Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents.

BACKGROUND: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents. METHODS: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. RESULTS: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. CONCLUSION: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

Humoral and Cellular Immunogenicity of 3 Doses of BNT162b2 in Children With Kidney Diseases.

Introduction: Patients with severe kidney diseases are at risk of complications from COVID-19; however, little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated 3-dose primary series of COVID-19 vaccination among 59 pediatric patients with chronic kidney disease (CKD) (mean age 12.9 years; 30 male) with or without immunosuppression, dialysis, or kidney transplant. Dosage was 0.1 ml BNT162b2 to those aged 5 to 11 years, and 0.3 ml BNT162b2 to those aged 11 to 18 years. Results: Three doses of either vaccine type elicited significant antibody responses that included spike receptor-binding domain (S-RBD) IgG (90.5%-93.8% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6%-79.3%). There were notable T cell responses. Weaker neutralization responses were observed among those on immunosuppression, especially those receiving higher number of immunosuppressants or on mycophenolate mofetil. Neutralization was reduced against Omicron BA.1 compared to wild type (WT, i.e., ancestral) (post-dose 3 sVNT% level; 82.7% vs. 27.4%; P < 0.0001). However, the T cell response against Omicron BA.1 was preserved, which likely confers protection against severe COVID-19. Infected patients exhibited hybrid immunity after vaccination, as evidenced by the higher Omicron BA.1 neutralization response among these infected patients who received 2 doses compared with those who were uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusion: An accelerated 3-dose primary series with BNT162b2 is immunogenic and safe in young children and adolescents with kidney diseases.

Altered neutrophil-to-lymphocyte ratio in patients with non-affective first episode psychosis and its relationship with symptom severity and cognitive impairment.

Signatures of immune dysregulation as clinical biomarker for psychosis have remained unclear. We aimed to compare the Neutrophil-to-lymphocyte ratio (NLR) of patients with acute non-affective first-episode psychosis (FEP) with healthy controls after accounting for emotional states. We also explored the associations of NLR with symptom severity, onset profile and cognitive functions. The NLR was enumerated from complete blood count taken within a week of assessment. All FEP patients were rated on the Positive and Negative Syndrome Scale (PANSS) and the Clinician Global Impression-Severity (CGI-S) with verbal memory and executive functions assessed with the Cambridge Neuropsychological Test Automated Battery. Prevailing emotional state was measured with Beck Depression Inventory-II and Beck Anxiety Inventory. Out of seventy-nine consecutive FEP patients presenting to the study site, twenty-seven subjects were eligible and recruited. Twenty-seven age-/sex-matched controls were recruited. FEP patients had an NLR of 1.886 over the controls after accounting for scores on emotional states. The NLR of FEP patients was positively associated with CGI-S scores, PANSS positive symptom, disorganization and excitation scores. There was no significant correlation between NLR with the duration of untreated psychosis and cognitive performances. These findings support using NLR as a clinical biomarker in FEP, purporting further prospective study to measure NLR changes in the course of treatment.

Hesitancy, reactogenicity and immunogenicity of the mRNA and whole-virus inactivated Covid-19 vaccines in pediatric neuromuscular diseases.

The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two widely used COVID-19 vaccines that confer immune protection to healthy individuals. However, hesitancy toward COVID-19 vaccination appeared to be common for patients with neuromuscular diseases (NMDs) due to the paucity of data on the safety and efficacy in this high-risk patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for NMDs and assessed the reactogenicity and immunogenicity of these two vaccines. Patients aged 8-18 years with no cognitive delay were invited to complete surveys in January and April 2022. Patients aged 2-21 years were enrolled for COVID-19 vaccination between June 2021 and April 2022, and they recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before and within 49 days after vaccination to measure serological antibody responses compared to healthy children and adolescents. Forty-one patients completed vaccine hesitancy surveys for both timepoints, while 22 joined the reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81-75.1, p = .010). Pain at the injection site, fatigue, and myalgia were the commonest ARs. Most ARs were mild (75.5%, n = 71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of either vaccine, similar to 280 healthy counterparts. There was lower neutralization against the Omicron BA.1 variant. BNT162b2 and CoronaVac were safe and immunogenic for patients with NMDs, even in those on low-dose corticosteroids.

