Search

Your search keyword '"Chan, Yi-Hao"' showing total 42 results
Start Over Author "Chan, Yi-Hao" Search Limiters Available in Library Collection
42 results on '"Chan, Yi-Hao"'

1. SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Author

Chan, Yi-Hao, Lundberg, Vanja, Le Pen, Jérémie, Yuan, Jiayi, Lee, Danyel, Pinci, Francesca, Volpi, Stefano, Nakajima, Koji, Bondet, Vincent, Åkesson, Sanna, Khobrekar, Noopur, Bodansky, Aaron, Du, Likun, Melander, Tina, Mariaggi, Alice-Andrée, Seeleuthner, Yoann, Saleh, Tariq, Chakravarty, Debanjana, Marits, Per, Dobbs, Kerry, Vonlanthen, Sofie, Hennings, Viktoria, Thörn, Karolina, Rinchai, Darawan, Bizien, Lucy, Chaldebas, Matthieu, Sobh, Ali, Özçelik, Tayfun, Keles, Sevgi, AlKhater, Suzan, Prando, Carolina, Meyts, Isabelle, Wilson, Michael, Rosain, Jérémie, Jouanguy, Emmanuelle, Aubart, Mélodie, Abel, Laurent, Mogensen, Trine, Pan-Hammarström, Qiang, Gao, Daxing, Duffy, Darragh, Cobat, Aurélie, Berg, Stefan, Notarangelo, Luigi, Harschnitz, Oliver, Rice, Charles, Studer, Lorenz, Casanova, Jean-Laurent, Ekwall, Olov, and Zhang, Shen-Ying

Subjects
Humans, Male, SARS-CoV-2, COVID-19, Brain Stem, Adolescent, Neurons, Encephalitis, Viral, Fibroblasts, Rhombencephalon
Abstract

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.

Published
2024

2. Discovering robust biomarkers of neurological disorders from functional MRI using graph neural networks: A Review

Author

Chan, Yi Hao, Girish, Deepank, Gupta, Sukrit, Xia, Jing, Kasi, Chockalingam, He, Yinan, Wang, Conghao, and Rajapakse, Jagath C.

Subjects
Computer Science - Machine Learning, Electrical Engineering and Systems Science - Signal Processing, Quantitative Biology - Neurons and Cognition
Abstract

Graph neural networks (GNN) have emerged as a popular tool for modelling functional magnetic resonance imaging (fMRI) datasets. Many recent studies have reported significant improvements in disorder classification performance via more sophisticated GNN designs and highlighted salient features that could be potential biomarkers of the disorder. In this review, we provide an overview of how GNN and model explainability techniques have been applied on fMRI datasets for disorder prediction tasks, with a particular emphasis on the robustness of biomarkers produced for neurodegenerative diseases and neuropsychiatric disorders. We found that while most studies have performant models, salient features highlighted in these studies vary greatly across studies on the same disorder and little has been done to evaluate their robustness. To address these issues, we suggest establishing new standards that are based on objective evaluation metrics to determine the robustness of these potential biomarkers. We further highlight gaps in the existing literature and put together a prediction-attribution-evaluation framework that could set the foundations for future research on improving the robustness of potential biomarkers discovered via GNNs.

Published
2024

3. Human TMEFF1 is a restriction factor for herpes simplex virus in the brain

Author

Chan, Yi-Hao, Liu, Zhiyong, Bastard, Paul, Khobrekar, Noopur, Hutchison, Kennen M., Yamazaki, Yasuhiro, Fan, Qing, Matuozzo, Daniela, Harschnitz, Oliver, Kerrouche, Nacim, Nakajima, Koji, Amin, Param, Yatim, Ahmad, Rinchai, Darawan, Chen, Jie, Zhang, Peng, Ciceri, Gabriele, Chen, Jia, Dobbs, Kerry, Belkaya, Serkan, Lee, Danyel, Gervais, Adrian, Aydın, Kürşad, Kartal, Ayse, Hasek, Mary L., Zhao, Shuxiang, Reino, Eduardo Garcia, Lee, Yoon Seung, Seeleuthner, Yoann, Chaldebas, Matthieu, Bailey, Rasheed, Vanhulle, Catherine, Lorenzo, Lazaro, Boucherit, Soraya, Rozenberg, Flore, Marr, Nico, Mogensen, Trine H., Aubart, Mélodie, Cobat, Aurélie, Dulac, Olivier, Emiroglu, Melike, Paludan, Søren R., Abel, Laurent, Notarangelo, Luigi, Longnecker, Richard, Smith, Greg, Studer, Lorenz, Casanova, Jean-Laurent, and Zhang, Shen-Ying

Published
2024
Full Text
View/download PDF

4. Multi-modal Graph Neural Network for Early Diagnosis of Alzheimer's Disease from sMRI and PET Scans

Author

Zhanga, Yanteng, He, Xiaohai, Chan, Yi Hao, Teng, Qizhi, and Rajapakse, Jagath C.

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

In recent years, deep learning models have been applied to neuroimaging data for early diagnosis of Alzheimer's disease (AD). Structural magnetic resonance imaging (sMRI) and positron emission tomography (PET) images provide structural and functional information about the brain, respectively. Combining these features leads to improved performance than using a single modality alone in building predictive models for AD diagnosis. However, current multi-modal approaches in deep learning, based on sMRI and PET, are mostly limited to convolutional neural networks, which do not facilitate integration of both image and phenotypic information of subjects. We propose to use graph neural networks (GNN) that are designed to deal with problems in non-Euclidean domains. In this study, we demonstrate how brain networks can be created from sMRI or PET images and be used in a population graph framework that can combine phenotypic information with imaging features of these brain networks. Then, we present a multi-modal GNN framework where each modality has its own branch of GNN and a technique is proposed to combine the multi-modal data at both the level of node vectors and adjacency matrices. Finally, we perform late fusion to combine the preliminary decisions made in each branch and produce a final prediction. As multi-modality data becomes available, multi-source and multi-modal is the trend of AD diagnosis. We conducted explorative experiments based on multi-modal imaging data combined with non-imaging phenotypic information for AD diagnosis and analyzed the impact of phenotypic information on diagnostic performance. Results from experiments demonstrated that our proposed multi-modal approach improves performance for AD diagnosis, and this study also provides technical reference and support the need for multivariate multi-modal diagnosis methods., Comment: 14 pages, 11 figures

Published
2023

7. Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose

Author

Renia, Laurent, Goh, Yun Shan, Rouers, Angeline, Le Bert, Nina, Chia, Wan Ni, Chavatte, Jean-Marc, Fong, Siew‐Wai, Chang, Zi Wei, Zhuo, Nicole Ziyi, Tay, Matthew Zirui, Chan, Yi-Hao, Tan, Chee Wah, Yeo, Nicholas Kim‐Wah, Amrun, Siti Naqiah, Huang, Yuling, Wong, Joel Xu En, Hor, Pei Xiang, Loh, Chiew Yee, Wang, Bei, Ngoh, Eve Zi Xian, Salleh, Siti Nazihah Mohd, Carissimo, Guillaume, Dowla, Samanzer, Lim, Alicia Jieling, Zhang, Jinyan, Lim, Joey Ming Er, Wang, Cheng-I., Ding, Ying, Pada, Surinder, Sun, Louisa Jin, Somani, Jyoti, Lee, Eng Sing, Ong, Desmond Luan Seng, Leo, Yee‐Sin, MacAry, Paul A., Lin, Raymond Tzer Pin, Wang, Lin-Fa, Ren, Ee Chee, Lye, David C., Bertoletti, Antonio, Young, Barnaby Edward, and Ng, Lisa F. P.

