Estimating the Effectiveness of First Dose of COVID-19 Vaccine Against Mortality in England: A Quasi-Experimental Study.

Estimating real-world vaccine effectiveness is vital to assessing the coronavirus disease 2019 (COVID-19) vaccination program and informing the ongoing policy response. However, estimating vaccine effectiveness using observational data is inherently challenging because of the nonrandomized design and potential for unmeasured confounding. We used a regression discontinuity design to estimate vaccine effectiveness against COVID-19 mortality in England using the fact that people aged 80 years or older were prioritized for the vaccine rollout. The prioritization led to a large discrepancy in vaccination rates among people aged 80-84 years compared with those aged 75-79 at the beginning of the vaccination campaign. We found a corresponding difference in COVID-19 mortality but not in non-COVID-19 mortality, suggesting that our approach appropriately addressed the issue of unmeasured confounding factors. Our results suggest that the first vaccine dose reduced the risk of COVID-19 death by 52.6% (95% confidence limits: 15.7, 73.4) in those aged 80 years, supporting existing evidence that a first dose of a COVID-19 vaccine had a strong protective effect against COVID-19 mortality in older adults. The regression discontinuity model's estimate of vaccine effectiveness is only slightly lower than those of previously published studies using different methods, suggesting that these estimates are unlikely to be substantially affected by unmeasured confounding factors.

Towards a Fully Automated Scanning Probe Microscope for Biomedical Applications.

The increase in capabilities of Scanning Probe Microscopy (SPM) has resulted in a parallel increase in complexity that limits the use of this technique outside of specialised research laboratories. SPM automation could substantially expand its application domain, improve reproducibility and increase throughput. Here, we present a bottom-up design in which the combination of positioning stages, orientation, and detection of the probe produces an SPM design compatible with full automation. The resulting probe microscope achieves sub-femtonewton force sensitivity whilst preserving low mechanical drift (2.0±0.2 nm/min in-plane and 1.0±0.1 nm/min vertically). The additional integration of total internal reflection microscopy, and the straightforward operations in liquid, make this instrument configuration particularly attractive to future biomedical applications.

Risk of death following COVID-19 vaccination or positive SARS-CoV-2 test in young people in England.

Several studies have reported associations between COVID-19 vaccination and risk of cardiac diseases, especially in young people; the impact on mortality, however, remains unclear. We use national, linked electronic health data in England to assess the impact of COVID-19 vaccination and positive SARS-CoV-2 tests on the risk of cardiac and all-cause mortality in young people (12 to 29 years) using a self-controlled case series design. Here, we show there is no significant increase in cardiac or all-cause mortality in the 12 weeks following COVID-19 vaccination compared to more than 12 weeks after any dose. However, we find an increase in cardiac death in women after a first dose of non mRNA vaccines. A positive SARS-CoV-2 test is associated with increased cardiac and all-cause mortality among people vaccinated or unvaccinated at time of testing.

Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study.

OBJECTIVE: To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination. DESIGN: Observational cohort study. SETTING: Community dwelling population, UK. PARTICIPANTS: 28 356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection. MAIN OUTCOME MEASURE: Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021. RESULTS: Mean age of participants was 46 years, 55.6% (n=15 760) were women, and 88.7% (n=25 141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval -18.6% to -6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval -0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval -14.1% to -3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (-1.2% to -0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination. CONCLUSIONS: The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.

Risk of covid-19 related deaths for SARS-CoV-2 omicron (B.1.1.529) compared with delta (B.1.617.2): retrospective cohort study.

OBJECTIVE: To assess the risk of covid-19 death after infection with omicron BA.1 compared with delta (B.1.617.2). DESIGN: Retrospective cohort study. SETTING: England, United Kingdom, from 1 December 2021 to 30 December 2021. PARTICIPANTS: 1 035 149 people aged 18-100 years who tested positive for SARS-CoV-2 under the national surveillance programme and had an infection identified as omicron BA.1 or delta compatible. MAIN OUTCOME MEASURES: The main outcome measure was covid-19 death as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause specific Cox proportional hazard regression models (censoring non-covid-19 deaths) were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, index of multiple deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Interactions between variant and sex, age, vaccination status, and comorbidities were also investigated. RESULTS: The risk of covid-19 death was 66% lower (95% confidence interval 54% to 75%) for omicron BA.1 compared with delta after adjusting for a wide range of potential confounders. The reduction in the risk of covid-19 death for omicron compared with delta was more pronounced in people aged 18-59 years (number of deaths: delta=46, omicron=11; hazard ratio 0.14, 95% confidence interval 0.07 to 0.27) than in those aged ≥70 years (number of deaths: delta=113, omicron=135; hazard ratio 0.44, 95% confidence interval 0.32 to 0.61, P<0.0001). No evidence of a difference in risk was found between variant and number of comorbidities. CONCLUSIONS: The results support earlier studies showing a reduction in severity of infection with omicron BA.1 compared with delta in terms of hospital admission. This study extends the research to also show a reduction in the risk of covid-19 death for the omicron variant compared with the delta variant.