abstract
Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2–specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1β, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3 + cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2 + CD163 + monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell–associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine–-associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.
- Published
- 2023
17. Nonsystematic Reporting Biases of the SARS-CoV-2 Variant Mu Could Impact Our Understanding of the Epidemiological Dynamics of Emerging Variants
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Mary E Petrone, Carolina Lucas, Bridget Menasche, Mallery I Breban, Inci Yildirim, Melissa Campbell, Saad B Omer, Edward C Holmes, Albert I Ko, Nathan D Grubaugh, Akiko Iwasaki, Craig B Wilen, Chantal B F Vogels, and Joseph R Fauver
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Genetics ,Ecology, Evolution, Behavior and Systematics - Abstract
Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC Mu. Mu likely emerged in South America in mid-2020, where its circulation was largely confined. In this study, we demonstrate that Mu was designated as a VOC ∼1 year after it emerged and find that the reporting of genomic data for Mu differed significantly than that of other VOCs within countries, states, and individual laboratories. Our findings suggest that nonsystematic biases in the reporting of genomic data may have delayed the global response to Mu. Until they are resolved, the surveillance gaps that affected the global response to Mu could impede the rapid and accurate assessment of future emerging variants.
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- 2023
18. Multiscale PHATE identifies multimodal signatures of COVID-19
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Manik, Kuchroo, Jessie, Huang, Patrick, Wong, Jean-Christophe, Grenier, Dennis, Shung, Alexander, Tong, Carolina, Lucas, Jon, Klein, Daniel B, Burkhardt, Scott, Gigante, Abhinav, Godavarthi, Bastian, Rieck, Benjamin, Israelow, Michael, Simonov, Tianyang, Mao, Ji Eun, Oh, Julio, Silva, Takehiro, Takahashi, Camila D, Odio, Arnau, Casanovas-Massana, John, Fournier, Shelli, Farhadian, Charles S, Dela Cruz, Albert I, Ko, Matthew J, Hirn, F Perry, Wilson, Julie G, Hussin, Guy, Wolf, Akiko, Iwasaki, and Yvette, Strong
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Exome Sequencing ,Biomedical Engineering ,COVID-19 ,Humans ,Transposases ,Molecular Medicine ,Bioengineering ,Single-Cell Analysis ,Applied Microbiology and Biotechnology ,Chromatin ,Article ,Biotechnology - Abstract
As the biomedical community produces datasets that are increasingly complex and high dimensional, there is a need for more sophisticated computational tools to extract biological insights. We present Multiscale PHATE, a method that sweeps through all levels of data granularity to learn abstracted biological features directly predictive of disease outcome. Built on a coarse-graining process called diffusion condensation, Multiscale PHATE learns a data topology that can be analyzed at coarse resolutions for high-level summarizations of data and at fine resolutions for detailed representations of subsets. We apply Multiscale PHATE to a coronavirus disease 2019 (COVID-19) dataset with 54 million cells from 168 hospitalized patients and find that patients who die show CD16(hi)CD66b(lo) neutrophil and IFN-γ(+) granzyme B(+) Th17 cell responses. We also show that population groupings from Multiscale PHATE directly fed into a classifier predict disease outcome more accurately than naive featurizations of the data. Multiscale PHATE is broadly generalizable to different data types, including flow cytometry, single-cell RNA sequencing (scRNA-seq), single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq), and clinical variables.
- Published
- 2022
19. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination
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Eddy Pérez-Then, Carolina Lucas, Valter Silva Monteiro, Marija Miric, Vivian Brache, Leila Cochon, Chantal B. F. Vogels, Amyn A. Malik, Elena De la Cruz, Aidelis Jorge, Margarita De los Santos, Patricia Leon, Mallery I. Breban, Kendall Billig, Inci Yildirim, Claire Pearson, Randy Downing, Emily Gagnon, Anthony Muyombwe, Jafar Razeq, Melissa Campbell, Albert I. Ko, Saad B. Omer, Nathan D. Grubaugh, Sten H. Vermund, and Akiko Iwasaki
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Vaccines, Synthetic ,COVID-19 Vaccines ,SARS-CoV-2 ,Vaccination ,COVID-19 ,Humans ,mRNA Vaccines ,General Medicine ,Antibodies, Viral ,Antibodies, Neutralizing ,BNT162 Vaccine ,General Biochemistry, Genetics and Molecular Biology - Abstract
The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.
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- 2022
20. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
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Albert C. Shaw, Chantal B.F. Vogels, Mario A Peña-Hernández, Julio Silva, Valter Vinicius Silva Monteiro, Joseph R. Fauver, Carolina Lucas, Melissa Campbell, Jiefang Huang, Akiko Iwasaki, Inci Yildirim, Nathan D. Grubaugh, Albert I. Ko, Saad B. Omer, Mallery I. Breban, Alexandra Tabachikova, Subhasis Mohanty, Jessica E. Rothman, M. Catherine Muenker, Peiwen Lu, and Jeff R. Gelhausen
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Adult ,Male ,Health Personnel ,T-Lymphocytes ,T cell ,Antibodies, Viral ,Article ,Neutralization ,Immunity ,medicine ,Humans ,Neutralizing antibody ,Gene ,BNT162 Vaccine ,Aged ,Retrospective Studies ,Vaccines, Synthetic ,Multidisciplinary ,biology ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Antibodies, Neutralizing ,Virology ,Immunity, Humoral ,Vaccination ,medicine.anatomical_structure ,Mutation ,Spike Glycoprotein, Coronavirus ,Humoral immunity ,biology.protein ,Female ,mRNA Vaccines ,Antibody ,2019-nCoV Vaccine mRNA-1273 - Abstract
The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination(1–6). We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.
- Published
- 2021
21. Distinguishing features of Long COVID identified through immune profiling
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Jon Klein, Jamie Wood, Jillian Jaycox, Peiwen Lu, Rahul M. Dhodapkar, Jeff R. Gehlhausen, Alexandra Tabachnikova, Laura Tabacof, Amyn A. Malik, Kathy Kamath, Kerrie Greene, Valter Silva Monteiro, Mario Peña-Hernandez, Tianyang Mao, Bornali Bhattacharjee, Takehiro Takahashi, Carolina Lucas, Julio Silva, Dayna Mccarthy, Erica Breyman, Jenna Tosto-Mancuso, Yile Dai, Emily Perotti, Koray Akduman, Tiffany J. Tzeng, Lan Xu, Inci Yildirim, Harlan M. Krumholz, John Shon, Ruslan Medzhitov, Saad B. Omer, David van Dijk, Aaron M. Ring, David Putrino, and Akiko Iwasaki
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Article - Abstract
SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID1–3. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions1–3; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.
- Published
- 2022
22. Diverse functional autoantibodies in patients with COVID-19
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Mary E. Petrone, Carolina Lucas, Shelli F. Farhadian, Isabel M. Ott, Emily S. Perotti, Wade L. Schulz, Charles S. Dela Cruz, Chantal B.F. Vogels, Ji Eun Oh, Neil S Zheng, Anne L. Wyllie, Jillian R. Jaycox, Yile Dai, Anne E. Watkins, Suzanne Fischer, Nathan D. Grubaugh, Jon Klein, Eric Wang, Aaron M. Ring, Tianyang Mao, Patrick Wong, Akiko Iwasaki, Chaney C. Kalinich, Feimei Liu, Ting Zhou, Julio Silva, Benjamin Israelow, John Fournier, Andreas Coppi, Shuangge Ma, Albert I. Ko, Melissa Campbell, John D. Huck, and Eric Song
- Subjects
0301 basic medicine ,Chemokine ,Multidisciplinary ,Innate immune system ,biology ,business.industry ,Autoantibody ,Case-control study ,Phenotype ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Antigen ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Medicine ,business ,Pathological - Abstract
COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-6. Although pathological innate immune activation is well-documented in severe disease1, the effect of autoantibodies on disease progression is less well-defined. Here we use a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling7 to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 healthcare workers with mild disease or asymptomatic infection, for autoantibodies against 2,770 extracellular and secreted proteins (members of the exoproteome). We found that patients with COVID-19 exhibit marked increases in autoantibody reactivities as compared to uninfected individuals, and show a high prevalence of autoantibodies against immunomodulatory proteins (including cytokines, chemokines, complement components and cell-surface proteins). We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signalling and by altering peripheral immune cell composition, and found that mouse surrogates of these autoantibodies increase disease severity in a mouse model of SARS-CoV-2 infection. Our analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics. Our findings suggest a pathological role for exoproteome-directed autoantibodies in COVID-19, with diverse effects on immune functionality and associations with clinical outcomes.
