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To describe maternal and umbilical cord blood anti-spike immunoglobulin (Ig)G levels at delivery with coronavirus disease 2019 (COVID-19) vaccination before and during pregnancy and to assess the association of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a vaccine booster dose with anti-spike maternal and umbilical cord IgG levels.We conducted a retrospective cohort study of women with self-reported COVID-19 vaccination (Pfizer-BioNTech, Moderna, or JohnsonJohnson/Janssen), including a booster dose, during or before pregnancy, who delivered at 34 weeks of gestation or more. Maternal and umbilical cord blood samples at delivery were analyzed for semi-quantitative anti-spike IgG. We examined the association between timing of maternal vaccination and maternal and umbilical cord anti-spike levels using a rank sum test. The relationships between a prior history of SARS-CoV-2 infection and maternal and umbilical cord anti-spike IgG levels, and between a booster dose and maternal and umbilical cord anti-spike levels, were also evaluated using a rank sum test.We included data from 1,359 vaccinated pregnant women, including 20 women who received a booster dose, and 1,362 umbilical cord samples. Maternal anti-spike IgG levels were detectable at delivery regardless of timing of vaccination throughout pregnancy among fully vaccinated women; however, early third-trimester vaccination was associated with the highest anti-spike IgG levels in maternal and umbilical cord blood. Among women with a history of SARS-CoV-2 infection, maternal and cord blood antibody response achieved with vaccination in early pregnancy was comparable with third-trimester vaccination in pregnant women without a history of SARS-CoV-2 infection. A booster dose in the third trimester was associated with maternal anti-spike IgG levels greater than third-trimester vaccination in women with or without a history of SARS-CoV-2 infection.Vaccination against COVID-19 before and throughout pregnancy was associated with detectable maternal anti-spike IgG levels at delivery. A complete vaccination course, prior history of SARS-CoV-2 infection, and a third-trimester booster dose were associated with the highest maternal and umbilical cord antibody levels.

Purpose Comorbidities making up metabolic syndrome (MetS), such as obesity, type 2 diabetes, and chronic cardiovascular disease can lead to increased risk of coronavirus disease-2019 (COVID-19) with a higher morbidity and mortality. SARS-CoV-2 antibodies are higher in severely or critically ill COVID-19 patients, but studies have not focused on levels in convalescent patients with MetS, which this study aimed to assess. Methods This retrospective study focused on adult convalescent outpatients with SARS-CoV-2 positive serology during the COVID-19 pandemic at NewYork Presbyterian/Weill Cornell. Data collected for descriptive and correlative analysis included SARS-COV-2 immunoglobin G (IgG) levels and history of MetS comorbidities from April 17, 2020 to May 20, 2020. Additional data, including SARS-CoV-2 IgG levels, body mass index (BMI), hemoglobin A1c (HbA1c) and lipid levels were collected and analyzed for a second cohort from May 21, 2020 to June 21, 2020. SARS-CoV-2 neutralizing antibodies were measured in a subset of the study cohort. Results SARS-CoV-2 IgG levels were significantly higher in convalescent individuals with MetS comorbidities. When adjusted for age, sex, race, and time duration from symptom onset to testing, increased SARS-CoV-2 IgG levels remained significantly associated with obesity (P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with HbA1c ≥6.5% compared to those with HbA1c Conclusion Postconvalescent SARS-CoV-2 IgG and neutralizing antibodies are elevated in obese patients, and a positive correlation exists between BMI and antibody levels.

For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear.We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons.We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test.Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P.001).The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.

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.

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 subjects: comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19 [RecoVax]; 49 never been diagnosed [NaïveVax]) to 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients.NaïveVax experienced a delay in generating SARS-CoV-2 total antibody levels (TAb) and neutralizing antibodies (SNAb) after the 1st vaccine dose (D1), but a rapid increase in antibody levels was observed after the 2nddose (D2). However, these never reached the robust levels observed in RecoVax. In fact, NaïveVax TAb and SNAb levels decreased 4-weeks post-D2 (p=0.003;p

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 antibodies1,2. 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 vaccines3,4. 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 individuals2,5–8. 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 concern4,9. 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.

