Weight trends amongst adults with diabetes or hypertension during the COVID-19 pandemic: an observational study using OpenSAFELY (preprint)

AimsTo describe patterns of weight change amongst adults living in England with Type 2 Diabetes (T2D) and/or hypertension during the COVID-19 pandemic. Design and SettingWith the approval of NHS England, we conducted an observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP. MethodWe estimated individual rates of weight gain during the pandemic ({delta}). We then estimated associations between clinical and sociodemographic characteristics and rapid weight gain (>0.5kg/m2/year) using multivariable logistic regression. ResultsWe extracted data on adults with T2D (n=1,231,455, 44% female, 76% white British) or hypertension (n=3,558,405, 50% female, 84% white British). Adults with T2D lost weight overall (median {delta} = -0.1kg/m2/year [IQR: -0.7, 0.4]), however, rapid weight gain was common (20.7%) and associated with sex (male vs female: aOR 0.78[95%CI 0.77, 0.79]); age, older age reduced odds (e.g. 60-69-year-olds vs 18-29-year-olds: aOR 0.66[0.61, 0.71]); deprivation, (least-deprived-IMD vs most-deprived-IMD: aOR 0.87[0.85, 0.89]); white ethnicity (Black vs White: aOR 0.70[0.69, 0.71]); mental health conditions (e.g. depression: aOR 1.13 [1.12, 1.15]); and diabetes treatment (non-insulin treatment vs no pharmacological treatment: aOR 0.68[0.67, 0.69]). Adults with hypertension maintained stable weight overall (median {delta} = 0.0kg/m2/year [-0.6, 0.5]), however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D. ConclusionAmongst adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common amongst females, younger adults, those living in more deprived areas, and those with mental health conditions. How this fits inPrevious studies, in the general population, have reported female sex, deprivation and comorbid mental health conditions increased risk of unhealthy weight gain during the pandemic, but it is not clear whether people living with hypertensions and/or type 2 diabetes experienced the same trends. We found that, during the pandemic, adults with hypertension maintained a stable weight whilst those with type 2 diabetes lost weight overall. However, underlying these overall trends, rapid weight gain was common amongst people with type 2 diabetes (20.7%) or hypertension (24.7%)), with female sex, younger age, deprivation, and comorbid mental health conditions associated with an increased odds of rapid weight gain in both populations. We have identified clinical and sociodemographic characteristics of individuals with hypertension and/or type 2 diabetes who could benefit from primary care interventions on weight and health behaviours to combat health inequalities in patterns of weight gain that were exacerbated by the pandemic.

Impact of COVID-19 on recorded blood pressure screening and hypertension management in England: An analysis of monthly changes in Quality and Outcomes Framework indicators in OpenSAFELY (preprint)

Background: Cardiovascular disease management in primary care in England was disrupted during the COVID-19 pandemic. Objective: We aim to describe the impact of the COVID-19 pandemic on blood pressure screening and hypertension management, based upon a national quality of care scheme (Quality and Outcomes Framework, QOF) across key demographic, regional, and clinical subgroups. To this end, we translate complex clinical quality of care schemes from text descriptions into reusable analytic code. Methods: With the approval of NHS England, a population based cohort study was conducted on 25.2 million patient records in situ using OpenSAFELY-TPP. We included all NHS patients registered at general practices using TPP software between March 2019 and March 2023. Individuals that were eligible for blood pressure screening and with a diagnosis of hypertension were identified according to the QOF 2021/22 business rules. We examined monthly changes in recorded blood pressure screening in the preceding 5 years in patients aged [≥] 45, recorded hypertension prevalence, and the recorded percentage of patients treated to target (i.e., [≤] 140/90 mmHg for patients [≤] 79 years and [≤] 150/90 mmHg for patients [≥] 80 years) in the preceding 12 months, within demographic, regional, and clinical subgroups as well as the variation across practices. Results: The overall percentage of patients aged [≥] 45 who had blood pressure screening recorded in the preceding 5 years decreased from 90% in March 2019 to 85% in March 2023. Recorded hypertension prevalence was relatively stable at 15% throughout the study period. The percentage of patients with a record of hypertension treated to target in the preceding 12 months reduced from a maximum of 71% in March 2020 to a minimum of 47% in February 2021 in patients aged [≤] 79 years, and from 85% in March 2020 to a minimum of 58% in February 2021 in patients aged [≥] 80 years before recovering. Blood pressure screening rates in the preceding 5 years remained stable in older age groups, patients with a record of learning disability, or care home status. Conclusions: There was substantial disruption to hypertension management QOF indicators during the pandemic, which can likely be attributed to a general reduction of blood pressure screening. OpenSAFELY can be used to continuously monitor monthly changes in national quality of care schemes to identify changes in key clinical subgroups early and support prioritisation of recovery from disrupted care caused by COVID-19.

Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: an observational cohort study using the OpenSAFELY platform (preprint)

Background We investigated which clinical and sociodemographic characteristics were associated with unhealthy patterns of weight gain amongst adults living in England during the pandemic. Methods With the approval of NHS England we conducted an observational cohort study of Body Mass Index (BMI) changes between March 2015 and March 2022 using the OpenSAFELY-TPP platform. We estimated individual rates of weight gain before and during the pandemic, and identified individuals with rapid weight gain (>0.5kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period and defined extreme-accelerators as the ten percent of individuals with the greatest increase (>1.84kg/m2/year). We estimated associations with these outcomes using multivariate logistic regression. Findings We extracted data on 17,742,365 adults (50.1% female, 76.1% White British). Median BMI increased from 27.8kg/m2[IQR:24.3 to 32.1] in 2019 (March 2019 to February 2020) to 28.0kg/m2 [24.4 to 32.6] in 2021. Rapid pandemic weight gain (n=3,214,155) was associated with female sex (male vs female: aOR 0.76 [95%CI:0.76 to 0.76]); younger age (50 to 59 years vs 18 to 29 years: aOR 0.60 [0.60 to 0.61]); White British ethnicity (Black Caribbean vs White British: aOR 0.91 [0.89 to 0.94]); deprivation (least-deprived-IMD-quintile vs most-deprived:aOR 0.77 [0.77 to 0.78]); and long-term conditions, of which mental health conditions had the greatest effect (e.g. depression (aOR 1.18[1.17 to 1.18])). Similar characteristics increased risk of extreme acceleration (n=2,768,695). Interpretation We found female sex, younger age, deprivation and mental health conditions increased risk of unhealthy patterns of pandemic weight gain. This highlights the need to incorporate sociodemographic, physical, and mental health characteristics when formulating post-pandemic research, policies, and interventions targeting BMI. Funding NIHR

The impact of the COVID-19 pandemic on Antipsychotic Prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: A federated analysis of 59 million patients primary care records in situ using OpenSAFELY (preprint)

Background: The COVID-19 pandemic significantly affected health and social care services. We aimed to explore whether this impacted the prescribing rates of antipsychotics within at-risk populations. Methods With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We then calculated the monthly prevalence of antipsychotic prescribing in the population, as well as the incidence of new prescriptions in each month over the study period (Jan 2019-Dec 2021). Results The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95% CI 82.30-83.19) in Q1 2019 to 90.1 (95% CI 89.68-90.60) in Q4 2021 and from 154.61 (95% CI 153.79-155.43) in Q1 2019 to 166.95 (95% CI 166.23-167.67) in Q4 2021 in care homes . There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the average monthly rate of prescribing per 1000 decreased from 122.97 (95% CI 122.29-123.66) in Q1 2019 to 119.29 (95% CI 118.68-119.91) in Q4 2021, and from 54.91 (95% CI 54.52-55.29) in Q1 2019 to 51.04 (95% CI 50.74-51.35) in Q4 2021 respectively. Conclusions During each of the lockdowns in 2020, we observed a significant spike in antipsychotic prescribing in the dementia and care home groups. We have shown that these peaks are likely due to prescribing of antipsychotics for palliative care purposes and may have been linked to pre-emptive prescribing, when on-site medical visits would have been restricted. Over the study period, we observed gradual increases in antipsychotic use in patients with dementia and in care homes and a decrease in their use in patients with learning disability or autism.

