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The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS‐CoV‐2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies and cellular immune phenotypes of asymptomatic patients with acute SARS‐CoV‐2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro‐inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro‐inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus‐specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS‐CoV‐2 was observed in asymptomatic patients. In addition, asymptomatic COVID‐19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro‐inflammatory and more protective immune responses against SARS‐CoV‐2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID‐19.
Yi‐Hao Chan; Siew‐Wai Fong; Chek‐Meng Poh; Guillaume Carissimo; Nicholas Kim‐Wah Yeo; Siti Naqiah Amrun; Yun Shan Goh; Jackwee Lim; Weili Xu; Rhonda Sin‐Ling Chee; Anthony Torres‐Ruesta; Cheryl Yi‐Pin Lee; Matthew Zirui Tay; Zi Wei Chang; Wen‐Hsin Lee; Bei Wang; Seow‐Yen Tan; Shirin Kalimuddin; Barnaby Edward Young; Yee‐Sin Leo; Cheng‐I Wang; Bernett Lee; Olaf Rötzschke; David Chien Lye; Laurent Renia; Lisa F.P. Ng. Asymptomatic COVID‐19: disease tolerance with efficient anti‐viral immunity against SARS‐CoV‐2. EMBO Molecular Medicine 2021, 13, e14045 .
AMA StyleYi‐Hao Chan, Siew‐Wai Fong, Chek‐Meng Poh, Guillaume Carissimo, Nicholas Kim‐Wah Yeo, Siti Naqiah Amrun, Yun Shan Goh, Jackwee Lim, Weili Xu, Rhonda Sin‐Ling Chee, Anthony Torres‐Ruesta, Cheryl Yi‐Pin Lee, Matthew Zirui Tay, Zi Wei Chang, Wen‐Hsin Lee, Bei Wang, Seow‐Yen Tan, Shirin Kalimuddin, Barnaby Edward Young, Yee‐Sin Leo, Cheng‐I Wang, Bernett Lee, Olaf Rötzschke, David Chien Lye, Laurent Renia, Lisa F.P. Ng. Asymptomatic COVID‐19: disease tolerance with efficient anti‐viral immunity against SARS‐CoV‐2. EMBO Molecular Medicine. 2021; 13 (6):e14045.
Chicago/Turabian StyleYi‐Hao Chan; Siew‐Wai Fong; Chek‐Meng Poh; Guillaume Carissimo; Nicholas Kim‐Wah Yeo; Siti Naqiah Amrun; Yun Shan Goh; Jackwee Lim; Weili Xu; Rhonda Sin‐Ling Chee; Anthony Torres‐Ruesta; Cheryl Yi‐Pin Lee; Matthew Zirui Tay; Zi Wei Chang; Wen‐Hsin Lee; Bei Wang; Seow‐Yen Tan; Shirin Kalimuddin; Barnaby Edward Young; Yee‐Sin Leo; Cheng‐I Wang; Bernett Lee; Olaf Rötzschke; David Chien Lye; Laurent Renia; Lisa F.P. Ng. 2021. "Asymptomatic COVID‐19: disease tolerance with efficient anti‐viral immunity against SARS‐CoV‐2." EMBO Molecular Medicine 13, no. 6: e14045.
Background The complications and sequelae of coronavirus disease 2019 (COVID-19) and their effect on long-term health are unclear, and the trajectory of associated immune dysregulation is poorly understood. Methods We conducted a prospective longitudinal multicenter cohort study at 4 public hospitals in Singapore. Patients with COVID-19 were monitored for a median of 6 months after recovery from acute infection. Clinical symptoms and radiologic data were collected, along with plasma samples for quantification of immune mediators. The relationship between clinical symptoms and immune cytokine profiles was investigated. Results Two hundred eighty-eight participants were recruited, and follow-up data were available for 183, 175, and 120 participants at days 30, 90, and 180 postsymptom onset, respectively. Symptoms related to COVID-19 were present in 31 (16.9%), 13 (7.4%), and 14 (11.7%) at days 30, 90, and 180. In a multivariable model, age >65 years, non-Chinese ethnicity, and the severity of acute infection were associated with increased likelihood of persistent symptoms. Recovered COVID-19 patients had elevated levels of proinflammatory interleukin (IL)-17A, stem cell factor, IL-12p70, and IL-1β and pro-angiogenic macrophage inflammatory protein 1β, brain-derived neurotrophic factor, and vascular endothelial growth factor at day 180 compared with healthy controls. Higher levels of monocyte chemoattractant protein-1 and platelet-derived growth factor-BB were detected in patients with persistent symptoms, versus symptom-free patients. Conclusions Approximately 10% of recovered patients had persistent symptoms 6 months after initial infection. Immune cytokine signatures of the recovered patients reflected ongoing chronic inflammation and angiogenesis. Patients with COVID-19 should be monitored closely for emerging long-term health consequences.
Sean Wei Xiang Ong; Siew-Wai Fong; Barnaby Edward Young; Yi-Hao Chan; Bernett Lee; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Nicholas Kim-Wah Yeo; Paul Tambyah; Surinder Pada; Seow Yen Tan; Ying Ding; Laurent Renia; Yee-Sin Leo; Lisa F P Ng; David Chien Lye. Persistent Symptoms and Association With Inflammatory Cytokine Signatures in Recovered Coronavirus Disease 2019 Patients. Open Forum Infectious Diseases 2021, 8, ofab156 .
AMA StyleSean Wei Xiang Ong, Siew-Wai Fong, Barnaby Edward Young, Yi-Hao Chan, Bernett Lee, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Nicholas Kim-Wah Yeo, Paul Tambyah, Surinder Pada, Seow Yen Tan, Ying Ding, Laurent Renia, Yee-Sin Leo, Lisa F P Ng, David Chien Lye. Persistent Symptoms and Association With Inflammatory Cytokine Signatures in Recovered Coronavirus Disease 2019 Patients. Open Forum Infectious Diseases. 2021; 8 (6):ofab156.