- Published
- 2021
23. Insights into the limited global spread of the immune evasive SARS-CoV-2 variant Mu
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Mary E. Petrone, Carolina Lucas, Bridget Menasche, Mallery I. Breban, Inci Yildirim, Melissa Campbell, Saad B. Omer, Albert I. Ko, Nathan D. Grubaugh, Akiko Iwasak, Craig B. Wilen, Chantal B.F. Vogels, and Joseph R. Fauver
- Subjects
Coronavirus ,COVID-19 - Abstract
SARS-CoV-2 ‘Variants of Concern’ (VOCs) continue to reshape the trajectory of the COVID-19 pandemic. However, why some VOCs, like Omicron, become globally dominant while the spread of others is limited is not fully understood. To address this question, we investigated the VOC Mu, which was first identified in Colombia in late 2020. Our study demonstrates that, although Mu is less sensitive to neutralization compared to variants that preceded it, it did not spread significantly outside of South and Central America. Additionally, we find evidence that the response to Mu was impeded by reporting delays and gaps in the global genomic surveillance system. Our findings suggest that immune evasion alone was not sufficient to outcompete highly transmissible variants that were circulating concurrently with Mu. Insights into the complex relationship between genomic and epidemiological characteristics of previous variants should inform our response to variants that are likely to emerge in the future.
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- 2022
24. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain
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Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty, Eric Song, Myoung-Hwa Lee, Jamie Wood, Belgin Yalçın, Kathryn R. Taylor, Selena Dutton, Lehi Acosta-Alvarez, Lijun Ni, Daniel Contreras-Esquivel, Jeff R. Gehlhausen, Jon Klein, Carolina Lucas, Tianyang Mao, Julio Silva, Mario A. Peña-Hernández, Alexandra Tabachnikova, Takehiro Takahashi, Laura Tabacof, Jenna Tosto-Mancuso, Erica Breyman, Amy Kontorovich, Dayna McCarthy, Martha Quezado, Marco Hefti, Daniel Perl, Rebecca Folkerth, David Putrino, Avi Nath, Akiko Iwasaki, and Michelle Monje
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myelin ,COVID-19 ,long-COVID ,microglia ,oligodendrocytes ,hippocampal neurogenesis ,Article ,cognitive impairment ,neuroinflammation - Abstract
Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI. We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection. Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection – without neuroinvasion - and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice. Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.
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- 2022
25. Lack of association between pandemic chilblains and SARS-CoV-2 infection
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Jeff R, Gehlhausen, Alicia J, Little, Christine J, Ko, Marc, Emmenegger, Carolina, Lucas, Patrick, Wong, Jon, Klein, Peiwen, Lu, Tianyang, Mao, Jillian, Jaycox, Eric, Wang, Nelson, Ugwu, Cate, Muenker, Dilgash, Mekael, Rhonda Q, Klein, Robert, Patrignelli, Richard, Antaya, Jennifer, McNiff, William, Damsky, Kathy, Kamath, John, Shon, Aaron M, Ring, Inci, Yildirim, Saad, Omer, Albert I, Ko, Adriano, Aguzzi, and Yvette, Strong
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Adult ,Chilblains ,Male ,Connecticut ,Young Adult ,Multidisciplinary ,SARS-CoV-2 ,viruses ,COVID-19 ,Humans ,Female ,Middle Aged ,Retrospective Studies - Abstract
An increased incidence of chilblains has been observed during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and attributed to viral infection. Direct evidence of this relationship has been limited, however, as most cases do not have molecular evidence of prior SARS-CoV-2 infection with PCR or antibodies. We enrolled a cohort of 23 patients who were diagnosed and managed as having SARS-CoV-2-associated skin eruptions (including 21 pandemic chilblains [PC]) during the first wave of the pandemic in Connecticut. Antibody responses were determined through endpoint titration enzyme-linked immunosorbent assay and serum epitope repertoire analysis. T cell responses to SARS-CoV-2 were assessed by T cell receptor sequencing and in vitro SARS-CoV-2 antigen-specific peptide stimulation assays. Immunohistochemical and PCR studies of PC biopsies and tissue microarrays for evidence of SARS-CoV-2 were performed. Among patients diagnosed and managed as "covid toes" during the pandemic, we find a percentage of prior SARS-CoV-2 infection (9.5%) that approximates background seroprevalence (8.5%) at the time. Immunohistochemistry studies suggest that SARS-CoV-2 staining in PC biopsies may not be from SARS-CoV-2. Our results do not support SARS-CoV-2 as the causative agent of pandemic chilblains; however, our study does not exclude the possibility of SARS-CoV-2 seronegative abortive infections.
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- 2022
26. A synthetic bispecific antibody capable of neutralizing SARS-CoV-2 Delta and Omicron
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Tom Z. Yuan, Carolina Lucas, Valter S. Monteiro, Akiko Iwasaki, Marisa L. Yang, Hector F. Nepita, Ana G. Lujan Hernandez, Joseph M. Taft, Lester Frei, Sai T. Reddy, Cédric R. Weber, Kevin P. Malobisky, Rodrigo Mesquita, and Aaron K. Sato
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virus diseases - Abstract
Bispecific antibodies have emerged as a promising strategy for curtailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape. This brief report highlights RBT-0813 (also known as TB493-04), a synthetic, humanized, receptor-binding domain (RBD)-targeted bispecific antibody that retains picomolar affinity to the Spike (S) trimers of all major variants of concern and neutralizes both SARS-CoV-2 Delta and Omicron in vitro.
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- 2022
27. Privacy-Preserving User Modeling for Digital Marketing Campaigns: The Case of a Data Monetization Platform
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Carolina Lucas, Emila Aguiar, Patrícia Macedo, Zhenze Wu, and Qiwei Han
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- 2022
28. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
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Hiromitsu Asashima, Subhasis Mohanty, Michela Comi, William E. Ruff, Kenneth B. Hoehn, Patrick Wong, Jon Klein, Carolina Lucas, Inessa Cohen, Sarah Coffey, Nikhil Lele, Leissa Greta, Khadir Raddassi, Omkar Chaudhary, Avraham Unterman, Brinda Emu, Steven H. Kleinstein, Ruth R. Montgomery, Akiko Iwasaki, Charles S. Dela Cruz, Naftali Kaminski, Albert C. Shaw, David A. Hafler, and Tomokazu S. Sumida
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General Biochemistry, Genetics and Molecular Biology - Published
- 2023
29. EFEITO DA FREQUÊNCIA ALIMENTAR NA SOBREVIVÊNCIA E NO DESENVOLVIMENTO DE LARVAS DE JUNDIÁ (Rhamdia quelen) EM CONDIÇÕES EXPERIMENTAIS
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Mateus Fossi Rodrigues, Atanásio Alves do Amaral, Elion Loureiro da Silva Lengruber, Ana Carolina Lucas Gomes, and Paulo José Fosse
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manejo alimentar ,biometria ,larvicultura de peixes ,General Medicine ,Biology ,desempenho zootécnico - Abstract
O objetivo desse trabalho foi avaliar o efeito da frequência alimentar no desempenho de larvas de jundiá, Rhamdia quelen, com base nas variáveis sobrevivência, comprimento final, taxa de crescimento específico e ganho de peso. Seis dias após a eclosão, as larvas foram distribuídas aleatoriamente em 24 bandejas de polietileno com 10 L de água, na densidade de 10 larvas L-1, totalizando 100 larvas por bandeja. Essas larvas foram submetidas a diferentes frequências alimentares (duas a sete vezes ao dia), com quatro repetições, em delineamento inteiramente casualizado. O peso inicial e o comprimento total inicial das larvas submetidas ao experimento foram 1,17 ± 0,39 mg e 6,20 ± 0,52 mm, respectivamente. A sobrevivência e o comprimento final das larvas não foram influenciados (p > 0,05) pelas frequências alimentares testadas, mas a taxa de crescimento específico e o ganho de peso foram influenciados. Estes foram maiores (p < 0,05) quando o alimento foi fornecido, no mínimo, três vezes ao dia. Considerando-se os resultados das variáveis analisadas e a relação custo-benefício, recomenda-se fornecer alimento três vezes ao dia, às larvas de jundiá, no primeiro mês de vida.