Published
2022
Full Text
View/download PDF

9. Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study

Author

Young, Barnaby E, Wei, Wycliffe E, Fong, Siew-Wai, Mak, Tze-Minn, Anderson, Danielle E, Chan, Yi-Hao, Pung, Rachael, Heng, Cheryl SY, Ang, Li Wei, Zheng, Adrian Kang Eng, Lee, Bernett, Kalimuddin, Shirin, Pada, Surinder, Tambyah, Paul A, Parthasarathy, Purnima, Tan, Seow Yen, Sun, Louisa, Smith, Gavin JD, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, Ng, Lisa FP, Maurer-Stroh, Sebastian, Lye, David Chien, and Lee, Vernon J

Published
2021
Full Text
View/download PDF

10. Relative deficiency in interferon‐γ‐secreting CD4+ T cells is strongly associated with poorer COVID‐19 vaccination responses in older adults.

Author

Ho, Vanda W. T., Boon, Low Heng, Cui, Jianzhou, Juequn, Zhou, Shunmuganathan, Bhuvaneshwari, Gupta, Rashi, Tan, Nikki Y. J., Qian, Xinlei, Purushotorman, Kiren, Amrun, Siti Naqiah, Goh, Yun‐Shan, Tay, Matthew Zi‐Rui, Rouers, Angeline, Chang, Zi Wei, Yeo, Nicholas Kim‐Wah, Chan, Yi‐Hao, Hor, Pei Xian, Loh, Chiew Yee, Yang, Yuling, and Torres Ruesta, Anthony

Subjects
OLDER people, COVID-19 pandemic, COVID-19 vaccines, T cells, CD4 antigen, IMMUNOGLOBULINS
Abstract

Although the two‐dose mRNA vaccination regime provides protection against SARS‐CoV‐2, older adults have been shown to exhibit poorer vaccination responses. In addition, the role of vaccine‐induced T‐cell responses is not well characterised. We aim to assess the impact of age on immune responses after two doses of the BNT162b2 mRNA vaccine, focussing on antigen‐specific T‐cells. A prospective 3‐month study was conducted on 15 young (median age 31 years, interquartile range (IQR) 25–35 years) and 14 older adults (median age 72 years, IQR 70–73 years). We assessed functional, neutralising antibody responses against SARS‐CoV‐2 variants using ACE‐2 inhibition assays, and changes in B and T‐cell subsets by high‐dimensional flow cytometry. Antigen‐specific T‐cell responses were also quantified by intracellular cytokine staining and flow cytometry. Older adults had attenuated T‐helper (Th) response to vaccination, which was associated with weaker antibody responses and decreased SARS‐CoV‐2 neutralisation. Antigen‐specific interferon‐γ (IFNγ)‐secreting CD4+ T‐cells to wild‐type and Omicron antigens increased in young adults, which was strongly positively correlated with their neutralising antibody responses. Conversely, this relationship was negative in older adults. Hence, older adults' relative IFNγ‐secreting CD4+ T cell deficiency might explain their poorer COVID‐19 vaccination responses. Further exploration into the aetiology is needed and would be integral in developing novel vaccination strategies and improving infection outcomes in older adults. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

11. Crosstalk between CD64+MHCII+ macrophages and CD4+ T cells drives joint pathology during chikungunya.

Author

Lum, Fok-Moon, Chan, Yi-Hao, Teo, Teck-Hui, Becht, Etienne, Amrun, Siti Naqiah, Teng, Karen WW, Hartimath, Siddesh V, Yeo, Nicholas KW, Yee, Wearn-Xin, Ang, Nicholas, Torres-Ruesta, Anthony M, Fong, Siew-Wai, Goggi, Julian L, Newell, Evan W, Renia, Laurent, Carissimo, Guillaume, and Ng, Lisa FP

Abstract

Communications between immune cells are essential to ensure appropriate coordination of their activities. Here, we observed the infiltration of activated macrophages into the joint-footpads of chikungunya virus (CHIKV)-infected animals. Large numbers of CD64+MHCII+ and CD64+MHCII- macrophages were present in the joint-footpad, preceded by the recruitment of their CD11b+Ly6C+ inflammatory monocyte precursors. Recruitment and differentiation of these myeloid subsets were dependent on CD4+ T cells and GM-CSF. Transcriptomic and gene ontology analyses of CD64+MHCII+ and CD64+MHCII- macrophages revealed 89 differentially expressed genes, including genes involved in T cell proliferation and differentiation pathways. Depletion of phagocytes, including CD64+MHCII+ macrophages, from CHIKV-infected mice reduced disease pathology, demonstrating that these cells play a pro-inflammatory role in CHIKV infection. Together, these results highlight the synergistic dynamics of immune cell crosstalk in driving CHIKV immunopathogenesis. This study provides new insights in the disease mechanism and offers opportunities for development of novel anti-CHIKV therapeutics. Synopsis: Activated CD64+MHCII+ macrophages are present in the joint-footpad during CHIKV infection and participate in a pathogenic immune crosstalk with CD4+ T cells to drive immunopathogenesis. CD64+MHCII+ macrophages could be an alternative host-directed therapeutic target against CHIKV infection. Mass cytometry reveals the presence of CD64+MHCII+ macrophages in the CHIKV-infected joint-footpad. IFNγ and GM-CSF secreted by CD4+ T cells are two mediators capable of regulating the levels of CD64+MHCII+ macrophages in CHIKV-infected joints. In vivo depletion of GM-CSF reduces CHIKV disease severity. CD64+MHCII+ macrophages are involved in multiple T-cell-related pathways as revealed by RNAseq analyses. CD64+MHCII+ macrophages are potential novel targets for the future development of anti-CHIKV therapeutics. Activated CD64+MHCII+ macrophages are present in the joint-footpad during CHIKV infection and participate in a pathogenic immune crosstalk with CD4+ T cells to drive immunopathogenesis. CD64+MHCII+ macrophages could be an alternative host-directed therapeutic target against CHIKV infection. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

12. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

Author

Carissimo, Guillaume, Xu, Weili, Kwok, Immanuel, Abdad, Mohammad Yazid, Chan, Yi-Hao, Fong, Siew-Wai, Puan, Kia Joo, Lee, Cheryl Yi-Pin, Yeo, Nicholas Kim-Wah, Amrun, Siti Naqiah, Chee, Rhonda Sin-Ling, How, Wilson, Chan, Stephrene, Fan, Bingwen Eugene, Andiappan, Anand Kumar, Lee, Bernett, Rötzschke, Olaf, Young, Barnaby Edward, Leo, Yee-Sin, Lye, David Chien, Renia, Laurent, Ng, Lai Guan, Larbi, Anis, and Ng, Lisa FP

Published
2020
Full Text
View/download PDF

14. Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Author

Rosain, Jérémie, primary, Neehus, Anna-Lena, additional, Manry, Jérémy, additional, Yang, Rui, additional, Le Pen, Jérémie, additional, Daher, Wassim, additional, Liu, Zhiyong, additional, Chan, Yi-Hao, additional, Tahuil, Natalia, additional, Türel, Özden, additional, Bourgey, Mathieu, additional, Ogishi, Masato, additional, Doisne, Jean-Marc, additional, Izquierdo, Helena M., additional, Shirasaki, Takayoshi, additional, Le Voyer, Tom, additional, Guérin, Antoine, additional, Bastard, Paul, additional, Moncada-Vélez, Marcela, additional, Han, Ji Eun, additional, Khan, Taushif, additional, Rapaport, Franck, additional, Hong, Seon-Hui, additional, Cheung, Andrew, additional, Haake, Kathrin, additional, Mindt, Barbara C., additional, Pérez, Laura, additional, Philippot, Quentin, additional, Lee, Danyel, additional, Zhang, Peng, additional, Rinchai, Darawan, additional, Al Ali, Fatima, additional, Ahmad Ata, Manar Mahmoud, additional, Rahman, Mahbuba, additional, Peel, Jessica N., additional, Heissel, Søren, additional, Molina, Henrik, additional, Kendir-Demirkol, Yasemin, additional, Bailey, Rasheed, additional, Zhao, Shuxiang, additional, Bohlen, Jonathan, additional, Mancini, Mathieu, additional, Seeleuthner, Yoann, additional, Roelens, Marie, additional, Lorenzo, Lazaro, additional, Soudée, Camille, additional, Paz, María Elvira Josefina, additional, González, María Laura, additional, Jeljeli, Mohamed, additional, Soulier, Jean, additional, Romana, Serge, additional, L’Honneur, Anne-Sophie, additional, Materna, Marie, additional, Martínez-Barricarte, Rubén, additional, Pochon, Mathieu, additional, Oleaga-Quintas, Carmen, additional, Michev, Alexandre, additional, Migaud, Mélanie, additional, Lévy, Romain, additional, Alyanakian, Marie-Alexandra, additional, Rozenberg, Flore, additional, Croft, Carys A., additional, Vogt, Guillaume, additional, Emile, Jean-François, additional, Kremer, Laurent, additional, Ma, Cindy S., additional, Fritz, Jörg H., additional, Lemon, Stanley M., additional, Spaan, András N., additional, Manel, Nicolas, additional, Abel, Laurent, additional, MacDonald, Margaret R., additional, Boisson-Dupuis, Stéphanie, additional, Marr, Nico, additional, Tangye, Stuart G., additional, Di Santo, James P., additional, Zhang, Qian, additional, Zhang, Shen-Ying, additional, Rice, Charles M., additional, Béziat, Vivien, additional, Lachmann, Nico, additional, Langlais, David, additional, Casanova, Jean-Laurent, additional, Gros, Philippe, additional, and Bustamante, Jacinta, additional

