Saturday, October 22, 2022

Waning of first- and second-dose ChAdOx1 and BNT162b2 COVID-19 vaccinations: a pooled target trial study of 12.9 million individuals in England, Northern Ireland, Scotland and Wales

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Abstract
Background
Several SARS-CoV-2 vaccines have been shown to provide protection against COVID-19 hospitalization and death. However, some evidence suggests that notable waning in effectiveness against these outcomes occurs within months of vaccination. We undertook a pooled analysis across the four nations of the UK to investigate waning in vaccine effectiveness (VE) and relative vaccine effectiveness (rVE) against severe COVID-19 outcomes.
Methods
We carried out a target trial design for first/second doses of ChAdOx1(Oxford–AstraZeneca) and BNT162b2 (Pfizer–BioNTech) with a composite outcome of COVID-19 hospitalization or death over the period 8 December 2020 to 30 June 2021. Exposure groups were matched by age, local authority area and propensity for vaccination. We pooled event counts across the four UK nations.
Results
For Doses 1 and 2 of ChAdOx1 and Dose 1 of BNT162b2, VE/rVE reached zero by approximately Days 60–80 and then went negative. By Day 70, VE/rVE was –25% (95% CI: –80 to 14) and 10% (95% CI: –32 to 39) for Doses 1 and 2 of ChAdOx1, respectively, and 42% (95% CI: 9 to 64) and 53% (95% CI: 26 to 70) for Doses 1 and 2 of BNT162b2, respectively. rVE for Dose 2 of BNT162b2 remained above zero throughout and reached 46% (95% CI: 13 to 67) after 98 days of follow-up.
Conclusions
We found strong evidence of waning in VE/rVE for Doses 1 and 2 of ChAdOx1, as well as Dose 1 of BNT162b2. This evidence may be used to inform policies on timings of additional doses of vaccine.
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Thursday, October 20, 2022

Evidence for human infection with avian influenza A(H9N2) virus via environmental transmission inside live poultry market in Xiamen, China

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Abstract

H9N2 avian influenza virus (AIV) has become prevalent in the live poultry market (LPM) worldwide, and environmental transmission mode is an important way for AIVs to infect human beings in the LPM. In order to find evidence for human infection with influenza A(H9N2) virus via environmental contamination, we evaluated one human isolate and three environmental isolates inside LPMs in Xiamen, China. The phylogeny, transmissibility, and pathogenicity of the four isolates were sorted out systematically. As for the H9N2 virus, which evolved alongside the "Avian-Environment-Human" spreading chain in LPMs from the summer of 2019 to the summer of 2020, its overall efficiency of contact and aerosol transmissibility improved, which might contribute to the increasing probability of human infection. This study indicated that environmental exposure might act as an important source of human infection in LPMs.

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In silico evaluation of the impact of Omicron variant of concern sublineage BA.4 and BA.5 on the sensitivity of RT‐qPCR assays for SARS‐CoV‐2 detection using whole genome sequencing

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ABSTRACT

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC) Omicron (B.1.1.529) has rapidly spread around the world, presenting a new threat to global public human health. Due to the large number of mutations accumulated by SARS-CoV-2 Omicron, concerns have emerged over potentially reduced diagnostic accuracy of reverse transcription polymerase chain reaction (RT-qPCR), the gold standard diagnostic test for diagnosing coronavirus disease 2019 (COVID-19). Thus, we aimed to assess the impact of the currently endemic Omicron sublineages BA.4 and BA.5 on the integrity and sensitivity of RT-qPCR assays used for coronavirus disease 2019 (COVID-19) diagnosis via in silico analysis. We employed whole genome sequencing data and evaluated the potential for false negatives or test failure due to mismatches between primers/probes and Omicron VoC viral genome.

