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"Yee, Jim"
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Evolution of antibody immunity to SARS-CoV-2
2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models
1
,
2
. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
In a cohort of 87 individuals with COVID-19, the memory B cell response at 6.2 months after the onset of disease evolves in a manner that is consistent with the persistence of SARS-CoV-2 antigen.
Journal Article
Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection
by
Hatziioannou, Theodora
,
Schaefer-Babajew, Dennis
,
Muecksch, Frauke
in
13/1
,
13/31
,
631/250/2152/2153/1291
2021
More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies
1
,
2
. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines
3
,
4
. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals
2
,
5
–
8
. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern
4
,
9
. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.
Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.
Journal Article
Towards a feature-based L2 pronunciation teaching approach: variations in Hong Kong English and ELF intelligibility
2025
Over the past decades, there has been a significant paradigm shift in L2 pronunciation teaching research, moving away from a native-speaker ideology towards a focus on intelligibility in international communication. ELF intelligibility studies have highlighted pronunciation features crucial for effective international communication. Using Hong Kong English (HKE) as a case of exemplification, this paper illustrates the development of a feature-based, intelligibility-oriented framework for L2 pronunciation teaching by (1) identifying variations in pronunciation features within a local variety and (2) prioritising features based on ELF intelligibility findings and their prominence. The study drew upon recorded interactions of HKE learners/speakers with different English proficiency/education levels (secondary/university students, professionals) (n = 120; 240 min), who engaged in a group discussion task. Focusing on segmental features, our analysis categorised key HKE features (individual consonants, initial/final consonant clusters, monophthongs/diphthongs) and arranged them based on their frequency of occurrences. Many of them are either less crucial for intelligibility according to the literature or less prominent on the HKE pronunciation continuum. The paper delineates HKE features deemed ‘more’ and ‘less’ important for intelligibility and those that should be the pedagogical focus. It concludes by discussing the application and advantages of an ELF intelligibility-oriented approach in contemporary L2 pronunciation teaching.
Journal Article
Contexts, Problems and Solutions in International Communication : Insights for Teaching English as a Lingua Franca
The globalisation of English in recent decades has focused scholarly attention on the use of English as a lingua franca (ELF) where second language English speakers are the overwhelming majority. This emerging field of research has significant implications for English language teaching (ELT) because it reveals the real-life use of English in international communication. Against this background, this study reports on the first-hand experiences of a wide range of English users in Hong Kong through interviews specifically focused on language use contexts, problems and solutions. The findings suggest that although the daily use of English by the interviewed English speakers tended to be context-specific and perhaps individualised according to its occupational nature, many of those interviewed reported that they had encountered similar problems with international communication, including accent variations, telephoning and cultural differences. It was also found that the participants altered their language use when communicating with English speakers with different language and cultural backgrounds and in different situations. This study highlights some important observations and recommendations based on the challenges and the solutions suggested by the people interviewed, with wider implications for the choice of appropriate ELT goals and approaches for contemporary English language education.
Journal Article
Rapid, robust, and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals
2021
Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.
Journal Article
Examining authenticity from an ELF perspective: the development of listening test papers in Hong Kong (1986–2018)
2021
The present study examined the degree of situational and interactional authenticity in Hong Kong’s listening examination papers throughout the history of colonisation and globalisation (1986–2018) with reference to world Englishes and particularly English as a lingua franca (ELF) research. By means of a detailed content analysis, the evaluation of situational authenticity was based on the context of language use (e.g., speech event type, nature of interaction, identity and accent of interlocutor) in the audio samples, while the evaluation of interactional authenticity centred on the speaker’s use of communicative strategies. Our findings suggest that the speech samples generally reflected the changing situations of language use over time by increasingly adopting dialogue (rather than monologue) and locally/globally relevant language use contexts, but only included native-speaker and (from 2012) Hong Kong English accents as speech models. Despite the lack of non-standardness and speakers of different cultures in the speech samples, there were numerous instances of explicitness strategies relevant to ELF interactions throughout the sample, probably owing to the intent of the listening examination to highlight key information for the candidates. The paper concludes by discussing the implications of these trends in listening paper design for the future development of English language teaching from an ELF perspective.