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- 2019
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30. Immunogenicity of heterologous BNT162b2 booster in fully vaccinated individuals with CoronaVac against SARS-CoV-2 variants Delta and Omicron: the Dominican Republic Experience
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Eddy Pérez-Then, Carolina Lucas, Valter Silva Monteiro, Marija Miric, Vivian Brache, Leila Cochon, Chantal B. F. Vogels, Elena De la Cruz, Aidelis Jorge, Margarita De los Santos, Patricia Leon, Mallery I. Breban, Kendall Billig, Inci Yildirim, Claire Pearson, Randy Downing, Emily Gagnon, Anthony Muyombwe, Jafar Razeq, Melissa Campbell, Albert Ko, Saad B. Omer, Nathan D. Grubaugh, Sten H. Vermund, and Akiko Iwasaki
- Abstract
The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and by its numerous spike mutations with potential to evade neutralizing antibodies elicited by COVID-19 vaccines. The Dominican Republic was among the first countries in recommending the administration of a third dose COVID-19 vaccine to address potential waning immunity and reduced effectiveness against variants. Here, we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants that had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that heterologous CoronaVac prime followed by BNT162b2 booster regimen induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and Delta variant, resembling the titers obtained after two doses of mRNA vaccines. While neutralization of Omicron was undetectable in participants that had received a two-dose regimen of CoronaVac vaccine, BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron, compared to two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 6.3-fold and 2.7-fold for Omicron compared to ancestral and Delta variant, respectively. Surprisingly, previous SARS-CoV-2 infection did not affect the neutralizing titers for Omicron in participants that received the heterologous regimen. Our findings have immediate implications for multiples countries that previously used a two-dose regimen of CoronaVac and reinforce the notion that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.
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- 2021
31. No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
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Alice Lu-Culligan, Alexandra Tabachnikova, Maria Tokuyama, Hannah J. Lee, Carolina Lucas, Valter Silva Monteiro, M. Catherine Muenker, Subhasis Mohanty, Jiefang Huang, Insoo Kang, Charles Dela Cruz, Shelli Farhadian, Melissa Campbell, Inci Yildirim, Albert C. Shaw, Albert I. Ko, Saad B. Omer, and Akiko Iwasaki
- Abstract
The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.
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- 2021
32. PD-1
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Hiromitsu, Asashima, Subhasis, Mohanty, Michela, Comi, William E, Ruff, Kenneth B, Hoehn, Patrick, Wong, Jon, Klein, Carolina, Lucas, Inessa, Cohen, Sarah, Coffey, Nikhil, Lele, Leissa, Greta, Khadir, Raddassi, Omkar, Chaudhary, Avraham, Unterman, Brinda, Emu, Steven H, Kleinstein, Ruth R, Montgomery, Akiko, Iwasaki, Charles S, Dela Cruz, Naftali, Kaminski, Albert C, Shaw, David A, Hafler, and Tomokazu S, Sumida
- Abstract
T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4
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- 2021
33. High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19
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Elsio A. Wunder, Jack Reifert, Debra Kessler, Jaymie R Sawyer, Patrick S. Daugherty, Minlu Zhang, Carolina Lucas, Elisabeth Baum-Jones, Yale Impact Team, Joel Bozekowski, Lynn Fitzgibbons, Gregory Jordan, Winston A. Haynes, M. Catherine Muenker, Albert I. Ko, Brian Martinez, Arnau Casanovas-Massana, Melissa Campbell, Rebecca Waitz, Lauren Pischel, Kathy Kamath, John Fournier, Charles S. Dela Cruz, Michael Jhatro, Jon Klein, Akiko Iwasaki, Abhilash Dhal, Larry L. Luchsinger, John Shon, and Shelli F. Farhadian
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QH301-705.5 ,viruses ,Adaptive immunity ,Medicine (miscellaneous) ,Context (language use) ,Cross Reactions ,Antibodies, Viral ,Article ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,Immune system ,Human proteome project ,Humans ,Biology (General) ,Data mining ,Bacterial display ,biology ,SARS-CoV-2 ,COVID-19 ,Diagnostic markers ,Virology ,Epitope mapping ,Viral infection ,Proteome ,biology.protein ,Antibody ,General Agricultural and Biological Sciences ,Epitope Mapping - Abstract
As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they are not readily adaptable to diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify proteome-independent epitope binding specificities which are then analyzed in the context of organisms of interest. When evaluating immune response in the context of SARS-CoV-2, we identify dominant epitope regions and motifs which demonstrate potential to classify mild from severe disease and relate to neutralization activity. We highlight SARS-CoV-2 epitopes that are cross-reactive with other coronaviruses and demonstrate decreased epitope signal for mutant SARS-CoV-2 strains. Collectively, the evolution of SARS-CoV-2 mutants towards reduced antibody response highlight the importance of data-driven development of the vaccines and therapies to treat COVID-19., Using a high throughput, random bacterial peptide display approach applied to patient serum samples, Haynes, Kamath, Bozekowski et al identify the antigens and epitopes that elicit a SARS-CoV-2 humoral response. They identify differences depending on disease severity and further in silico analysis suggests decreased epitope signal for Q677P but not for D614G mutant SARSCoV-2 strains.
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- 2021
34. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
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Carolina Lucas, Craig B. Wilen, Mallery I. Breban, Akiko Iwasaki, Tianyang Mao, Yale SARS-CoV Genome Surveillance Initiative, Anna Marie Pyle, Nathan D. Grubaugh, Bridget L. Menasche, Maria Luisa Gomez-Calvo, Chantal B.F. Vogels, Melissa M. Linehan, Huiping Dong, Olga Fedorova, Benjamin Israelow, and Marie L. Landry
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Agonist ,Innate immune system ,business.industry ,RIG-I ,medicine.drug_class ,Immunology ,RNA ,Context (language use) ,Acquired immune system ,medicine.anatomical_structure ,Interferon ,Immunology and Allergy ,Medicine ,business ,Respiratory tract ,medicine.drug - Abstract
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I)–dependent manner. SLR14 demonstrated remarkable prophylactic protective capacity against lethal SARS-CoV-2 infection and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity in the absence of the adaptive immune system. In the context of infection with variants of concern (VOCs), SLR14 conferred broad protection against emerging VOCs. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and treatment of chronically infected immunosuppressed patients.
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- 2021
35. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals
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Yale SARS-CoV Genomic Surveillance Initiative, Saad B. Omer, Peiwen Lu, Carolina Lucas, Subhasis Mohanty, Albert I. Ko, Mallery I. Breban, Joseph R. Fauver, M. Catherine Munker, Jiefang Huang, Nathan D. Grubaugh, Chantal B.F. Vogels, Akiko Iwasaki, Melissa Campbell, Alexandra Tabachikova, Inci Yildirim, Jessica E. Rothman, Julio Silva, Albert C. Shaw, Valter Vinicius Silva Monteiro, and Gelhausen Jeffrey R
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Vaccination ,medicine.anatomical_structure ,biology ,Immunity ,T cell ,Humoral immunity ,biology.protein ,Antibody titer ,medicine ,Antibody ,Neutralizing antibody ,Virology ,Neutralization - Abstract
The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1–6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain than previously infected individuals 7 days after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination in the time-points analysed. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2) or with E484K (without N501Y/T). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.