Pregnant women were excluded from initial clinical trials for coronavirus disease 2019 (COVID-19) vaccines1,2; thus, the understanding of the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies is limited.3,4

Over 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 excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 COVID-19-convalescent individuals assessed at 1.3, 6.2 and 12 months after infection, 41% of whom also received mRNA vaccines3,4. 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 from 6 to 12 months. Vaccination increases all components of the humoral response, and as expected, results in serum neutralizing activities against variants of concern that are comparable to or greater than neutralizing activity against the original Wuhan Hu-1 achieved by vaccination of naïve individuals2,5-8. 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 variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand dramatically 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.

SummaryPregnant women were excluded from initial clinical trials for COVID-19 vaccines1–2, thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied4–5.

The association of mortality with early humoral response to SARS-CoV-2 infection within the first few days after onset of symptoms (DAOS) has not been thoroughly investigated partly due to a lack of sufficiently sensitive antibody testing methods. Here we report two sensitive and automated testing-on-a-probe (TOP) biosensor assays for SARS-CoV-2 viral specific total antibodies (TAb) and surrogate neutralizing antibodies (SNAb), which are suitable for clinical use. The TOP assays employ an RBD-coated quartz probe using a Cy5-Streptavidin-polysacharide conjugate to improved sensitivity and minimize interference. Disposable cartridge containing pre-dispensed reagents requires no liquid manipulation or fluidics during testing. The TOP-TAb assay exhibited higher sensitivity in the 0-7 DAOS window than a widely used FDA-EUA assay. The rapid and automated TOP-SNAb correlated well with two well-established SARS-CoV-2 virus neutralization tests. The clinical utility of the TOP assays was demonstrated by evaluating early antibody responses in 120 SARS-CoV-2 RT-PCR positive adult hospitalized patients. Higher TAb and SNAb positivity rates and more robust antibody responses at patient’s initial hospital presentation were seen in inpatients who survived COVID-19 than those who died in the hospital. Survival analysis using the Cox Proportional Hazards Model showed that patients who had negative TAb and/or SNAb at initial hospital presentation were at a higher risk of in-hospital mortality. Furthermore, TAb and SNAb levels at presentation were inversely associated with SARS-CoV-2 viral load based on concurrent RT-PCR testing. Overall, the sensitive and automated TAb and SNAb assays allow detection of early SARS-CoV-2 antibodies which associate with mortality., Highlights • Novel testing-on-a probe (TOP) biosensors employ Cy5-Streptavidin-polysaccharide with improved conjugation chemistry. • TOP assays allow rapid, sensitive, specific and fully automated detection of SARS-CoV-2 total (TAb) and surrogate neutralizing antibodies (SNAb). • Simple dip-and-read steps on a clinically available platform. • Disposable cartridge containing pre-dispensed reagents requiring no liquid manipulation or fluidics. • TOP-TAb and TOP-SNAb positivity rate and magnitude at initial hospital presentation are associated with in-hospital mortality.

BACKGROUND: Circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA may represent a more reliable indicator of infection than nasal RNA, but quantitative reverse transcription PCR (RT-qPCR) lacks diagnostic sensitivity for blood samples. METHODS: A CRISPR-augmented RT-PCR assay that sensitively detects SARS-CoV-2 RNA was employed to analyze viral RNA kinetics in longitudinal plasma samples from nonhuman primates (NHPs) after virus exposure; to evaluate the utility of blood SARS-CoV-2 RNA detection for coronavirus disease 2019 (COVID-19) diagnosis in adults cases confirmed by nasal/nasopharyngeal swab RT-PCR results; and to identify suspected COVID-19 cases in pediatric and at-risk adult populations with negative nasal swab RT-qPCR results. All blood samples were analyzed by RT-qPCR to allow direct comparisons. RESULTS: CRISPR-augmented RT-PCR consistently detected SARS-CoV-2 RNA in the plasma of experimentally infected NHPs from 1 to 28 days after infection, and these increases preceded and correlated with rectal swab viral RNA increases. In a patient cohort (n = 159), this blood-based assay demonstrated 91.2% diagnostic sensitivity and 99.2% diagnostic specificity versus a comparator RT-qPCR nasal/nasopharyngeal test, whereas RT-qPCR exhibited 44.1% diagnostic sensitivity and 100% specificity for the same blood samples. This CRISPR-augmented RT-PCR assay also accurately identified patients with COVID-19 using one or more negative nasal swab RT-qPCR results. CONCLUSION: Results of this study indicate that sensitive detection of SARS-CoV-2 RNA in blood by CRISPR-augmented RT-PCR permits accurate COVID-19 diagnosis, and can detect COVID-19 cases with transient or negative nasal swab RT-qPCR results, suggesting that this approach could improve COVID-19 diagnosis and the evaluation of SARS-CoV-2 infection clearance, and predict the severity of infection. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04358211. FUNDING: Department of Defense, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the National Center for Research Resources.

