Defining within-host SARS-CoV-2 RNA viral load kinetics during acute COVID-19 infection within different respiratory compartments and their respective associations with host infectiousness: a protocol for a systematic review and meta-analysis.

Introduction: Understanding how RNA viral load changes (viral load kinetics) during acute infection in SARS-CoV-2 can help to identify when and which patients are most infectious. We seek to summarise existing data on the longitudinal RNA viral load kinetics of SARS-CoV-2 sampled from different parts of the respiratory tract (nose, nasopharynx, oropharynx, saliva and exhaled breath) and how this may vary with age, sex, ethnicity, immune status, disease severity, vaccination, treatment and virus variant.

Methods And Analysis: We will conduct a systematic review and meta-analysis, using studies identified through MEDLINE and EMBASE (via Ovid).

Recent advances in the influenza virus vaccine landscape: a comprehensive overview of technologies and trials.

SUMMARYIn the United Kingdom (UK) in 2022/23, influenza virus infections returned to the levels recorded before the COVID-19 pandemic, exerting a substantial burden on an already stretched National Health Service (NHS) through increased primary and emergency care visits and subsequent hospitalizations. Population groups ≤4 years and ≥65 years of age, and those with underlying health conditions, are at the greatest risk of influenza-related hospitalization. Recent advances in influenza virus vaccine technologies may help to mitigate this burden.

Learnings from the vaccines taskforce: an apotheosis in mission, purpose and handling risk.

The Vaccines Task Force was established by the UK government in March 2020, with the objective of securing early access to effective COVID-19 vaccines for the UK population and internationally. The VTF was successful in securing the earliest access to the Oxford/Astra Zeneca and Pfizer/BioNTech vaccines, allowing the UK to be the first country in the world to deploy an approved COVID-19 vaccine. The VTF also played a critical role in supporting efforts to distribute vaccines globally, as one of COVAX's earliest and largest donors.

Effectiveness of pneumococcal vaccination in adults with common immune-mediated inflammatory diseases in the UK: a case-control study.

Background: People with immune-mediated inflammatory disease are at increased risk of pneumococcal pneumonia. The effectiveness of pneumococcal vaccination in people with immune-mediated inflammatory diseases has not been evaluated. We investigated the effectiveness of pneumococcal vaccination in preventing morbidity and mortality associated with pneumonia in patients with immune-mediated inflammatory diseases.

Uptake, safety and effectiveness of inactivated influenza vaccine in inflammatory bowel disease: a UK-wide study.

Objective: To investigate (1) the UK-wide inactivated influenza vaccine (IIV) uptake in adults with inflammatory bowel disease (IBD), (2) the association between vaccination against influenza and IBD flare and (3) the effectiveness of IIV in preventing morbidity and mortality.

Design: Data for adults with IBD diagnosed before the 1 September 2018 were extracted from the Clinical Practice Research Datalink Gold. We calculated the proportion of people vaccinated against seasonal influenza in the 2018-2019 influenza cycle.

Uptake and safety of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide observational study.

Objective: The uptake and safety of pneumococcal vaccination in people with immune mediated inflammatory diseases (IMIDs) is poorly understood. We investigated the UK wide pneumococcal vaccine uptake in adults with IMIDs and explored the association between vaccination and IMID flare.

Methods: Adults with IMIDs diagnosed on or before 01/09/2018, prescribed steroid-sparing drugs within the last 12 months and contributing data to the Clinical Practice Research Datalink Gold were included.

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial.

Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases.

Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK.

Cost-utility analysis of molnupiravir for high-risk, community-based adults with COVID-19: an economic evaluation of the PANORAMIC trial.

Background: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations.

Aim: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over 6 months.

Design And Setting: An economic evaluation of the PANORAMIC trial in the UK.

Real world evidence for public health decision-making on vaccination policies: perspectives from an expert roundtable.

Introduction: Influenza causes significant morbidity and mortality, but influenza vaccine uptake remains below most countries' targets. Vaccine policy recommendations vary, as do procedures for reviewing and appraising the evidence.

Areas Covered: During a series of roundtable discussions, we reviewed procedures and methodologies used by health ministries in four European countries to inform vaccine recommendations.