Chicago/Turabian StyleSean Wei Xiang Ong; Siew-Wai Fong; Barnaby Edward Young; Yi-Hao Chan; Bernett Lee; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Nicholas Kim-Wah Yeo; Paul Tambyah; Surinder Pada; Seow Yen Tan; Ying Ding; Laurent Renia; Yee-Sin Leo; Lisa F P Ng; David Chien Lye. 2021. "Persistent Symptoms and Association With Inflammatory Cytokine Signatures in Recovered Coronavirus Disease 2019 Patients." Open Forum Infectious Diseases 8, no. 6: ofab156.
Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.
Jackwee Lim; Kia Joo Puan; Liang Wei Wang; Karen Wei Weng Teng; Chiew Yee Loh; Kim Peng Tan; Guillaume Carissimo; Yi-Hao Chan; Chek Meng Poh; Cheryl Yi-Pin Lee; Siew-Wai Fong; Nicholas Kim-Wah Yeo; Rhonda Sin-Ling Chee; Siti Naqiah Amrun; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres-Ruesta; Norman Leo Fernandez; Wilson How; Anand K. Andiappan; Wendy Lee; Kaibo Duan; Seow-Yen Tan; Gabriel Yan; Shirin Kalimuddin; David Chien Lye; Yee-Sin Leo; Sean W. X. Ong; Barnaby E. Young; Laurent Renia; Lisa F.P. Ng; Bernett Lee; Olaf Rötzschke. Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response. 2021, 1 .
AMA StyleJackwee Lim, Kia Joo Puan, Liang Wei Wang, Karen Wei Weng Teng, Chiew Yee Loh, Kim Peng Tan, Guillaume Carissimo, Yi-Hao Chan, Chek Meng Poh, Cheryl Yi-Pin Lee, Siew-Wai Fong, Nicholas Kim-Wah Yeo, Rhonda Sin-Ling Chee, Siti Naqiah Amrun, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres-Ruesta, Norman Leo Fernandez, Wilson How, Anand K. Andiappan, Wendy Lee, Kaibo Duan, Seow-Yen Tan, Gabriel Yan, Shirin Kalimuddin, David Chien Lye, Yee-Sin Leo, Sean W. X. Ong, Barnaby E. Young, Laurent Renia, Lisa F.P. Ng, Bernett Lee, Olaf Rötzschke. Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response. . 2021; ():1.
Chicago/Turabian StyleJackwee Lim; Kia Joo Puan; Liang Wei Wang; Karen Wei Weng Teng; Chiew Yee Loh; Kim Peng Tan; Guillaume Carissimo; Yi-Hao Chan; Chek Meng Poh; Cheryl Yi-Pin Lee; Siew-Wai Fong; Nicholas Kim-Wah Yeo; Rhonda Sin-Ling Chee; Siti Naqiah Amrun; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres-Ruesta; Norman Leo Fernandez; Wilson How; Anand K. Andiappan; Wendy Lee; Kaibo Duan; Seow-Yen Tan; Gabriel Yan; Shirin Kalimuddin; David Chien Lye; Yee-Sin Leo; Sean W. X. Ong; Barnaby E. Young; Laurent Renia; Lisa F.P. Ng; Bernett Lee; Olaf Rötzschke. 2021. "Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response." , no. : 1.
Patients with kidney diseases should be prioritized for COVID-19 vaccination and the available data suggest that replication-defective viral-vectored vaccines and mRNA vaccines are safe to use. As vaccine responses are likely to be lower in patients with kidney diseases than in the general population, highly potent vaccines should be preferred.
Martin Windpessl; Annette Bruchfeld; Hans-Joachim Anders; Holly Kramer; Meryl Waldman; Laurent Renia; Lisa F. P. Ng; Zhou Xing; Andreas Kronbichler. COVID-19 vaccines and kidney disease. Nature Reviews Nephrology 2021, 17, 291 -293.
AMA StyleMartin Windpessl, Annette Bruchfeld, Hans-Joachim Anders, Holly Kramer, Meryl Waldman, Laurent Renia, Lisa F. P. Ng, Zhou Xing, Andreas Kronbichler. COVID-19 vaccines and kidney disease. Nature Reviews Nephrology. 2021; 17 (5):291-293.
Chicago/Turabian StyleMartin Windpessl; Annette Bruchfeld; Hans-Joachim Anders; Holly Kramer; Meryl Waldman; Laurent Renia; Lisa F. P. Ng; Zhou Xing; Andreas Kronbichler. 2021. "COVID-19 vaccines and kidney disease." Nature Reviews Nephrology 17, no. 5: 291-293.
Objectives The emergence of a SARS‐CoV‐2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross‐neutralise against the G614 variant. Methods Antibody profiling against the SARS‐CoV‐2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS‐CoV‐2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID‐19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). Results Profiling of the anti‐SARS‐CoV‐2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. Conclusions Cross‐reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS‐CoV‐2. More importantly, there should be negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed.
Cheryl Yi‐Pin Lee; Siti Naqiah Amrun; Rhonda Sin‐Ling Chee; Yun Shan Goh; Tze‐Minn Mak; Sophie Octavia; Nicholas Kim‐Wah Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres‐Ruesta; Guillaume Carissimo; Chek Meng Poh; Siew‐Wai Fong; Wang Bei; Sandy Lee; Barnaby Edward Young; Seow‐Yen Tan; Yee‐Sin Leo; David C Lye; Raymond Tp Lin; Sebastien Maurer‐Stroh; Bernett Lee; Cheng‐I Wang; Laurent Renia; Lisa Fp Ng. Human neutralising antibodies elicited by SARS‐CoV‐2 non‐D614G variants offer cross‐protection against the SARS‐CoV‐2 D614G variant. Clinical & Translational Immunology 2021, 10, e1241 .