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.

Key Points Question Are the quantity and quality of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) different among children, adolescents, and young adults? Findings In this cross-sectional study evaluating 31 426 SARS-CoV-2 antibody tests performed between April 9 and August 31, 2020, immunoglobin G levels were found to vary in different age groups, despite similar seroprevalence in the pediatric and adult patient populations. SARS-CoV-2 immunoglobin G and total antibody levels, neutralizing activity, and avidity exhibited negative correlations with age in patients aged 1 to 24 years. Meaning This analysis revealed distinct antibody responses in different age groups, suggesting that age-targeted strategies for disease screening and management as well as vaccine development may be warranted., This cross-sectional study investigates the association of age with the quantity and quality of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses., Importance 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. Objective To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses. Design, Setting, and Participants 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. Main Outcomes and Measures 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). Results 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

To study how severity and progression of coronavirus disease (COVID-19) affect cytokine profiles in pregnant women.69 third-trimester, pregnant women were tested for COVID-19 infection and SARS-CoV-2 specific IgM and IgG antibodies. Patients were stratified according to SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) status and serology (IgM and IgG) status. Cytokines G-CSF, HGF, IL-18, IL-1Ra, IL-2Ra, IL-8, and IP-10 were measured via ELISA. Retrospective chart review for COVID-19 symptoms and patient vitals was conducted, and cytokine levels were compared between SARS-CoV-2 positive and negative cohorts, by seronegative and seropositive infection, by time course since onset of infection, and according to NIH defined clinical severity.IL-18, IL-1Ra, and IP-10 increased in the 44 RT-PCR positive pregnant women compared to the 25 RT-PCR negative pregnant controls. Elevated cytokine levels were found in early infections, defined by positive RT-PCR and seronegative status, and higher cytokine levels were also associated with more severe disease. By IgM seroconversion, IL-8 and IP-10 returned to levels seen in uninfected patients, while IL-18 levels remained significantly elevated.Cytokine profiles of third-trimester pregnant women vary with the time course of infection and are correlated with clinical severity.

Background Low initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers dropping to undetectable levels within months after infection have raised concerns about long-term immunity. Both the antibody levels and the avidity of the antibody–antigen interaction should be examined to understand the quality of the antibody response. Methods A testing-on-a-probe “plus” panel (TOP-Plus) was developed to include a newly developed avidity assay built into the previously described SARS-CoV-2 TOP assays that measured total antibody (TAb), surrogate neutralizing antibody (SNAb), IgM, and IgG on a versatile biosensor platform. TAb and SNAb levels were compared with avidity in previously infected individuals at 1.3 and 6.2 months after infection in paired samples from 80 patients with coronavirus disease 2019 (COVID-19). Sera from individuals vaccinated for SARS-CoV-2 were also evaluated for antibody avidity. Results The newly designed avidity assay in this TOP panel correlated well with a reference Bio-Layer Interferometry avidity assay (r = 0.88). The imprecision of the TOP avidity assay was Conclusions This highly precise and versatile TOP-Plus panel with the ability to measure SARS-CoV-2 TAb, SNAb, IgG, and IgM antibody levels and avidity of individual sera on one sensor can become a valuable asset in monitoring not only patients infected with SARS-CoV-2 but also the status of individuals’ COVID-19 vaccination response.

