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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., Competing Interests: Declaration of interests NC is compensated by AstraZeneca for membership of data monitoring and safety committees for clinical trials. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The first dose of COVID-19 vaccines led to an overall reduction in cardiovascular events, and in rare cases, cardiovascular complications. There is less information about the effect of second and booster doses on cardiovascular diseases. Using longitudinal health records from 45.7 million adults in England between December 2020 and January 2022, our study compared the incidence of thrombotic and cardiovascular complications up to 26 weeks after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs., (© 2024. The Author(s).)

Background: The UK delivered its first "booster" COVID-19 vaccine doses in September 2021, initially to individuals at high risk of severe disease, then to all adults. The BNT162b2 Pfizer-BioNTech vaccine was used initially, then also Moderna mRNA-1273., Methods: With the approval of the National Health Service England, we used routine clinical data to estimate the effectiveness of boosting with BNT162b2 or mRNA-1273 compared with no boosting in eligible adults who had received two primary course vaccine doses. We matched each booster recipient with an unboosted control on factors relating to booster priority status and prior COVID-19 immunization. We adjusted for additional factors in Cox models, estimating hazard ratios up to 182 days (6 months) following booster dose. We estimated hazard ratios overall and within the following periods: 1-14, 15-42, 43-69, 70-97, 98-126, 127-152, and 155-182 days. Outcomes included a positive SARS-CoV-2 test, COVID-19 hospitalization, COVID-19 death, non-COVID-19 death, and fracture., Results: We matched 8,198,643 booster recipients with unboosted controls. Adjusted hazard ratios over 6-month follow-up were: positive SARS-CoV-2 test 0.75 (0.74, 0.75); COVID-19 hospitalization 0.30 (0.29, 0.31); COVID-19 death 0.11 (0.10, 0.14); non-COVID-19 death 0.22 (0.21, 0.23); and fracture 0.77 (0.75, 0.78). Estimated effectiveness of booster vaccines against severe COVID-19-related outcomes peaked during the first 3 months following the booster dose. By 6 months, the cumulative incidence of positive SARS-CoV-2 test was higher in boosted than unboosted individuals., Conclusions: We estimate that COVID-19 booster vaccination, compared with no booster vaccination, provided substantial protection against COVID-19 hospitalization and COVID-19 death but only limited protection against positive SARS-CoV-2 test. Lower rates of fracture in boosted than unboosted individuals may suggest unmeasured confounding. Observational studies should report estimated vaccine effectiveness against nontarget and negative control outcomes., Competing Interests: Disclosure: B.G. has received research funding from the Bennett Foundation, the Laura and John Arnold Foundation, the NIHR, the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK, the Health Foundation, the World Health Organization, UKRI, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies program; he receives personal income from speaking and writing for lay audiences on the misuse of science; he is also a non-executive director of NHS Digital; A.M. is on the NHS Digital Professional Advisory Group (representing the Royal College of General Practitioners), advising on the use of general practice data for COVID-19 related research and planning; until September 2019 he was interim chief medical officer of NHS Digital. The other authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The symptom profiles of acute SARS-CoV-2 infection and long-COVID in children and young people (CYP), risk factors, and associated healthcare needs, are poorly defined. The Schools Infection Survey 1 (SIS-1) was a nationwide study of SARS-CoV-2 infection in primary and secondary schools in England during the 2020/21 school year. The Covid-19 Mapping and Mitigation in Schools (CoMMinS) study was conducted in schools in the Bristol area over a similar period. Both studies conducted testing to identify current and previous SARS-CoV-2 infection, and recorded symptoms and school attendance. These research data have been linked to routine electronic health record (EHR) data., Aims: To better understand the short- and long-term consequences of SARS-CoV-2 infection, and their risk factors, in CYP., Methods: Retrospective cohort and nested case-control analyses will be conducted for SIS-1 and CoMMinS data linked to EHR data for the association between (1) acute symptomatic SARS-CoV-2 infection and risk factors; (2) SARS-CoV-2 infection and long-term effects on health: (a) persistent symptoms; (b) any new diagnosis; (c) a new prescription in primary care; (d) health service attendance; (e) a high rate of school absence., Results: Our study will improve understanding of long-COVID in CYP by characterising the trajectory of long-COVID in CYP in terms of things like symptoms and diagnoses of conditions. The research will inform which groups of CYP are more likely to get acute- and long-term outcomes of SARS-CoV-2 infection, and patterns of related healthcare-seeking behaviour, relevant for healthcare service planning. Digested information will be produced for affected families, doctors, schools, and the public, as appropriate., Conclusion: Linked SIS-1 and CoMMinS data represent a unique and rich resource for understanding the impact of SARS-CoV-2 infection on children's health, benefiting from enhanced SARS-CoV-2 testing and ability to assess a wide range of outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Looker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years., (© 2024. The Author(s).)