AMA StyleCheryl Yi‐Pin Lee, Siti Naqiah Amrun, Rhonda Sin‐Ling Chee, Yun Shan Goh, Tze‐Minn Mak, Sophie Octavia, Nicholas Kim‐Wah Yeo, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres‐Ruesta, Guillaume Carissimo, Chek Meng Poh, Siew‐Wai Fong, Wang Bei, Sandy Lee, Barnaby Edward Young, Seow‐Yen Tan, Yee‐Sin Leo, David C Lye, Raymond Tp Lin, Sebastien Maurer‐Stroh, Bernett Lee, Cheng‐I Wang, Laurent Renia, Lisa Fp Ng. Human neutralising antibodies elicited by SARS‐CoV‐2 non‐D614G variants offer cross‐protection against the SARS‐CoV‐2 D614G variant. Clinical & Translational Immunology. 2021; 10 (2):e1241.
Chicago/Turabian StyleCheryl Yi‐Pin Lee; Siti Naqiah Amrun; Rhonda Sin‐Ling Chee; Yun Shan Goh; Tze‐Minn Mak; Sophie Octavia; Nicholas Kim‐Wah Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres‐Ruesta; Guillaume Carissimo; Chek Meng Poh; Siew‐Wai Fong; Wang Bei; Sandy Lee; Barnaby Edward Young; Seow‐Yen Tan; Yee‐Sin Leo; David C Lye; Raymond Tp Lin; Sebastien Maurer‐Stroh; Bernett Lee; Cheng‐I Wang; Laurent Renia; Lisa Fp Ng. 2021. "Human neutralising antibodies elicited by SARS‐CoV‐2 non‐D614G variants offer cross‐protection against the SARS‐CoV‐2 D614G variant." Clinical & Translational Immunology 10, no. 2: e1241.
Guillaume Carissimo; Lisa F P Ng. A promiscuous interaction of SARS-CoV-2 with bacterial products. Journal of Molecular Cell Biology 2020, 12, 914 -915.
AMA StyleGuillaume Carissimo, Lisa F P Ng. A promiscuous interaction of SARS-CoV-2 with bacterial products. Journal of Molecular Cell Biology. 2020; 12 (12):914-915.
Chicago/Turabian StyleGuillaume Carissimo; Lisa F P Ng. 2020. "A promiscuous interaction of SARS-CoV-2 with bacterial products." Journal of Molecular Cell Biology 12, no. 12: 914-915.
In December 2019, a novel coronavirus was isolated from the respiratory epithelium of patients with unexplained pneumonia in Wuhan, China. This pathogen, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a pathogenic condition that has been termed coronavirus disease 2019 (COVID-19) and has reached pandemic proportions. As of 17 September 2020, more than 30 million confirmed SARS-CoV-2 infections have been reported in 204 different countries, claiming more than 1 million lives worldwide. Accumulating evidence suggests that SARS-CoV-2 infection can lead to a variety of clinical conditions, ranging from asymptomatic to life-threatening cases. In the early stages of the disease, most patients experience mild clinical symptoms, including a high fever and dry cough. However, 20% of patients rapidly progress to severe illness characterized by atypical interstitial bilateral pneumonia, acute respiratory distress syndrome and multiorgan dysfunction. Almost 10% of these critically ill patients subsequently die. Insights into the pathogenic mechanisms underlying SARS-CoV-2 infection and COVID-19 progression are emerging and highlight the critical role of the immunological hyper-response — characterized by widespread endothelial damage, complement-induced blood clotting and systemic microangiopathy — in disease exacerbation. These insights may aid the identification of new or existing therapeutic interventions to limit the progression of early disease and treat severe cases. This Review describes our current understanding of the pathogenic mechanisms involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the progression of coronavirus disease 2019 (COVID-19), focusing on the immunological hyper-response and the induction of widespread endothelial damage, complement-associated blood clotting and systemic microangiopathy, as well as the effects of these processes on the kidney. The authors also discuss therapeutic interventions that currently hold most promise.
Luca Perico; Ariela Benigni; Federica Casiraghi; Lisa F. P. Ng; Laurent Renia; Giuseppe Remuzzi. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nature Reviews Nephrology 2020, 17, 46 -64.
AMA StyleLuca Perico, Ariela Benigni, Federica Casiraghi, Lisa F. P. Ng, Laurent Renia, Giuseppe Remuzzi. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nature Reviews Nephrology. 2020; 17 (1):46-64.
Chicago/Turabian StyleLuca Perico; Ariela Benigni; Federica Casiraghi; Lisa F. P. Ng; Laurent Renia; Giuseppe Remuzzi. 2020. "Immunity, endothelial injury and complement-induced coagulopathy in COVID-19." Nature Reviews Nephrology 17, no. 1: 46-64.
SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.
Guillaume Carissimo; Weili Xu; Immanuel Kwok; Mohammad Yazid Abdad; Yi-Hao Chan; Siew-Wai Fong; Kia Joo Puan; Cheryl Yi-Pin Lee; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Wilson How; Stephrene Chan; Bingwen Eugene Fan; Anand Kumar Andiappan; Bernett Lee; Olaf Rötzschke; Barnaby Edward Young; Yee-Sin Leo; David Chien Lye; Laurent Renia; Lai Guan Ng; Anis Larbi; Lisa Fp Ng. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19. Nature Communications 2020, 11, 1 -12.
AMA StyleGuillaume Carissimo, Weili Xu, Immanuel Kwok, Mohammad Yazid Abdad, Yi-Hao Chan, Siew-Wai Fong, Kia Joo Puan, Cheryl Yi-Pin Lee, Nicholas Kim-Wah Yeo, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Wilson How, Stephrene Chan, Bingwen Eugene Fan, Anand Kumar Andiappan, Bernett Lee, Olaf Rötzschke, Barnaby Edward Young, Yee-Sin Leo, David Chien Lye, Laurent Renia, Lai Guan Ng, Anis Larbi, Lisa Fp Ng. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19. Nature Communications. 2020; 11 (1):1-12.