Optimizing mood prior to influenza vaccination in older adults: A three-arm randomized controlled trial.

Objective: This trial explored the psychological and immunological effects of two brief interventions, targeting improving positive mood, administered to older adults immediately prior to influenza vaccination. The primary aim was to examine whether the interventions resulted in greater positive mood compared to usual care, and if so, which was superior. Secondary outcomes included antibody responses to vaccination and feasibility of collecting clinical outcome data (e.

Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity.

Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the [Formula: see text] ratio. Because of the ceiling effect in oxyhaemoglobin saturation, [Formula: see text] ratio ceases to reflect pulmonary oxygenation function at high [Formula: see text] values.

Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease.

Introduction: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.

Methods And Analysis: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses.

Risk prediction of covid-19 related death or hospital admission in adults testing positive for SARS-CoV-2 infection during the omicron wave in England (QCOVID4): cohort study.

Objectives: To derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period when the omicron variant of the virus was predominant in England, and to evaluate performance compared with a high risk cohort from NHS Digital.

Design: Cohort study.

Setting: QResearch database linked to English national data on covid-19 vaccinations, SARS-CoV-2 test results, hospital admissions, and cancer and mortality data, 11 December 2021 to 31 March 2022, with follow-up to 30 June 2022.

Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (Com-COV3): A randomised controlled trial.

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.

Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial.

Background: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave.

Persistence of immune response in heterologous COVID vaccination schedules in the Com-COV2 study - A single-blind, randomised trial incorporating mRNA, viral-vector and protein-adjuvant vaccines.

Background: Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development.

Methods: Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose 'ChAd' (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or 'BNT' (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8-12 weeks later with either the homologous vaccine, or 'Mod' (mRNA-1273, Spikevax, Moderna) or 'NVX' (NVX-CoV2373, Nuvaxovid, Novavax).

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial.

Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.

Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial.

Burden of respiratory syncytial virus infection in older and high-risk adults: a systematic review and meta-analysis of the evidence from developed countries.

Background: Respiratory syncytial virus (RSV) significantly impacts the health of older and high-risk adults (those with comorbidities). We aimed to synthesise the evidence on RSV disease burden and RSV-related healthcare utilisation in both populations.

Methods: We searched Embase and MEDLINE for papers published between 2000 and 2019 reporting the burden and clinical presentation of symptomatic RSV infection and the associated healthcare utilisation in developed countries in adults aged ≥60 years or at high risk.

The impact of repeated vaccination on relative influenza vaccine effectiveness among vaccinated adults in the United Kingdom.

Annual seasonal influenza vaccination is recommended for individuals at high risk of developing post-infection complications in many locations. However, reduced vaccine immunogenicity and effectiveness have been observed among repeat vaccinees in some influenza seasons. We investigated the impact of repeated influenza vaccination on relative vaccine effectiveness (VE) among individuals who were recommended for influenza vaccination in the United Kingdom with a retrospective cohort study using primary healthcare data from the Clinical Practice Research Datalink, a primary care database in the United Kingdom.

Lessons learned from 2 years of influenza vaccinations in the UK and USA during the COVID-19 pandemic as respiratory viruses return.

During the COVID-19 pandemic, immunization programs for other respiratory infections, notably influenza continued worldwide but attracted less public or political attention than COVID-19 vaccinations. Due to non-pharmaceutical intervention measures the global influenza burden decreased substantially; but with lifting of restrictions a rebound in other respiratory virus pathogens is both plausible and likely. This article discusses lessons identified from the UK and USA, and provides recommendations for future influenza vaccination programs in light of emerging data from the southern hemisphere and the need for harmonization with COVID-19 vaccination, focusing on operational delivery and messaging to practitioners and the public.

Is vaccination against COVID-19 associated with autoimmune rheumatic disease flare? A self-controlled case series analysis.

Objectives: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and autoimmune rheumatic disease (AIRD) flare.

Material And Methods: Patients with AIRDs vaccinated against COVID-19 who consulted for disease flare between 1 December 2020 and 31 December 2021 were ascertained in Clinical Practice Research Datalink (Aurum). AIRD flare was defined as consultation for AIRD with CS prescription on the same day or the next day.