Published
2023
Full Text
View/download PDF

15. Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children

Author

Lee, Danyel, Le Pen, Jérémie, Yatim, Ahmad, Dong, Beihua, Aquino, Yann, Ogishi, Masato, Pescarmona, Rémi, Talouarn, Estelle, Rinchai, Darawan, Zhang, Peng, Perret, Magali, Liu, Zhiyong, Jordan, Iolanda, Elmas Bozdemir, Sefika, Bayhan, Gulsum Iclal, Beaufils, Camille, Bizien, Lucy, Bisiaux, Aurelie, Lei, Weite, Hasan, Milena, Chen, Jie, Gaughan, Christina, Asthana, Abhishek, Libri, Valentina, Luna, Joseph, Jaffré, Fabrice, Hoffmann, H.-Heinrich, Michailidis, Eleftherios, Moreews, Marion, Seeleuthner, Yoann, Bilguvar, Kaya, Mane, Shrikant, Flores, Carlos, Zhang, Yu, Arias, Andrés, Bailey, Rasheed, Schlüter, Agatha, Milisavljevic, Baptiste, Bigio, Benedetta, Le Voyer, Tom, Materna, Marie, Gervais, Adrian, Moncada-Velez, Marcela, Pala, Francesca, Lazarov, Tomi, Levy, Romain, Neehus, Anna-Lena, Rosain, Jérémie, Peel, Jessica, Chan, Yi-Hao, Morin, Marie-Paule, Pino-Ramirez, Rosa Maria, Belkaya, Serkan, Lorenzo, Lazaro, Anton, Jordi, Delafontaine, Selket, Toubiana, Julie, Bajolle, Fanny, Fumadó, Victoria, Dediego, Marta, Fidouh, Nadhira, Rozenberg, Flore, Pérez-Tur, Jordi, Chen, Shuibing, Evans, Todd, Geissmann, Frédéric, Lebon, Pierre, Weiss, Susan, Bonnet, Damien, Duval, Xavier, Pan-Hammarström, Qiang, Planas, Anna, Meyts, Isabelle, Haerynck, Filomeen, Pujol, Aurora, Sancho-Shimizu, Vanessa, Dalgard, Clifford, Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Boisson, Bertrand, Maniatis, Tom, Zhang, Qian, Bastard, Paul, Notarangelo, Luigi, Béziat, Vivien, Perez de Diego, Rebeca, Rodriguez-Gallego, Carlos, Su, Helen, Lifton, Richard, Jouanguy, Emmanuelle, Cobat, Aurélie, Alsina, Laia, Keles, Sevgi, Haddad, Elie, Abel, Laurent, Belot, Alexandre, Quintana-Murci, Lluis, Rice, Charles, Silverman, Robert, Zhang, Shen-Ying, Casanova, Jean-Laurent, Alavoine, Loubna, Behillil, Sylvie, Burdet, Charles, Charpentier, Charlotte, Dechanet, Aline, Descamps, Diane, Ecobichon, Jean-Luc, Enouf, Vincent, Frezouls, Wahiba, Houhou, Nadhira, Kafif, Ouifiya, Lehacaut, Jonathan, Letrou, Sophie, Lina, Bruno, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Piquard, Valentine, Quintin, Caroline, Thy, Michael, Tubiana, Sarah, van der Werf, Sylvie, Vignali, Valérie, Visseaux, Benoit, Yazdanpanah, Yazdan, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Deplanque, Dominique, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Laine, Fabrice, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Malvy, Denis, Nguyen, Duc, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Chirouze, Catherine, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefèvre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Christelle, Kouakam, Nicolas, Leturque, Roufai, Layidé, Amat, Karine, Couffin-Cadiergues, Sandrine, Espérou, Hélène, Hendou, Samia, Abolhassani, Hassan, Aguilera-Albesa, Sergio, Aiuti, Alessandro, Akcan, Ozge Metin, Akcay, Nihal, Alkan, Gulsum, Alkhater, Suzan, Allende, Luis Miguel, Alper, Yosunkaya, Amenzoui, Naima, Anderson, Mark, Arkin, Lisa, Aubart, Melodie, Avramenko, Iryna, Aydemir, Şehnaz, Gayretli Aydin, Zeynep Gökçe, Aytekin, Caner, Aytekin, Gökhan, Erol Aytekin, Selma, Bando, Silvia Yumi, Beland, Kathie, Biggs, Catherine, Bilbao Aburto, Agurtzane, Blanchard-Rohner, Geraldine, Blázquez-Gamero, Daniel, Bloomfield, Marketa, Bogunovic, Dusan, Bondarenko, Anastasia, Borghesi, Alessandro, Bousfiha, Amed Aziz, Boyarchuk, Oksana, Brodin, Petter, Bryceson, Yenan, Bucciol, Giorgia, Calcaterra, Valeria, Casari, Giorgio, Cavalcanti, Andre, Celik, Jale Bengi, Chrousos, George, Colobran, Roger, Condino-Neto, Antonio, Conti, Francesca, Cooper, Megan, Coskuner, Taner, Cyrus, Cyril, D’auria, Enza, Drolet, Beth, Bursal Duramaz, Burcu, El Zein, Loubna, Elnagdy, Marwa, Emiroglu, Melike, Erdeniz, Emine Hafize, Fabi, Marianna, Baris Feldman, Hagit, Fellay, Jacques, Fencl, Filip, Filippatos, Filippos, Freiss, Julie, Fremuth, Jiri, Gagro, Alenka, Garcia-Solis, Blanca, Vergine, Gianluca, González-Montelongo, Rafaela, Gul, Yahya, Gülhan, Belgin, Gultekin, Sara Sebnem Kilic, Gut, Marta, Halwani, Rabih, Hammarström, Lennart, Hatipoğlu, Nevin, Heath, James, Henrickson, Sarah, Hernandez-Brito, Elisa, Hoffman, Ilse, Hoste, Levi, Hsieh, Elena, Íñigo-Campos, Antonio, Itan, Yuval, Jabandziev, Petr, Kandemir, Bahar, Kanık-Yüksek, Saliha, Kapakli, Hasan, Karbuz, Adem, Kasapcopur, Ozgur, Kechiche, Robin, Kendir Demirkol, Yasemin, Kilic, Omer, Hansen, Stella Kim, Klocperk, Adam, Lau, Yu-Lung, Lebl, Jan, Lorenzo-Salazar, José, Lucas, Carrie, Maglorius, Majistor, Marque, Laura, Novoa Medina, Yeray, Montesdeoca Melián, Abián, Mentis, Alexios-Fotios, Pato, Michele, Michos, Athanasios, Milner, Joshua, Mogensen, Trine, Muñoz-Barrera, Adrián, Nepesov, Serdar, Farela Neves, João, Ng, Ashley, Ng, Lisa, Novelli, Antonio, Novelli, Giuseppe, Oz, Fatma Nur, Ocejo-Viñals, J. Gonzalo, Okada, Satoshi, Orbak, Zerrin, Kilic, Ahmet Osman, Ouair, Hind, Öz, Şadiye Kübra Tüter, Özçelik, Tayfun, Özkan, Esra Akyüz, Parlakay, Aslınur Özkaya, Pato, Carlos, Paz-Artal, Estela, Pelham, Simon, Pellier, Isabelle, Philippot, Quentin, Planas-Serra, Laura, Plassart, Samira, Pokorna, Petra, Polat, Meltem, Poli, Cecilia, Prando, Carolina, Renia, Laurent, Rivière, Jacques, Rodríguez-Palmero, Agustí, Roussel, Lucie, Rubio-Rodriguez, Luis, Salifu, Moro, Sasek, Lumir, Sasia, Laura, Scherbina, Anna, Schmitt, Erica, Sediva, Anna, Sevketoglu, Esra, Slaba, Katerina, Slaby, Ondrej, Sobh, Ali, Solé-Violán, Jordi, Soler-Palacin, Pere, de Somer, Lien, Sözeri, Betül, Spaan, András, Stepanovskiy, Yuriy, Tangye, Stuart, Tanir, Gonul, Tatsi, Elizabeth Barbara, Thorball, Christian, Hancerli Torun, Selda, Turvey, Stuart, Uddin, Mohammed, Uyar, Emel, Valencia-Ramos, Juan, van den Rym, Ana Maria, Vatansev, Hulya, Castillo de Vera, Martín, Vermeulen, François, Vinh, Donald, Volokha, Alla, von Bernuth, Horst, Wouters, Carine, Yahşi, Aysun, Yarar, Volkan, Yesilbas, Osman, Yıldız, Mehmet, Zatz, Mayana, Zawadzki, Pawel, Zuccotti, Gianvincenzo, Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive, modélisation et santé (GEMS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sidra Medicine [Doha, Qatar], BIOASTER Technology Research Institute, Lyon, France, St. Giles Laboratory of Human Genetics of Infectious Diseases, Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique Evolutive Humaine - Human Evolutionary Genetics, Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Shanghai Jiaotong University, Sheffield Hallam University, Institut Jean Lamour (IJL), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JBP Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the ANR-RHU program (ANR-21-RHUS-08), the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU Program ANR-21-RHUS-08 (COVIFERON), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Cité University. We acknowledge support from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under award R01AI104887 to R.H.S. and S.R.W. The Laboratory of Human Evolutionary Genetics (Institut Pasteur) is supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID) and 'Milieu Intérieur' (ANR-10-LABX-69-01), the Fondation de France (no. 00106080), the FRM (Equipe FRM DEQ20180339214 team), and the ANR COVID-19-POPCELL (ANR-21-CO14-0003-01). A.Puj. is supported by ACCI20-759 CIBERER, EasiGenomics H2020 Marató TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1, AEI/FEDER, UE), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). The CoV-Contact Cohort was funded by the French Ministry of Health and the European Commission (RECOVER project). Our studies are also funded by the Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr, 65269705) and ANID COVID0999 funding in Chile. G. Novelli and A. Novelli are supported by Regione Lazio (Research Group Projects 2020) No. A0375-2020-36663, GecoBiomark. A.M.P., M.L.D., and J.P.-T. are supported by the Inmungen-CoV2 project of CSIC. This work was supported in part by the Intramural Research Program of the NIAID, NIH. The research work of A.M.P, M.L.D., and J.P.-T. was funded by the European Commission –NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). I.M. is a senior clinical investigator at FWO Vlaanderen supported by a VIB GC PID grant, by FWO grants G0B5120N (DADA2) and G0E8420N, and by the Jeffrey Modell Foundation. I.M. holds an ERC-StG MORE2ADA2 grant and is also supported by ERN-RITA.​ A.Y. is supported by fellowships from the European Academy of Dermatology and Venereology and the Swiss National Science Foundation and by an Early Career Award from the Thrasher Research Fund. Y.-H.C. is supported by an A*STAR International Fellowship (AIF). M.O. was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society (HNMS), the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the National Cancer Institute (NCI) F99 Award (F99CA274708). A.A.A. was supported by Ministerio de Ciencia Tecnología e Innovación MINCIENCIAS, Colombia (111584467551/CT 415-2020). D.L. is supported by a fellowship from the FRM for medical residents and fellows. E.H. received funding from the Bank of Montreal Chair of Pediatric Immunology, Foundation of CHU Sainte-Justine, CIHR grants PCC-466901 and MM1-181123, and a Canadian Pediatric Society IMPACT study. Q.P.-H. received funding from the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444, a George Mason University Fast Grant, the G. Harold and Leila Y. Mathers Charitable Foundation, the Meyer Foundation, and the Bawd Foundation. R.P.L. is on the board of directors of both Roche and the Roche subsidiary Genentech. J.L.P. was supported by a Francois Wallace Monahan Postdoctoral Fellowship at the Rockefeller University and by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-21-CO14-0003,COVID-19-POPCELL,Facteurs génétiques et infectieux à l'origine de la variabilité populationnelle de la réponse immunitaire à l'infection par le SARS-CoV-2(2021), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 101057100,UNDINE, Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Cabildo de Tenerife, Fundació La Marató de TV3, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Consejo Superior de Investigaciones Científicas (España), European Commission, and Pérez-Tur, Jordi