Chicago/Turabian StyleGuillaume Carissimo; Weili Xu; Immanuel Kwok; Mohammad Yazid Abdad; Yi-Hao Chan; Siew-Wai Fong; Kia Joo Puan; Cheryl Yi-Pin Lee; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Wilson How; Stephrene Chan; Bingwen Eugene Fan; Anand Kumar Andiappan; Bernett Lee; Olaf Rötzschke; Barnaby Edward Young; Yee-Sin Leo; David Chien Lye; Laurent Renia; Lai Guan Ng; Anis Larbi; Lisa Fp Ng. 2020. "Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19." Nature Communications 11, no. 1: 1-12.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Sequencing the viral genome as the outbreak progresses is important, particularly in the identification of emerging isolates with different pathogenic potential and to identify whether nucleotide changes in the genome will impair clinical diagnostic tools such as real-time PCR assays. Although single nucleotide polymorphisms and point mutations occur during the replication of coronaviruses, one of the biggest drivers in genetic change is recombination. This can manifest itself in insertions and/or deletions in the viral genome. Therefore, sequencing strategies that underpin molecular epidemiology and inform virus biology in patients should take these factors into account. A long amplicon/read length-based RT-PCR sequencing approach focused on the Oxford Nanopore MinION/GridION platforms was developed to identify and sequence the SARS-CoV-2 genome in samples from patients with or suspected of COVID-19. The protocol, termed Rapid Sequencing Long Amplicons (RSLAs) used random primers to generate cDNA from RNA purified from a sample from a patient, followed by single or multiplex PCRs to generate longer amplicons of the viral genome. The base protocol was used to identify SARS-CoV-2 in a variety of clinical samples and proved sensitive in identifying viral RNA in samples from patients that had been declared negative using other nucleic acid-based assays (false negative). Sequencing the amplicons revealed that a number of patients had a proportion of viral genomes with deletions.
Shona C. Moore; Rebekah Penrice-Randall; Muhannad Alruwaili; Nadine Randle; Stuart Armstrong; Catherine Hartley; Sam Haldenby; Xiaofeng Dong; Abdulrahman Alrezaihi; Mai Almsaud; Eleanor Bentley; Jordan Clark; Isabel García-Dorival; Paul Gilmore; Ximeng Han; Benjamin Jones; Lisa Luu; Parul Sharma; Ghada Shawli; Yani Sun; Qin Zhao; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Jake Dunning; En-Min Zhou; Tom Solomon; Michael Beadsworth; James Cruise; Derrick W. Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard Vipond; Lisa Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; James Stewart; Alistair Darby; Malcolm Semple; Lance Turtle; Julian A. Hiscox. Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism. Viruses 2020, 12, 1164 .
AMA StyleShona C. Moore, Rebekah Penrice-Randall, Muhannad Alruwaili, Nadine Randle, Stuart Armstrong, Catherine Hartley, Sam Haldenby, Xiaofeng Dong, Abdulrahman Alrezaihi, Mai Almsaud, Eleanor Bentley, Jordan Clark, Isabel García-Dorival, Paul Gilmore, Ximeng Han, Benjamin Jones, Lisa Luu, Parul Sharma, Ghada Shawli, Yani Sun, Qin Zhao, Steven T. Pullan, Daniel P. Carter, Kevin Bewley, Jake Dunning, En-Min Zhou, Tom Solomon, Michael Beadsworth, James Cruise, Derrick W. Crook, David A. Matthews, Andrew D. Davidson, Zana Mahmood, Waleed Aljabr, Julian Druce, Richard Vipond, Lisa Ng, Laurent Renia, Peter J. M. Openshaw, J. Kenneth Baillie, Miles W. Carroll, James Stewart, Alistair Darby, Malcolm Semple, Lance Turtle, Julian A. Hiscox. Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism. Viruses. 2020; 12 (10):1164.
Chicago/Turabian StyleShona C. Moore; Rebekah Penrice-Randall; Muhannad Alruwaili; Nadine Randle; Stuart Armstrong; Catherine Hartley; Sam Haldenby; Xiaofeng Dong; Abdulrahman Alrezaihi; Mai Almsaud; Eleanor Bentley; Jordan Clark; Isabel García-Dorival; Paul Gilmore; Ximeng Han; Benjamin Jones; Lisa Luu; Parul Sharma; Ghada Shawli; Yani Sun; Qin Zhao; Steven T. Pullan; Daniel P. Carter; Kevin Bewley; Jake Dunning; En-Min Zhou; Tom Solomon; Michael Beadsworth; James Cruise; Derrick W. Crook; David A. Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard Vipond; Lisa Ng; Laurent Renia; Peter J. M. Openshaw; J. Kenneth Baillie; Miles W. Carroll; James Stewart; Alistair Darby; Malcolm Semple; Lance Turtle; Julian A. Hiscox. 2020. "Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism." Viruses 12, no. 10: 1164.