Journal Article
The Predictive Value of sFlt-1/PlGF Ratio for Postpartum Preeclampsia
by
Zhao, Zhen
,
Grossman, Tracy
,
Li, Yaxin
in
Non-pharmacological intervention
,
Placenta growth factor
,
Postpartum
2024
Abstract
Background
Preeclampsia (PE) is a leading cause of maternal mortality, affecting 5% to 8% of pregnancies worldwide. Postpartum PE typically develops within the first 48 hours and can occur up to 6 weeks after childbirth and requires immediate clinical management. However, overdiagnosis may lead to unnecessary hospital admissions and overuse of medical resources. The ratio of soluble fms like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) has been evaluated as a tool to predict PE, but its utility in the postpartum setting is yet to be established.
Methods
In this study, we conducted a non-interventional, prospective study at NewYork-Presbysterian-Weill Cornell Hospital, measuring serum sFlt-1 and PlGF levels using Elecsys® and cobas e411 analyzer. The primary aim was to determine the predictive accuracy of the sFlt-1/PlGF ratio in postpartum PE, focusing on its sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) using a cutoff 38, as established in the PROGNOSIS study.
Results
Among 47 participants, 9 (19.1%) developed postpartum PE. The sFlt-1/PlGF ratio was significantly higher for the women who developed PE (55.9, IQR, 48.6-196.2) than for women without PE (19.9, IQR, 5.8-29.1). There was no significant difference in age, first-trimester body-mass index (BMI), gestational week of delivery, smoking status and nulliparous between PE and non-PE groups. Moreover, the sFlt-1/PlGF ratio at 38 cutoff point had a sensitivity of 77.8% (95% CI, 45.0-93.7) and a specificity of 81.6% (95% CI, 66.6-90.8), with a PPV of 50.0% (95% CI, 33.9-66.1). Notably, it demonstrated a high NPV of 93.9% (95% CI, 80.4-98.3).
Conclusion
Our findings suggest that the sFlt-1/PlGF ratio may be used as a predictor of postpartum PE, highlighting its significance in managing postpartum PE.
Journal Article
Association of Age With SARS-CoV-2 Antibody Response
2021
Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults.
To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses.
This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years.
SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years).
Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = -0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443 [188-851] RFU). In the subset cohort aged 1 to 24 years, IgG, TAb, SNAb and avidity were negatively correlated with age (eg, IgG: r = -0.51; P < .001). Children exhibited higher median (IQR) IgG levels, TAb levels, and SNAb activity compared with adolescents (eg, IgG levels: 473 [233-656] RFU vs 191 [82-349] RFU; P < .001) and young adults (eg, IgG levels: 473 [233-656] RFU vs 85 [38-150] RFU; P < .001). Adolescents also exhibited higher median (IQR) TAb levels, IgG levels, and SNAb activity than young adults (eg, TAb levels: 961 [290-2074] RFU vs 370 [125-697]; P = .006). In addition, children had higher antibody binding avidity compared with young adults, but the difference was not significant.
The results of this study suggest that SARS-CoV-2 viral specific antibody response profiles are distinct in different age groups. Age-targeted strategies for disease screening and management as well as vaccine development may be warranted.
Journal Article
Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study
by
Yang, He S.
,
Zhao, Zhen
,
Kim, Robert J.
in
Internal Medicine
,
Medicine
,
Medicine & Public Health
2024
Background
Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results.
Objective
To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety.
Design
Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control.
Participants
Consecutive emergency department (ED) patients with at least one cTn test resulted.
Intervention
Multifaceted
hs-cTn intervention bundle,
including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection.
Main Measures
Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences.
Key Results
The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45–50,
P
< 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50–51,
P
< 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89–1.1,
P
= 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44–2.9,
P
= 0.81).
Conclusions
Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.
Journal Article
Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study
2024
Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results.
To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety.
Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control.
Consecutive emergency department (ED) patients with at least one cTn test resulted.
Multifaceted hs-cTn intervention bundle, including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection.
Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences.
The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45-50, P < 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50-51, P < 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89-1.1, P = 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44-2.9, P = 0.81).
Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.
Journal Article