Background Pregnant women and their neonates represent 2 vulnerable populations with an interdependent immune system that are highly susceptible to viral infections. The immune response of pregnant women to severe acute respiratory syndrome coronavirus 2 and the interplay of how the maternal immune response affects the neonatal passive immunity have not been studied systematically. Objective We characterized the serologic response in pregnant women and studied how this serologic response correlates with the maternal clinical presentation and with the rate and level of passive immunity that the neonate received from the mother. Study Design Women who gave birth and who tested positive for immunoglobulin M or immunoglobulin G against severe acute respiratory syndrome coronavirus 2 using semiquantitative detection in a New York City hospital between March 22, 2020, and May 31, 2020, were included in this study. A retrospective chart review of the cases that met the inclusion criteria was conducted to determine the presence of coronavirus disease 2019 symptoms and the use of oxygen support. Serology levels were compared between the symptomatic and asymptomatic patients using a Welch 2 sample t test. Further chart review of the same patient cohort was conducted to identify the dates of self-reported onset of coronavirus disease 2019 symptoms and the timing of the peak immunoglobulin M and immunoglobulin G antibody levels after symptom onset was visualized using local polynomial regression smoothing on log2-scaled serologic values. To study the neonatal serology response, umbilical cord blood samples of the neonates born to the subset of serology positive pregnant women were tested for serologic antibody responses. The maternal antibody levels of serology positive vs the maternal antibody levels of serology negative neonates were compared using the Welch 2 sample t test. The relationship between the quantitative maternal and quantitative neonatal serologic data was studied using a Pearson correlation and linear regression. A multiple linear regression analysis was conducted using maternal symptoms, maternal serology levels, and maternal use of oxygen support to determine the predictors of neonatal immunoglobulin G levels. Results A total of 88 serology positive pregnant women were included in this study. The antibody levels were higher in symptomatic pregnant women than in asymptomatic pregnant women. Serology studies in 34 women with symptom onset data revealed that the maternal immunoglobulin M and immunoglobulin G levels peak around 15 and 30 days after the onset of coronavirus disease 2019 symptoms, respectively. Furthermore, studies of 50 neonates born to this subset of serology positive women showed that passive immunity in the form of immunoglobulin G is conferred in 78% of all neonates. The presence of passive immunity is dependent on the maternal antibody levels, and the levels of neonatal immunoglobulin G correlate with maternal immunoglobulin G levels. The maternal immunoglobulin G levels and maternal use of oxygen support were predictive of the neonatal immunoglobulin G levels. Conclusion We demonstrated that maternal serologies correlate with symptomatic maternal infection, and higher levels of maternal antibodies are associated with passive neonatal immunity. The maternal immunoglobulin G levels and maternal use of oxygen support, a marker of disease severity, predicted the neonatal immunoglobulin G levels. These data will further guide the screening for this uniquely linked population of mothers and their neonates and can aid in developing maternal vaccination strategies.

The study reported in this paper adopted both direct (a large-scale questionnaire survey) and indirect (a verbal-guise test) measures to investigate gender differences in second language (L2) learners’ attitudes towards different English varieties in secondary schools in Hong Kong. The investigation considered various factors affecting students’ attitudes to language including their affective feelings, cultural identity, awareness of language variations, experience of language use, perceived intelligibility of English accents and, more importantly, situational language choices. Consistent with previous studies, the findings suggest that the female learners were more positively oriented towards native speaker (NS) pronunciation and tended to adopt it as their teaching model and learning target; they also had greater confidence than males in their ability to understand British English pronunciation. However, their greater sensitivity to NS standards was found to be limited to high-stakes English-speaking contexts. In contrast, male learners had greater tolerance or acceptance of local pronunciation. This paper concludes by discussing the implications of L2 learners’ gender differences in attitudes for English language education and the design of English language teaching materials and assessments.

This study examined the choice of English pronunciation goals by Hong Kong’s major stakeholders (i.e. professionals, teachers and students) via semi-structured individual/focus group interv...

Highlights • Comprehensive evaluation of 2 SARS-CoV-2 antibody assays with excellent agreement. • Rigorously validated antibody tests are reliable to detect antibody kinetic change. • Three types of seroconversion were observed in hospitalized COVID-19 patients. • Convalescent sera show a wide range of antibody levels. • Current antibody testing is not useful in early screening for COVID-19., Background In the ongoing COVID-19 pandemic, there is an urgent need for comprehensive performance evaluation and clinical utility assessment of serological assays to understand the immune response to SARS-CoV-2. Methods IgM/IgG and total antibodies against SARS-CoV-2 were measured by a cyclic enhanced fluorescence assay (CEFA) and a microsphere immunoassay (MIA), respectively. Independent performance evaluation included imprecision, reproducibility, specificity and cross-reactivity (CEFA n = 320, MIA n = 364). Clinical utility was evaluated by both methods in 87 patients at initial emergency department visit, 28 during subsequent hospitalizations (106 serial samples), and 145 convalescent patients. Totally 916 patients and 994 samples were evaluated. Results Agreement of CEFA and MIA was 90.4%-94.5% (Kappa: 0.81–0.89) in 302 samples. CEFA and MIA detected SARS-CoV-2 antibodies in 26.2% and 26.3%, respectively, of ED patients. Detection rates increased over time reaching 100% after 21 days post-symptom onset. Longitudinal antibody kinetic changes by CEFA and MIA measurements correlated well and exhibited three types of seroconversion. Convalescent sera showed a wide range of antibody levels. Conclusion Rigorously validated CEFA and MIA assays are reliable for detecting antibodies to SARS-CoV-2 and show promising clinical utility when evaluating immune response in hospitalized and convalescent patients, but are not useful for early screening at patient’s initial ED visit.