BackgroundDengue and Chikungunya viruses can cause large-scale epidemics with attack rates exceeding 80%. In Tanzania, there have been repeated outbreaks of dengue fever, the most recent one in 2018 and 2019 mostly reported in coastal areas. Despite its importance, there is limited knowledge on epidemiology of dengue (DENV) and chikungunya (CHIKV) in Tanzania. This study was conducted to investigate the prevalence of DENV and CHIKV in Kilombero district, South-Eastern Tanzania.MethodsA cross-sectional study was conducted at Kibaoni Health Center, in Kilombero district, in the rainy and dry seasons of 2018. Febrile patients of any age and gender were enrolled. Blood samples were taken and screened for DENV and CHIKV viral RNA by real-time RT-PCR assays.ResultsA total of 294 patients were recruited. Most were females (65%), and aged between 14⍰25 years (33%). DENV and CHIKV were detected in 29 (9.9%) and 3 (1.0%) patients, respectively. DENV was detected across all age groups and during both dry and rainy seasons. Although all four DENV serotypes were detected, serotypes 1 and 3 dominated and were present in 14 patients (42.4%) each. Additionally, the study showed DENV-1 and DENV-3 co-infections.ConclusionThis study reveals the co-circulation of all four DENV serotypes and CHIKV in Kilombero district. Importantly, we report the first occurrence of DENV-4 in Tanzania. Unlike previous DENV outbreaks caused by DENV-2, the 2018 outbreak was dominated by DENV-1 and DENV-3. Occurrence of all serotypes suggests the possibility of having severe clinical outcomes in future DENV epidemics in Tanzania.
Beatrice Chipwaza; Robert David Sumaye; Maja Weisser; Winfrid Gingo; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Fredros O. Okumu; Lisa F.P. Ng. Occurrence of Four Dengue Virus Serotypes and Chikungunya Virus in Kilombero, Tanzania during Dengue Outbreak in 2018. 2020, 1 .
AMA StyleBeatrice Chipwaza, Robert David Sumaye, Maja Weisser, Winfrid Gingo, Nicholas Kim-Wah Yeo, Siti Naqiah Amrun, Fredros O. Okumu, Lisa F.P. Ng. Occurrence of Four Dengue Virus Serotypes and Chikungunya Virus in Kilombero, Tanzania during Dengue Outbreak in 2018. . 2020; ():1.
Chicago/Turabian StyleBeatrice Chipwaza; Robert David Sumaye; Maja Weisser; Winfrid Gingo; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Fredros O. Okumu; Lisa F.P. Ng. 2020. "Occurrence of Four Dengue Virus Serotypes and Chikungunya Virus in Kilombero, Tanzania during Dengue Outbreak in 2018." , no. : 1.
The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions.
Cheryl Yi-Pin Lee; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Yun Shan Goh; Tze Minn Mak; Sophie Octavia; Nicholas Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres; Guillaume Carissimo; Chek Meng Poh; Siew-Wai Fong; Bei Wang; Sandy Lee; Barnaby Young; Seow Yen Tan; Yee Sin Leo; David Chien Boon Lye; Raymond Tp Lin; Sebastian Maurer-Stroh; Bernett T. K. Lee; Cheng-I Wang; Laurent Renia; Lisa F. P. Ng. Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant. 2020, 1 .
AMA StyleCheryl Yi-Pin Lee, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Yun Shan Goh, Tze Minn Mak, Sophie Octavia, Nicholas Yeo, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres, Guillaume Carissimo, Chek Meng Poh, Siew-Wai Fong, Bei Wang, Sandy Lee, Barnaby Young, Seow Yen Tan, Yee Sin Leo, David Chien Boon Lye, Raymond Tp Lin, Sebastian Maurer-Stroh, Bernett T. K. Lee, Cheng-I Wang, Laurent Renia, Lisa F. P. Ng. Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant. . 2020; ():1.
Chicago/Turabian StyleCheryl Yi-Pin Lee; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Yun Shan Goh; Tze Minn Mak; Sophie Octavia; Nicholas Yeo; Zi Wei Chang; Matthew Zirui Tay; Anthony Torres; Guillaume Carissimo; Chek Meng Poh; Siew-Wai Fong; Bei Wang; Sandy Lee; Barnaby Young; Seow Yen Tan; Yee Sin Leo; David Chien Boon Lye; Raymond Tp Lin; Sebastian Maurer-Stroh; Bernett T. K. Lee; Cheng-I Wang; Laurent Renia; Lisa F. P. Ng. 2020. "Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant." , no. : 1.
Background Viral load is a major contributor to outcome in patients with Ebola virus disease (EVD), with high values leading to a fatal outcome. Evidence from the 2013–2016 Ebola virus (EBOV) outbreak indicated that different genotypes of the virus can have different phenotypes in patients. Additionally, due to the error-prone nature of viral RNA synthesis in an individual patient, the EBOV genome exists around a dominant viral genome sequence. The minor variants within a patient may contribute to the overall phenotype in terms of viral protein function. To investigate the effects of these minor variants, blood samples from patients with acute EVD were deeply sequenced. Results We examine the minor variant frequency between patients with acute EVD who survived infection with those who died. Non-synonymous differences in viral proteins were identified that have implications for viral protein function. The greatest frequency of substitution was identified at three codon sites in the L gene—which encodes the viral RNA-dependent RNA polymerase (RdRp). Recapitulating this in an assay for virus replication, these substitutions result in aberrant viral RNA synthesis and correlate with patient outcome. Conclusions Together, these findings support the notion that in patients who survived EVD, in some cases, the genetic variability of the virus resulted in deleterious mutations that affected viral protein function, leading to reduced viral load. Such mutations may also lead to persistent strains of the virus and be associated with recrudescent infections.
Xiaofeng Dong; Jordana Munoz-Basagoiti; Natasha Y. Rickett; Georgios Pollakis; William A. Paxton; Stephan Günther; Romy Kerber; Lisa F. P. Ng; Michael J. Elmore; N’Faly Magassouba; Miles W. Carroll; David A. Matthews; Julian A. Hiscox. Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease. Genome Biology 2020, 21, 1 -20.
AMA StyleXiaofeng Dong, Jordana Munoz-Basagoiti, Natasha Y. Rickett, Georgios Pollakis, William A. Paxton, Stephan Günther, Romy Kerber, Lisa F. P. Ng, Michael J. Elmore, N’Faly Magassouba, Miles W. Carroll, David A. Matthews, Julian A. Hiscox. Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease. Genome Biology. 2020; 21 (1):1-20.