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- 2021
36. Longitudinal Immune Profiling of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection in a Solid Organ Transplant Recipient
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Joseph R. Fauver, Ji Eun Oh, John Shon, Shelli F. Farhadian, Marwan M. Azar, Tara Alpert, Nathan D. Grubaugh, Jonathan Klein, Patrick Wong, Charles S. Dela Cruz, Anne L. Wyllie, M. Catherine Muenker, Chantal B.F. Vogels, Winston A. Haynes, Kathy Kamath, Peiwen Lu, Paul Trubin, Arnau Casanovas-Massana, Chaney C. Kalinich, Anderson F. Brito, Feimei Liu, Aaron M. Ring, Akiko Iwasaki, Julio Silva, Adam J. Moore, Carolina Lucas, Albert I. Ko, Tianyang Mao, Mary E. Petrone, Benjamin Israelow, and Mario A Peña-Hernández
- Subjects
Male ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Secondary infection ,Antibodies, Viral ,Neutralization ,Article ,SARS-CoV-2 reinfection ,Immune profiling ,Major Articles and Brief Reports ,Immunology and Allergy ,Medicine ,Humans ,Phylogeny ,Aged ,biology ,business.industry ,SARS-CoV-2 ,immune profiling ,pathogen adaptation ,COVID-19 ,Organ Transplantation ,Antibodies, Neutralizing ,Transplant Recipients ,Titer ,Infectious Diseases ,Reinfection ,Immunology ,biology.protein ,Antibody ,Solid organ transplantation ,business ,solid organ transplant recipient - Abstract
BackgroundThe underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19).MethodsA 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections.ResultsWhole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti–SARS-CoV-2 antibodies that were likely present at the time of reinfection.ConclusionsThe development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.
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- 2021
37. Kynurenic acid may underlie sex-specific immune responses to COVID-19
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Caroline H. Johnson, Akiko Iwasaki, Nicholas J. W. Rattray, Patrick Wong, Tianyang Mao, Jon Klein, Ji Eun Oh, M. Catherine Muenker, David Broadhurst, Arnau Casanovas-Massana, Takehiro Takahashi, Yuping Cai, Julio Silva, Daniel J. Kim, Hong Yan, Benjamin Israelow, Adam J. Moore, Carolina Lucas, Albert I. Ko, Sajid A. Khan, and Shuanagge Ma
- Subjects
0301 basic medicine ,Chemokine ,medicine.medical_specialty ,medicine.medical_treatment ,T cell ,Biochemistry ,Proinflammatory cytokine ,RS ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,Kynurenic acid ,Internal medicine ,medicine ,Research Resource ,Molecular Biology ,biology ,Case-control study ,Glutamate receptor ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,STKE Research Resources ,Coronavirus ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,Endocrinology ,chemistry ,biology.protein ,030217 neurology & neurosurgery - Abstract
Compared to females, male COVID-19 patients have more kynurenic acid, which may underlie their poorer immune response., Sex-specific metabolism and COVID-19 Males and females have different immune responses to SARS-CoV-2 infection, with male sex being a risk factor for mortality, particularly among older individuals. Cai et al. performed metabolomics analysis of serum from COVID-19 patients and uninfected health care workers and identified 17 metabolites that were associated with the disease. However, in male COVID-19 patients only, the amount of the tryptophan metabolite kynurenic acid (KA) correlated with age, inflammation, and disease outcome. KA inhibits glutamate release, and glutamate abundance was reduced in patients who deteriorated. Together, these findings indicate that KA is associated with sex-specific differences in immune responses to COVID-19, suggesting that it might be targeted in male patients., Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males.
- Published
- 2021
38. A stem-loop RNA RIG-I agonist confers prophylactic and therapeutic protection against acute and chronic SARS-CoV-2 infection in mice
- Author
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Tianyang Mao, Melissa M. Linehan, Olga Fedorova, Yale SARS-CoV Genome Surveillance Initiative, Akiko Iwasaki, Craig B. Wilen, Marie L. Landry, Carolina Lucas, Benjamin Israelow, Nathan D. Grubaugh, Chantal B.F. Vogels, Huiping Dong, Bridget L. Menasche, Anna Marie Pyle, and Mallery I. Breban
- Subjects
Agonist ,medicine.drug_class ,viruses ,Innate Immunity and Inflammation ,Context (language use) ,Antiviral Agents ,Article ,Infectious Disease and Host Defense ,Mice ,Interferon ,Medicine ,Animals ,skin and connective tissue diseases ,Mice, Inbred BALB C ,Innate immune system ,business.industry ,RIG-I ,SARS-CoV-2 ,fungi ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Acquired immune system ,Immunity, Innate ,COVID-19 Drug Treatment ,Disease Models, Animal ,medicine.anatomical_structure ,Viral replication ,Immunology ,Interferon Type I ,RNA ,business ,Covid-19 ,Respiratory tract ,medicine.drug - Abstract
A stem-loop RNA (SLR) RIG-I agonist is effective in preventing and treating acute SARS-CoV-2 infection in mice. A single injection of SLR can clear chronic SARS-CoV-2 in immunocompromised mice. SLR is effective against the ancestral virus as well as variants of concern., As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I)–dependent manner. SLR14 demonstrated remarkable prophylactic protective capacity against lethal SARS-CoV-2 infection and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity in the absence of the adaptive immune system. In the context of infection with variants of concern (VOCs), SLR14 conferred broad protection against emerging VOCs. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and treatment of chronically infected immunosuppressed patients., Graphical Abstract
- Published
- 2021
39. Plasmodium infection induces cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein
- Author
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Roch K. Dabiré, Arnau Casanovas-Massana, Amy K. Bei, Aaron M. Ring, Akiko Iwasaki, Renata B. Filler, Amadou Moctar Mbaye, Daniel Hodson, Sarah Lapidus, Babacar Diouf, Madison S. Strine, Inés Vigan-Womas, Juan Carlos Quintero Vélez, Choukri Ben-Mamoun, Kathy Kamath, Yile Dai, Ousmane Faye, Albert I. Ko, Alassane Mbengue, Seynabou D. Sene, Nivison Nery, Michael Cappello, Baba Dieye, Federico Costa, Rokhaya Faye, Khadidiatou Mangou, Craig B. Wilen, Jason R. Andrews, Jon Klein, Fabrice A. Somé, Yannick Mbarga, Mitermayer G. Reis, Michael T. Wilson, Adam J. Moore, Carolina Lucas, Elisabeth Baum-Jones, Awa B. Deme, Fatoumata Diallo, M. Catherine Muenker, Amadou A. Sall, Younous Diedhiou, Mariama N. Pouye, Aida Sadikh Badiane, Ariktha Srivathsan, Moussa Moïse Diagne, Cheikh Tidiane Diagne, Yap Boum, Mouhamad Sy, Ben Z. Katz, John Shon, Carole Else Eboumbou Moukoko, Ibrahima Ndiaye, Bacary D. Sadio, Daouda Ndiaye, Sunil Parikh, Feimei Liu, Jean-Bosco Ouédraogo, Adam V. Wisnewski, Melissa Campbell, and John D. Huck
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Glycan ,biology ,virus diseases ,Carbohydrate ,biology.organism_classification ,Virology ,Plasmodium ,Article ,In vitro ,Epitope ,Sialic acid ,chemistry.chemical_compound ,chemistry ,Immunity ,biology.protein ,Antibody - Abstract
Individuals with acute malaria infection generated high levels of antibodies that cross-react with the SARS-CoV-2 Spike protein. Cross-reactive antibodies specifically recognized the sialic acid moiety on N-linked glycans of the Spike protein and do not neutralize in vitro SARS-CoV-2. Sero-surveillance is critical for monitoring and projecting disease burden and risk during the pandemic; however, routine use of Spike protein-based assays may overestimate SARS-CoV-2 exposure and population-level immunity in malaria-endemic countries.
