Defining clinical subtypes of adult asthma using electronic health records : analysis of a large UK primary care database with external validation

Acknowledgments EMFH was supported by a Medical Research Council PhD Studentship (eHERC/Farr). This work is carried out with the support of the Asthma UK Centre for Applied Research [AUKAC-2012-01] and Health Data Research UK which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust. The funders had no role in the study and the decision to submit this work to be considered for publication. This Project is based in part/wholly on Data from the Optimum Patient Care Research Database (opcrd.co.uk) obtained under licence from Optimum Patient Care Limited and its execution is approved by recognised experts affiliated to the Respiratory Effectiveness Group. However, the interpretation and conclusion contained in this report are those of the author/s alone. This study makes use of anonymised data held in the Secure Anonymised Information Linkage (SAIL) Databank. We would like to acknowledge all the data providers who make anonymised data available for research. SAIL is not responsible for the interpretation of these data.Peer reviewedPublisher PD

Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP

Objective To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England. Design Matched cohort study, emulating a comparative effectiveness trial. Setting Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant. Participants 3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1. Intervention Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose. Main outcome measures Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose. Results 1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras. Conclusions This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance

Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people

Background: Some studies have shown that the incidence of type 2 diabetes increases after a diagnosis of COVID-19, although the evidence is not conclusive. However, the effects of the COVID-19 vaccine on this association, or the effect on other diabetes subtypes, are not clear. We aimed to investigate the association between COVID-19 and incidence of type 2, type 1, gestational and non-specific diabetes, and the effect of COVID- 19 vaccination, up to 52 weeks after diagnosis. Methods: In this retrospective cohort study, we investigated the diagnoses of incident diabetes following COVID-19 diagnosis in England in a pre-vaccination, vaccinated, and unvaccinated cohort using linked electronic health records. People alive and aged between 18 years and 110 years, registered with a general practitioner for at least 6 months before baseline, and with available data for sex, region, and area deprivation were included. Those with a previous COVID-19 diagnosis were excluded. We estimated adjusted hazard ratios (aHRs) comparing diabetes incidence after COVID-19 diagnosis with diabetes incidence before or in the absence of COVID-19 up to 102 weeks after diagnosis. Results were stratified by COVID-19 severity (categorised as hospitalised or non-hospitalised) and diabetes type. Findings: 16 669 943 people were included in the pre-vaccination cohort (Jan 1, 2020–Dec 14, 2021), 12 279 669 in the vaccinated cohort, and 3 076 953 in the unvaccinated cohort (both June 1–Dec 14, 2021). In the pre-vaccination cohort, aHRs for the incidence of type 2 diabetes after COVID-19 (compared with before or in the absence of diagnosis) declined from 4·30 (95% CI 4·06–4·55) in weeks 1–4 to 1·24 (1·14–1.35) in weeks 53–102. aHRs were higher in unvaccinated people (8·76 [7·49–10·25]) than in vaccinated people (1·66 [1·50–1·84]) in weeks 1–4 and in patients hospitalised with COVID-19 (pre-vaccination cohort 28·3 [26·2–30·5]) in weeks 1–4 declining to 2·04 [1·72–2·42] in weeks 53–102) than in those who were not hospitalised (1·95 [1·78–2·13] in weeks 1–4 declining to 1·11 [1·01–1·22] in weeks 53–102). Type 2 diabetes persisted for 4 months after COVID-19 in around 60% of those diagnosed. Patterns were similar for type 1 diabetes, although excess incidence did not persist beyond 1 year after a COVID-19 diagnosis. Interpretation: Elevated incidence of type 2 diabetes after COVID-19 is greater, and persists for longer, in people who were hospitalised with COVID-19 than in those who were not, and is markedly less apparent in people who have been vaccinated against COVID-19. Testing for type 2 diabetes after severe COVID-19 and the promotion of vaccination are important tools in addressing this public health problem. Funding: UK National Institute for Health and Care Research, UK Research and Innovation (UKRI) Medical Research Council, UKRI Engineering and Physical Sciences Research Council, Health Data Research UK, Diabetes UK, British Heart Foundation, and the Stroke Association