Chicago/Turabian StyleXiaofeng Dong; Jordana Munoz-Basagoiti; Natasha Y. Rickett; Georgios Pollakis; William A. Paxton; Stephan Günther; Romy Kerber; Lisa F. P. Ng; Michael J. Elmore; N’Faly Magassouba; Miles W. Carroll; David A. Matthews; Julian A. Hiscox. 2020. "Variation around the dominant viral genome sequence contributes to viral load and outcome in patients with Ebola virus disease." Genome Biology 21, no. 1: 1-20.
Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. Methods We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study—a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed. Findings Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14–28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00–0·48]) compared with infection with wild-type virus only. Interpretation The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines. Funding National Medical Research Council Singapore.
Barnaby E Young; Siew-Wai Fong; Yi-Hao Chan; Tze-Minn Mak; Li Wei Ang; Danielle E Anderson; Cheryl Yi-Pin Lee; Siti Naqiah Amrun; Bernett Lee; Yun Shan Goh; Yvonne C F Su; Wycliffe E Wei; Shirin Kalimuddin; Louis Yi Ann Chai; Surinder Pada; Seow Yen Tan; Louisa Sun; Purnima Parthasarathy; Yuan Yi Constance Chen; Timothy Barkham; Raymond Tzer Pin Lin; Sebastian Maurer-Stroh; Yee-Sin Leo; Lin-Fa Wang; Laurent Renia; Vernon J Lee; Gavin J D Smith; David Lye; Lisa F P Ng. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. The Lancet 2020, 396, 603 -611.
AMA StyleBarnaby E Young, Siew-Wai Fong, Yi-Hao Chan, Tze-Minn Mak, Li Wei Ang, Danielle E Anderson, Cheryl Yi-Pin Lee, Siti Naqiah Amrun, Bernett Lee, Yun Shan Goh, Yvonne C F Su, Wycliffe E Wei, Shirin Kalimuddin, Louis Yi Ann Chai, Surinder Pada, Seow Yen Tan, Louisa Sun, Purnima Parthasarathy, Yuan Yi Constance Chen, Timothy Barkham, Raymond Tzer Pin Lin, Sebastian Maurer-Stroh, Yee-Sin Leo, Lin-Fa Wang, Laurent Renia, Vernon J Lee, Gavin J D Smith, David Lye, Lisa F P Ng. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. The Lancet. 2020; 396 (10251):603-611.
Chicago/Turabian StyleBarnaby E Young; Siew-Wai Fong; Yi-Hao Chan; Tze-Minn Mak; Li Wei Ang; Danielle E Anderson; Cheryl Yi-Pin Lee; Siti Naqiah Amrun; Bernett Lee; Yun Shan Goh; Yvonne C F Su; Wycliffe E Wei; Shirin Kalimuddin; Louis Yi Ann Chai; Surinder Pada; Seow Yen Tan; Louisa Sun; Purnima Parthasarathy; Yuan Yi Constance Chen; Timothy Barkham; Raymond Tzer Pin Lin; Sebastian Maurer-Stroh; Yee-Sin Leo; Lin-Fa Wang; Laurent Renia; Vernon J Lee; Gavin J D Smith; David Lye; Lisa F P Ng. 2020. "Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study." The Lancet 396, no. 10251: 603-611.
Background Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Methods Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. Findings Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. Interpretation IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs). Funding Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001) and CCGSFPOR20002. ATR is supported by the Singapore International Graduate Award (SINGA), A*STAR.
Siti Naqiah Amrun; Cheryl Yi-Pin Lee; Bernett Lee; Siew-Wai Fong; Barnaby Edward Young; Rhonda Sin-Ling Chee; Nicholas Kim-Wah Yeo; Anthony Torres-Ruesta; Guillaume Carissimo; Chek Meng Poh; Zi Wei Chang; Matthew Zirui Tay; Yi-Hao Chan; Mark I-Cheng Chen; Jenny Guek-Hong Low; Paul A. Tambyah; Shirin Kalimuddin; Surinder Pada; Seow-Yen Tan; Louisa Jin Sun; Yee-Sin Leo; David Lye; Laurent Renia; Lisa F.P. Ng. Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity. EBioMedicine 2020, 58, 102911 -102911.
AMA StyleSiti Naqiah Amrun, Cheryl Yi-Pin Lee, Bernett Lee, Siew-Wai Fong, Barnaby Edward Young, Rhonda Sin-Ling Chee, Nicholas Kim-Wah Yeo, Anthony Torres-Ruesta, Guillaume Carissimo, Chek Meng Poh, Zi Wei Chang, Matthew Zirui Tay, Yi-Hao Chan, Mark I-Cheng Chen, Jenny Guek-Hong Low, Paul A. Tambyah, Shirin Kalimuddin, Surinder Pada, Seow-Yen Tan, Louisa Jin Sun, Yee-Sin Leo, David Lye, Laurent Renia, Lisa F.P. Ng. Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity. EBioMedicine. 2020; 58 ():102911-102911.
Chicago/Turabian StyleSiti Naqiah Amrun; Cheryl Yi-Pin Lee; Bernett Lee; Siew-Wai Fong; Barnaby Edward Young; Rhonda Sin-Ling Chee; Nicholas Kim-Wah Yeo; Anthony Torres-Ruesta; Guillaume Carissimo; Chek Meng Poh; Zi Wei Chang; Matthew Zirui Tay; Yi-Hao Chan; Mark I-Cheng Chen; Jenny Guek-Hong Low; Paul A. Tambyah; Shirin Kalimuddin; Surinder Pada; Seow-Yen Tan; Louisa Jin Sun; Yee-Sin Leo; David Lye; Laurent Renia; Lisa F.P. Ng. 2020. "Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity." EBioMedicine 58, no. : 102911-102911.
SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 γδ T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.