Challenges in estimating waning effectiveness of two doses of BNT162b2 and ChAdOx1 COVID-19 vaccines beyond six months: an OpenSAFELY cohort study using linked electronic health records (preprint)

Quantifying the waning effectiveness of second COVID-19 vaccination beyond six months and against the omicron variant is important for scheduling subsequent doses. With the approval of NHS England, we estimated effectiveness up to one year after second dose, but found that bias in such estimates may be substantial.

Eleven key measures for monitoring general practice clinical activity during COVID-19 using federated analytics on 48 million adults' primary care records through OpenSAFELY (preprint)

Background The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to describe this impact on primary care activity and monitor its recovery. Objectives To develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods With the approval of NHS England we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. We developed SNOMED-CT codelists for key measures of primary care clinical activity selected by a expert clinical advisory group and conducted a population cohort-based study to describe trends and variation in these measures January 2019-December 2021, and pragmatically classified their level of recovery one year into the pandemic using the percentage change in the median practice level rate. Results We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data.

Changes in COVID-19-related mortality across key demographic and clinical subgroups: an observational cohort study using the OpenSAFELY platform on 18 million adults in England (preprint)

Objectives To quantify in absolute and relative terms how population-level COVID-19 death rates have changed in demographic and clinical subgroups. Design Retrospective cohort study on behalf of NHS England. Setting Linked primary care and death registry data from the OpenSAFELY-TPP platform, covering the first three pandemic waves in England (wave 1: March 23 to May 30, 2020; wave 2: September 7, 2020 to April 24, 2021; and wave 3, delta: May 28 to December 14, 2021). Participants In total, 18.7, 18.8, and 18.7 million adults were included for waves 1, 2, and 3 respectively. Main outcome measures COVID-19-related mortality based on linked death registry records. Results The crude rate of COVID-19-related death per 1,000 person-years decreased from 4.48 in wave 1 (95%CI 4.41;4.55), to 2.70 in wave 2 (95%CI 2.67;2.73), to 0.64 in wave 3 (95%CI 0.63;0.66). The death rate decreased by 90% between waves 1 and 3 in patients aged 80+, but by only 20% in patients aged 18-39. This higher proportional reduction in death rates was also seen for other groups, such as neurological disease, learning disability and severe mental illness. Conversely, death rates in transplant recipients stayed constant across successive waves at 10 per 1,000 person-years. There was also only a small decrease in death rates between waves in people with kidney disease, haematological malignancies or conditions associated with immunosuppression. Consequently, the relative hazard of COVID-19-related death decreased over time for some variables (e.g. age), remained similar for some (e.g. sex, ethnicity), and increased for others (e.g. transplant). Conclusions COVID-19 death rates decreased over the first three pandemic waves. An especially large decrease was seen in older age groups and people with neurological disease, learning disability or severe mental illness. Some demographic inequalities in death rates persisted over time. Groups more likely to experience impaired vaccine effectiveness did not see the same benefit in COVID-19 mortality reduction.

Comparative effectiveness of BNT162b2 versus mRNA-1273 boosting in England: a cohort study in OpenSAFELY-TPP (preprint)

Introduction The COVID-19 booster vaccination programme in England used both BNT162b2 and mRNA-1273 vaccines. Direct comparisons of the effectiveness against severe COVID-19 of these two vaccines for boosting have not been made in trials or observational data. Methods On behalf of NHS England, we used the OpenSAFELY-TPP database to match adult recipients of each vaccine type on date of vaccination, primary vaccine course, age, and other characteristics. Recipients were eligible if boosted between 29 October 2021 and 31 January 2022, and followed up for 12 weeks. Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death. We estimated the cumulative incidence of each outcome, and quantified comparative effectiveness using risk differences (RD) and hazard ratios (HRs). Results 1,528,431 people were matched in each group, contributing a total 23,150,504 person-weeks of follow-up. The 12-week risks per 1,000 people of positive SARS-CoV-2 test were 103.2 (95%CI 102.4 to 104.0) for BNT162b2 and 96.0 (95.2 to 96.8) for mRNA-1273: the HR comparing mRNA-1273 with BNT162b2 was 0.92 (95%CI 0.91 to 0.92). For COVID-19 hospitalisations the 12-week risks per 1,000 were 0.65 (95%CI 0.56 to 0.75) and 0.44 (0.36 to 0.54): HR 0.67 (95%CI 0.58 to 0.78). COVID-19 deaths were rare: the 12-week risks per 1,000 were 0.03 (95%CI 0.02 to 0.06) and 0.01 (0.01 to 0.02): HR 1.23 (95%CI 0.59 to 2.56). Comparative effectiveness was generally similar within subgroups. Conclusion Booster vaccination with mRNA-1273 COVID-19 vaccine was more effective than BNT162b2 in preventing SARS-CoV-2 infection and COVID-19 hospitalisation during the first 12 weeks after vaccination.