Immunogenicity against wild-type and Omicron SARS-CoV-2 after a third dose of inactivated COVID-19 vaccine in healthy adolescents.

Introduction: Two doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data. Methods: With an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored. Results: A homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified. Discussion: The primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity.

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents.

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity.

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents.

We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N = 116) and CoronaVac (CC, N = 123) versus adults after 2 doses of the same vaccine (BB, N = 147; CC, N = 141) but not in adolescents after 1-dose BNT162b2 (B, N = 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents.

Survey data on the attitudes of adolescents in Hong Kong towards the COVID-19 vaccination.

To our best knowledge, this article presents a novel data set on Hong Kong's adolescents' attitude towards the COVID-19 vaccination, excluding their parental opinions. This research used a cross-sectional questionnaire survey, which collects data from the population at a single point in time. Our questionnaire was designed in both English and Chinese for the adolescents' convenience, using a self-designed, online questionnaire website, which was sent to 30 secondary schools across Hong Kong at the beginning of June 2021, to be completed by 31st June 2021. This gathered a total of 2609 surveys, excluding those which did not fit into the criteria. As the data has identified factors that affect vaccine hesitancy, government authorities can use the data to choose effective ways to promote the COVID-19 vaccination and to educate the general population about the benefits of receiving it.

The Effects of Repetitive Transcranial Magnetic Stimulation Antidepressant Response on Cold Cognition: A Single-Arm Prospective Longitudinal Study.

PURPOSE: The cognitive neuropsychological model of depression suggests that the cognitive deficits observed in depressed subjects are the result of attenuated top-down cognitive control resulting in increased bottom-up emotional processing. Remediation of cognitive impairments in cold cognition has been proposed as a valuable treatment for depression. The study aimed to examine the effects of clinical response to repetitive transcranial magnetic stimulation (rTMS) on cold cognition over the course of 8 weeks in medication-refractory depressed subjects. MATERIALS AND METHODS: Twenty-two medication-refractory depressed subjects received twenty sessions of high-frequency rTMS targeting the left dorsolateral prefrontal cortex, one of the key nodes of the cognitive control network. Cold cognition and antidepressant treatment response were monitored at baseline, week 2, 4 and 8. Clinical response was defined as ≥50% reduction in Montgomery-Åsberg Depression Rating Scale score at week 8. Longitudinal changes in cold cognition were modeled using (generalized) linear mixed models. It was hypothesized that the excitatory effects of rTMS would improve cognition in the domains of executive function, memory, and attention. Additionally, responders were expected to show larger cognitive improvements than nonresponders. RESULTS: A decrease in median latency was observed on a task that measured executive function, irrespective of treatment response status. Further, responders showed significantly larger improvements in A-Prime (the ability to detect target sequences) on a sustained attention task. Post hoc analysis indicated higher levels of rumination in non-responders. CONCLUSION: Our findings suggest that distractions during tasks with low perceptual complexity affected nonresponders disproportionately possibly due to higher rumination levels. Overall, cold cognition in medication-resistant depressed subjects was minimally affected by rTMS, substantiating the safety of rTMS treatment. LIMITATIONS: The sample size was small, and the study did not include a control group.

Physical measurements of Chinese children in Hong Kong-A pilot study in preschools and kindergartens.

