Transforming and evaluating the UK Biobank to the OMOP Common Data Model for COVID-19 research and beyond.

OBJECTIVE: The COVID-19 pandemic has demonstrated the value of real-world data for public health research. International federated analyses are crucial for informing policy makers. Common data models (CDM) are critical for enabling these studies to be performed efficiently. Our objective was to convert the UK Biobank, a study of 500,000 participants with rich genetic and phenotypic data to the Observational Medical Outcomes Partnership (OMOP) CDM. MATERIALS AND METHODS: We converted UK Biobank data to OMOP CDM v. 5.3. We transformedparticipant research data on diseases collected at recruitment and electronic health records (EHR) from primary care, hospitalizations, cancer registrations, and mortality from providers in England, Scotland, and Wales. We performed syntactic and semantic validations and compared comorbidities and risk factors between source and transformed data. RESULTS: We identified 502,505 participants (3,086 with COVID-19) and transformed 690 fields (1,373,239,555 rows) to the OMOP CDM using eight different controlled clinical terminologies and bespoke mappings. Specifically, we transformed self-reported non-cancer illnesses 946,053 (83.91% of all source entries), cancers 37,802 (70.81%), medications 1,218,935 (88.25%), and prescriptions 864,788 (86.96%). In EHR, we transformed 1,3028,182 (99.95%) hospital diagnoses, 6,465,399 (89.2%) procedures, 337,896,333 primary care diagnoses (CTV3, SNOMED-CT), 139,966,587 (98.74%) prescriptions (dm+d) and 77,127 (99.95%) deaths (ICD-10). We observed good concordance across demographic, risk factor, and comorbidity factors between source and transformed data. DISCUSSION AND CONCLUSION: Our study demonstrated that the OMOP CDM can be successfully leveraged to harmonize complex large-scale biobanked studies combining rich multimodal phenotypic data. Our study uncovered several challenges when transforming data from questionnaires to the OMOP CDM which require further research. The transformed UK Biobank resource is a valuable tool that can enable federated research, like COVID-19 studies.

Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study.

BACKGROUND: There are few data on the incidence of thrombosis among COVID-19 cases, with most research concentrated on hospitalised patients. We aimed to estimate the incidence of venous thromboembolism, arterial thromboembolism, and death among COVID-19 cases and to assess the impact of these events on the risks of hospitalisation and death. METHODS: We conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality. FINDINGS: Overall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07-6·36] for those not hospitalised and 1·63 [1·39-1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65-3·75] and 1·93 [1·57-2·37]). INTERPRETATION: Risks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency. FUNDING: European Medicines Agency.

Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study.

Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US. Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards). Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use. Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.

The impact of COVID-19 certification mandates on the number of cases of and hospitalizations with COVID-19 in the UK: A difference-in-differences analysis

Background Mandatory COVID-19 certification, showing proof of vaccination, negative test, or recent infection to access to public venues, was introduced at different times in the four countries of the UK. We aim to study its effects on the incidence of cases and hospital admissions. Methods We performed Negative binomial segmented regression and ARIMA analyses for four countries (England, Northern Ireland, Scotland and Wales), and fitted Difference-in-Differences models to compare the latter three to England, as a negative control group, since it was the last country where COVID-19 certification was introduced. The main outcome was the weekly averaged incidence of COVID-19 cases and hospital admissions. Results COVID-19 certification led to a decrease in the incidence of cases and hospital admissions in Northern Ireland, as well as in Wales during the second half of November. The same was seen for hospital admissions in Wales and Scotland during October. In Wales the incidence rate of cases in October already had a decreasing tendency, as well as in England, hence a particular impact of COVID-19 certification was less obvious. Method assumptions for the Difference-in-Differences analysis did not hold for Scotland. Additional NBSR and ARIMA models suggest similar results, while also accounting for correlation in the latter. The assessment of the effect in England itself leads one to believe that this intervention might not be strong enough for the Omicron variant, which was prevalent at the time of introduction of COVID-19 certification in the country. Conclusions Mandatory COVID-19 certification reduced COVID-19 transmission and hospitalizations when Delta predominated in the UK, but lost efficacy when Omicron became the most common variant.

Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.

Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.

Characteristics and outcomes of COVID-19 patients with and without asthma from the United States, South Korea, and Europe.

Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma.Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions.Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients.Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients.[Box: see text]Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .

Integrating real-world data from Brazil and Pakistan into the OMOP common data model and standardized health analytics framework to characterize COVID-19 in the Global South.