Effectiveness of BNT162b2 booster doses in England: an observational study in OpenSAFELY-TPP (preprint)

Background The UK COVID-19 vaccination programme delivered its first "booster" doses in September 2021, initially in groups at high risk of severe disease then across the adult population. The BNT162b2 Pfizer-BioNTech vaccine was used initially, with Moderna mRNA-1273 subsequently also used. Methods We used the OpenSAFELY-TPP database, covering 40% of English primary care practices and linked to national coronavirus surveillance, hospital episodes, and death registry data, to estimate the effectiveness of boosting with BNT162b2 compared with no boosting in eligible adults who had received two primary course vaccine doses between 16 September and 16 December 2021 when the Delta variant of SARS-CoV-2 was dominant. Follow up was for up to 10 weeks. Each booster recipient was matched with an unboosted control on factors relating to booster priority status and prior immunisation. Additional factors were adjusted for in Cox models estimating hazard ratios (HRs). Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, COVID-19 death and non-COVID-9 death. Booster vaccine effectiveness was defined as 1-HR. Results Among 4,352,417 BNT162b2 booster recipients matched with unboosted controls, estimated effectiveness of a booster dose compared with two doses only was 50.7% (95% CI 50.1-51.3) for positive SARS-CoV-2 test, 80.1% (78.3-81.8) for COVID-19 hospitalisation, 88.5% (85.0-91.1) for COVID-19 death, and 80.3% (79.0-81.5) for non-COVID-19 death. Estimated effectiveness was similar among those who had received a BNT162b2 or ChAdOx1-S two-dose primary vaccination course, but effectiveness against severe COVID-19 was slightly lower in those classified as clinically extremely vulnerable (76.3% (73.1-79.1) for COVID-19 hospitalisation, and 85.1% (79.6-89.1) for COVID-19 death). Estimated effectiveness against each outcome was lower in those aged 18-65 years than in those aged 65 and over. Conclusion Our findings are consistent with strong protection of BNT162b2 boosting against positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death.

OpenSAFELY NHS Service Restoration Observatory 2: changes in primary care activity across six clinical areas during the COVID-19 pandemic (preprint)

Background The COVID-19 pandemic has disrupted healthcare activity across a broad range of clinical services. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible. Aims Using routinely collected data, our aim was to describe changes in the volume and variation of coded clinical activity in general practice in: (i) cardiovascular disease, (ii) diabetes, (iii) mental health, (iv) female and reproductive health, (v) screening, and (vi) processes related to medication. Design and setting With the approval of NHS England, we conducted a cohort study of 23.8 million patient records in general practice, in-situ using OpenSAFELY. Methods We selected common primary care activity using CTV3 codes and keyword searches from January 2019 - December 2020, presenting median and deciles of code usage across practices per month. Results We identified substantial and widespread changes in clinical activity in primary care since the onset of the COVID-19 pandemic, with generally good recovery by December 2020. A few exceptions showed poor recovery and warrant further investigation, such as mental health, e.g. "Depression interim review" (median across practices in December 2020 -41.6% compared to December 2019). Conclusions Granular NHS GP data at population-scale can be used to monitor disruptions to healthcare services and guide the development of mitigation strategies. The authors are now developing real-time monitoring dashboards for key measures identified here as well as further studies, using primary care data to monitor and mitigate the indirect health impacts of Covid-19 on the NHS.