Normal growth is essential to a developing child. Most syndromes with dysmorphic features demonstrate recognizable patterns of disproportionate growth, thus physical measurements are an important aspect of patient evaluation. Delineating the abnormal growth pattern depends greatly on the accuracy of the normal range. However, the currently available reference data are restricted in terms of ethnicity and geographical location, hence may not be applicable to all children worldwide. In Hong Kong, reference data are limited only to the neonatal period. The aim of our pilot study is to obtain a set of region-specific physical measurement data for Chinese children in Hong Kong. Two to six year olds were recruited from preschools and kindergartens in different regions of Hong Kong. Twenty-six parameters found in previous publications were measured with minor modifications. Three medical personnel trained by a clinical geneticist obtained these parameters. Satisfactory inter-rater reliability was achieved in a training cohort prior to the study. Raw measurement data collected were normalized and fitted into growth curves modeled by LMS method. We recruited 448 children (55.6% male) between 2 and 6 years old from five preschools and kindergartens. Growth curves with essential percentile lines were drawn. Significant differences were identified in 11 parameters when compared with Caucasian children, including canthal distances and facial width/height. Our current pilot study presents the first local- and ethnicity-specific data on physical measurements of 2-6 year olds. Our findings highlighted the substantial ethnic variability in physical measurements and the need for an ethnic-specific reference for Chinese children. © 2016 Wiley Periodicals, Inc.

Human oropharynx as natural reservoir of Streptobacillus hongkongensis.

Recently, we reported the isolation of Streptobacillus hongkongensis sp. nov. from patients with quinsy or septic arthritis. In this study, we developed a PCR sequencing test after sulfamethoxazole/trimethoprim and nalidixic acid enrichment for detection of S. hongkongensis. During a three-month study period, among the throat swabs from 132 patients with acute pharyngitis and 264 controls, PCR and DNA sequencing confirmed that S. hongkongensis and S. hongkongensis-like bacteria were detected in 16 patients and 29 control samples, respectively. Among these 45 positive samples, five different sequence variants were detected. Phylogenetic analysis based on the 16S rRNA gene showed that sequence variant 1 was clustered with S. hongkongensis HKU33(T)/HKU34 with high bootstrap support; while the other four sequence variants formed another distinct cluster. When compared with the 16S rRNA gene of S. hongkongensis HKU33(T), the five sequence variants possessed 97.5-100% sequence identities. Among sequence variants 2-5, their sequences showed ≥99.5% nucleotide identities to each other. Forty-two individuals (93.3%) only harbored one sequence variant. We showed that the human oropharynx is a reservoir of S. hongkongensis, but the bacterium is not associated with acute pharyngitis. Another undescribed novel Streptobacillus species is probably also residing in the human oropharynx.

A multidimensional risk factor model for suicide attempts in later life.

BACKGROUND: Elderly suicide is a public health problem worldwide, and the risk factors are multidimensional. Chronic mental health problems, personality traits, stressful life events, comorbid medical conditions, social isolation, unemployment, and poverty are associated with higher risk for suicide in later life. There was a relative paucity of data on the neurobiological markers of elderly suicide. OBJECTIVE: This study examines the conjoint roles of cerebrovascular risk factors (CVRFs) and other established biopsychosocial risk factors in older adults who had made a recent suicide attempt. DESIGN: A cross-sectional, case-controlled study. SETTING: A tertiary care setting in a public sector and a community setting. SUBJECTS AND METHODS: Cases (N=77) were nondemented Chinese adults aged ≥65 years, enrolled in a regional psychogeriatric service following a suicide attempt; comparison subjects (N=99) were community-dwelling nondemented older adults with no lifetime history of suicide. Measures of sociodemographic profile, life events, suicidal behavior, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I psychopathology, personality traits, functional status, physical health, CVRFs, and executive cognitive functions were administered. RESULTS: WEIGHTED SUM OF CVRF SCORE WAS SIGNIFICANTLY HIGHER IN OLDER WOMEN WHO HAD MADE A RECENT SUICIDE ATTEMPT (MEAN: 10.56; standard deviation [SD]: 5.46) than comparison subjects (mean: 7.24; SD: 4.04) (t=3.52, P=0.001; df=99). Logistic regression showed that CVRF score (Exp[B]: 1.289, P=0.033), DSM-IV depressive disorders (current) (Exp[B]: 348, P<0.001), number of life events in the past 12 weeks (Exp[B]: 10.4; P<0.001), and being married (Exp[B]: 12.2, P<0.048) significantly increased odds for suicide attempt status in older women (Nagelkerke R (2): 0.844). Association of CVRF score and suicide attempt status was not observed in older men for whom number of life events in the past 12 weeks (Exp[B]: 9.164; P<0.001), higher neuroticism (Exp[B]: 1.028; P=0.048), and impaired performance on a Modified Card Sorting Test (Exp[B]: 0.646; P=0.032) significantly increased odds for suicide attempt status in a logistic regression model (Nagelkerke R (2): 0.611). CONCLUSION: Risk factors for cerebrovascular diseases may be associated with higher risk for attempted suicide in older women, but not in older men. Older men and women have distinct risk factor profiles that may inform targeted intervention and prevention strategies.

