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Working paperElliott P, Eales O, Bodinier B, et al., 2022,
Post-peak dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022
Background: Rapid transmission of the SARS-CoV-2 Omicron variant has led to the highestever recorded case incidence levels in many countries around the world.Methods: The REal-time Assessment of Community Transmission-1 (REACT-1) study hasbeen characterising the transmission of the SARS-CoV-2 virus using RT-PCR test results fromself-administered throat and nose swabs from randomly-selected participants in England atages 5 years and over, approximately monthly since May 2020. Round 17 data were collectedbetween 5 and 20 January 2022 and provide data on the temporal, socio-demographic andgeographical spread of the virus, viral loads and viral genome sequence data for positiveswabs.Results: From 102,174 valid tests in round 17, weighted prevalence of swab positivity was4.41% (95% credible interval [CrI], 4.25% to 4.56%), which is over three-fold higher than inDecember 2021 in England. Of 3,028 sequenced positive swabs, 2,393 lineages weredetermined and 2,374 (99.2%) were Omicron including 19 (0.80% of all Omicron lineages)cases of BA.2 sub-lineage and one BA.3 (0.04% of all Omicron) detected on 17 January 2022,and only 19 (0.79%) were Delta. The growth of the BA.2 Omicron sub-lineage against BA.1and its sub-lineage BA.1.1 indicated a daily growth rate advantage of 0.14 (95% CrI, 0.03,0.28) for BA.2, which corresponds to an additive R advantage of 0.46 (95% CrI, 0.10, 0.92).Within round 17, prevalence was decreasing overall (R=0.95, 95% CrI, 0.93, 0.97) butincreasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). Those 75 years andolder had a swab-positivity prevalence of 2.46% (95% CI, 2.16%, 2.80%) reflecting a highlevel of infection among a highly vulnerable group. Among the 3,613 swab-positiveindividuals reporting whether or not they had had previous infection, 2,334 (64.6%)reported previous confirmed COVID-19. Of these, 64.4% reported a positive test from 1 to30 days before their swab date. Risks of infection were increased among essential/keyworkers
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Journal articleSullivan MK, Lees JS, Drake TM, et al., 2022,
Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study.
, Nephrology Dialysis Transplantation, Vol: 37, Pages: 271-284, ISSN: 0931-0509BACKGROUND: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. METHODS: A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between 17 January 2020 and 5 December 2020. RESULTS: Of 85 687 patients, 2198 (2.6%) received acute kidney replacement therapy (KRT). Of 41 294 patients with biochemistry data, 13 000 (31.5%) had biochemical AKI: 8562 stage 1 (65.9%), 2609 stage 2 (20.1%) and 1829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD) [adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81], male sex (aOR 2.43: 2.18-2.71) and Black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and Black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67), stage 2 aOR 2.41 (2.20-2.64), stage 3 aOR 3.50 (3.14-3.91) and KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. CONCLUSIONS: AKI is common in adults hospitalized with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely.
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Journal articleHerrera C, Veazey R, Lemke MM, et al., 2022,
Ex vivo evaluation of mucosal responses to vaccination with ALVAC and AIDSVAX of non-human primates
, Vaccines, Vol: 10, ISSN: 2076-393XNon-human primates (NHPs) remain the most relevant challenge model for the evaluation of HIV vaccine candidates; however, discrepancies with clinical trial results have emphasized the need to further refine the NHP model. Furthermore, classical evaluation of vaccine candidates is based on endpoints measured systemically. We assessed the mucosal responses elicited upon vaccination with ALVAC and AIDSVAX using ex vivo Rhesus macaque mucosal tissue explant models. Following booster immunization with ALVAC/AIDSVAX, anti-gp120 HIV-1CM244-specific IgG and IgA were detected in culture supernatant cervicovaginal and colorectal tissue explants, as well as systemically. Despite protection from ex vivo viral challenge, no neutralization was observed with tissue explant culture supernatants. Priming with ALVAC induced distinct cytokine profiles in cervical and rectal tissue. However, ALVAC/AIDSVAX boosts resulted in similar modulations in both mucosal tissues with a statistically significant decrease in cytokines linked to inflammatory responses and lymphocyte differentiation. With ALVAC/AIDSVAX boosts, significant correlations were observed between cytokine levels and specific IgA in cervical explants and specific IgG and IgA in rectal tissue. The cytokine secretome revealed differences between vaccination with ALVAC and ALVAC/AIDSVAX not previously observed in mucosal tissues and distinct from the systemic response, which could represent a biosignature of the vaccine combination.