Subjects
Multidisciplinary, Settore MED/03, [SDV]Life Sciences [q-bio], Medicine and Health Sciences, CoV-Contact Cohort§
Abstract

62 páginas, 5 figuras, 2 tablas, Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R21AI160576), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High-Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JBP Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10- LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the ANR GenMISC (ANR-21-COVR-039), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the ANR-RHU program (ANR-21-RHUS-08), the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the ANR-RHU Program ANR-21- RHUS-08 (COVIFERON), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Cité University. We acknowledge support from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under award R01AI104887 to R.H.S. and S.R.W. The Laboratory of Human Evolutionary Genetics (Institut Pasteur) is supported by the Institut Pasteur, the Collège de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID) and “Milieu Intérieur” (ANR-10-LABX-69-01), the Fondation de France (no. 00106080), the FRM (Equipe FRM DEQ20180339214 team), and the ANR COVID-19-POPCELL (ANR-21-CO14-0003-01). A.Puj. is supported by ACCI20-759 CIBERER, EasiGenomics H2020 Marató TV3 COVID 2021-31-33, the HORIZON-HLTH-2021-ID: 101057100 (UNDINE), the Horizon 2020 program under grant no. 824110 (EasiGenomics grant no. COVID-19/PID12342), and the CERCA Program/Generalitat de Catalunya. The Canarian Health System sequencing hub was funded by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación MAPFRE Guanarteme (OA21/131), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The CoV-Contact Cohort was funded by the French Ministry of Health and the European Commission (RECOVER project). Our studies are also funded by the Ministry of Health of the Czech Republic Conceptual Development of Research Organization (FNBr, 65269705) and ANID COVID0999 funding in Chile. G. Novelli and A. Novelli are supported by Regione Lazio (Research Group Projects 2020) No. A0375-2020-36663, GecoBiomark. A.M.P., M.L.D., and J.P.-T. are supported by the Inmungen-CoV2 project of CSIC. This work was supported in part by the Intramural Research Program of the NIAID, NIH. The research work of A.M..P, M.L.D., and J.P.-T. was funded by the European Commission –NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). I.M. is a senior clinical investigator at FWO Vlaanderen supported by a VIB GC PID grant, by FWO grants G0B5120N (DADA2) and G0E8420N, and by the Jeffrey Modell Foundation. I.M. holds an ERC-StG MORE2ADA2 grant and is also supported by ERN-RITA. A.Y. is supported by fellowships from the European Academy of Dermatology and Venereology and the Swiss National Science Foundation and by an Early Career Award from the Thrasher Research Fund. Y.-H.C. is supported by an A*STAR International Fellowship (AIF). M.O. was supported by the David Rockefeller Graduate Program, the New York Hideyo Noguchi Memorial Society (HNMS), the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the National Cancer Institute (NCI) F99 Award (F99CA274708). A.A.A. was supported by Ministerio de Ciencia Tecnología e Innovación MINCIENCIAS, Colombia (111584467551/CT 415-2020). D.L. is supported by a fellowship from the FRM for medical residents and fellows. E.H. received funding from the Bank of Montreal Chair of Pediatric Immunology, Foundation of CHU Sainte-Justine, CIHR grants PCC-466901 and MM1-181123, and a Canadian Pediatric Society IMPACT study. Q.P.-H. received funding from the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, and the Knut and Alice Wallenberg Foundation. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, R01AI091707-10S1, and R01AI161444; a George Mason University Fast Grant; the G. Harold and Leila Y. Mathers Charitable Foundation; the Meyer Foundation; and the Bawd Foundation. R.P.L. is on the board of directors of both Roche and the Roche subsidiary Genentech. J.L.P. was supported by a Francois Wallace Monahan Postdoctoral Fellowship at the Rockefeller University and by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018).