In conjunction with the government of Singapore’s vision to have efficient and extensive Mass Rapid Transit (MRT) system across Singapore Island, more and more rail tunnels are planned to be constructed in close proximity to sensitive buildings and infrastructures in recent years. This being a particular challenge for major infrastructure works in the urban environment. In contract C937 of Downtown Line Stage 3 (DTL3), twin bored tunnels connect Fort Canning station to Bencoolen Station, under Fort Canning Hill, with the alignment overcrossing the existing North East Line (NEL) rail tunnel, undercrossing North South Line (NSL) and Circle Line (CCL) with clear distance of less than one bored tunnel diameter. This inevitably poses great challenges to tunnelling over and under existing live tunnels without disruption to daily operation of MRT. Further compounding the challenge is the ground condition comprising of Jurong Formation steeply variable sedimentary deposits transitioning into Fort Canning Boulder Bed a colluvial deposit of quartzite boulders in a stiff clay matrix. To successfully negotiate this challenge, requires all involved parties to make contributions in their areas of expertise and work as team together to ensure that the works progress smoothly and as planned. The designer provides an overall approach demonstrating that the work can be safely carried out and provides key parameters for the contractor who carries out the tunnelling with construction control, which in turn is supervised by the supervision engineers ensuring work is carried out safely. The client, who provides the vision in the first place, has overall responsibility for the work providing continuity and ensuring that the component parts of the job are co-ordinated and carried out successfully. In addition, different monitoring levels were also established to reduce the train speed if necessary and also bus bridging service as a contingency measure. This paper summarizes the approach to the tunnelling, key tunnelling parameters during undercrossing of existing live MRT tunnels, instrumentation monitoring as well as measured railway track and structure movements due to proximity tunnelling. It reflects upon the on crucial contributory factors that ensure success within the project and serves as a reference as to how engineering boundaries can be challenged underground.

A major controversy in the fields of World Englishes (WE) and English as a lingua franca (ELF) has been the application of exonormative Inner Circle norms to ELT classrooms in diverse multilingual societies. This article seeks to examine the suitability of adopting a WE and/or an ELF-oriented pedagogical model, as well as the corresponding research findings, in Hong Kong's ELT classroom. More specifically, the study investigated the use of English by the local professionals and, furthermore, evaluated the comparability of Hong Kong's sociolinguistic reality to typical WE and ELF contexts via a structured questionnaire survey and semi-structured interviews.

The study reported in this article examined Hong Kong students' attitudes towards English accents from three interrelated perspectives: (1) their awareness of accents, (2) their perception of accents in relation to the dimensions of status and solidarity, and (3) their choice of accents in various local language-using contexts. By means of the verbal-guise technique, it explored the issue from multiple perspectives by comparing the attitudes among English learners at differing stages of study (i.e., junior secondary, senior secondary, and university students). These participants had different perceptions of English based on their prior knowledge, learning experience, and exposure to English. The findings indicate that the university students perceived the local accent more negatively than their secondary counterparts in the dimensions of both status and solidarity, despite their greater awareness of accents. Nevertheless, all the participants showed fewer reservations about the use of second language English accents in more casual and interactive English-speaking situations. The article concludes by discussing the potential for the design of language awareness tasks in TESOL materials and assessments for secondary school as a crucial step to initiate attitudinal changes.

The present study evaluates the impact of the fine-tuning medium of instruction (MOI) policy in Hong Kong in the early stages of its implementation. It explores the key stakeholders’ perspectives on a school-based policy via a case study, which gathered multiple sources of qualitative data (i.e. focus groups/interviews, open-ended questionnaires, school documents and lesson observations). The findings reveal that the increased amount of English-medium teaching encouraged by the new policy has led to the emergence of numerous controversial pedagogical and practical issues, many of which resemble those also occurring in bilingual education programmes worldwide. The evidence suggests that the school-based MOI policy and practices have only benefited the more capable students but sacrificed the interests and learning needs of less able students. The paper, therefore, highlights the need to inform local teachers and administrators on how to confront these difficulties based on their own experience so as to max...