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- 2021
40. Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient
- Author
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Anne L. Wyllie, Winston A. Haynes, Mary E. Petrone, Adam J. Moore, Aaron M. Ring, Peiwen Lu, Carolina Lucas, Anderson F. Brito, Akiko Iwasaki, Joseph R. Fauver, Shelli F. Farhadian, Marwan M. Azar, Ji Eun Oh, Chaney C. Kalinich, Charles S. Dela Cruz, Feimei Liu, Julio Silva, Mario A Peña-Hernández, Albert I. Ko, John Shon, Chantal B.F. Vogels, Benjamin Goldman-Israelow, Kathy Kamath, Tianyang Mao, Arnau Casanovas-Massana, M. C. Muenker, Y. I. R. Team, Jon Klein, Tara Alpert, Paul Trubin, Nathan D. Grubaugh, and Patrick Wong
- Subjects
biology ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Host factors ,Immune profiling ,Immune system ,Immunology ,biology.protein ,Renal allograft ,Medicine ,Antibody ,business ,Solid organ transplantation ,Pathogen - Abstract
The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal-transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection 7 months after primary infection. To elucidate the immunological mechanisms responsible for reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses that was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we identified the development of neutralizing antibodies and humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation.
- Published
- 2021
41. Delayed production of neutralizing antibodies correlates with fatal COVID-19
- Author
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Alfred Ian Lee, Adam V. Wisnewski, Hyung J. Chun, Adam J. Moore, Anne L. Wyllie, Carolina Lucas, M. Catherine Muenker, Albert I. Ko, C-Hong Chang, Annsea Park, Jiefang Huang, Shelli F. Farhadian, Tianyang Mao, Julio Silva, Albert C. Shaw, Patrick Wong, Feimei Liu, Arnau Casanovas-Massana, Benjamin Israelow, Aaron M. Ring, John Fournier, Akiko Iwasaki, Arvind Venkataraman, Ji Eun Oh, Maria E. Sundaram, Saad B. Omer, Jon Klein, Maria Tokuyama, Subhasis Mohanty, Charles S. Dela Cruz, Joseph Zell, Melissa Campbell, Chantal B.F. Vogels, Peiwen Lu, Wade L. Schulz, Inci Yildirim, and Nathan D. Grubaugh
- Subjects
0301 basic medicine ,biology ,business.industry ,Antiviral antibody ,General Medicine ,Asymptomatic ,General Biochemistry, Genetics and Molecular Biology ,Immunoglobulin G ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Immunity ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Medicine ,Antibody ,Seroconversion ,medicine.symptom ,Neutralizing antibody ,business - Abstract
Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.
- Published
- 2021
42. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
- Author
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Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty, Eric Song, Myoung-Hwa Lee, Jamie Wood, Michael R. O’Dea, Selena Dutton, Kiarash Shamardani, Kamsi Nwangwu, Rebecca Mancusi, Belgin Yalçın, Kathryn R. Taylor, Lehi Acosta-Alvarez, Karen Malacon, Michael B. Keough, Lijun Ni, Pamelyn J. Woo, Daniel Contreras-Esquivel, Angus Martin Shaw Toland, Jeff R. Gehlhausen, Jon Klein, Takehiro Takahashi, Julio Silva, Benjamin Israelow, Carolina Lucas, Tianyang Mao, Mario A. Peña-Hernández, Alexandra Tabachnikova, Robert J. Homer, Laura Tabacof, Jenna Tosto-Mancuso, Erica Breyman, Amy Kontorovich, Dayna McCarthy, Martha Quezado, Hannes Vogel, Marco M. Hefti, Daniel P. Perl, Shane Liddelow, Rebecca Folkerth, David Putrino, Avindra Nath, Akiko Iwasaki, and Michelle Monje
- Subjects
Mice ,SARS-CoV-2 ,Neoplasms ,Influenza, Human ,Animals ,COVID-19 ,Humans ,Microglia ,Myelin Sheath ,General Biochemistry, Genetics and Molecular Biology - Abstract
COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.
- Published
- 2022
43. Case Study: Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient
- Author
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Mary E. Petrone, Tianyang Mao, Jonathan Klein, Patrick Wong, Anderson F. Brito, Mario A Peña-Hernández, Marwan M. Azar, Tara Alpert, M. Catherine Muenker, Aaron M. Ring, Peiwen Lu, Paul Trubin, Akiko Iwasaki, Arnau Casanovas-Massana, Chaney C. Kalinich, Benjamin Israelow, Feimei Liu, Ji Eun Oh, Nathan D. Grubaugh, Julio Silva, Charles S. Dela Cruz, Albert I. Ko, John Shon, Chantal B.F. Vogels, Kathy Kamath, Adam J. Moore, Carolina Lucas, Shelli F. Farhadian, Joseph R. Fauver, Anne L. Wyllie, and Winston A. Haynes
- Subjects
biology ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Article ,Virus ,Immune profiling ,Immune system ,Immunology ,biology.protein ,Medicine ,Antibody ,business ,Solid organ transplantation ,Neutralizing antibody ,Pathogen - Abstract
SummaryPrior to the emergence of antigenically distinct SARS-CoV-2 variants, reinfections were reported infrequently - presumably due to the generation of durable and protective immune responses. However, case reports also suggested that rare, repeated infections may occur as soon as 48 days following initial disease onset. The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection - confirmed by whole virus genome sequencing - 7 months after primary infection. To elucidate the immunological mechanisms responsible for SARS-CoV-2 reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses. The patient’s immune system was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we also identified the development of neutralizing antibodies and the formation of humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation in this patient. In summary, our study suggests that a low neutralizing antibody presence alone is not sufficient to confer resistance against reinfection. Thus, patients with solid organ transplantation, or patients who are otherwise immunosuppressed, who recover from infection with SARS-CoV-2 may not develop sufficient protective immunity and are at risk of reinfection.
- Published
- 2021
44. Reply to: A finding of sex similarities rather than differences in COVID-19 outcomes
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Patrick Wong, Albert C. Shaw, Isabel M. Ott, Mallory K. Ellingson, Benjamin Israelow, Saad B. Omer, John Fournier, Charles S. Dela Cruz, Wade L. Schulz, Peiwen Lu, Anne L. Wyllie, Takehiro Takahashi, Eric Wang, Arvind Venkataraman, Nathan D. Grubaugh, Sarah Lapidus, Camila D. Odio, Amit Meir, Chantal B.F. Vogels, Jonathan Sun, Julio Silva, Arnau Casanovas-Massana, Rebecca Earnest, Tianyang Mao, Adam J. Moore, Carolina Lucas, Albert I. Ko, Annsea Park, Jon Klein, Maria Tokuyama, Aaron M. Ring, Akiko Iwasaki, Feimei Liu, Shelli F. Farhadian, and Ji Eun Oh
- Subjects
2019-20 coronavirus outbreak ,Multidisciplinary ,Coronavirus disease 2019 (COVID-19) ,Sex factors ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Medicine ,business ,Virology ,Sex characteristics - Published
- 2021
45. Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality
- Author
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Anne L. Wyllie, Saad B. Omer, Benjamin Israelow, Wade L. Schulz, Adam J. Moore, Melissa Campbell, John Fournier, Michael Chiorazzi, Charles S. Dela Cruz, Carolina Lucas, Patrick Wong, Jon Klein, Albert I. Ko, Maria Tokuyama, Annsea Park, Maria E. Sundaram, Yale Impact Team, Peiwen Lu, Mary E. Petrone, Edwin Ruiz Fuentes, Annie Watkins, Shuangge Ma, Shelli F. Farhadian, Chantal B.F. Vogels, Tianyang Mao, Arnau Casanovas-Massana, Aaron M. Ring, Arvind Venkataraman, Catherine M. Muenker, Ji Eun Oh, Akiko Iwasaki, Julio Silva, Joseph Zell, Maura Nakahata, Isabel M. Ott, Nathan D. Grubaugh, Chaney C. Kalinich, and Feimei Liu
- Subjects
Saliva ,Coronavirus disease 2019 (COVID-19) ,business.industry ,T cell ,Article ,Immune system ,medicine.anatomical_structure ,Follicular phase ,Immunology ,Medicine ,CXCL10 ,Platelet ,business ,Viral load - Abstract
While several clinical and immunological parameters correlate with disease severity and mortality in SARS-CoV-2 infection, work remains in identifying unifying correlates of coronavirus disease 2019 (COVID-19) that can be used to guide clinical practice. Here, we examine saliva and nasopharyngeal (NP) viral load over time and correlate them with patient demographics, and cellular and immune profiling. We found that saliva viral load was significantly higher in those with COVID-19 risk factors; that it correlated with increasing levels of disease severity and showed a superior ability over nasopharyngeal viral load as a predictor of mortality over time (AUC=0.90). A comprehensive analysis of immune factors and cell subsets revealed strong predictors of high and low saliva viral load, which were associated with increased disease severity or better overall outcomes, respectively. Saliva viral load was positively associated with many known COVID-19 inflammatory markers such as IL-6, IL-18, IL-10, and CXCL10, as well as type 1 immune response cytokines. Higher saliva viral loads strongly correlated with the progressive depletion of platelets, lymphocytes, and effector T cell subsets including circulating follicular CD4 T cells (cTfh). Anti-spike (S) and anti-receptor binding domain (RBD) IgG levels were negatively correlated with saliva viral load showing a strong temporal association that could help distinguish severity and mortality in COVID-19. Finally, patients with fatal COVID-19 exhibited higher viral loads, which correlated with the depletion of cTfh cells, and lower production of anti-RBD and anti-S IgG levels. Together these results demonstrated that viral load – as measured by saliva but not nasopharyngeal — is a dynamic unifying correlate of disease presentation, severity, and mortality over time.