Published
2023

19. Decreased memory B cell frequencies in COVID‐19 delta variant vaccine breakthrough infection

Author

Tay, Matthew Zirui, primary, Rouers, Angeline, additional, Fong, Siew‐Wai, additional, Goh, Yun Shan, additional, Chan, Yi‐Hao, additional, Chang, Zi Wei, additional, Xu, Weili, additional, Tan, Chee Wah, additional, Chia, Wan Ni, additional, Torres‐Ruesta, Anthony, additional, Amrun, Siti Naqiah, additional, Huang, Yuling, additional, Hor, Pei Xiang, additional, Loh, Chiew Yee, additional, Yeo, Nicholas Kim‐Wah, additional, Wang, Bei, additional, Ngoh, Eve Zi Xian, additional, Salleh, Siti Nazihah Mohd, additional, Chavatte, Jean‐Marc, additional, Lim, Alicia Jieling, additional, Maurer‐Stroh, Sebastian, additional, Wang, Lin‐Fa, additional, Lin, Raymond Valentine Tzer Pin, additional, Wang, Cheng‐I, additional, Tan, Seow‐Yen, additional, Young, Barnaby Edward, additional, Leo, Yee‐Sin, additional, Lye, David C, additional, Renia, Laurent, additional, and Ng, Lisa FP, additional

Published
2022
Full Text
View/download PDF

20. Malaria abrogates O’nyong–nyong virus pathologies by restricting virus infection in nonimmune cells

Author

Torres-Ruesta, Anthony, primary, Teo, Teck-Hui, additional, Chan, Yi-Hao, additional, Amrun, Siti Naqiah, additional, Yeo, Nicholas Kim-Wah, additional, Lee, Cheryl Yi-Pin, additional, Nguee, Samantha Yee-Teng, additional, Tay, Matthew Zirui, additional, Nosten, Francois, additional, Fong, Siew-Wai, additional, Lum, Fok-Moon, additional, Carissimo, Guillaume, additional, Renia, Laurent, additional, and Ng, Lisa FP, additional

Published
2022
Full Text
View/download PDF

21. Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity

Author

Young, Barnaby E, Ong, Sean W X, Ng, Lisa F P, Anderson, Danielle E, Chia, Wan Ni, Chia, Po Ying, Ang, Li Wei, Mak, Tze-Minn, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Fong, Siew-Wai, Chan, Yi-Hao, Tan, Chee Wah, Lee, Bernett, Rötzschke, Olaf, Ding, Ying, Tambyah, Paul, Low, Jenny G H, Cui, Lin, Barkham, Timothy, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, Lye, David Chien, Lim, Poh Lian, Peng Ang, Brenda Sze, Lee, Cheng Chuan, U Lee, Lawrence Soon, Ling, Li Min, Ng, Oon Tek, Chan, Monica, Marimuthu, Kalisvar, Vasoo, Shawn, Wong, Chen Seong, Lee, Tau Hong, Sadarangani, Sapna, Lin, Ray Junhao, Sadasiv, Mucheli Sharavan, Ling Ng, Deborah Hee, Choy, Chiaw Yee, En Tan, Glorijoy Shi, Tan, Yu Kit, Sutjipto, Stephanie, Lee, Pei Hua, Tay, Jun Yang, Yeo, Tsin Wen, Khoo, Bo Yan, Tay, Woo Chiao, Ng, Gabrielle, Mah, Yun Yuan, Tan, Wilnard, De, Partha Pratim, Pooja, Rao, Chia, Jonathan W Z, Constance Chen, Yuan Yi, Mendis, Shehara, Toh, Boon Kiat, Choon Fong, Raymond Kok, Lin Oh, Helen May, Fong Chien, Jaime Mei, Shafi, Humaira, Cheong, Hau Yiang, Tan, Thean Yen, Tan, Thuan Tong, Tan, Ban Hock, Wijaya, Limin, Venkatachalam, Indumathi, Chua, Ying Ying, Zhi Cherng, Benjamin Pei, Zi Chan, Yvonne Fu, Wong, Hei Man, Thien, Siew Yee, Meng Goh, Kenneth Choon, Ling Tan, Shireen Yan, Ean Oon, Lynette Lin, Chan, Kian Sing, Lin, Li, Gin Chan, Douglas Su, Ooi, Say Tat, Narayana, Deepak Rama, Somani, Jyoti, Ling Oon, Jolene Ee, Yan, Gabriel Zherong, Allen, David Michael, Jureen, Roland, Yan, Benedict, Foo, Randy, Kang, Adrian, Sivalingam, Velraj, How, Wilson, Fernandez, Norman Leo, Yeo, Nicholas Kim-Wah, Chee, Rhonda Sin-Ling, Amrun, Siti Naqiah, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, and Saw Swee Hock School of Public Health, NUS

Subjects
0301 basic medicine, Microbiology (medical), biology, Viral culture, business.industry, 030106 microbiology, COVID-19, medicine.disease, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, Infectious Diseases, Immune system, Immunoglobulin M, Viral pneumonia, Immunology, Severity of illness, medicine, biology.protein, Cytokines, Medicine [Science], 030212 general & internal medicine, Seroconversion, Antibody, business
Abstract

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.

Published
2020

22. Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

Author

Lim, Jackwee, primary, Puan, Kia Joo, additional, Wang, Liang Wei, additional, Teng, Karen Wei Weng, additional, Loh, Chiew Yee, additional, Tan, Kim Peng, additional, Carissimo, Guillaume, additional, Chan, Yi-Hao, additional, Poh, Chek Meng, additional, Lee, Cheryl Yi-Pin, additional, Fong, Siew-Wai, additional, Yeo, Nicholas Kim-Wah, additional, Chee, Rhonda Sin-Ling, additional, Amrun, Siti Naqiah, additional, Chang, Zi Wei, additional, Tay, Matthew Zirui, additional, Torres-Ruesta, Anthony, additional, Leo Fernandez, Norman, additional, How, Wilson, additional, Andiappan, Anand Kumar, additional, Lee, Wendy, additional, Duan, Kaibo, additional, Tan, Seow-Yen, additional, Yan, Gabriel, additional, Kalimuddin, Shirin, additional, Lye, David Chien, additional, Leo, Yee-Sin, additional, Ong, Sean W. X., additional, Young, Barnaby E., additional, Renia, Laurent, additional, Ng, Lisa F. P., additional, Lee, Bernett, additional, and Rötzschke, Olaf, additional