COVID-19 and Mental Illnesses in Vaccinated and Unvaccinated People

IMPORTANCE: Associations have been found between COVID-19 and subsequent mental illness in both hospital- and population-based studies. However, evidence regarding which mental illnesses are associated with COVID-19 by vaccination status in these populations is limited. OBJECTIVE: To determine which mental illnesses are associated with diagnosed COVID-19 by vaccination status in both hospitalized patients and the general population. DESIGN, SETTING, AND PARTICIPANTS: This study was conducted in 3 cohorts, 1 before vaccine availability followed during the wild-type/Alpha variant eras (January 2020-June 2021) and 2 (vaccinated and unvaccinated) during the Delta variant era (June-December 2021). With National Health Service England approval, OpenSAFELY-TPP was used to access linked data from 24 million people registered with general practices in England using TPP SystmOne. People registered with a GP in England for at least 6 months and alive with known age between 18 and 110 years, sex, deprivation index information, and region at baseline were included. People were excluded if they had COVID-19 before baseline. Data were analyzed from July 2022 to June 2024. EXPOSURE: Confirmed COVID-19 diagnosis recorded in primary care secondary care, testing data, or the death registry. MAIN OUTCOMES AND MEASURES: Adjusted hazard ratios (aHRs) comparing the incidence of mental illnesses after diagnosis of COVID-19 with the incidence before or without COVID-19 for depression, serious mental illness, general anxiety, posttraumatic stress disorder, eating disorders, addiction, self-harm, and suicide. RESULTS: The largest cohort, the pre-vaccine availability cohort, included 18 648 606 people (9 363 710 [50.2%] female and 9 284 896 [49.8%] male) with a median (IQR) age of 49 (34-64) years. The vaccinated cohort included 14 035 286 individuals (7 308 556 [52.1%] female and 6 726 730 [47.9%] male) with a median (IQR) age of 53 (38-67) years. The unvaccinated cohort included 3 242 215 individuals (1 363 401 [42.1%] female and 1 878 814 [57.9%] male) with a median (IQR) age of 35 (27-46) years. Incidence of most outcomes was elevated during weeks 1 through 4 after COVID-19 diagnosis, compared with before or without COVID-19, in each cohort. Incidence of mental illnesses was lower in the vaccinated cohort compared with the pre-vaccine availability and unvaccinated cohorts: aHRs for depression and serious mental illness during weeks 1 through 4 after COVID-19 were 1.93 (95% CI, 1.88-1.98) and 1.49 (95% CI, 1.41-1.57) in the pre-vaccine availability cohort and 1.79 (95% CI, 1.68-1.90) and 1.45 (95% CI, 1.27-1.65) in the unvaccinated cohort compared with 1.16 (95% CI, 1.12-1.20) and 0.91 (95% CI, 0.85-0.98) in the vaccinated cohort. Elevation in incidence was higher and persisted longer after hospitalization for COVID-19. CONCLUSIONS AND RELEVANCE: In this study, incidence of mental illnesses was elevated for up to a year following severe COVID-19 in unvaccinated people. These findings suggest that vaccination may mitigate the adverse effects of COVID-19 on mental health

Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.

OBJECTIVE: To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England. DESIGN: Matched cohort study, emulating a comparative effectiveness trial. SETTING: Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant. PARTICIPANTS: 3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1. INTERVENTION: Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose. MAIN OUTCOME MEASURES: Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose. RESULTS: 1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras. CONCLUSIONS: This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance

Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study.

OBJECTIVE: To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England. DESIGN: Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England. SETTING: Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR). PARTICIPANTS: A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR. MAIN OUTCOME MEASURES: Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models. RESULTS: 992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake. CONCLUSION: Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study

Association of COVID-19 with mental illnesses in vaccinated and unvaccinated people: a population-based cohort study in OpenSAFELY

Importance: COVID-19 is associated with subsequent mental illness in both hospital- and population-based studies. However, evidence regarding which mental illnesses are associated with COVID-19 by vaccination status in these populations is limited. Objective: Determine which mental illnesses are associated with diagnosed COVID-19 by vaccination status in both hospitalised patients and the general population Design: We defined three cohorts: a ‘pre-vaccine availability’ cohort followed during the wild-type/Alpha variant eras (January 2020-June 2021), and ‘vaccinated’ and ‘unvaccinated’ cohorts followed during the Delta variant era (June-December 2021). Setting: With NHS England approval, we used OpenSAFELY-TPP to access linked data from 24 million people registered with English general practices (GPs) using TPP SystmOne. Participants: People registered with an English GP for at least six months and alive with a known age between 18 and 110 years, sex, deprivation, and region at baseline. People were excluded if they had COVID-19 before baseline. Cohort specific criteria also applied. Exposure: Confirmed COVID-19 diagnosis recorded in primary care; secondary care; testing data or the death registry. Main outcomes and measures: Adjusted hazard ratios (aHRs) comparing the incidence of mental illnesses after diagnosis of COVID-19 with the incidence before or without COVID-19 for depression, serious mental illness, general anxiety, post-traumatic stress disorder, eating disorders, addiction, self-harm, and suicide. Results: The largest cohort, pre-vaccine availability, included 18,648,606 people with a median age of 49 years. This cohort was 50.2% female. Incidence of most outcomes was elevated during weeks 1-4 after COVID-19 diagnosis, compared with before or without COVID-19, in each cohort. Vaccination mitigated the adverse effects of COVID-19 on mental health: aHRs (95% CIs) for depression and for serious mental illness during weeks 1-4 after COVID-19 were 1.93 (1.88-1.98) and 1.49 (1.41-1.57) in the pre-vaccine availability cohort and 1.79 (1.68-1.90) and 1.45 (1.27-1.65) in the unvaccinated cohort, compared with 1.16 (1.12-1.20) and 0.91 (0.85-0.98) in the vaccinated cohort. Elevation in incidence was higher, and persisted for longer, after hospitalised COVID-19. Conclusions and Relevance: Incidence of mental illnesses is elevated for up to a year following severe COVID-19 in unvaccinated people. Vaccination mitigates the adverse effect of COVID-19 on mental health.</p

