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Objectives: Limited evidence exists for the diagnostic performance of point-of-care tests for SARS-CoV-2 and influenza in community healthcare. We carried out a prospective diagnostic accuracy study of the LumiraDx™ SARS-CoV-2 and influenza A or B assay in primary care., Methods: Total of 913 adults and children with symptoms of current SARS-CoV-2 infection were recruited from 18 UK primary care practices during a period when Omicron was the predominant COVID variant of concern (June 2022 to December 2022). Trained health care staff performed the index test, with diagnostic accuracy parameters estimated for SARS-CoV-2 and influenza against real-time reverse-transcription PCR (rtRT-PCR)., Results: 151/887 participants were SARS-CoV-2 rtRT-PCR positive, 109 positive for Influenza A, 6 for Influenza B. Index test sensitivity for SARS-CoV-2 was 80.8% (122 of the 151, 95% CI, 73.6-86.7%) and specificity 98.9% (728 of the 736, 95% CI, 97.9-99.5%). For influenza A, sensitivity was 61.5% (67 of the 109, 95% CI, 51.7-70.6%) and specificity 99.4% (771 of the 776, 95% CI, 98.5-99.8%). Sensitivity to detect SARS-CoV-2 and influenza dropped sharply at rtRT-PCR cycle thresholds (Ct) > 30., Discussions: The LumiraDx™ SARS-CoV-2 and influenza A/B assay had moderate sensitivity for SARS-CoV-2 in symptomatic patients in primary care, with lower performance with high rtRT-PCR Ct. Negative results in this patient group cannot definitively rule out SARS-CoV-2 or influenza., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents., Methods: A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (1:1:1) to either 30 µg BNT162b2 (BNT-30), 10 µg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 µg dose of BNT162b2. The primary outcome was solicited systemic reactions in the week following vaccination. Secondary outcomes included immunogenicity and safety. 'Breakthrough infection' analyses were exploratory., Findings: 148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naïve participants, NVX participants had an 89% reduction in risk of self-reported 'breakthrough infection' compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI: 0.01, 0.86]) up until day 132 after second dose. BNT-10 recipients were more likely to have a 'breakthrough infection' compared to BNT-30 (aHR 2.14 [95% CI: 1.02, 4.51]) up to day 132 and day 236 post-second dose. Antibody responses at 132 and 236 days after second dose were similar for all vaccine schedules., Interpretation: Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic. The enhanced performance of the heterologous schedule using NVX-CoV2373 against the Omicron SARS-CoV-2 variant suggests this mRNA prime and protein-subunit boost schedule may provide a greater breadth of protection than the licensed homologous schedule., Funding: National Institute for Health Research and Vaccine Task Force., Trial Registration: International Standard Randomised Controlled Trial Number registry: 12348322., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MDS acted until September 2022 on behalf of the University of Oxford as an Investigator on research studies funded or supported by the vaccine manufacturers GlaxoSmithKline, Janssen, AstraZeneca, Novavax, MCM vaccines and Pfizer. He received no direct personal benefit for this work. From September 2022 he has been an employee at Moderna Biotech and holds stock options in this company. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust as an Investigator and/or providing consultative advice on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vaccine manufacturers including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck and Valneva vaccines and antimicrobials. He receives no personal financial payment for this work. KC acts on behalf of University Hospital Southampton NHS Foundation Trust as an investigator and/or providing consultative advice on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Janssen, Medimmune, Merck, Pfizer, Sanofi and Valneva. She receives no personal financial payment for this work. AMM acts on behalf of the University of Oxford as an investigator on research studies funded + /- sponsored by vaccine manufacturers including Pfizer, GlaxoSmithKline, Janssen, Valneva SE and Novavax. She receives no personal financial benefit for this work. PTH acts on behalf of St George’s University of London as an Investigator on clinical trials and studies of COVID-19 vaccines funded or sponsored by vaccine manufacturers including Janssen, Pfizer, AstraZeneca, Moderna, Novavax and Valneva. He receives no personal financial payment for this work. He is a member of the JCVI. JSN-V-T was seconded to the Department of Health and Social Care (DHSC) from October 2017-March 2022 as Deputy Chief Medical Officer, England, receiving no benefits, other than salary, for this work. Since leaving DHSC he has received a lecture fee from AstraZeneca and will undertake paid consulting for Moderna BioTech from 3rd May 2023. The views expressed in this paper are those of its authors and not necessarily those of DHSC or JCVI., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care., Methods: Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups., Results: Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms., Conclusions: Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile's minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced., Registration: ISRCTN142269., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: The authorship declares funding support for this study from the University of Oxford Medical Sciences Division Benefactors Urgent COVID-19 Fund, the National Institute for Health and Care (NIHR) School of Primary Care Research, and Urgent Public Health funding for the CONDOR Platform from the NIHR and Asthma+Lung UK. The RAPTOR-C19 study team received analysers and assays free of charge from Becton Dickinson for evaluation in this study. GNH declares funding from the National Institute for Health and Care Research (NIHR) paid to the University of Oxford. KD declares grant funding from Alere Inc and Cepheid Inc paid to her institution for unrelated research. TRF declares NIHR support from the NIHR Community Healthcare MIC for diagnostic evaluation research. AJW declares grant funding received by the University of Oxford through a Wellcome Trust Enriching Engagement grant which has supported unrelated patient participation work carried out by the Royal College of General Practitioners Research Surveillance Centre (based at the University of Oxford) for surveillance work. GE declares funding support from the NIHR Community Healthcare MIC recieved by the University of Oxford. AM declares the support of a Wellcome Trust Doctoral Research Fellowship and an NIHR In-practice Fellowship unrelated to this research. PJT declares support from the NIHR Community Healthcare MIC for diagnostic evaluation research. PJT has provided expert support to the Longitude Prize AMR competition administration which is unrelated to this project and for which the University of Oxford received an honorarium. RB declares grant funding for this project from the NIHR and Asthma+Lung UK, with additional funding from the Department of Health and Social Care paid to his host institution. RB declares grants from Siemens Healthineers, Abbott Point-of-Care and Ancon, all paid to his institution for unrelated research. He declares consulting fees received by his institution from Roche, Siemens, Aptamer Group, LumiraDx, Beckman Coulter and Radiometer, with personal fees received from Psyros Diagnostics. RB has received support for attending meetings / travel from Roche and EMCREG International. RB has participated on data safety monitoring boards or advisory boards for the unrelated FORCE Trial, REWIRE Trial, TARGET-CTA, and Magnetocardiography study (MAGNETIC - sponsored by Creavo). RB is the Deputy National Specialty Lead for Trauma & Emergency Care, National Institute for Health and Care Research Clinical Research Network. RB declares receipt of donated reagents for research not detailed in this paper from Roche, LumiraDx, BD, iXensor, Abbott Point-of-Care, Randox, Avacta, Menarini, loan of analysers from Randox and Menarini, and assays run free of charge for research purposes by Chronomics, My110, and Ancon. JJL declares funding from an NIHR Doctoral Research Fellowship which is unrelated to this research. LM declares support from the NIHR Community Healthcare MIC and other NIHR grants to the University of Oxford in support of this work. EL declares unrelated project funding received by the UKHSA Vaccine Evaluation Unit for contract research from GSK, Pfizer and Sanofi. MZ declares her unpaid activities as the Chair of the charitable organisation ISIRV and her membership of the UK SAGE, NERVTAG and JCVI groups. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Nicholson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications., Methods and Analysis: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50-64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 'hot hubs' and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes., Ethics and Dissemination: Ethical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals., Trial Registration Number: ISRCTN86534580., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)