Methods

In silico sensitivity of 12 RT-qPCR tests (containing 30 primers and probe sets) developed for detection of SARS-CoV-2 reported by the World Health Organization (WHO) or available in the literature, was assessed for specifically detecting SARS-CoV-2 Omicron BA.4 and BA.5 sublineages, obtained after removing redundancy from publicly available genomes from National Center for Biotechnology Information (NCBI) and Global Initiative on Sharing Avian Influenza Data (GISAID) databases. Mismatches between amplicon regions of SARS-CoV-2 Omicron VoC and primers and probe sets were evaluated, and clustering analysis of corresponding amplicon sequences was carried out.

Results

From the 1164 representative SARS-CoV-2 Omicron VoC BA.4 sublineage genomes analyzed, a substitution in the first five nucleotides (C to T) of the amplicon's 3' end were observed in all samples resulting in 0% sensitivity for assays HKUnivRdRp/Hel (mismatch in reverse primer) and CoremCharite N (mismatch in both forward and reverse primers). Due to a mismatch in the forward primer's 5' end (3-nucleotide substitution, GGG to AAC), the sensitivity of ChinaCDC N assay was at 0.69%. The 10 nucleotide mismatches in the reverse primer resulted in 0.09% sensitivity for Omicron sublineage BA.4 for Thai N assay. Of the 1926 BA.5 sublineage genomes, HKUnivRdRp/Hel assay also had 0% sensitivity. A sensitivity of 3.06% was observed for ChinaCDC N assay because of a mismatch in the forward primer's 5' end (3-nucleotide substitution, GGG to AAC). Similarly, due to the 10 nucleotide mismatches in the reverse primer, Thai N assay's sensitivity was low at 0.21% for sublineage BA.5. Further, 8 assays for BA.4 sublineage retained high sensitivity (more than 97%) and 9 assays for BA.5 sublineage retained more than 99% sensitivity.

Conclusion

We observed four assays (HKUnivRdRp/Hel, ChinaCDC N, Thai N, CoremCharite N) that could potentially result in false negative results for SARS-CoV-2 Omicron VoCs BA.4 and BA.5 sublineages. Interestingl y, CoremCharite N had 0% sensitivity for Omicron Voc BA.4 but 99.53% sensitivity for BA.5. In addition, 66.67% of the assays for BA.4 sublineage and 75% of the assays for BA.5 sublineage retained high sensitivity. Further, amplicon clustering and additional substitutions analysis along with sensitivity analysis could be used for modification and development of RT-qPCR assays for detecting SARS-CoV-2 Omicron VoC sublineages.

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The development of the Standardized Tool for the Assessment of Bruxism (STAB): An international road map

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Abstract

This paper summarizes the background reasoning and work that led to the selection of the items included in the Standardized Tool for the Assessment of Bruxism (STAB), also introducing the list of items. The instrument is currently being tested for face validity and on-field comprehension.

The underlying premise is that the different motor activities included in the bruxism spectrum (e.g., clenching versus grinding, with or without teeth contact) potentially need to be discriminated from each other, based on their purportedly different etiology, comorbidities, and potential consequences. Focus should be on a valid impression of the activities' frequency, intensity, and duration.

The methods that can be used for the above purposes can be grouped into strategies that collect information from the patient's history (subject-based), from the clinical assessment performed by an examiner (clinically based), or from the use of instruments to measure certain outcomes (instrumentally based). The three strategies can apply to all aspects of bruxism (i.e., status, comorbid conditions, etiology, and consequences).

The STAB will help gathering information on many aspects, factors, and conditions that are currently poorly investigated in the field of bruxism. To this purpose, it is divided into two axes. Axis A includes the self-reported information on bruxism status and potential consequences (subject-based report) together with the clinical (examiner report) and instrumental assessment (technology report). Axis B includes the self-reported information (subject-based report) on factors and conditions that may have an etiological or comorbid role for bruxism. This comprehensive multidimensional assessment system will allow building predictive model for clinical and research purposes.
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Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis

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imageBackground: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. Methods: In this population-based case–control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989–2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NOx), carbon monoxide (CO), and fine particles (PM2.5) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NOx, CO). Results: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m3) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = –1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NOx (SD = 20 µg/m3) (–4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m3) (–3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM2.5) (SD = 2.37 µg/m3) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. Conclusions: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis.
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Gestational Hypertensive Disorders and Maternal Breast Cancer Risk