Diabetes following SARS-CoV-2 infection: Incidence, persistence, and implications of COVID-19 vaccination. A retrospective cohort study of sixteen million people in England.

Background Type 2 diabetes (T2DM) incidence is increased after diagnosis of COVID-19. We investigated the the long-term effect of COVID-19 on the incidence of T2DM and other types of diabetes, and the impact of vaccination on the relationship. Methods With NHS England approval, we studied incident diabetes diagnoses following COVID-19 diagnosis in pre-vaccination (N=16,674,867, January 2020-December 2021), vaccinated (N =12,279,669), and unvaccinated (N=3,076,953) cohorts (June-December 2021), using linked electronic health records. We estimated adjusted hazard ratios (aHRs) comparing diabetes incidence post-COVID-19 diagnosis with incidence before or without diagnosis up to 102 weeks post-diagnosis. Results were stratified by COVID-19 severity (hospitalised/non-hospitalised) and diabetes type. Findings In the pre-vaccination cohort, aHRS for T2DM incidence after COVID-19 (compared to before or without diagnosis) declined from 4.30 (95% CI: 4.06,4.55) in weeks 1-4 to 1.24 (1.14,1.35) in weeks 53-102. aHRS were higher in unvaccinated than vaccinated people (8.76 (7.49,10.03)) versus 1.66 (1.50,1.84) in weeks 1-4) and for hospitalised COVID-19 (pre-vaccination cohort 28.3 (26.2,30.5) in weeks 1-4 declining to 2.04 (1.72,2.42) in weeks 53-102), than non-hospitalised COVID-19 (1.95 (1.78,2.13) in weeks 1-4, 1.11 (1.01,1.22) in weeks 53-102). T2DM persisted for 4 months after COVID-19 for ~60% of those diagnosed. Patterns were similar for Type 1 diabetes, though excess incidence did not persist beyond 6 months post-COVID-1

Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people

Background Type 2 diabetes (T2DM) incidence is increased after diagnosis of COVID-19. We investigated the the long-term effect of COVID-19 on the incidence of T2DM and other types of diabetes, and the impact of vaccination on the relationship. Methods With NHS England approval, we studied incident diabetes diagnoses following COVID-19 diagnosis in pre-vaccination (N=16,674,867, January 2020-December 2021), vaccinated (N =12,279,669), and unvaccinated (N=3,076,953) cohorts (June-December 2021), using linked electronic health records. We estimated adjusted hazard ratios (aHRs) comparing diabetes incidence post-COVID-19 diagnosis with incidence before or without diagnosis up to 102 weeks post-diagnosis. Results were stratified by COVID-19 severity (hospitalised/non-hospitalised) and diabetes type. Findings In the pre-vaccination cohort, aHRS for T2DM incidence after COVID-19 (compared to before or without diagnosis) declined from 4.30 (95% CI: 4.06,4.55) in weeks 1-4 to 1.24 (1.14,1.35) in weeks 53-102. aHRS were higher in unvaccinated than vaccinated people (8.76 (7.49,10.03)) versus 1.66 (1.50,1.84) in weeks 1-4) and for hospitalised COVID-19 (pre-vaccination cohort 28.3 (26.2,30.5) in weeks 1-4 declining to 2.04 (1.72,2.42) in weeks 53-102), than non-hospitalised COVID-19 (1.95 (1.78,2.13) in weeks 1-4, 1.11 (1.01,1.22) in weeks 53-102). T2DM persisted for 4 months after COVID-19 for ~60% of those diagnosed. Patterns were similar for Type 1 diabetes, though excess incidence did not persist beyond 6 months post-COVID-1