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Journal articleCretu A-M, Monti F, Maronne S, et al., 2022,
Interaction data are identifiable even across long periods of time
, Nature Communications, Vol: 13, Pages: 1-11, ISSN: 2041-1723Fine-grained records of people’s interactions, both offline and online, arecollected at large scale. These data contain sensitive information about whom wemeet, talk to, and when. We demonstrate here how people’s interaction behavioris stable over long periods of time and can be used to identify individuals inanonymous datasets. Our attack learns the profile of an individual using geometric deep learning and triplet loss optimization. In a mobile phone metadatadataset of more than 40k people, it correctly identifies 52% of individuals basedon their 2-hop interaction graph. We further show that the profiles learned byour method are stable over time and that 24% of people are still identifiableafter 20 weeks. Our results suggest that people with well-balanced interactiongraphs are more identifiable. Applying our attack to Bluetooth close-proximitynetworks, we show that even 1-hop interaction graphs are enough to identifypeople more than 26% of the time. Our results provide strong evidence thatdisconnected and even re-pseudonymized interaction data can be linked together making them personal data under the European Union’s General DataProtection Regulation.
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Journal articleDavies HJ, Bachtiger P, Williams I, et al., 2022,
Wearable in-ear PPG: detailed respiratory variations enable classification of COPD
, IEEE Transactions on Biomedical Engineering, Vol: 69, ISSN: 0018-9294An ability to extract detailed spirometry-like breath-ing waveforms from wearable sensors promises to greatly improve respiratory health monitoring. Photoplethysmography (PPG) has been researched in depth for estimation of respiration rate, given that it varies with respiration through overall intensity, pulse amplitude and pulse interval. We compare and contrast the extraction of these three respiratory modes from both the ear canal and finger and show a marked improvement in the respiratory power for respiration induced intensity variations and pulse amplitude variations when recording from the ear canal. We next employ a data driven multi-scale method, noise assisted multivariate empirical mode decomposition (NA-MEMD), which allows for simultaneous analysis of all three respiratory modes to extract detailed respiratory waveforms from in-ear PPG. For rigour, we considered in-ear PPG recordings from healthy subjects, both older and young, patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) and healthy subjects with artificially obstructed breathing. Specific in-ear PPG waveform changes are observed for COPD, such as a decreased inspiratory duty cycle and an increased inspiratory magnitude, when compared with expiratory magnitude. These differences are used to classify COPD from healthy and IPF waveforms with a sensitivity of 87% and an overall accuracy of 92%. Our findings indicate the promise of in-ear PPG for COPD screening and unobtrusive respiratory monitoring in ambulatory scenarios and in consumer wearables.
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Journal articleDai C, Wang S, Mo Y, et al., 2022,
Suggestive annotation of brain MR images with gradient-guided sampling
, Medical Image Analysis, Vol: 77, Pages: 1-12, ISSN: 1361-8415Machine learning has been widely adopted for medical image analysis in recent years given its promising performance in image segmentation and classification tasks. The success of machine learning, in particular supervised learning, depends on the availability of manually annotated datasets. For medical imaging applications, such annotated datasets are not easy to acquire, it takes a substantial amount of time and resource to curate an annotated medical image set. In this paper, we propose an efficient annotation framework for brain MR images that can suggest informative sample images for human experts to annotate. We evaluate the framework on two different brain image analysis tasks, namely brain tumour segmentation and whole brain segmentation. Experiments show that for brain tumour segmentation task on the BraTS 2019 dataset, training a segmentation model with only 7% suggestively annotated image samples can achieve a performance comparable to that of training on the full dataset. For whole brain segmentation on the MALC dataset, training with 42% suggestively annotated image samples can achieve a comparable performance to training on the full dataset. The proposed framework demonstrates a promising way to save manual annotation cost and improve data efficiency in medical imaging applications.
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Journal articleGilmore A, Wilson H, Cairns T, et al., 2022,
Immune gene expression and functional networks in distinct lupus nephritis classes
, Lupus Science & Medicine, Vol: 9, ISSN: 2053-8790Objective: To explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) kidney biopsy tissue.Methods: Immune gene transcript analysis was performed using the NanoString nCounter platform on RNA from LN (n=55), thin basement membrane disease (TBM, n=14) and membranous nephropathy (MN, n=9) FFPE kidney biopsy tissue. LN samples consisted of single class III (n=11), IV (n=23) and V (n=21) biopsies with no mixed lesions. Differential gene expression was performed with NanoString nSolver, with visualisations of volcano plots and heatmaps generated in R. Significant transcripts were interrogated to identify functional networks using STRING and Gene ontogeny terms. Results: In comparison to TBM, we identified 52 significantly differentially expressed genes common to all three LN classes. Pathway analysis showed enrichment for type I interferon (IFN) signalling, complement and MHC II pathways, with most showing the highest expression in class IV LN. Our class IV LN biopsies also showed significant upregulation of NF-κB signalling and immunological enrichment in comparison to class V LN biopsies. Transcripts from the type I IFN pathway distinguished class V LN from MN. Conclusion: Our whole kidney section transcriptomic analysis provided insights into the molecular profile of class III, IV and V LN. The data highlighted important pathways common to all three classes and pathways enriched in our class IV LN biopsies. The ability to reveal molecular pathways in LN using FFPE whole biopsy sections could have clinical utility in treatment selection for LN.
