Impact of host genetic polymorphisms on response to inactivated influenza vaccine in children.

In randomized controlled trials of influenza vaccination, 550 children received trivalent-inactivated influenza vaccine, permitting us to explore relationship between vaccine response and host single nucleotide polymorphisms (SNPs) in 23 candidate genes with adjustment of multiple testing. For host SNPs in TLR7-1817G/T (rs5741880), genotype GT was associated with lower odds (OR: 0.22, 95% CI: 0.09, 0.53) of have post-vaccination hemagglutination-inhibiting (HAI) titers ≥40, compared with genotype GG and TT combined under the over-dominant model. For host SNPs in TLR8-129G/C (rs3764879), genotype GT was associated with lower odds (OR: 0.47; 95% CI: 0.28, 0.80) of have post vaccination HAI titers ≥40 compared with genotype GG and AA combined under the over-dominant model. Our results could contribute to the development of better vaccines that may offer improved protection to all recipients.

Electronic Structure and Photoactivity of Organoarsenic Hybrid Polyoxometalates.

Organofunctionalization of polyoxometalates (POMs) allows the preparation of hybrid molecular systems with tunable electronic properties. Currently, there are only a handful of approaches that allow for the fine-tuning of POM frontier molecular orbitals in a predictable manner. Herein, we demonstrate a new functionalization method for the Wells-Dawson polyoxotungstate [P2W18O62]6- using arylarsonic acids which enables modulation of the redox and photochemical properties. Arylarsonic groups facilitate orbital mixing between the organic and inorganic moieties, and the nature of the organic substituents significantly impacts the redox potentials of the POM core. The photochemical response of the hybrid POMs correlates with their computed and experimentally estimated lowest unoccupied molecular orbital energies, and the arylarsonic hybrids are found to exhibit increased visible light photosensitivity comparable with that of arylphosphonic analogues. Arylarsonic hybridization offers a route to stable and tunable organic-inorganic hybrid systems for a range of redox and photochemical applications.

Effectiveness of BNT162b2 and CoronaVac COVID-19 vaccination against asymptomatic and symptomatic infection of SARS-CoV-2 omicron BA.2 in Hong Kong: a prospective cohort study.

BACKGROUND: COVID-19 vaccines provide protection against symptomatic infection that might require medical attention and against severe outcomes; however, there is a paucity of evidence regarding the effectiveness of the BNT162b2 and CoronaVac vaccines and their booster regimens against asymptomatic or mild omicron infections in the community. We aimed to measure the effectiveness of BNT162b2 and CoronaVac vaccines against asymptomatic and symptomatic SARS-CoV-2 omicron infections, during a period of omicron BA.2 predominance in Hong Kong. METHODS: In this prospective cohort study in a population that was generally infection-naive before the large omicron BA.2 wave between January and late May, 2022, we established a public health surveillance platform to monitor the evolving activity of SARS-CoV-2 infections in the community. We recruited a cohort of individuals aged 5 years and older between March 1 and March 7, 2022, from the general population. Individuals were enrolled from all 18 districts of Hong Kong, according to a predefined age-stratified quota, primarily by random digit dialing (generating suitable eight-digit local telephone numbers by randomly picking sets of the first four digits from a sampling frame, and randomly generating the last four digits), and supplemented by our existing cohorts (which included cohorts for studying influenza vaccination from school-based vaccination programmes and cohorts for SARS-CoV-2 seroprevalence from the community), to ensure representativeness of the population in Hong Kong. Participants did weekly rapid antigen testing with a self-collected pooled nasal and throat swab, regardless of symptom and exposure status, from March 1 to April 15, 2022. Individuals reporting a history of SARS-CoV-2 infection confirmed by laboratory PCR testing before enrolment were excluded from the vaccine effectiveness analysis to avoid potential bias due to infection-induced immunity. The primary outcomes of the study were the incidence of SARS-CoV-2 infection, including asymptomatic and symptomatic infections, and the vaccine effectiveness of BNT162b2 and CoronaVac vaccines. The effectiveness of one, two, and three doses of vaccination was estimated with a Cox proportional hazards regression model with time-dependent covariates, allowing for changes in vaccination status over time, after adjustment for demographic factors and pre-existing medical conditions. FINDINGS: Of the 8636 individuals included in the analysis, 7233 (84%) received at least two doses of vaccine, 3993 (46%) received booster doses, and 903 (10%) reported SARS-CoV-2 infection. Among these infections 589 (65·2%) were symptomatic and 314 (34·8%) were asymptomatic at the time of testing. Statistically significant protection against asymptomatic and symptomatic SARS-CoV-2 omicron infection was found only for those who received a BNT162b2 or CoronaVac booster dose, with a vaccine effectiveness of 41·4% (23·2 to 55·2; p=0·0001) and 32·4% (9·0 to 49·8; p=0·0098), respectively. The vaccine effectiveness of BNT162b2 and CoronaVac boosters was further increased to 50·9% (95% CI 31·0-65·0; p<0·0001) and 41·6% (15·0-59·8; p=0·0049), respectively, for symptomatic omicron infections. A similar pattern of vaccine effectiveness (55·8%, 22·9-74·6; p=0·0040) was also conferred after receipt of a BNT162b2 booster by individuals who received a CoronaVac primary vaccination series. INTERPRETATION: Two doses of either vaccine did not provide significant protection against COVID-19 infection. However, receipt of a BNT162b2 booster or CoronaVac booster was associated with a significantly lower risk of omicron BA.2 infection and symptomatic infection. Our findings confirm the effectiveness of booster doses to protect against mild and asymptomatic infection. FUNDING: Henry Fok Foundation and Hong Kong Health Bureau.