OBJECTIVES: The aim of this work is to demonstrate the use of a standardized health informatics framework to generate reliable and reproducible real-world evidence from Latin America and South Asia towards characterizing coronavirus disease 2019 (COVID-19) in the Global South. MATERIALS AND METHODS: Patient-level COVID-19 records collected in a patient self-reported notification system, hospital in-patient and out-patient records, and community diagnostic labs were harmonized to the Observational Medical Outcomes Partnership common data model and analyzed using a federated network analytics framework. Clinical characteristics of individuals tested for, diagnosed with or tested positive for, hospitalized with, admitted to intensive care unit with, or dying with COVID-19 were estimated. RESULTS: Two COVID-19 databases covering 8.3 million people from Pakistan and 2.6 million people from Bahia, Brazil were analyzed. 109 504 (Pakistan) and 921 (Brazil) medical concepts were harmonized to Observational Medical Outcomes Partnership common data model. In total, 341 505 (4.1%) people in the Pakistan dataset and 1 312 832 (49.2%) people in the Brazilian dataset were tested for COVID-19 between January 1, 2020 and April 20, 2022, with a median [IQR] age of 36 [25, 76] and 38 (27, 50); 40.3% and 56.5% were female in Pakistan and Brazil, respectively. 1.2% percent individuals in the Pakistan dataset had Afghan ethnicity. In Brazil, 52.3% had mixed ethnicity. In agreement with international findings, COVID-19 outcomes were more severe in men, elderly, and those with underlying health conditions. CONCLUSIONS: COVID-19 data from 2 large countries in the Global South were harmonized and analyzed using a standardized health informatics framework developed by an international community of health informaticians. This proof-of-concept study demonstrates a potential open science framework for global knowledge mobilization and clinical translation for timely response to healthcare needs in pandemics and beyond.

The impact of COVID-19 certification mandates on the number of cases of and hospitalizations with COVID-19 in the UK: A difference-in-differences analysis.

Background: Mandatory COVID-19 certification, showing proof of vaccination, negative test, or recent infection to access to public venues, was introduced at different times in the four countries of the UK. We aim to study its effects on the incidence of cases and hospital admissions. Methods: We performed Negative binomial segmented regression and ARIMA analyses for four countries (England, Northern Ireland, Scotland and Wales), and fitted Difference-in-Differences models to compare the latter three to England, as a negative control group, since it was the last country where COVID-19 certification was introduced. The main outcome was the weekly averaged incidence of COVID-19 cases and hospital admissions. Results: COVID-19 certification led to a decrease in the incidence of cases and hospital admissions in Northern Ireland, as well as in Wales during the second half of November. The same was seen for hospital admissions in Wales and Scotland during October. In Wales the incidence rate of cases in October already had a decreasing tendency, as well as in England, hence a particular impact of COVID-19 certification was less obvious. Method assumptions for the Difference-in-Differences analysis did not hold for Scotland. Additional NBSR and ARIMA models suggest similar results, while also accounting for correlation in the latter. The assessment of the effect in England itself leads one to believe that this intervention might not be strong enough for the Omicron variant, which was prevalent at the time of introduction of COVID-19 certification in the country. Conclusions: Mandatory COVID-19 certification reduced COVID-19 transmission and hospitalizations when Delta predominated in the UK, but lost efficacy when Omicron became the most common variant.

Corrigendum: Transmissibility, hospitalization, and intensive care admissions due to omicron compared to delta variants of SARS-CoV-2 in Catalonia: A cohort study and ecological analysis.

[This corrects the article DOI: 10.3389/fpubh.2022.961030.].

Risk of COVID-19 Diagnosis and Hospitalisation in Patients with Osteoarthritis or Back Pain Treated with Ibuprofen Compared to Other NSAIDs or Paracetamol: A Network Cohort Study.

OBJECTIVE: We aimed to investigate whether ibuprofen use, compared with other non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs), cyclooxygenase-2 inhibitors (COX-2i) or paracetamol, increases the risk of coronavirus disease 2019 (COVID-19) diagnosis or hospitalisation. DESIGN: A prevalent user and active comparator cohort study. SETTING: Two US claims databases (Open Claims and PharMetrics Plus) mapped to the Observational Medical Outcomes Partnership Common Data Model. PARTICIPANTS: Insured patients with a history of osteoarthritis or back pain and receiving ibuprofen, other ns-NSAIDs, COX-2i or paracetamol between 1 November, 2019 and 31 January, 2020 (study enrolment window 1) or between 1 February, 2020 and 31 October, 2020 (study enrolment window 2). MAIN OUTCOME MEASURES: Large-scale propensity score matching and empirical calibration were used to minimise confounding. Incidence and hazard ratios of COVID-19 diagnosis and hospitalisation according to drug/s use were estimated and pooled in the same study period across data sources using a fixed-effects meta-analysis. Index treatment episode was the primary risk evaluation window, censored at the time of discontinuation. RESULTS: A total of 633,562 and 1,063,960 participants were included in periods 1 and 2, respectively, for the ibuprofen versus ns-NSAIDs comparison, 311,669 and 524,470 for ibuprofen versus COX-2i, and 492,002 and 878,598 for ibuprofen versus paracetamol. Meta-analyses of empirically calibrated hazard ratios revealed no significantly differential risk of COVID-19 outcomes in users of ibuprofen versus any of the other studied analgesic classes: hazard ratios were 1.13 (0.96-1.33) for the ibuprofen-ns-NSAIDs comparison, 1.03 (0.83-1.28) for the ibuprofen-COX-2i comparison and 1.13 (0.74-1.73) for ibuprofen-paracetamol comparison on COVID-19 diagnosis in the February 2020-October 2020 window. Similar hazard ratios were found on COVID-19 hospitalisation and across both study periods. CONCLUSIONS: In patients with osteoarthritis or back pain, we found no differential risks of incident COVID-19 diagnosis or COVID-19 hospitalisation for ibuprofen users compared with other ns-NSAIDs, COX-2i or paracetamol. Our findings support regulatory recommendations that NSAIDs, including ibuprofen, should be prescribed as indicated in the same way as before the COVID-19 pandemic, especially for those who rely on ibuprofen or NSAIDs to manage chronic arthritis or musculoskeletal pain symptoms.

Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in Catalonia, Spain.

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Here we compare rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 with the background (expected) rates in the general population. In addition, we compare the rates of the same adverse events among persons infected with SARS-CoV-2 with background rates. Primary care and linked hospital data from Catalonia, Spain informed the study, with participants vaccinated with BNT162b2 or ChAdOx1 (27/12/2020-23/06/2021), COVID-19 cases (01/09/2020-23/06/2021) or present in the database as of 01/01/2017. We included 2,021,366 BNT162b2 (1,327,031 with 2 doses), 592,408 ChAdOx1, 174,556 COVID-19 cases, and 4,573,494 background participants. Standardised incidence ratios for venous thromboembolism were 1.18 (95% CI 1.06-1.32) and 0.92 (0.81-1.05) after first- and second dose BNT162b2, and 0.92 (0.71-1.18) after first dose ChAdOx1. The standardised incidence ratio for venous thromboembolism in COVID-19 was 10.19 (9.43-11.02). Standardised incidence ratios for arterial thromboembolism were 1.02 (0.95-1.09) and 1.04 (0.97-1.12) after first- and second dose BNT162b2, 1.06 (0.91-1.23) after first-dose ChAdOx1 and 4.13 (3.83-4.45) for COVID-19. Standardised incidence ratios for thrombocytopenia were 1.49 (1.43-1.54) and 1.40 (1.35-1.45) after first- and second dose BNT162b2, 1.28 (1.19-1.38) after first-dose ChAdOx1 and 4.59 (4.41- 4.77) for COVID-19. While rates of thrombosis with thrombocytopenia were generally similar to background rates, the standardised incidence ratio for pulmonary embolism with thrombocytopenia after first-dose BNT162b2 was 1.70 (1.11-2.61). These findings suggest that the safety profiles of BNT162b2 and ChAdOx1 are similar, with rates of adverse events seen after vaccination typically similar to background rates. Meanwhile, rates of adverse events are much increased for COVID-19 cases further underlining the importance of vaccination.

Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom.

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified. A further cohort consisted of people with no prior COVID-19 vaccination who were infected with SARS-Cov-2 identified by a first positive PCR test between 1 September 2020 and 2 May 2021. The fourth general population cohort for background rates included those people in the database as of 1 January 2017. In total, we included 3,768,517 ChAdOx1 and 1,832,841 BNT162b2 vaccinees, 401,691 people infected with SARS-CoV-2, and 9,414,403 people from the general population. An increased risk of venous thromboembolism was seen after first dose of ChAdOx1 (standardized incidence ratio: 1.12 [95% CI: 1.05 to 1.20]), BNT162b2 (1.12 [1.03 to 1.21]), and positive PCR test (7.27 [6.86 to 7.72]). Rates of cerebral venous sinus thrombosis were higher than otherwise expected after first dose of ChAdOx1 (4.14 [2.54 to 6.76]) and a SARS-CoV-2 PCR positive test (3.74 [1.56 to 8.98]). Rates of arterial thromboembolism after vaccination were no higher than expected but were increased after a SARS-CoV-2 PCR positive test (1.39 [1.21 to 1.61]). Rates of venous thromboembolism with thrombocytopenia were higher than expected after a SARS-CoV-2 PCR positive test (5.76 [3.19 to 10.40]).

International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients.