- Published
- 2021
46. Impact of B.1.1.7 variant mutations on antibody recognition of linear SARS-CoV-2 epitopes
- Author
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Carolina Lucas, Winston A. Haynes, John Shon, Kathy Kamath, and Akiko Iwasaki
- Subjects
chemistry.chemical_classification ,education.field_of_study ,Strain (chemistry) ,Population ,Biology ,Virology ,Epitope ,Nucleoprotein ,Immune system ,chemistry ,Antigen ,biology.protein ,Antibody ,education ,Glycoprotein - Abstract
In 579 COVID patients’ samples collected between March and July of 2020, we examined the effects of non-synonymous mutations harbored by the circulating B.1.1.7 strain on linear antibody epitope signal for spike glycoprotein and nucleoprotein. At the antigen level, the mutations only substantially reduced signal in 0.5% of the population. Although some epitope mutations reduce measured signal in up to 6% of the population, these are not the dominant epitopes for their antigens. Given dominant epitope patterns observed, our data suggest that the mutations would not result in immune evasion of linear epitopes for a large majority of these COVID patients.
- Published
- 2021
47. EFEITO DA FREQUÊNCIA ALIMENTAR NA SOBREVIVÊNCIA E NO DESENVOLVIMENTO DE LARVAS DE JUNDIÁ (RHAMDIA QUELEN) EM CONDIÇÕES EXPERIMENTAIS
- Author
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Ana Carolina Lucas Gomes, Paulo José Fosse, Mateus Fossi Rodrigues, Elion Loureiro da Silva Lengruber, and Atanásio Alves do Amaral
- Published
- 2021
48. Diverse Functional Autoantibodies in Patients with COVID-19
- Author
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Suzanne Fischer, Mary E. Petrone, Jon Klein, Nathan D. Grubaugh, Julio Silva, Albert I. Ko, Patrick Wong, Anne L. Wyllie, Ting Zhou, Anne E. Watkins, Aaron M. Ring, Tianyang Mao, Benjamin Israelow, John Fournier, Akiko Iwasaki, Wade L. Schulz, Yile Dai, Eric Wang, Charles S. Dela Cruz, Chantal B.F. Vogels, Melissa Campbell, Shelli F. Farhadian, John D. Huck, Chaney C. Kalinich, Neil S Zheng, Eric Song, Feimei Liu, Carolina Lucas, Ji Eun Oh, Isabel M. Ott, Emily S. Perotti, and Yale Impact Team
- Subjects
Chemokine ,Innate immune system ,biology ,business.industry ,Autoantibody ,Phenotype ,Immune system ,Antigen ,Immunology ,Extracellular ,biology.protein ,Medicine ,business ,Pathological - Abstract
COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–8. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.
- Published
- 2020
49. Fundamentos e Práticas Pediátricas e Neonatais - Volume 2
- Author
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Ângela Gil Patrus Pena, Ana Luiza Gonçalves Silva, Fernanda Vaz de Melo Bacha, Fernanda Lustosa Cabral Gomez, Júlia Barroso Chiari, Lorena Ribeiro Padrão, ANA CAROLINA PRIOSTE DE OLIVEIRA, ANA LUIZA YAEKASHI GRILLO, DAVI SALOMÃO DE PAULA, GLAUCO HERNANDES GALLATE, GUSTAVO MIRANDA RAMOS BORGES, HEITOR BUENO HIRATA, HIAGGO FILMIANO ROCHA, ISABELLA ELIAS SOARES, JOÃO PEDRO NAVARRO SILVA, JÚLIO CÉSAR CIPRIANO BASÍLIO, LUANA PERRONE CAMILO, JONAS MUNCK DE OLIVEIRA, GIOVANA MOREIRA BORDIM, LARYSSA DE SÁ BRAGANÇA GONÇALVES, LAURA CUNHA SOARES, MARIA JÚLIA MARTINS MACHADO, THIAGO LOPES MONTEIRO, DIEGO JUNQUEIRA SARKIS, LUIZA SOARES FONSECA, Érika de Lima Souza, ISABEL GOULART FONSECA, LAVÍNIA DA SILVA DIAS, MARINA GUERRA MAIA COELHO, ARIANNY HELLEN DE OLIVEIRA SOARES, BEATRIZ PESSANHA DIAS TEIXEIRA, BRENDA DE SOUZA FERREIRA, CARLA MENEGHETTI GALDINO, GABRIELA CARNEIRO NEVES, GABRIELA DE PAULA FAGUNDES NETTO, HUGO DUARTE MASCARENHAS DE CASTRO, IGOR CRUZ DE PAULA, ISABELLA GUIMARÃES SILVA ALÍPIO, Jonas Munck de OLIVEIRA, LAILA SOUZA RIBEIRO, LAIS RODRIGUES MAIA, LARISSA VALDIER CERQUEIRA, LETÍCIA GIANCOLI JABOUR, MARIANA CAMPOS, MATHEUS FRANCO ARAUJO, RAFAEL BATITUCCI BARBEITOS, VICTOR DOS REIS CUNHA, MARIA CLARA LARA REIS, ARMANDO REIS, ANA LAURA CAMPOS RITTER BENITES, ANDREZA ALMEIDA FERREIRA DE SOUZA, MELISSA ÁVILA MACHADO, Gabriela Saldes Campos Pereira, ANDRESSA DE CÁSSIA COUTINHO MONESI, ISADORA SPINELLI, FLAVIA FRUGOLI RAMOS, THAIS REAIDI EL TAWIL, MARIA CAROLINA LUCAS DIAS, SILVANA SALGADO NADER, MÁRCIA KOJA BREIGEIRON, LUIZA MARIA GERHARDT, WILIAM WEGNER, CAROLINE DA CUNHA CAMPOS MAGALHÃES, SIMONE BAGGIO DE CASTRO, BRENDA VELLUMA SOARES DE AZEVEDO, CAMILA MARQUES DE ARAUJO MARTINS, MANUELLA FERNANDES LEITE, WAGNER JOSÉ RAIA NERI, PAULO ROBERTO DA SILVA, JESSIKA DOS SANTOS COSTA, LETÍCIA CAROLINA MALAQUIAS PEREIRA, JOÃO VICTOR BRAGA MENDES, ELISA GIANNINI BARREIRO, JULIANA VALENTINI, GABRIEL NASCIMENTO RAMOS, LARISSA VERISSIMO RAMOS SILVA, LETÍCIA AZEVEDO GAZZI, RIANNE SOARES VALÉRIO, SALETE