The present study evaluates the pronunciation target in Hong Kong's ELT education at senior secondary level with reference to the pedagogical proposals of World Englishes (WE) and English as a lingua franca (ELF). It triangulates information from various documents, namely the new ELT curriculum, public examination papers and reports, and three sets of listening and speaking commercial textbooks. The findings suggest that the new curriculum apparently has taken account of the WE and/or ELF perspectives in its design such as (i) promoting communicative competence, (ii) downplaying the importance of NS norms, and (iii) exposing students to more varieties of accent, but seems to be conceptually still guided by native-speaker norms. In practice, one breakthrough in the listening examination is the inclusion of Hong Kong English phonological features in localised tasks. However, the commercial textbooks seem to be lagging behind this development in the curriculum, though textbook writers do seek to include ELF-using contexts in some of the textbook tasks due to Hong Kong's global status. The paper argues that an important step in the move towards a WE/ELF-oriented pronunciation teaching is to recognise the role of English in particular sociolinguistic settings because by embedding the tasks in a simulated authentic language-using context, it is likely that teachers and students will be aware that the speech and pronunciation of non-native speakers are most relevant.

This study seeks to explore the controversial issue of pronunciation modelling in the secondary classroom in association with the medium-of-instruction (MOI) policy in Hong Kong. The investigation centres on two dimensions: (1) students' exposure to English accents throughout their weekly school timetable by means of a data log sheet and (2) the phonological differences between the speech of local subject and English language teachers. The findings suggest that students' main source of English exposure at school is the English pronunciation of both English language and content-area teachers in English-medium lessons, who shared numerous Hong Kong English (HKE) features although in differing proportions. The paper concludes by prioritising the educated HKE vowel and consonant features and promoting an internationally intelligible endonormative model in the globalised world. 本研究旨在探討具爭議的英語發音模式，與香港中學教學語言政策的關係。調查主要涉及兩範疇：（1）從學生填寫的數據記錄表推算他們在每周課堂接觸的英語口音；（2）比較本地學科教師與英語教師在英語語音上的差異。結果顯示，學生在以英語授課的課堂上，接觸的主要是本地英語教師及學科教師的英語發音，當中帶有相同但數量不一的香港英語特點。最後，本研究按優次具列各組受教育的香港英語元音及輔音，從而提倡一種國際互通的本土語言規範模式。

The 2010/2011 academic year marked an important turning point in the development of Hong Kong's medium-of-instruction (MOI) policy as it offered secondary schools greater autonomy in determining their MOI policy. This paper examines the implementation of the new fine-tuning MOI policy in a representative secondary school. It compares its school-based language policy with students' (Years 7, 8 and 10) self-reported data about their actual use of English over a five-day week. At the junior secondary level (Years 7 and 8), the findings indicate a close alignment of policy and practice only in the English-medium subjects, whereas in some other subjects, the proportion of use of English could not be clearly determined due largely to the complexity of the school-based policy and teachers' flexibility and autonomy in practice. Furthermore, it is revealed that a highly sophisticated language-using situation at the senior secondary level (Year 10) poses potential challenges for the transition of students ...

One of the decisive factors in Schneider's innovative Dynamic Model for the transition from phase 3 (nativisation) to phase 4 (endonormative stabilisation) for the case of Hong Kong English (HKE) is the parameter of local acceptance. This paper examines the attitudes of young professionals towards native vis-a-vis non-native English accents in a number of English-speaking contexts in Hong Kong by means of the verbal-guise technique, focus group discussions and a written task. The findings suggest that many of the participants have the ability to distinguish native speakers’ from non-native speakers’ accents. Although an Anglophone-centric attitude is still found to be prominent in high-stakes English-using situations, there seems to be a tendency that the less formal and more interactive the communication context, the fewer reservations the participants have about non-native accents. The correlation analysis indicates a lack of association between the participants’ perceived intelligibility and their preferred accents in nearly all of the designated contexts for the case of HKE and, thus, the paper offers explanations based on the tension between English pronunciation as economic capital and identity carrier in local people's perception. It concludes by discussing the implications of this contextual variation in pronunciation acceptance for future attitudinal studies.