Guillaume Carissimo; Weili Xu; Immanuel Kwok; Mohammad Yazid Abdad; Yi-Hao Chan; Siew-Wai Fong; Kia Joo Puan; Cheryl Yi-Pin Lee; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Wilson How; Stephrene Chan; Eugene Bingwen Fan; Anand Kumar Andiappan; Bernett Lee; Olaf Rötzschke; Barnaby Edward Young; Yee-Sin Leo; David C. Lye; Laurent Renia; Lai Guan Ng; Anis Larbi; Lisa F.P. Ng. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19. bioRxiv 2020, 1 .
AMA StyleGuillaume Carissimo, Weili Xu, Immanuel Kwok, Mohammad Yazid Abdad, Yi-Hao Chan, Siew-Wai Fong, Kia Joo Puan, Cheryl Yi-Pin Lee, Nicholas Kim-Wah Yeo, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Wilson How, Stephrene Chan, Eugene Bingwen Fan, Anand Kumar Andiappan, Bernett Lee, Olaf Rötzschke, Barnaby Edward Young, Yee-Sin Leo, David C. Lye, Laurent Renia, Lai Guan Ng, Anis Larbi, Lisa F.P. Ng. Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19. bioRxiv. 2020; ():1.
Chicago/Turabian StyleGuillaume Carissimo; Weili Xu; Immanuel Kwok; Mohammad Yazid Abdad; Yi-Hao Chan; Siew-Wai Fong; Kia Joo Puan; Cheryl Yi-Pin Lee; Nicholas Kim-Wah Yeo; Siti Naqiah Amrun; Rhonda Sin-Ling Chee; Wilson How; Stephrene Chan; Eugene Bingwen Fan; Anand Kumar Andiappan; Bernett Lee; Olaf Rötzschke; Barnaby Edward Young; Yee-Sin Leo; David C. Lye; Laurent Renia; Lai Guan Ng; Anis Larbi; Lisa F.P. Ng. 2020. "Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19." bioRxiv , no. : 1.
Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus.
Chek Meng Poh; Guillaume Carissimo; Bei Wang; Siti Naqiah Amrun; Cheryl Yi-Pin Lee; Rhonda Sin-Ling Chee; Siew-Wai Fong; Nicholas Kim-Wah Yeo; Wen-Hsin Lee; Anthony Torres-Ruesta; Yee-Sin Leo; Mark I-Cheng Chen; Seow-Yen Tan; Louis Yi Ann Chai; Shirin Kalimuddin; Shirley Seah Gek Kheng; Siew-Yee Thien; Barnaby Edward Young; David Lye; Brendon John Hanson; Cheng-I Wang; Laurent Renia; Lisa F. P. Ng. Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients. Nature Communications 2020, 11, 1 -7.
AMA StyleChek Meng Poh, Guillaume Carissimo, Bei Wang, Siti Naqiah Amrun, Cheryl Yi-Pin Lee, Rhonda Sin-Ling Chee, Siew-Wai Fong, Nicholas Kim-Wah Yeo, Wen-Hsin Lee, Anthony Torres-Ruesta, Yee-Sin Leo, Mark I-Cheng Chen, Seow-Yen Tan, Louis Yi Ann Chai, Shirin Kalimuddin, Shirley Seah Gek Kheng, Siew-Yee Thien, Barnaby Edward Young, David Lye, Brendon John Hanson, Cheng-I Wang, Laurent Renia, Lisa F. P. Ng. Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients. Nature Communications. 2020; 11 (1):1-7.
Chicago/Turabian StyleChek Meng Poh; Guillaume Carissimo; Bei Wang; Siti Naqiah Amrun; Cheryl Yi-Pin Lee; Rhonda Sin-Ling Chee; Siew-Wai Fong; Nicholas Kim-Wah Yeo; Wen-Hsin Lee; Anthony Torres-Ruesta; Yee-Sin Leo; Mark I-Cheng Chen; Seow-Yen Tan; Louis Yi Ann Chai; Shirin Kalimuddin; Shirley Seah Gek Kheng; Siew-Yee Thien; Barnaby Edward Young; David Lye; Brendon John Hanson; Cheng-I Wang; Laurent Renia; Lisa F. P. Ng. 2020. "Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients." Nature Communications 11, no. 1: 1-7.
O'nyong-nyong virus (ONNV) is an arthritogenic alphavirus that caused two large epidemics in 1959 and 1996, affecting millions of people in Africa. More recently, sero-surveillance of healthy blood donors conducted in 2019 revealed high rates of unreported ONNV infection in Uganda. Due to similar clinical symptoms with other endemic mosquito-borne pathogens in the region, including chikungunya virus, dengue virus and malaria, ONNV infections are often un- or misdiagnosed. Elucidating the immunopathogenic factors of this re-emerging arbovirus is critical with the expanding geographic distribution of competent vectors. This study reports the establishment of an immune competent C57BL6/J mouse model to mechanistically characterize ONNV infection and assess potential treatment efficacy. This mouse model successfully recapitulated arthralgia and viremia profiles seen in ONNV patients. Furthermore, longitudinal in-vivo PET imaging with [18F]FB-IL-2 (CD25+CD4+ binding probe) and histopathological assessment in this model demonstrated the pathogenic role of CD4+ T cells in driving joint pathology. Concordantly, in vivo CD4+ T cell depletion, or suppression with fingolimod, an FDA-approved immunomodulating drug, abrogated CD4+ T cell-mediated disease. This study demonstrates the importance of this immune competent ONNV model for future studies on factors influencing disease pathogenesis, which could shape the discovery of novel therapeutic strategies for arthritogenic alphaviruses.
Yi-Hao Chan; Teck-Hui Teo; Anthony Torres-Ruesta; Siddesh V. Hartimath; Rhonda Sin-Ling Chee; Shivashankar Khanapur; Fui Fong Yong; Boominathan Ramasamy; Peter Cheng; Ravisankar Rajarethinam; Edward Robins; Julian L. Goggi; Fok-Moon Lum; Guillaume Carissimo; Laurent Rénia; Lisa F. P. Ng. Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection. Frontiers in Immunology 2020, 11, 1 .