PEREIRA DA SILVA, ALYNE COUTO CARVALHO DA FONSECA MACHADO, ELITON EDMILSON DO COUTO, GUSTAVO FINAMOR SALES, INGRED STEPHANY DOMINGUES DA SILVA, VALDECIR BOENO SPENAZATO, ARELLY BETHÂNIA FONSECA BARBOSA, LYVI MAIRA SILVEIRA, MARIA EDUARDA SIRINA PEREIRA, ZEFERINO CAMPOS DELLORTO, CAROLINA PENNA DE FARIA, GUSTAVO ALEXANDRE RIBONDI MARCARINI, ISABELA FERNANDES COELHO CUNHA, ISRAEL FELIPE DOMINGOS DE BARROS, MARIANNA PAULA NUNES ARAÚJO, ISIS DE FREITAS ESPESCHIT, AMANDA BATISTA BARRETO, GIOVANNA SHERLY DE SÁ GUEDES MARINS, MYLENA MARIA FERRAZ PEREIRA, Marcos Reis Gonçalves, Caroline Nascimento Santos, MIRELLA DE FREITAS DAUD, GIULIA DALESSANDRO SANZOVO, HELEN FIGUEIREDO FUMAGALLI, RAFAEL MACEDO DE ALMEIDA, MARCELA BERTOLDO HARADA, PAULA VIEIRA PENHA, LUIZA DE CASTRO CANÇADO BRAGA, GABRIELA DE ARAÚJO CANDOLATO, LUÍSA RIBEIRO DIAS GODOY, CLARA CABRAL DE MAGALHÃES, JÚLIA PEREIRA LOPES, Carine Carvalho Vaz de Lima, VINÍCIUS FONSECA BERNARDES, Mateus Gomes Polo, Lucas Henrique de Carvalho Machado, MARIANA MAGNO BARBOSA, Julia De Oliveira Chagas, CARINE CARVAHO VAZ DE LIMA, Eugênio F Magalhães, ISABELA BRAGA DA SILVA, ISABELLA STEPHANIE SIMÕES, JULIA RIBEIRO SACHI, MARIA LUÍZA COBRA VILELA, MARINA RODRIGES PESCI, REBECA RIBEIRO DE GUSMÃO, FLÁVIA ELISA FIRMINO LINO, LEONARDO GURGEL RÊGO, LUÍSA DE SOUZA EZEQUIEL, MARIA GORETH DE ANDRADE MORENO FILHA, ANNA JÚLIA ARRAES ALVES DE SOUZA, NAYARA DA SILVA GALDINO, MAYRA LOURES DE OLIVEIRA, LARISSA GONÇALVES CAMPOS, LARISSA REZENDE LIMA PEREIRA, RAMON FELIPE ALVES TEIXEIRA, ANA KELLY TEIXEIRA ROCHA, DANIEL SOUSA MACHADO, GUSTAVO COELHO PEREIRA LINHARES, JORGE LACERDA DE QUEIROZ, LAÍS TRIGO MIRANDA, SAMILA ALVES GARCIA, SARA EDUARDA OLIVEIRA DA CRUZ, TATIANE COSTA PEREIRA, Stefany Monteiro Peixoto, MARIA CLARA CASTILHO RODRIGUES, AMANDA VILELA SANTOS, RODRIGO AUGUSTO SILVA VIEIRA, MATHEUS CAMELO FERREIRA FARIA, GUSTAVO NETTO DO CARMO CARNEIRO, MIRIAN GABRIELA MARTINS PEREIRA, THULIO CESAR TEIXEIRA, DANYELLY RODRIGUES MACHADO AZEVEDO, THULIO CÉSAR TEIXEIRA, Amanda Vilela Santos, STEFANY MONTEIRO PEIXOTO, LUCAS HENRIQUE DE CARVALHO MACHADO, MARIANA NUNES LIMA DIAS, JOÃO HENRIQUE SANTOS MARTINS, Ricardo Henrique Freitas Tavares, ANA CAROLINA AMORIM OLIVEIRA, ANA PAULA AMORIM OLIVEIRA, ANA PAULA MACEDO PRUDENTE DE QUEIROZ, DANIELLE ALVES BARRETO, DOUGLAS NORTON SANTOS ARAGÃO, FERNANDA PRISCILLA BARBOSA SILVA, ISABELLA TATYANE MENEZES BARROS, MYLLA BÁRBARA GOIS SANTANA, TATIANE DE OLIVEIRA SANTOS, Halley Ferraro Oliveira, Maria Fernanda de Oliveira Filardi, Ana Carolina de Oliveira Filardi, Ana Tereza Teixeira Tavares, Antônio Mascarenhas Oliveira, Bruno Mialarett Borja, Fernanda Jardim Gripp, Henrique Figueiredo Silva, Julia Pimenta Gomes, Laila Mameri Pires, Letícia Pereira Mendonça, Leonardo Ferreira Melo, Priscila Nogueira Rodrigues, Sofia Silva e Souza, GABRIELLA SILVEIRA HERCULANO, CAMILA DUARTE XAVIER, GIOVANA VERUSSA MARTINS, ROBERTA PEREIRA ARES, MATHEUS WINTONIAK BAU, DANIELA MARIA PEREIRA, HENRIQUE RIVERA SIMÕES, LETÍCIA NISTAL, TIFFANY SOARES LEITE, ANA LUÍSA DE CAMARGO, Anna Lillian Canuto Bittencourt, VINÍCIUS BARBOSA DOS SANTOS SALES, ELISA BENETTI DE PAIVA MACIEL, ROBERTA ESTEVES VIEIRA DE CASTRO, MICHELLE KAORI MENEZES FUKUDA, TAINÁ BATISTA ARRUDA, PAULA GUIRÃO GIRON, GIOVANNA MOYSÉS, KARINA MARTINS BAPTISTA, MARIA LUIZA RODRIGUES NASCIMENTO, LETICIA NISTAL, PAULO HENRIQUE NUNES, MARIANA FIGUEIRA, PRISCILA PRATA CURSI, ANNA LILLIAN CANUTO BITTENCOURT, ALINE BRITO OLIVEIRA GUIMARÃES, ANA MOZER VIEIRA DE JESUS, ANDREANE MENESES ANDRADE, EDUARDA MEDEIROS CAMPOS, Gabriela Guilhoto Cabral Lamonica, FERNANDA FONTES PRADO REIS, GABRIELA GUILHOTO CABRAL LAMONICA, JULIA NATALINE OLIVEIRA BARBOSA, JULIA SILVA ALMEIDA DE OLIVEIRA, LETYCIA SANTOS RODRIGUES, LORENA RODRIGUES DE CARVALHO, LUANA ASANO FARINA, NAYSA GABRIELLY ALVES DE ANDRADE, RAFAELLA ROSA LOBO DE ANDRADE, THAYSER NAYARAH ESTANISLAU SOUSA, ANA PAULA EMERICK CORRÊA, CAMILA VIDOTTI CASTRO CORRÊA, MAÍRA LUCÍLIA MONTEIRO FERREIRA, ANDREA BIANCARDI MOROZINI, CATARINA AMORIM BACCARINI PIRES, HELOÍSA AUGUSTA CASTRALLI, MARIANA SOARES VIEIRA, NATAN MARTINS MACHADO, PAULA JANÓLIO CARDOSO SILVA, Iane Brito Leal, PEDRO REGES PEREIRA MEIRA, BEATRIZ LUDUVICE SOARES, JÚLIA SOUZA DINIZ, LUANA ROCHA DE SOUZA, MILENA PEREIRA DE ÁVILA, MATEUS BEZERRA DE FIGUEIREDO, Ana Cecília de Menêzes Nóbrega, JOÃO VINÍCIUS SANTOS LIMA, LUMA CAROLYNE ARAÚJO COSTA, MARIANA DO SACRAMENTO CHAGAS, MARÍLIA ALVES MENEZES, MATHEUS ALVES NUNES DE CARVALHO, HALLEY FERRARO OLIVEIRA, ANA CECÍLIA DE MENÊZES NÓBREGA, EDSON ELOI MARTINS, LAURA COELHO PIRES ROCHA, LÍCIA BRANT MOREIRA FERREIRA, VICTÓRIA