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Journal articlePenagos M, Durham SR, 2022,
Allergen immunotherapy for long-term tolerance and prevention
, Journal of Allergy and Clinical Immunology, Vol: 149, ISSN: 0091-6749Allergen immunotherapy is effective for the treatment of allergic rhinitis, allergic asthma and Hymenoptera venom allergy. In view of potential side effects, cost, and the necessary patient commitment, an important question is whether allergen immunotherapy provides persistent clinical benefits after treatment discontinuation. Here we appraise the existing evidence for long-term effects of both subcutaneous and sublingual immunotherapy in terms of clinical efficacy, immune mechanisms, prevention of asthma development and prevention of new allergen sensitisations. Evidence from large, randomised, double-blind, placebo-controlled clinical trials that include a follow-up phase after treatment cessation demonstrate long-term efficacy. The data strongly support recommendations in international guidelines that both sublingual and subcutaneous immunotherapy should be continued for a minimum of 3 years to achieve disease modification and long-term tolerance. Grass pollen immunotherapy for seasonal rhinitis may inhibit the onset of asthma symptoms and requirements for asthma medication. Whether early intervention in infancy with mite sublingual immunotherapy may prevent asthma remains to be tested.
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Journal articleRosadas C, Khan M, Parker E, et al., 2022,
Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utility
, Journal of Virological Methods, Vol: 302, ISSN: 0166-0934Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity. The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA), providing the most sensitive format has been exploited in a novel hybrid manner employing a solid-phase S1 preferentially presenting RBD, coupled with a labelled RBD conjugate, used in a two-step sequential assay for detection and measurement of antibody to RBD (anti-RBD). This class and species neutral assay showed a specificity of 100% on 825 pre COVID-19 samples and a potential sensitivity of 99.6% on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralisation and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine and in humans immunised with both AstraZeneca and Pfizer vaccines. This assay detects anti-RBD at presentation with illness, demonstrates its elevation with disease severity, its sequel to asymptomatic infection and its persistence after the loss of antibody to the nucleoprotein (anti-NP). It also provides serological confirmation of prior infection and offers a secure measure for seroprevalence and studies of vaccine immunisation in human and animal populations. The hybrid DABA also displays the attributes necessary for the detection and quantification of anti-RBD to be used in clinical practice. An absence of detectable anti-RBD by this assay predicates the need for passive immune prophylaxis in at-risk patients.
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Journal articleAceves-Martins M, Quinton R, Brazzelli M, et al., 2022,
Identifying the outcomes important to men with hypogonadism: A qualitative evidence synthesis
, Andrology, Vol: 10, ISSN: 2047-2919OBJECTIVE: Men with male hypogonadism (MH) experience sexual dysfunction, which improves with testosterone replacement therapy (TRT). However, randomised controlled trials provide little consensus on functional and behavioural symptoms in hypogonadal men; these are often better captured by qualitative information from individual patient experience. METHODS: We systematically searched major electronic databases to identify qualitative data from men with hypogonadism, with or without TRT. Two independent authors performed the selection, extraction, and thematic analysis of data. Quality of eligible studies was assessed using the Critical Appraisals Skills Programme and Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research tools. RESULTS: We analysed data from five studies published in nine reports that assessed a total of 284 participants. Published data were only available within North America, with no ethnic minority or other underserved groups included. In addition to sexual dysfunction, men with MH experienced adverse changes in physical strength, perceptions of masculinity, cognitive function, and quality of life. The experience of MH appeared dependent on the source(s) of educational material. DISCUSSION: We propose a patient-centred approach to clinician interactions rather than focusing on discreet MH symptoms. Current evidence about the experience of MH is limited to North America and predominantly white ethnicity, which may not be broadly applicable to other geographic regions. Broadening our understanding of the MH experience may improve the targeting of information to patients. In addition, a multidisciplinary approach may better address symptoms neither attributable to MH nor alleviated by TRT.
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