Performance of saline and water gargling for SARS-CoV-2 reverse transcriptase PCR testing: a systematic review and meta-analysis.

The performance of gargling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase (RT)-PCR testing has not been previously reviewed. This review systematically assessed the performance of saline and water gargling for SARS-CoV-2 RT-PCR testing in the settings of diagnosing and monitoring viral shedding.We included original studies comparing the performance of gargling and (oropharyngeal-)nasopharyngeal swabs for SARS-CoV-2 RT-PCR testing. Studies conducted in either suspected individuals or confirmed cases were included and analysed separately. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were examined using random-effects models.Gargles achieved a high overall sensitivity (91%), specificity (97%), PPV (95%) and NPV (91%) for SARS-CoV-2 RT-PCR testing. Studies using saline gargle and water gargle have an overall sensitivity of 97% and 86%, respectively. The sensitivity values were largely maintained for saline and water gargling on stratified analysis, for both diagnosis (96% and 92%) and viral shedding monitoring (98% and 78%). A higher sensitivity was also reported by studies using sterile saline (100%), a smaller amount of gargling solution (92% versus 87%) and a longer gargling duration (95% versus 86%).Our results supported the use of gargling as a sampling approach for SARS-CoV-2 RT-PCR testing, which achieved a high sensitivity for both diagnosis and viral shedding monitoring purposes. Further investigation on the comparative performance of different gargling mediums is needed to draw a definitive conclusion.

Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis.

BACKGROUND: The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation. FINDINGS: Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93-100), whereas lower sensitivities were achieved by saliva (85%, 75-93) and nasal swabs (86%, 77-93) and a much lower sensitivity by throat swabs (68%, 35-94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90-100) and nasal swabs (96%, 87-100) and a slightly lower positive predictive value by saliva (93%, 88-97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45-96). Comparably high specificities (range 97-99%) and negative predictive value (range 95-99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I2 ≥30%) was observed in studies on saliva and nasal swabs. INTERPRETATION: Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens. FUNDING: Hong Kong Research Grants Council.

Factors that influence length of stay for in-patient gynaecology surgery: is the Case Mix Group (CMG) or type of procedure more important?

OBJECTIVES: To compare the association between the Case Mix Group (CMG) code and length of stay (LOS) with the association between the type of procedure and LOS in patients admitted for gynaecology surgery. METHODS: We examined the records of women admitted for surgery in CMG 579 (major uterine/adnexal procedure, no malignancy) or 577 (major surgery ovary/adnexa with malignancy) between April 1997 and March 1999. Factors thought to influence LOS included age, weight, American Society of Anesthesiologists (ASA) score, physician, day of the week on which surgery was performed, and procedure type. Procedures were divided into six categories, four for CMG 579 and two for CMG 577. Data were abstracted from the hospital information costing system (T2 system) and by retrospective chart review. Multivariable analysis was performed using linear regression with backwards elimination. RESULTS: There were 606 patients in CMG 579 and 101 patients in CMG 577, and the corresponding median LOS was four days (range 1-19) for CMG 579 and nine days (range 3-30) for CMG 577. Combined analysis of both CMGs 577 and 579 revealed the following factors as highly significant determinants of LOS: procedure, age, physician, and ASA score. Although confounded by procedure type, the CMG did not significantly account for differences in LOS in the model if procedure was considered. Pairwise comparisons of procedure categories were all found to be statistically significant, even when controlled for other important variables. CONCLUSION: The type of procedure better accounts for differences in LOS by describing six statistically distinct procedure groups rather than the traditional two CMGs. It is reasonable therefore to consider changing the current CMG codes for gynaecology to a classification based on the type of procedure.