Published
2021
Full Text
View/download PDF

23. Resistance of SARS-CoV-2 Delta variant to neutralization by BNT162b2-elicited antibodies in Asians

Author

Wang, Bei, primary, Goh, Yun Shan, additional, Fong, Siew-Wai, additional, Young, Barnaby Edward, additional, Ngoh, Eve Zi Xian, additional, Chavatte, Jean-Marc, additional, Salleh, Siti Nazihah Mohd, additional, Yeo, Nicholas Kim-Wah, additional, Amrun, Siti Naqiah, additional, Hor, Pei Xiang, additional, Loh, Chiew Yee, additional, Lee, Chia Yin, additional, Chan, Yi-Hao, additional, Chang, Zi Wei, additional, Tay, Matthew Zirui, additional, Rouers, Angeline, additional, Torres-Ruesta, Anthony, additional, Carissimo, Guillaume, additional, Soh, Mun Kuen, additional, Lee, Raphael Tze Chuen, additional, Xu, Yani, additional, Pada, Surinder, additional, Lin, Raymond Tzer Pin, additional, Leo, Yee-Sin, additional, Lye, David C., additional, Maurer-Stroh, Sebastian, additional, Ng, Lisa F.P., additional, Renia, Laurent, additional, and Wang, Cheng-I, additional

Published
2021
Full Text
View/download PDF

24. Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir

Author

Chan, Yi-Hao, primary, Young, Barnaby E., additional, Fong, Siew-Wai, additional, Ding, Ying, additional, Goh, Yun Shan, additional, Chee, Rhonda Sin-Ling, additional, Tan, Seow-Yen, additional, Kalimuddin, Shirin, additional, Tambyah, Paul A., additional, Leo, Yee-Sin, additional, Ng, Lisa F. P., additional, Lye, David Chien, additional, and Renia, Laurent, additional

Published
2021
Full Text
View/download PDF

25. Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study

Author

Chia, Wan Ni, primary, Zhu, Feng, additional, Ong, Sean Wei Xiang, additional, Young, Barnaby Edward, additional, Fong, Siew-Wai, additional, Le Bert, Nina, additional, Tan, Chee Wah, additional, Tiu, Charles, additional, Zhang, Jinyan, additional, Tan, Seow Yen, additional, Pada, Surinder, additional, Chan, Yi-Hao, additional, Tham, Christine Y L, additional, Kunasegaran, Kamini, additional, Chen, Mark I-C, additional, Low, Jenny G H, additional, Leo, Yee-Sin, additional, Renia, Laurent, additional, Bertoletti, Antonio, additional, Ng, Lisa F P, additional, Lye, David Chien, additional, and Wang, Lin-Fa, additional

Published
2021
Full Text
View/download PDF

26. Asymptomatic COVID‐19: disease tolerance with efficient anti‐viral immunity against SARS‐CoV‐2

Author

Chan, Yi‐Hao, primary, Fong, Siew‐Wai, additional, Poh, Chek‐Meng, additional, Carissimo, Guillaume, additional, Yeo, Nicholas Kim‐Wah, additional, Amrun, Siti Naqiah, additional, Goh, Yun Shan, additional, Lim, Jackwee, additional, Xu, Weili, additional, Chee, Rhonda Sin‐Ling, additional, Torres‐Ruesta, Anthony, additional, Lee, Cheryl Yi‐Pin, additional, Tay, Matthew Zirui, additional, Chang, Zi Wei, additional, Lee, Wen‐Hsin, additional, Wang, Bei, additional, Tan, Seow‐Yen, additional, Kalimuddin, Shirin, additional, Young, Barnaby Edward, additional, Leo, Yee‐Sin, additional, Wang, Cheng‐I, additional, Lee, Bernett, additional, Rötzschke, Olaf, additional, Lye, David Chien, additional, Renia, Laurent, additional, and Ng, Lisa F P, additional

Published
2021
Full Text
View/download PDF

27. Persistent Symptoms and Association With Inflammatory Cytokine Signatures in Recovered Coronavirus Disease 2019 Patients

Author

Ong, Sean Wei Xiang, primary, Fong, Siew-Wai, additional, Young, Barnaby Edward, additional, Chan, Yi-Hao, additional, Lee, Bernett, additional, Amrun, Siti Naqiah, additional, Chee, Rhonda Sin-Ling, additional, Yeo, Nicholas Kim-Wah, additional, Tambyah, Paul, additional, Pada, Surinder, additional, Tan, Seow Yen, additional, Ding, Ying, additional, Renia, Laurent, additional, Leo, Yee-Sin, additional, Ng, Lisa F P, additional, and Lye, David Chien, additional

Published
2021
Full Text
View/download PDF

28. Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation

Author

Chioh, Florence WJ, primary, Fong, Siew-Wai, additional, Young, Barnaby E, additional, Wu, Kan-Xing, additional, Siau, Anthony, additional, Krishnan, Shuba, additional, Chan, Yi-Hao, additional, Carissimo, Guillaume, additional, Teo, Louis LY, additional, Gao, Fei, additional, Tan, Ru San, additional, Zhong, Liang, additional, Koh, Angela S, additional, Tan, Seow-Yen, additional, Tambyah, Paul A, additional, Renia, Laurent, additional, Ng, Lisa FP, additional, Lye, David C, additional, and Cheung, Christine, additional

Published
2021
Full Text
View/download PDF

29. Viral dynamics and immune correlates of COVID-19 disease severity

Author

Young, Barnaby E, Ong, Sean W X, Ng, Lisa F P, Anderson, Danielle E, Chia, Wan Ni, Chia, Po Ying, Ang, Li Wei, Mak, Tze-Minn, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Fong, Siew-Wai, Chan, Yi-Hao, Tan, Chee Wah, Lee, Bernett, Rötzschke, Olaf, Ding, Ying, Tambyah, Paul, Low, Jenny G H, Cui, Lin, Barkham, Timothy, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, and Lye, David Chien

Subjects
immunology, AcademicSubjects/MED00290, Severe acute respiratory syndrome-related coronavirus, SARS-CoV-2, Major Article, viral culture, COVID-19, serology, Humans, Antibodies, Viral, cytokines
Abstract

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of SARS-CoV-2 infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age 46 years, 56% male, 38% with comorbidities). Respiratory samples (n=74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n=30), and plasma samples for levels of inflammatory cytokines and chemokines (n=81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results 57 (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen including 12 (12%) invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median of 12.5 days (IQR 9-18) for IgM and 15.0 days (IQR 12-20) for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB and IL-1RA significantly correlated with disease severity. Conclusion We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offers targets for host-directed immunotherapy which should be evaluated in randomised controlled trials.

