Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...

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Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning. Results Anti-spike IgG levels remained stably detected after a positive result, e.g., in 94% (95% credibility interval, CrI, 91-96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post first PCR-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. Higher maximum observed anti-nucleocapsid titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives. Conclusion SARS-CoV-2 anti-nucleocapsid antibodies wane within months, and faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.

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BackgroundVaccine nationalism has become a key topic of discussion during the development, testing, and rollout of COVID-19 vaccines. Media attention has highlighted the ways that global, coordinated access to vaccines has been limited during the pandemic. It has also exposed how some countries have secured vaccine supply, through bilateral purchase agreements and the way pharmaceutical companies have priced, negotiated, and delivered these supplies. Much of the focus of this debate has been on the vaccine supply ‘winners’ and ‘losers’, but the voices of public opinion have been more limited.MethodsWe explore the concepts of vaccine nationalism and internationalism from the perspective of vaccine trial participants, using an empirical perspectives study that involved interviews with phase I/II COVID-19 vaccine trial participants in Oxford, UK. We surveyed and interviewed participants between September and October 2020 about their views, motivations and experiences in taking part in the trial.ResultsFirst, we show how trial participants describe national and international ideas about vaccination as intertwined and challenge claims that these positions are mutually exclusive or oppositional. Second, we analyse these viewpoints further to show that vaccine nationalism is closely connected with national pride and metaphors of a country’s scientific achievements. Participants held a global outlook and were highly supportive of the prioritisation of vaccines by global need, but many were also pessimistic that such a solution could be possible.ConclusionTrial participants constitute an informed public group, with situated public expertise that the global community could draw on as an expert opinion. We argue that vaccine nationalism is strongly attached to national character and, therefore, it is more difficult for ownership of a vaccine to be though of as international.

Aim of the study: To evaluate changes in the elasticity of the coracohumeral ligament in patients with adhesive capsulitis of the shoulder treated with ultrasound-guided rotator interval injections. Methods: Shear wave elastography was used to evaluate elasticity of the coracohumeral ligament in symptomatic and asymptomatic shoulders in the shoulder-neutral position and 30° external rotation. A total of 24 shoulders were assessed. Symptomatic shoulders were treated with targeted steroid injection via the rotator interval and manipulation under local anaesthetic block. Follow-up assessment of the elasticity of the coracohumeral ligament was obtained at 10 weeks post-injection. Results: In all subjects, the coracohumeral ligament elastic modulus was larger at 30° external rotation than in the neutral position. In patients with adhesive capsulitis, the coracohumeral ligament thickness and elastic modulus was significantly greater in the symptomatic shoulder in the neutral position and 30° ER. Treated patients had an excellent response with improved Oxford Shoulder Score and reduced visual analogue scale pain scores. Median Oxford Shoulder Score was 13.5 pre-injection and 34 at 10 weeks postinjection. Median visual analogue scale pain scores measured 8.5 pre-injection, 3.5 at 1 day, 2 at 1 week, and 2.5 at 10 weeks. Improved Oxford Shoulder Score and visual analogue scale pain score was associated with a trend to normalisation of the elastic modus of the coracohumeral ligament. Conclusion: In patients with adhesive capsulitis of the shoulder, shear wave elastography demonstrated the coracohumeral ligament is stiffer in the symptomatic shoulder than in the unaffected shoulder. Treatment with the ultrasound-guided rotator interval injection is associated with improved Oxford Shoulder Score, reduced visual analogue scale pain scores, and reduced stiffness in the coracohumeral ligament.