Changes in English medication safety indicators throughout the COVID-19 pandemic: a federated analysis of 57 million patients' primary care records in situ using OpenSAFELY (preprint)

Objective: To describe the impact of the COVID-19 pandemic on safe prescribing, using the PINCER prescribing indicators; to implement complex prescribing indicators at national scale using GP data. Design: Population based cohort study, with the approval of NHS England using the OpenSAFELY platform. Setting: Electronic health record data from 56.8 million NHS patients' general practice records. Participants: All NHS patients registered at a GP practice using TPP or EMIS computer systems and recorded as at risk of at least one potentially hazardous PINCER indicator between September 2019 and September 2021. Main outcome measure: Monthly trends and between-practice variation for compliance with 13 PINCER measures between September 2019 and September 2021. Results: The indicators were successfully implemented across GP data in OpenSAFELY. Hazardous prescribing remained largely unchanged during the COVID-19 pandemic, with only small reductions in achievement of the PINCER indicators. There were transient delays in blood test monitoring for some medications, particularly ACE inhibitors. All indicators exhibited substantial recovery by September 2021. We identified 1,813,058 patients at risk of at least one hazardous prescribing event. Conclusion: Good performance was maintained during the COVID-19 pandemic across a diverse range of widely evaluated measures of safe prescribing.

Waning effectiveness of BNT162b2 and ChAdOx1 COVID-19 vaccines over six months since second dose: a cohort study using linked electronic health records (preprint)

Summary Background The rate at which COVID-19 vaccine effectiveness wanes over time is crucial for vaccination policies, but is incompletely understood with conflicting results from different studies. Methods This cohort study, using the OpenSAFELY-TPP database and approved by NHS England, included individuals without prior SARS-CoV-2 infection assigned to vaccines priority groups 2-12 defined by the UK Joint Committee on Vaccination and Immunisation. We compared individuals who had received two doses of BNT162b2 or ChAdOx1 with unvaccinated individuals during six 4-week comparison periods, separately for subgroups aged 65+ years; 16-64 years and clinically vulnerable; 40-64 years and 18-39 years. We used Cox regression, stratified by first dose eligibility and geographical region and controlled for calendar time, to estimate adjusted hazard ratios (aHRs) comparing vaccinated with unvaccinated individuals, and quantified waning vaccine effectiveness as ratios of aHRs per-4-week period. The outcomes were COVID-19 hospitalisation, COVID-19 death, positive SARS-CoV-2 test, and non-COVID-19 death. Findings The BNT162b2, ChAdOx1 and unvaccinated groups comprised 1,773,970, 2,961,011 and 2,433,988 individuals, respectively. Waning of vaccine effectiveness was similar across outcomes and vaccine brands: e.g. in the 65+ years subgroup ratios of aHRs versus unvaccinated for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test ranged from 1.23 (95% CI 1.15-1.32) to 1.27 (1.20-1.34) for BNT162b2 and 1.16 (0.98-1.37) to 1.20 (1.14-1.27) for ChAdOx1. Despite waning, rates of COVID-19 hospitalisation and COVID-19 death were substantially lower among vaccinated individuals compared to unvaccinated individuals up to 26 weeks after second dose, with estimated aHRs <0.20 (>80% vaccine effectiveness) for BNT162b2, and <0.26 (>74%) for ChAdOx1. By weeks 23-26, rates of SARS-CoV-2 infection in fully vaccinated individuals were similar to or higher than those in unvaccinated individuals: aHRs ranged from 0.85 (0.78-0.92) to 1.53 (1.07-2.18) for BNT162b2, and 1.21 (1.13-1.30) to 1.99 (1.94-2.05) for ChAdOx1. Interpretation The rate at which estimated vaccine effectiveness waned was strikingly consistent for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test, and similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the Omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination doses.

Trends, regional variation and clinical characteristics of recipients of antivirals and neutralising monoclonal antibodies for non-hospitalised COVID-19: a descriptive cohort study of 23.4 million people in OpenSAFELY (preprint)