AMA StyleYi-Hao Chan, Teck-Hui Teo, Anthony Torres-Ruesta, Siddesh V. Hartimath, Rhonda Sin-Ling Chee, Shivashankar Khanapur, Fui Fong Yong, Boominathan Ramasamy, Peter Cheng, Ravisankar Rajarethinam, Edward Robins, Julian L. Goggi, Fok-Moon Lum, Guillaume Carissimo, Laurent Rénia, Lisa F. P. Ng. Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection. Frontiers in Immunology. 2020; 11 ():1.
Chicago/Turabian StyleYi-Hao Chan; Teck-Hui Teo; Anthony Torres-Ruesta; Siddesh V. Hartimath; Rhonda Sin-Ling Chee; Shivashankar Khanapur; Fui Fong Yong; Boominathan Ramasamy; Peter Cheng; Ravisankar Rajarethinam; Edward Robins; Julian L. Goggi; Fok-Moon Lum; Guillaume Carissimo; Laurent Rénia; Lisa F. P. Ng. 2020. "Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection." Frontiers in Immunology 11, no. : 1.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
Matthew Zirui Tay; Chek Meng Poh; Laurent Rénia; Paul A. Macary; Lisa F. P. Ng. The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology 2020, 20, 363 -374.
AMA StyleMatthew Zirui Tay, Chek Meng Poh, Laurent Rénia, Paul A. Macary, Lisa F. P. Ng. The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology. 2020; 20 (6):363-374.
Chicago/Turabian StyleMatthew Zirui Tay; Chek Meng Poh; Laurent Rénia; Paul A. Macary; Lisa F. P. Ng. 2020. "The trinity of COVID-19: immunity, inflammation and intervention." Nature Reviews Immunology 20, no. 6: 363-374.
Since December 2019, the novel coronavirus, SARS-CoV-2, has garnered global attention due to its rapid transmission, which has infected more than two million people worldwide. Early detection of SARS-CoV-2 is one of the crucial interventions to control virus spread and dissemination. Molecular assays have been the gold standard to directly detect for the presence of viral genetic material in infected individuals. However, insufficient viral RNA at the point of detection may lead to false negative results. As such, it is important to also employ immune-based assays to determine one's exposure to SARS-CoV-2, as well as to assist in the surveillance of individuals with prior exposure to SARS-CoV-2. Within a span of 4 months, extensive studies have been done to develop serological systems to characterize the antibody profiles, as well as to identify and generate potentially neutralizing antibodies during SARS-CoV-2 infection. The vast diversity of novel findings has added value to coronavirus research, and a strategic consolidation is crucial to encompass the latest advances and developments. This review aims to provide a concise yet extensive collation of current immunoassays for SARS-CoV-2, while discussing the strengths, limitations and applications of antibody detection in SARS-CoV-2 research and control.
Cheryl Yi-Pin Lee; Raymond T. P. Lin; Laurent Renia; Lisa F. P. Ng. Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control. Frontiers in Immunology 2020, 11, 879 .
AMA StyleCheryl Yi-Pin Lee, Raymond T. P. Lin, Laurent Renia, Lisa F. P. Ng. Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control. Frontiers in Immunology. 2020; 11 ():879.
Chicago/Turabian StyleCheryl Yi-Pin Lee; Raymond T. P. Lin; Laurent Renia; Lisa F. P. Ng. 2020. "Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control." Frontiers in Immunology 11, no. : 879.
The ongoing SARS-CoV-2 pandemic demands rapid identification of immunogenic targets for the design of efficient vaccines and serological detection tools. In this report, using pools of overlapping linear peptides and functional assays, we present two immunodominant regions on the spike glycoprotein that were highly recognized by neutralizing antibodies in the sera of COVID-19 convalescent patients. One is highly specific to SARS-CoV-2, and the other is a potential pan-coronavirus target.
Chek Meng Poh; Guillaume Carissimo; Bei Wang; Siti Naqiah Amrun; Cheryl Yi-Pin Lee; Rhonda Sin-Ling Chee; Nicholas Kim-Wah Yeo; Wen-Hsin Lee; Yee-Sin Leo; Mark I-Cheng Chen; Seow-Yen Tan; Louis Yi Ann Chai; Shirin Kalimuddin; Siew-Yee Thien; Barnaby Edward Young; David C. Lye; Cheng-I Wang; Laurent Renia; Lisa F.P. Ng. Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein. 2020, 1 .
AMA StyleChek Meng Poh, Guillaume Carissimo, Bei Wang, Siti Naqiah Amrun, Cheryl Yi-Pin Lee, Rhonda Sin-Ling Chee, Nicholas Kim-Wah Yeo, Wen-Hsin Lee, Yee-Sin Leo, Mark I-Cheng Chen, Seow-Yen Tan, Louis Yi Ann Chai, Shirin Kalimuddin, Siew-Yee Thien, Barnaby Edward Young, David C. Lye, Cheng-I Wang, Laurent Renia, Lisa F.P. Ng. Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein. . 2020; ():1.
Chicago/Turabian StyleChek Meng Poh; Guillaume Carissimo; Bei Wang; Siti Naqiah Amrun; Cheryl Yi-Pin Lee; Rhonda Sin-Ling Chee; Nicholas Kim-Wah Yeo; Wen-Hsin Lee; Yee-Sin Leo; Mark I-Cheng Chen; Seow-Yen Tan; Louis Yi Ann Chai; Shirin Kalimuddin; Siew-Yee Thien; Barnaby Edward Young; David C. Lye; Cheng-I Wang; Laurent Renia; Lisa F.P. Ng. 2020. "Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein." , no. : 1.