MOREIRA HANNAS GUIMARÃES, BRUNA LATIF RODRIGUES CARVALHO, THALITA MARTINS LAGE, VALÉRIA LOPES CUPERTINO, NATÁLIA QUINTÃO BARROS, ANA FLÁVIA ANDRADE EMERY SANTOS, ISABELLA ALVARENGA ABREU, ANA BEATRIZ GOMES SILVA, MÁRCIA ELENA ANDRADE SANTOS, ANALINA FURTADO VALADÃO, BÁRBARA MARTINS MELLO DE OLIVEIRA, PEDRO HENRIQUE AQUINO GIL DE FREITAS, LUISA TEIXEIRA HOHL, NATÁLIA NICHELE BARBOSA, RACHEL MOCELIN DIAS COELHO, JOÃO PEDRO DA SILVEIRA, GABRIEL DANTAS LOPES, Gabriel Dantas Lopes, Larissa Dantas Sobral, Maria Alice Menezes Moura, LARISSA DANTAS SOBRA, MARIA ALICE MENEZES MOURA, PEDRO SADDI DE CARVALHO, CLARICE MARQUES MOTTA ANDRADE, DANIELA TEIXEIRA BARREIROS, HELOISA DE MATOS ANTUNES, MARCELO DOS SANTOS MOURÃO, MARIA LUIZA MOTA VIDAL, ISAAC PÊGO SANTOS, NAHIMAN ASSAD FERREIRA SALEH, JULIANA FERNANDES SAAR GARCIA, NATÁLIA ARAÚJO BARRETO, JAIRA VANESSA DE CARVALHO MATOS, ANA JOVINA BARRETO BISPO, HANNAH BRYSKIER GLEITZMANN, NAIANE CRISTINA FERREIRA MENDES, MIRELLY GRACE RAMOS CISNEIROS, Mayara Raquel de Jesus Castro, ÍRIS GABRIELA SANTOS TAVARES, LARISSA DANTAS SOBRAL, RAFAELLA RANGEL BARBOSA, VITÓRIA REZENDE ROCHA MONTEIRO, NICOLLE FRAGA COELHO, ANNA LUISA LUPI VENTURA DE ASSIS, LUIZA GABRIELA NORONHA SANTIAGO, LETÍCIA THAIS DE OLIVEIRA ALVES, LETÍCIA MACHADO COUTO, MARIA EDUARDA RODRIGUES FERREIRA, MARIA EDUARDA LIMA DIAS, LARISSA CAMARGOS GUEDES, LENILSON DO NASCIMENTO MELO, MARIA RIKELLY FROTA AGUIAR, DANIELE ALCOFORADO COSTA, JAIANE CRUZ DOS SANTOS, LEONARA MARIA ALVES COELHO, NATHANAEL ALVES DOS SANTOS, ANA CLARA SILVA SALES, DAIANE CARVALHO DE SOUSA, NATANIEL FRANÇA CARVALHO, DACYLLA SAMPAIO COSTA, BRUNA MARIA DE CARVALHO PEREIRA, EDUARDO DE MELO PRADO, Renata Canalle, CAMYLLA MACHADO MARQUES, LUANA NASCIMENTO, EVILANNA LIMA ARRUDA, LUCILA CASTANHEIRA NASCIMENTO, ANA CAROLINA ANDRADE BIAGGI LEITE, WILLYANE DE ANDRADE ALVARENGA, REBECCA ORTIZ LA BANCA, RHYQUELLE RHIBNA NERIS, MICHELLE DAREZZO RODRIGUES NUNES, ROSYAN CARVALHO DE ANDRADE, LOUISE BITTENCOURT PAES ABREU DOS SANTOS, MARCOS VENICIO ESPER, ESTEFÂNIA ANDRÉIA MARQUES, NAIARA BARROS POLITA, FERNANDA MACHADO SILVA-RODRIGUES, RAFAELA TONHOLLI PINHO, BÁRBARA CALDEIRA PIRES, JOICE RIBEIRO LOPES, GABRIELA GUIMARÃES NOGUEIRA, Ana Carolina De Souza Soares, GERALDO DE BARROS RIBEIRO, BEATRIZ GOMES DE CASTRO, BRUNA DOS SANTOS DE CARVALHO, GIOVANA JUNQUEIRA FRANCHI BRAGHETTA, GIULIA JUNQUEIRA FRANCHI BRAGHETTA, LUANA PIMENTEL BRITO, THALLITA VASCONCELOS DAS GRAÇAS, AMANDHA VICTÓRIA DE PINHO GONZAGA RODRIGUES, BYANKA PORTO FRAGA, FERNANDA LUIZA BUARQUE DE GUSMÃO, LETÍCIA MARIA CARDOSO LIMA RODRIGUES, REBECCA SCHUSTER DOREA LEITE, YSLLA SILVA ARGOLO, FELLIPE MATOS MELO CAMPOS, LAURA MARIA DALLOGLIO, MALU GALLON, ISABELLA MALTAURO JULIANO, ISABELA AKEMI GUIRAO SUMIDA, MARINA DEINA, FERNANDA BONILLA COLOMÉ, Carlyne Alves de Sousa, GLÍCIA MARIA DE OLIVEIRA DAMASCENO, Edilany Aguiar Lima, DÉBORA PINHEIRO CISNE, Rosalice Araújo de Sousa Albuquerque, João Victor Reis Campos, MATEUS GOMES POLO, JOSÉ CARLOS BOSCHI, BIANCA ZUCARELI, IASMIM MEDEIROS, AMANDA MARAN FILGUEIRA, Larychelle de P Antunes, Amanda M Filgueira, Felipe C M Ninomiya, MAISA SANTOS VALDERRAMAS TALON, DÉBORA RODRIGUES MARTINS, GABRIELA COSTA CARVALHO, LAÍS RODRIDUES MAIA, LUCAS MIZRAHY LIMA, VICTÓRIA MARQUES CÂNDIDO, VÍVIAN MARIA GOMES DE OLIVEIRA, WILLIANE CROLMAN DE OLIVEIRA, BÁRBARA COSTA NICÁCIO, NAYARA ZINATO CÁRIA, LESLIÊ APARECIDA DE FREITAS, CACILDA ANDRADE DE SÁ, MÁRCIA HELENA FÁVERO DE SOUZA, JOSÉ ARIMATÉA DE OLIVEIRA NERY, GABRIELA LEAL BEZERRA, RAFAELA ODÍSIO NUNES, and Guilherme Barroso
- Published
- 2020
50. Diverse functional autoantibodies in patients with COVID-19
- Author
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Eric Y, Wang, Tianyang, Mao, Jon, Klein, Yile, Dai, John D, Huck, Jillian R, Jaycox, Feimei, Liu, Ting, Zhou, Benjamin, Israelow, Patrick, Wong, Andreas, Coppi, Carolina, Lucas, Julio, Silva, Ji Eun, Oh, Eric, Song, Emily S, Perotti, Neil S, Zheng, Suzanne, Fischer, Melissa, Campbell, John B, Fournier, Anne L, Wyllie, Chantal B F, Vogels, Isabel M, Ott, Chaney C, Kalinich, Mary E, Petrone, Anne E, Watkins, Charles, Dela Cruz, Shelli F, Farhadian, Wade L, Schulz, Shuangge, Ma, Nathan D, Grubaugh, Albert I, Ko, Akiko, Iwasaki, and Yvette, Strong
- Subjects
Male ,Proteome ,COVID-19 ,Complement System Proteins ,Disease Models, Animal ,Mice ,Organ Specificity ,Case-Control Studies ,Antigens, Surface ,Disease Progression ,Animals ,Cytokines ,Humans ,Female ,Autoantibodies - Abstract
COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses
- Published
- 2020
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