ObjectivesAscertain patient eligibility status and describe coverage of antivirals and neutralising monoclonal antibodies (nMAB) as treatment for COVID-19 in community settings in England. DesignCohort study, approved by NHS England. SettingRoutine clinical data from 23.4m people linked to data on COVID-19 infection and treatment, within the OpenSAFELY-TPP database. ParticipantsNon-hospitalised COVID-19 patients at high-risk of severe outcomes. InterventionsNirmatrelvir/ritonavir (Paxlovid), sotrovimab, molnupiravir, casirivimab or remdesivir, administered in the community by COVID-19 Medicine Delivery Units. ResultsWe identified 102,170 non-hospitalised patients with COVID-19 between 11th December 2021 and 28th April 2022 at high-risk of severe outcomes and therefore potentially eligible for antiviral and/or nMAB treatment. Of these patients, 18,210 (18%) received treatment; sotrovimab, 9,340 (51%); molnupiravir, 4,500 (25%); Paxlovid, 4,290 (24%); casirivimab, 50 (<1%); and remdesivir, 20 (<1%). The proportion of patients treated increased from 8% (180/2,380) in the first week of treatment availability to 22% (420/1870) in the latest week. The proportion treated varied by high risk group, lowest in those with Liver disease (12%; 95% CI 11 to 13); by treatment type, with sotrovimab favoured over molnupiravir/Paxlovid in all but three high risk groups: Down syndrome (36%; 95% CI 31 to 40), Rare neurological conditions (46%; 95% CI 44 to 48), and Primary immune deficiencies (49%; 95% CI 48 to 51); by ethnicity, from Black (10%; 95% CI 9 to 11) to White (18%; 95% CI 18 to 19); by NHS Region, from 11% (95% CI 10 to 12) in Yorkshire and the Humber to 23% (95% CI 22 to 24) in the East of England); and by deprivation level, from 12% (95% CI 12 to 13) in the most deprived areas to 21% (95% CI 21 to 22) in the least deprived areas. There was also lower coverage among unvaccinated patients (5%; 95% CI 4 to 7), those with dementia (5%; 95% CI 4 to 6) and care home residents (6%; 95% CI 5 to 6). ConclusionsUsing the OpenSAFELY platform we were able to identify patients who were potentially eligible to receive treatment and assess the coverage of these new treatments amongst these patients. Targeted activity may be needed to address apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, socioeconomically deprived areas, and care homes. What is already known about this topicSince the emergence of COVID-19, a number of approaches to treatment have been tried and evaluated. These have mainly consisted of treatments such as dexamethasone, which were used in UK hospitals,from early on in the pandemic to prevent progression to severe disease. Until recently (December 2021), no treatments have been widely used in community settings across England. What this study addsFollowing the rollout of antiviral medicines and neutralising monoclonal antibodies (nMABs) as treatment for patients with COVID-19, we were able to identify patients who were potentially eligible to receive antivirals or nMABs and assess the coverage of these new treatments amongst these patients, in as close to real-time as the available data flows would support. While the proportion of the potentially eligible patients receiving treatment increased over time, rising from 8% (180/2,380) in the first week of the roll out to 22% (420/1870) in the last week of April 2022, there were variations in coverage between key clinical, geographic, and demographic subgroup. How this study might affect research, practice, or policyTargeted activity may therefore be needed to address lower treatment rates observed among certain geographic areas and key groups including ethnic minorities, people living in areas of higher deprivation, and in care homes.

Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY (preprint)

Background While the vaccines against COVID-19 are considered to be highly effective, COVID-19 vaccine breakthrough is likely and a small number of people will still fall ill, be hospitalised, or die from COVID-19, despite being fully vaccinated. With the continued increase in numbers of positive SARS-CoV-2 tests, describing the characters of individuals who have experienced a COVID-19 vaccine breakthrough could be hugely important in helping to determine who may be at greatest risk. Method We conducted a retrospective cohort study using routine clinical data from the OpenSAFELY TPP database of fully vaccinated individuals, linked to secondary care and death registry data, and described the characteristics of those experiencing a COVID-19 vaccine breakthrough. Results As of 30th June 2021, a total of 10,782,870 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 43 days (IQR: 23-64). From within this population, a total of 16,815 (0.1%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate was 12.33 (95% CI 12.14-12.51). There were 955 COVID-19 hospital admissions and 145 COVID-19-related deaths; corresponding incidence rates of 0.70 (95% CI 0.65-0.74) and 0.12 (95% CI 0.1-0.14), respectively. When broken down by the initial priority group, higher rates of hospitalisation and death were seen in those in care homes. Comorbidities with the highest rates of breakthrough COVID-19 included renal replacement therapy, organ transplant, haematological malignancy, and immunocompromised. Conclusion The majority of COVID-19 vaccine breakthrough cases in England were mild with relatively few fully vaccinated individuals being hospitalised or dying as a result. However, some concerning differences in rates of breakthrough cases were identified in several clinical and demographic groups, The continued increase in numbers of positive SARS-CoV-2 tests are concerning and, as numbers of fully vaccinated individuals increases and follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, aimed at identifying individuals at higher risk, are therefore required.