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imageBackground: Preeclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. Methods: Women ages 35–74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported diagnoses of eclampsia, preeclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race–ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. Results: The prevalence of gestational hypertensive disease was 12%. During follow-up (mean = 10.9 years), 3,198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR = 1.0; 95% CI = 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. Conclusions: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a first-degree family history of breast cancer.
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Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function

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AbstractThe synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO4) to induce hair cell loss and retraction of nerve terminals, and then allowed animals to recover in dexamethasone for 48  h. Consistent with previous work, we observed significantly more regenerated hair cells in dexamethasone-treated larvae. Importantly, we found that th...
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Wednesday, October 19, 2022

Autoimmune seronegative limbic encephalitis following ChAdOx1‐S/nCoV‐19 vaccination in a patient with ankylosing spondylitis

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Abstract

Here we present a case in which a patient developed autoimmune seronegative limbic encephalitis following ChAdOx1-S/nCoV-19 (AZD1222; AstraZeneca) vaccination. Although it is known that vaccines containing SARS-CoV-2 antigens might enhance autoimmunity, such cases are rarely reported. We discuss this case with the present literature.

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Sequence Analysis of Epstein‐Barr virus RPMS1 Gene in malignant hematopathy

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Abstract

The RPMS1 gene is the only member of the BamHI-A rightward transcripts (BARTs) family for which a full-length cDNA has been identified, and RPMS1 transcript has been confirmed in many EBV-positive malignancies. However, the effects of sequence variations of RPMS1 in hematological malignancies and their biological significance are unclear. To explore the association between RPMS1 gene variations and hematological malignancy, the RPMS1 gene of 391 EBV-positive samples from patients with EBV-positive leukemia, myelodysplastic syndromes (MDS) and lymphoma in northern China were sequenced. On the basis of phylogenetic tree and mutation characteristics of RPMS1, all the sequences were divided into five major types: RPMS1-A, RPMS1-B, RPMS1-C, RPMS1-E, and RPMS1-F. RPMS1-A type, similar to the prototype B95-8, was identified in 71.87% (281/391) of samples and was the major typ e in all subpopulations. The frequency of RPMS1-F type was significantly higher in all malignant hematopathy groups than in healthy donors. The Hodgkin lymphoma (HL) group contained more RPMS1-F than other malignant hematopathy groups, and acute myeloid leukemia (AML) contained more RPMS1-C type than other malignant hematopathy groups. Therefore, RPMS1-A is the main type of RPMS1 gene in northern China, and RPMS1-F may be associated with hematologic malignancies.

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Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B

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Abstract

Objectives

We aimed to develop and validate a novel combined score to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B (CHB).

Methods

The serum levels of hub genes were examined by qRT-PCR in three cohorts of CHB patients.

Results

For significant liver fibrosis (≥S2), the areas under the receiver operating characteristics curves (AUROCs) of the combined score were 0.838, 0.842 and 0.881 in the three cohorts, respectively. And for advanced liver fibrosis (≥S3), the AUROCs were 0.794, 0.801 and 0.901, respectively. Compared with the results of AUROCs for aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) in the validation cohorts, better clinical diagnostic value for assessing the progression of liver fibrosis was found in the combined score. Additionally, univariate ordered logistic regression analysis indicated that the combined score could serve as a more superior and stable risk factor than APRI and FIB-4 in the assessment of liver fibrosis. For CHB patients with normal alanine aminotransferase (ALT), our results further emphasized the diagnostic value of the combined score for significant fibrosis (≥S2) and advanced fibrosis (≥S3). Moreover, it was found that patients with the high combined score, who were associated with the advanced fibrosis stage, had higher levels of drug sensitivity and immune checkpoint expression.

Conclusion

The novel combined score could serve as a potential biomarker and contribute to improving the assessment of fibrosis stage in CHB patients.

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