COVID-19 and influenza vaccine uptake among pregnant women in national cohorts of England and Wales

Vaccines against COVID-19 and influenza can reduce the adverse outcomes caused by infections during pregnancy, but vaccine uptake among pregnant women has been suboptimal. We examined the COVID-19 and influenza vaccine uptake and disparities in pregnant women during the COVID-19 pandemic to inform vaccination interventions. We used data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database in England and the Secure Anonymised Information Linkage Databank in Wales. The uptake of at least one dose of vaccine was 40.2% for COVID-19 and 41.8% for influenza among eligible pregnant women. We observed disparities in COVID-19 and influenza vaccine uptake, with socioeconomically deprived and ethnic minority groups showing lower vaccination rates. The suboptimal uptake of COVID-19 and influenza vaccines, especially in those from socioeconomically deprived backgrounds and Black, mixed or other ethnic groups, underscores the necessity for interventions to reduce vaccine hesitancy and enhance acceptance in pregnant women

AZD1222 effectiveness against severe COVID-19 in individuals with comorbidity or frailty: the RAVEN cohort study

Objectives Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations. Methods Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity. Results Over 4.5 million AZD1222 recipients were matched (mean follow-up ∼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the ‘fit’ (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1). Conclusions Based on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed

Adverse events after first and second doses of COVID-19 vaccination in England: a national vaccine surveillance platform self-controlled case series study

Objectives: To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines. Design: We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021. Setting: England, UK. Participants: Individuals experiencing AEIs after receiving first and second doses of COVID-19 vaccines. Main outcome measures: AEIs determined based on events reported in clinical trials and in primary care during post-license surveillance. Results: A total of 7,952,861 individuals were vaccinated with COVID-19 vaccines within the study period. Among them, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs. Within the first seven days post-vaccination, 4.85% of all the AEIs were reported. There was a 3–7% decrease in the overall RI of AEIs in the seven days after receiving both doses of Pfizer-BioNTech BNT162b2 (RI = 0.93; 95% CI: 0.91–0.94) and 0.96; 95% CI: 0.94–0.98), respectively) and Oxford-AstraZeneca ChAdOx1 (RI = 0.97; 95% CI: 0.95–0.98) for both doses), but a 20% increase after receiving the first dose of Moderna mRNA-1273 (RI = 1.20; 95% CI: 1.00–1.44)). Conclusions: COVID-19 vaccines are associated with a small decrease in the incidence of medically attended AEIs. Sentinel networks could routinely report common AEI rates, which could contribute to reporting vaccine safety

Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales

Background UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. Methods We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Findings Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32–1.51)), older adults (≥80 years vs 18–49 years; 10.43 (8.06–13.50)), underweight (BMI <18.5 vs BMI 25.0–29.9; 2.94 (2.51–3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15–10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23–1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21–1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Interpretation Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. Funding National Core Studies—Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh

COVID-19 and influenza vaccine uptake among pregnant women in national cohorts of England and Wales

Vaccines against COVID-19 and influenza can reduce the adverse outcomes caused by infections during pregnancy, but vaccine uptake among pregnant women has been suboptimal. We examined the COVID-19 and influenza vaccine uptake and disparities in pregnant women during the COVID-19 pandemic to inform vaccination interventions. We used data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database in England and the Secure Anonymised Information Linkage Databank in Wales. The uptake of at least one dose of vaccine was 40.2% for COVID-19 and 41.8% for influenza among eligible pregnant women. We observed disparities in COVID-19 and influenza vaccine uptake, with socioeconomically deprived and ethnic minority groups showing lower vaccination rates. The suboptimal uptake of COVID-19 and influenza vaccines, especially in those from socioeconomically deprived backgrounds and Black, mixed or other ethnic groups, underscores the necessity for interventions to reduce vaccine hesitancy and enhance acceptance in pregnant women

Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people : meta-analysis of UK prospective cohorts

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5–17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5–11 year-olds were less likely to receive their first vaccine compared to 16–17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06–0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13–0.29)

Adverse events following first and second dose COVID-19 vaccination in England, October 2020 to September 2021 : a national vaccine surveillance platform self-controlled case series study

Background Post-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines. Aim To estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands. Methods We used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021. Results Within 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3–7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91–0.94 and RI: 0.96; 95% CI: 0.94–0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95–0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00–1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28–1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97–1.78). Conclusion COVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety

Adverse events after first and second doses of COVID-19 vaccination in England: a national vaccine surveillance platform self-controlled case series study

Objectives To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines. Design We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021. Setting England, UK. Participants Individuals experiencing AEIs after receiving first and second doses of COVID-19 vaccines. Main outcome measures AEIs determined based on events reported in clinical trials and in primary care during post-license surveillance. Results A total of 7,952,861 individuals were vaccinated with COVID-19 vaccines within the study period. Among them, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs. Within the first seven days post-vaccination, 4.85% of all the AEIs were reported. There was a 3–7% decrease in the overall RI of AEIs in the seven days after receiving both doses of Pfizer-BioNTech BNT162b2 (RI = 0.93; 95% CI: 0.91–0.94) and 0.96; 95% CI: 0.94–0.98), respectively) and Oxford-AstraZeneca ChAdOx1 (RI = 0.97; 95% CI: 0.95–0.98) for both doses), but a 20% increase after receiving the first dose of Moderna mRNA-1273 (RI = 1.20; 95% CI: 1.00–1.44)). Conclusions COVID-19 vaccines are associated with a small decrease in the incidence of medically attended AEIs. Sentinel networks could routinely report common AEI rates, which could contribute to reporting vaccine safety

Plasma Protein Biomarkers for the Prediction of CSF Amyloid and Tau and [18F]-Flutemetamol PET Scan Result

Background: Blood biomarkers may aid in recruitment to clinical trials of Alzheimer's disease (AD) modifying therapeutics by triaging potential trials participants for amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) A\u3b2 and tau tests. Objective: To discover a plasma proteomic signature associated with CSF and PET measures of AD pathology. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics were performed in plasma from participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD, recruited to the Amsterdam Dementia Cohort, stratified by CSF Tau/A\u3b242 (n = 50). Technical replication and independent validation were performed by immunoassay in plasma from SCD, MCI, and AD participants recruited to the Amsterdam Dementia Cohort with CSF measures (n = 100), MCI participants enrolled in the GE067-005 study with [18F]-Flutemetamol PET amyloid measures (n = 173), and AD, MCI and cognitively healthy participants from the EMIF 500 study with CSF A\u3b242 measurements (n = 494). Results: 25 discovery proteins were nominally associated with CSF Tau/A\u3b242 (P < 0.05) with associations of ficolin-2 (FCN2), apolipoprotein C-IV and fibrinogen \u3b2 chain confirmed by immunoassay (P < 0.05). In the GE067-005 cohort, FCN2 was nominally associated with PET amyloid (P < 0.05) replicating the association with CSF Tau/A\u3b242. There were nominally significant associations of complement component 3 with PET amyloid, and apolipoprotein(a), apolipoprotein A-I, ceruloplasmin, and PPY with MCI conversion to AD (all P < 0.05). In the EMIF 500 cohort FCN2 was trending toward a significant relationship with CSF A\u3b242 (P 48 0.05), while both A1AT and clusterin were nominally significantly associated with CSF A\u3b242 (both P < 0.05). Conclusion: Associations of plasma proteins with multiple measures of AD pathology and progression are demonstrated. To our knowledge this is the first study to report an association of FCN2 with AD pathology. Further testing of the proteins in larger independent cohorts will be important