Published
2020

30. Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity

Author

Amrun, Siti Naqiah, primary, Lee, Cheryl Yi-Pin, additional, Lee, Bernett, additional, Fong, Siew-Wai, additional, Young, Barnaby Edward, additional, Chee, Rhonda Sin-Ling, additional, Yeo, Nicholas Kim-Wah, additional, Torres-Ruesta, Anthony, additional, Carissimo, Guillaume, additional, Poh, Chek Meng, additional, Chang, Zi Wei, additional, Tay, Matthew Zirui, additional, Chan, Yi-Hao, additional, Chen, Mark I-Cheng, additional, Low, Jenny Guek-Hong, additional, Tambyah, Paul A., additional, Kalimuddin, Shirin, additional, Pada, Surinder, additional, Tan, Seow-Yen, additional, Sun, Louisa Jin, additional, Leo, Yee-Sin, additional, Lye, David C., additional, Renia, Laurent, additional, and Ng, Lisa F.P., additional

Published
2020
Full Text
View/download PDF

31. Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection

Author

Chan, Yi-Hao, primary, Teo, Teck-Hui, additional, Torres-Ruesta, Anthony, additional, Hartimath, Siddesh V., additional, Chee, Rhonda Sin-Ling, additional, Khanapur, Shivashankar, additional, Yong, Fui Fong, additional, Ramasamy, Boominathan, additional, Cheng, Peter, additional, Rajarethinam, Ravisankar, additional, Robins, Edward G., additional, Goggi, Julian L., additional, Lum, Fok-Moon, additional, Carissimo, Guillaume, additional, Rénia, Laurent, additional, and Ng, Lisa F. P., additional

Published
2020
Full Text
View/download PDF

33. Associations of viral ribonucleic acid (RNA) shedding patterns with clinical illness and immune responses in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infection

Author

Lee, Pei Hua, primary, Tay, Woo Chiao, additional, Sutjipto, Stephanie, additional, Fong, Siew‐Wai, additional, Ong, Sean Wei Xiang, additional, Wei, Wycliff Enli, additional, Chan, Yi‐Hao, additional, Ling, Li Min, additional, Young, Barnaby E, additional, Toh, Matthias Paul HS, additional, Renia, Laurent, additional, Ng, Lisa FP, additional, Leo, Yee‐Sin, additional, Lye, David C, additional, and Lee, Tau Hong, additional

Published
2020
Full Text
View/download PDF

36. Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

Author

Chan, Yi‐Hao, primary, Teo, Teck‐Hui, additional, Utt, Age, additional, Tan, Jeslin JL, additional, Amrun, Siti Naqiah, additional, Abu Bakar, Farhana, additional, Yee, Wearn‐Xin, additional, Becht, Etienne, additional, Lee, Cheryl Yi‐Pin, additional, Lee, Bernett, additional, Rajarethinam, Ravisankar, additional, Newell, Evan, additional, Merits, Andres, additional, Carissimo, Guillaume, additional, Lum, Fok‐Moon, additional, and Ng, Lisa FP, additional

Published
2019
Full Text
View/download PDF

38. Immunological observations and transcriptomic analysis of trimester‐specific full‐term placentas from three Zika virus‐infected women

Author

Lum, Fok‐Moon, primary, Narang, Vipin, additional, Hue, Susan, additional, Chen, Jie, additional, McGovern, Naomi, additional, Rajarethinam, Ravisankar, additional, Tan, Jeslin JL, additional, Amrun, Siti Naqiah, additional, Chan, Yi‐Hao, additional, Lee, Cheryl YP, additional, Chua, Tze‐Kwang, additional, Yee, Wearn‐Xin, additional, Yeo, Nicholas KW, additional, Tan, Thiam‐Chye, additional, Liu, Xuan, additional, Haldenby, Sam, additional, Leo, Yee‐sin, additional, Ginhoux, Florent, additional, Chan, Jerry KY, additional, Hiscox, Julian, additional, Chong, Chia‐Yin, additional, and Ng, Lisa FP, additional

Published
2019
Full Text
View/download PDF

39. Fever Patterns, Cytokine Profiles, and Outcomes in COVID-19.

Author

Ng, Deborah H L, Choy, Chiaw Yee, Chan, Yi-Hao, Young, Barnaby E, Fong, Siew-Wai, Ng, Lisa F P, Renia, Laurent, Lye, David C, Chia, Po Ying, and Team, National Centre for Infectious Diseases COVID-19 Outbreak Research

Subjects
COVID-19, DENGUE hemorrhagic fever, FEVER, INTENSIVE care units, VIRUS diseases
Abstract

Background Prolonged fever is associated with adverse outcomes in dengue viral infection. Similar fever patterns are observed in COVID-19 with unclear significance. Methods We conducted a hospital-based case–control study of patients admitted for COVID-19 with prolonged fever (fever >7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). Fever was defined as a temperature of ≥38.0°C. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. Results A total of 142 patients were included in the study; 12.7% (18/142) of cases had prolonged fever, and 9.9% (14/142) had saddleback fever. Those with prolonged fever had a median duration of fever (interquartile range [IQR]) of 10 (9–11) days for prolonged fever cases, while fever recurred at a median (IQR) of 10 (8–12) days for those with saddleback fever. Both prolonged (27.8% vs 0.9%; P  < .01) and saddleback fever (14.3% vs 0.9%; P  = .03) were associated with hypoxia compared with controls. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P  = .05). Patients with prolonged fever had higher induced protein–10 and lower interleukin-1α levels compared with those with saddleback fever at the early acute phase of disease. Conclusions Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Patients with saddleback fever appeared to have good outcomes regardless of the fever. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

41. Caribbean and La Réunion Chikungunya Virus Isolates Differ in Their Capacity To Induce Proinflammatory Th1 and NK Cell Responses and Acute Joint Pathology

Author

Teo, Teck-Hui, primary, Her, Zhisheng, additional, Tan, Jeslin J. L., additional, Lum, Fok-Moon, additional, Lee, Wendy W. L., additional, Chan, Yi-Hao, additional, Ong, Ruo-Yan, additional, Kam, Yiu-Wing, additional, Leparc-Goffart, Isabelle, additional, Gallian, Pierre, additional, Rénia, Laurent, additional, de Lamballerie, Xavier, additional, and Ng, Lisa F. P., additional

Published
2015
Full Text
View/download PDF

42. Resistance of SARS-CoV-2 Delta variant to neutralization by BNT162b2-elicited antibodies in Asians.

Author

Wang B, Goh YS, Fong SW, Young BE, Ngoh EZX, Chavatte JM, Salleh SNM, Yeo NK, Amrun SN, Hor PX, Loh CY, Lee CY, Chan YH, Chang ZW, Tay MZ, Rouers A, Torres-Ruesta A, Carissimo G, Soh MK, Lee RTC, Xu Y, Pada S, Lin RTP, Leo YS, Lye DC, Maurer-Stroh S, Ng LFP, Renia L, and Wang CI

Abstract

Competing Interests: A patent application for the SFB assay has been filed (Singapore patent 10202009679P: A Method Of Detecting Antibodies And Related Products. YSG, LFPN, and LR). A patent application on the identified linear epitopes S14P5 and S20P2 has also been filed (PCT/SG2021/050178: Antibody-binding linear B cell epitopes of SARS-CoV and SARS-CoV-2. NKWY, SNA, GC, and LFPN). All other authors declare no conflict of interest.

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results