Purpose: Alpha-1 blockers, often used to treat benign prostatic hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storm release. The proposed treatment based on this hypothesis currently lacks support from reliable real-world evidence, however. We leverage an international network of large-scale healthcare databases to generate comprehensive evidence in a transparent and reproducible manner. Methods: In this international cohort study, we deployed electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We assessed association between alpha-1 blocker use and risks of three COVID-19 outcomes-diagnosis, hospitalization, and hospitalization requiring intensive services-using a prevalent-user active-comparator design. We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We pooled database-specific estimates through random effects meta-analysis. Results: Our study overall included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH medications. We observed no significant difference in their risks for any of the COVID-19 outcomes, with our meta-analytic HR estimates being 1.02 (95% CI: 0.92-1.13) for diagnosis, 1.00 (95% CI: 0.89-1.13) for hospitalization, and 1.15 (95% CI: 0.71-1.88) for hospitalization requiring intensive services. Conclusion: We found no evidence of the hypothesized reduction in risks of the COVID-19 outcomes from the prevalent-use of alpha-1 blockers-further research is needed to identify effective therapies for this novel disease.

Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines: international network cohort study from five European countries and the US.

OBJECTIVE: To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. DESIGN: International network cohort study. SETTING: Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. PARTICIPANTS: Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. MAIN OUTCOME MEASURES: Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. RESULTS: Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. CONCLUSIONS: In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

Socioeconomic Inequalities in COVID-19 Vaccination and Infection in Adults, Catalonia, Spain.

Evidence on the impact of the COVID-19 vaccine rollout on socioeconomic COVID-19-related inequalities is scarce. We analyzed associations between socioeconomic deprivation index (SDI) and COVID-19 vaccination, infection, and hospitalization before and after vaccine rollout in Catalonia, Spain. We conducted a population-based cohort study during September 2020-June 2021 that comprised 2,297,146 adults >40 years of age. We estimated odds ratio of nonvaccination and hazard ratios (HRs) of infection and hospitalization by SDI quintile relative to the least deprived quintile, Q1. Six months after rollout, vaccination coverage differed by SDI quintile in working-age (40-64 years) persons: 81% for Q1, 71% for Q5. Before rollout, we found a pattern of increased HR of infection and hospitalization with deprivation among working-age and retirement-age (>65 years) persons. After rollout, infection inequalities decreased in both age groups, whereas hospitalization inequalities decreased among retirement-age persons. Our findings suggest that mass vaccination reduced socioeconomic COVID-19-related inequalities.

International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients

Purpose: Alpha-1 blockers, often used to treat benign prostatic hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storm release. The proposed treatment based on this hypothesis currently lacks support from reliable real-world evidence, however. We leverage an international network of large-scale healthcare databases to generate comprehensive evidence in a transparent and reproducible manner. Methods: In this international cohort study, we deployed electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We assessed association between alpha-1 blocker use and risks of three COVID-19 outcomes—diagnosis, hospitalization, and hospitalization requiring intensive services—using a prevalent-user active-comparator design. We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We pooled database-specific estimates through random effects meta-analysis. Results: Our study overall included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH medications. We observed no significant difference in their risks for any of the COVID-19 outcomes, with our meta-analytic HR estimates being 1.02 (95% CI: 0.92–1.13) for diagnosis, 1.00 (95% CI: 0.89–1.13) for hospitalization, and 1.15 (95% CI: 0.71–1.88) for hospitalization requiring intensive services. Conclusion: We found no evidence of the hypothesized reduction in risks of the COVID-19 outcomes from the prevalent-use of alpha-1 blockers—further research is needed to identify effective therapies for this novel disease.

Genetic risk and incident venous thromboembolism in middle-aged and older adults following COVID-19 vaccination.

BACKGROUND: COVID-19 vaccination has been associated with increased venous thromboembolism (VTE) risk. However, it is unknown whether genetic predisposition to VTE is associated with an increased risk of thrombosis following vaccination. METHODS: Using data from the UK Biobank, which contains in-depth genotyping and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants. We prospectively assessed associations between PRS and incident VTE immediately after first- and the second-dose vaccination and among historical unvaccinated cohorts during the pre- and early pandemic. We estimated hazard ratios (HR) for PRS-VTE associations using Cox models. RESULTS: Of 359 310 individuals receiving one dose of a COVID-19 vaccine, 160 327 (44.6%) were males, and the mean age at the vaccination date was 69.05 (standard deviation [SD] 8.04) years. After 28- and 90-days' follow-up, 88 and 299 individuals developed VTE, respectively, equivalent to an incidence rate of 0.88 (95% confidence interval [CI] 0.70-1.08) and 0.92 (0.82-1.04) per 100 000 person-days. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (1.15-1.73) in 28 days and 1.36 (1.22-1.52) in 90 days). Similar associations were found in the historical unvaccinated cohorts. CONCLUSIONS: The strength of genetic susceptibility with post-COVID-19-vaccination VTE is similar to that seen in historical data. Additionally, the observed PRS-VTE associations were equivalent for adenovirus- and mRNA-based vaccines. These findings suggest that, at the population level, the VTE that occurred after the COVID-19 vaccination has a similar genetic etiology to the conventional VTE.