Late-onset Diogenes syndrome in Chinese - an elderly case series in Hong Kong.

We review a consecutive case series of elders presenting to a regional psychogeriatric service in Hong Kong in 1996-2001. Eighteen elders (aged 65 and over) fulfilled the classical symptoms of Diogenes syndrome (extreme squalor, neglected physical state, unhygienic condition & social isolation with or without hoarding). A diverse clinical and socio-demographic profile was observed. Most of our clients suffered from different stages of dementia. Other diagnoses such as schizophrenia and alcohol abuse were diagnosed in this cohort as comorbid or independent conditions. Neither psychopathology nor social situations could adequately account for the initiation and perpetuation of Diogenes syndrome in some cases. The plausible psychological etiologies are discussed in the context of existential values in Chinese culture and changes in traditional family dynamics as the society modernizes.

Correlational study of the Chinese version of the executive interview (C-EXIT25) to other cognitive measures in a psychogeriatric population in Hong Kong Chinese.

OBJECTIVES: This study is designed to pilot test the feasibility and correlational properties of the adapted Chinese version of Executive Interview (C-EXIT25) to other cognitive measures in a psychogeriatric population in Hong Kong Chinese. METHOD: Eighty-five community dwelling elders from different levels of residential care facilities were assessed with C-EXIT25, Cantonese version of Mini-Mental State Examination (C-MMSE), Chinese version of Mattis Dementia Rating Scale (CDRS) and Nelson's Modified Card Sorting Test (MCST). RESULTS: The C-EXIT25 has high internal consistency (Cronbach's alpha = 0.7995) and inter-rater reliability (r = 0.91). The C-EXIT25 has superior correlational property to performance indices of MCST than the C-MMSE and CDRS, after adjusting for age, gender and educational level. It also discriminates among subjects at different stages on Clinical Dementia Rating. CONCLUSIONS: The C-EXIT25 is a potentially feasible and valid bedside tool for assessment of executive cognitive functions in the psychogeriatric population in Hong Kong Chinese.

Elderly suicide and the 2003 SARS epidemic in Hong Kong.

BACKGROUND: Hong Kong was struck by the community outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003. In the same year, the elderly suicide rate in Hong Kong showed a sharp upturn from a previous downward trend. METHODS: Secondary analyses using Poisson Regression Models on the suicide statistics from the Census and Statistics Department of the Hong Kong Government were performed. RESULTS: In a Poisson Regression Model on the annual suicide rates in elders aged 65 and over in years 1986-2003, 2002 served as the reference year. Suicide rates in 1986-1997 were significantly higher than the reference year, with an Incident Rate Ratio (IRR) of 1.34 to 1.61. However, rates in 1998-2001 did not differ from the reference year significantly, representing stabilization of suicide rates for 4 years after 1997. The elderly suicide rate increased to 37.46/100,000 in 2003, with an IRR of 1.32 (p=0.0019) relative to 2002. Such trend is preserved when female elderly suicide rates in 1993-2003 were analyzed, while suicide rates in elderly men and younger age groups did not follow this pattern. DISCUSSIONS: Mechanistic factors such as breakdown of social network and limited access to health care might account for the findings. These factors could have potentiated biopsychosocial risk factors for suicide at individual levels, particularly in elderly. Female elders, by way of their previous readiness to utilize social and health services instituted in the past decade, are thus more susceptible to the effects of temporary suspension of these services during the SARS epidemic. CONCLUSIONS: The SARS epidemic was associated with increased risk of completed suicide in female elders, but not in male elders or the population under 65 years of age.