Innovative £50 headset and free app sent by post to manage glue ear -the most common childhood hearing loss- when services were closed during the C19 pandemic

BackgroundHearing loss from glue ear affects ∼1 in 10 children starting school in UK/Europe. Of all children globally with a hearing loss, fewer than 10% of children have access to hearing aids: affordable solutions are needed. Studies showed children with OME hear better with bone conducting headsets. During COVID-19 we investigated whether children with glue ear (also known as Otitis Media with Effusion, OME) without access to audiology or grommet surgery during the Covid pandemic, could be aided remotely with £50 bone conduction kits and the HearGlueEar app.ObjectivesCould families pair and set up a product set (requiring Bluetooth connectivity) themselvesCould children’s quality of life be improved with remotely managed hearing support.Can glue ear be successfully managed remotely.Does this management affect the number of grommet operations required?MethodsStarting July 2020, during COVID-19, children aged 3–11 years with OME and on a grommet waiting list were invited to a single arm, prospective study. They received the kit, instructions and HearGlueEar app by post. By 3 weeks parents were asked to charge and pair the devices, attend a remote consultation and complete an OMQ-14 questionnaire. Remote follow-up lasted 3 months.Results82% (26 children) of those waiting for grommet operation list at the time of first lockdown in 2020 joined the study.Children experienced more challenging listening situations during the pandemic with remote learning, social distancing and masks obscuring lip reading.Families and the children felt empowered to manage their child’s condition at home and school.100% of families set up the product set remotely without professional help. Although some families needed additional support through the study therefore contact with a professional to trouble shoot was important.Quality of life (OMQ-14) responses were 90% positive. Comments included: ‘Other people have said, wow his speech is clearer.’, ‘It is making a real difference at home.’, ‘He said over and over again, ‘I can hear everybody, wow.’, ‘It is no exaggeration to say this has made an astronomical improvement to his quality of life’. ‘She is getting on really well with the headphones - pairing them with the iPad at home is simply brilliant.’ One child said ‘I can hear my best friend again’.20% of those in the study avoided grommet operations: either choosing this management option as an alternative or successfully supporting their child’s hearing until the glue ear self-resolved.ConclusionsPosting a bone conduction kit, HearGlueEar app and remote consultation is an effective management option for children with glue ear. This reduced the need for some grommet operations affording cost-savings and relieved hospital waiting lists. Children’s hearing was supported at home and at school as well as challenges experienced in the pandemic with on-line education, social distancing and communicating with face coverings.https://medrxiv.org/cgi/content/short/2021.01.21.21249496v1

Recording of 'COVID-19 vaccine declined' among vaccination priority groups: a cohort study on 57.9 million NHS patients' primary care records in situ using OpenSAFELY (preprint)

BackgroundAll patients in England within vaccine priority groups were offered a COVID-19 vaccine by mid-April 2021. Clinical record systems contain codes to denote when such an offer has been declined by a patient (although these can in some cases be entered for a variety of other reasons including vaccination delay, or other administrative issues). We set out to describe the patterns of usage of codes for COVID-19 vaccines being declined. MethodsWith the approval of NHS England and using the full pseudonymised primary care records for 57.9 million NHS patients, we identified all patients in key vaccine priority groups: aged over 50, or over 16 and at increased risk from COVID-19 (Clinically Extremely Vulnerable [CEV] or otherwise "at risk"). We describe the proportion of patients recorded as declining a COVID-19 vaccination for each priority group, and by other clinical and demographic factors; whether patients recorded as "declined" subsequently went on to receive a vaccination; and the distribution of code usage across GP practices. ResultsOf 24.5 million patients in priority groups as of May 25th 2021, 89.2% had received a vaccine, 8.8% had neither a vaccination nor a decline recorded, and 663,033 (2.7%) had a decline code recorded. Of patients with a recorded decline, 125,587 (18.9%) were subsequently vaccinated. Subsequent vaccination was slightly more common in the South Asian population than other ethnicities (e.g. 32.3% vs 22.8%, over 65s). The proportion of declining-unvaccinated patients varied strongly with ethnicity (Black 15.3%, South Asian 5.6%, White 1.5% in over 80s); and was higher in patients from more deprived areas. COVID-19 vaccine decline codes were present in almost all practices (98.8%), but with wide variation between practices in rates of usage. Among all priority groups, declining-unvaccinated status was most common in CEV (3.3%). ConclusionsClinical codes indicative of COVID-19 vaccinations being declined are widely used in English general practice. They are substantially more common among Black and South Asian patients, and patients from more deprived areas. There is a need for more detailed survey and/or qualitative research with patients and clinicians to determine the most common reasons for these recorded declines.