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear., Methods: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history., Results: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses., Conclusions: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

Objectives: To investigate how the COVID-19 pandemic affected the number of people aged 50+ years presenting to primary care with features that could potentially indicate cancer, and to explore how reporting differed by patient characteristics and in face-to-face vs remote consultations., Design, Setting and Participants: A retrospective cohort study of general practitioner (GP), nurse and paramedic primary care consultations in 21 practices in South-West England covering 123 947 patients. The models compared potential cancer indicators reported in April-July 2019 with April-July 2020., Main Outcome Measures: Potential indicators of cancer were identified using code lists for symptoms, signs, test results and diagnoses listed in the National Institute for Health and Care Excellence suspected cancer referral guidance (NG12)., Results: During April-July 2019, 17% of registered patients aged 50+ years reported a potential cancer indicator in a consultation with a GP or nurse. During April-July 2020, this reduced to 11% (incidence rate ratio (IRR) 0.64, 95% CI 0.62 to 0.67, p<0.001). Reductions in potential cancer indicators were stable across age group, sex, ethnicity, index of multiple deprivation quintile and shielding status, but less marked in patients with mental health conditions than without (IRR 0.75, 95% CI 0.72 to 0.79, interaction p<0.001). Proportions of GP consultations with potential indicators of cancer reduced between 2019 and 2020 for face-to-face consultations (IRR 0.84, 95% CI 0.76 to 0.92, p<0.001) and increased for remote consultations (IRR 1.17, 95% CI 1.07 to 1.29, p=0.001), although it remained lower in remote consulting than face-to-face in April-July 2020. This difference was greater for nurse/paramedic consultations (face-to-face: IRR 0.61, 95% CI 0.44 to 0.83, p=0.002; remote: IRR 1.60, 95% CI 1.10 to 2.333, p=0.014)., Conclusion: The number of patients consulting with presentations that could potentially indicate cancer reduced during the first wave of the COVID-19 pandemic. Patients should be encouraged to continue contacting primary care for persistent signs and symptoms, and GPs and nurses should be encouraged to probe patients for further information during remote consulting, in the absence of non-verbal cues., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: To reduce contagion of COVID-19, in March 2020 UK general practices implemented predominantly remote consulting via telephone, video, or online consultation platforms., Aim: To investigate the rapid implementation of remote consulting and explore impact over the initial months of the COVID-19 pandemic., Design and Setting: Mixed-methods study in 21 general practices in Bristol, North Somerset and South Gloucestershire., Method: Longitudinal observational quantitative analysis compared volume and type of consultation in April to July 2020 with April to July 2019. Negative binomial models were used to identify if changes differed among different groups of patients. Qualitative data from 87 longitudinal interviews with practice staff in four rounds investigated practices' experience of the move to remote consulting, challenges faced, and solutions. A thematic analysis utilised Normalisation Process Theory., Results: There was universal consensus that remote consulting was necessary. This drove a rapid change to 90% remote GP consulting (46% for nurses) by April 2020. Consultation rates reduced in April to July 2020 compared to 2019; GPs and nurses maintained a focus on older patients, shielding patients, and patients with poor mental health. Telephone consulting was sufficient for many patient problems, video consulting was used more rarely, and was less essential as lockdown eased. SMS-messaging increased more than three-fold. GPs were concerned about increased clinical risk and some had difficulties setting thresholds for seeing patients face-to-face as lockdown eased., Conclusion: The shift to remote consulting was successful and a focus maintained on vulnerable patients. It was driven by the imperative to reduce contagion and may have risks; post-pandemic, the model will need adjustment., (© The Authors.)

Background: Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. Methods and findings: In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. Conclusions: In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group. In a population-based cohort study, William Whiteley and colleagues investigate the association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events in England. Author summary: Why was this study done: Cases of venous and arterial thromboses in unusual locations, such as the cerebral veins, and with low platelet levels, have been reported after vaccination with ChAdOx1-S COVID-19 vaccine. Case finding efforts in vaccinated people may lead to overestimation of risk associated with vaccines, if diagnostic thresholds vary between vaccinated and unvaccinated people. Effects of vaccination on rates of common venous and arterial events—such as stroke, myocardial infarction (MI), deep vein thrombosis (DVT), and pulmonary embolism (PE)—are difficult to measure based on case reports. Population-level data may give better estimates. What did the researchers do and find: We used nationally collated data from electronic health records on 46 million adults, of whom 21 million were vaccinated during the study, and compared the incidence of venous and arterial events before and after the first vaccination with ChAdOx1-S and BNT162b2 COVID-19 vaccines. Overall rates of major arterial and venous events were lower after vaccination with both ChAdOx1-S and BNT162b2, after adjusting for potential confounding factors. In people <70 years, rates of hospitalisation due to intracranial venous thrombosis (ICVT) or due to thrombocytopenia were higher after vaccination with ChAdOx1-S but not BNT162b2, although the absolute increase in the risk of these events was very small. What do these findings mean: In adults ≥70 years, a first vaccination with either ChAdOx1-S and BNT162b2 was not associated with an increase in rates major arterial or venous thrombotic events. In adults <70 years, the small increased risks of ICVT and hospitalisation with thrombocytopenia after first vaccination with ChAdOx1-S are likely to be outweighed by the vaccines' effect in reducing COVID-19 mortality and morbidity. The main limitations of the study were its reliance on the accuracy of coded electronic health records, and the potential for residual confounding. [ABSTRACT FROM AUTHOR]