Saving Human Lives and Rights: Recommendations for Protecting Human Rights when Adopting COVID-19 Vaccine Passports (preprint)

Since the first case was reported to the World Health Organisation in December 2019, SARS-CoV-2 (COVID-19) has caused social and economic devastation on a scale not seen since World War 2. As the milestone of 2 years of ‘living with the virus’ approaches, Governments and businesses are desperate to develop interventions that can facilitate the reopening of society whilst still protecting public health. As the roll-out of COVID-19 vaccinations has gathered pace worldwide, particularly in wealthier countries, those responsible for developing such interventions have begun to focus on the use of digital ‘COVID-19 Vaccine Passports’, which can be used to prove that an individual has had an approved COVID-19 vaccination (both doses where applicable). Governments hope that Vaccine Passports may be used to facilitate international travel and permit increased domestic liberties, for example allowing people to access public venues, to attend large gatherings, or to return to work without compromising personal safety and public health. “Yellow Fever certificates”, required to enter a specific list of countries maintained by the World Health Organisation, provide a precedent for this type of intervention. However, there are concerns that the use of COVID-19 Vaccine Passports could be viewed as a mechanism for introducing a mandatory vaccination policy, and there are also concerns that due to issues related to the unequal global distribution of effective vaccines and ‘the digital divide’ their use could exacerbate inequalities. Here we discuss the ethical and human rights implications of COVID-19 vaccine passports, based on a systematised literature review and documentary analysis. We find that in the context of a global public health emergency, COVID-19 vaccine passports (or, as we discuss, the broader status passes) are ethically and legally permissible under relevant human rights and international health regulations, provided they are designed, implemented, and used in accordance with the least infringement principle and the value of equality. We then set out 18 concrete recommendations for supranational bodies, national governments, and businesses to help ensure they develop and deploy COVID-19 Vaccine Passports accordingly.

Clinical coding of long COVID in English primary care: a federated analysis of 58 million patient records in situ using OpenSAFELY (preprint)

BackgroundLong COVID is a term to describe new or persistent symptoms at least four weeks after onset of acute COVID-19. Clinical codes to describe this phenomenon were released in November 2020 in the UK, but it is not known how these codes have been used in practice. MethodsWorking on behalf of NHS England, we used OpenSAFELY data encompassing 96% of the English population. We measured the proportion of people with a recorded code for long COVID, overall and by demographic factors, electronic health record software system, and week. We also measured variation in recording amongst practices. ResultsLong COVID was recorded for 23,273 people. Coding was unevenly distributed amongst practices, with 26.7% of practices having not used the codes at all. Regional variation was high, ranging between 20.3 per 100,000 people for East of England (95% confidence interval 19.3-21.4) and 55.6 in London (95% CI 54.1-57.1). The rate was higher amongst women (52.1, 95% CI 51.3-52.9) compared to men (28.1, 95% CI 27.5-28.7), and higher amongst practices using EMIS software (53.7, 95% CI 52.9-54.4) compared to TPP software (20.9, 95% CI 20.3-21.4). ConclusionsLong COVID coding in primary care is low compared with early reports of long COVID prevalence. This may reflect under-coding, sub-optimal communication of clinical terms, under-diagnosis, a true low prevalence of long COVID diagnosed by clinicians, or a combination of factors. We recommend increased awareness of diagnostic codes, to facilitate research and planning of services; and surveys of clinicians experiences, to complement ongoing patient surveys.