The role of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complications.

OBJECTIVE: To study the association between COVID-19 vaccination and the risk of post-COVID-19 cardiac and thromboembolic complications. METHODS: We conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the UK, Spain and Estonia. Vaccine rollout was grouped into four stages with predefined enrolment periods. Each stage included all individuals eligible for vaccination, with no previous SARS-CoV-2 infection or COVID-19 vaccine at the start date. Vaccination status was used as a time-varying exposure. Outcomes included heart failure (HF), venous thromboembolism (VTE) and arterial thrombosis/thromboembolism (ATE) recorded in four time windows after SARS-CoV-2 infection: 0-30, 31-90, 91-180 and 181-365 days. Propensity score overlap weighting and empirical calibration were used to minimise observed and unobserved confounding, respectively.Fine-Gray models estimated subdistribution hazard ratios (sHR). Random effect meta-analyses were conducted across staggered cohorts and databases. RESULTS: The study included 10.17 million vaccinated and 10.39 million unvaccinated people. Vaccination was associated with reduced risks of acute (30-day) and post-acute COVID-19 VTE, ATE and HF: for example, meta-analytic sHR of 0.22 (95% CI 0.17 to 0.29), 0.53 (0.44 to 0.63) and 0.45 (0.38 to 0.53), respectively, for 0-30 days after SARS-CoV-2 infection, while in the 91-180 days sHR were 0.53 (0.40 to 0.70), 0.72 (0.58 to 0.88) and 0.61 (0.51 to 0.73), respectively. CONCLUSIONS: COVID-19 vaccination reduced the risk of post-COVID-19 cardiac and thromboembolic outcomes. These effects were more pronounced for acute COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough versus unvaccinated SARS-CoV-2 infection.

The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia.

BACKGROUND: Although vaccines have proved effective to prevent severe COVID-19, their effect on preventing long-term symptoms is not yet fully understood. We aimed to evaluate the overall effect of vaccination to prevent long COVID symptoms and assess comparative effectiveness of the most used vaccines (ChAdOx1 and BNT162b2). METHODS: We conducted a staggered cohort study using primary care records from the UK (Clinical Practice Research Datalink [CPRD] GOLD and AURUM), Catalonia, Spain (Information System for Research in Primary Care [SIDIAP]), and national health insurance claims from Estonia (CORIVA database). All adults who were registered for at least 180 days as of Jan 4, 2021 (the UK), Feb 20, 2021 (Spain), and Jan 28, 2021 (Estonia) comprised the source population. Vaccination status was used as a time-varying exposure, staggered by vaccine rollout period. Vaccinated people were further classified by vaccine brand according to their first dose received. The primary outcome definition of long COVID was defined as having at least one of 25 WHO-listed symptoms between 90 and 365 days after the date of a PCR-positive test or clinical diagnosis of COVID-19, with no history of that symptom 180 days before SARS-Cov-2 infection. Propensity score overlap weighting was applied separately for each cohort to minimise confounding. Sub-distribution hazard ratios (sHRs) were calculated to estimate vaccine effectiveness against long COVID, and empirically calibrated using negative control outcomes. Random effects meta-analyses across staggered cohorts were conducted to pool overall effect estimates. FINDINGS: A total of 1 618 395 (CPRD GOLD), 5 729 800 (CPRD AURUM), 2 744 821 (SIDIAP), and 77 603 (CORIVA) vaccinated people and 1 640 371 (CPRD GOLD), 5 860 564 (CPRD AURUM), 2 588 518 (SIDIAP), and 302 267 (CORIVA) unvaccinated people were included. Compared with unvaccinated people, overall HRs for long COVID symptoms in people vaccinated with a first dose of any COVID-19 vaccine were 0·54 (95% CI 0·44-0·67) in CPRD GOLD, 0·48 (0·34-0·68) in CPRD AURUM, 0·71 (0·55-0·91) in SIDIAP, and 0·59 (0·40-0·87) in CORIVA. A slightly stronger preventative effect was seen for the first dose of BNT162b2 than for ChAdOx1 (sHR 0·85 [0·60-1·20] in CPRD GOLD and 0·84 [0·74-0·94] in CPRD AURUM). INTERPRETATION: Vaccination against COVID-19 consistently reduced the risk of long COVID symptoms, which highlights the importance of vaccination to prevent persistent COVID-19 symptoms, particularly in adults. FUNDING: National Institute for Health and Care Research.

"The burden of post-acute COVID-19 symptoms in a multinational network cohort analysis".

Persistent symptoms following the acute phase of COVID-19 present a major burden to both the affected and the wider community. We conducted a cohort study including over 856,840 first COVID-19 cases, 72,422 re-infections and more than 3.1 million first negative-test controls from primary care electronic health records from Spain and the UK (Sept 2020 to Jan 2022 (UK)/March 2022 (Spain)). We characterised post-acute COVID-19 symptoms and identified key symptoms associated with persistent disease. We estimated incidence rates of persisting symptoms in the general population and among COVID-19 patients over time. Subsequently, we investigated which WHO-listed symptoms were particularly differential by comparing their frequency in COVID-19 cases vs. matched test-negative controls. Lastly, we compared persistent symptoms after first infections vs. reinfections.Our study shows that the proportion of COVID-19 cases affected by persistent post-acute COVID-19 symptoms declined over the study period. Risk for altered smell/taste was consistently higher in patients with COVID-19 vs test-negative controls. Persistent symptoms were more common after reinfection than following a first infection. More research is needed into the definition of long COVID, and the effect of interventions to minimise the risk and impact of persistent symptoms.

Transforming the Information System for Research in Primary Care (SIDIAP) in Catalonia to the OMOP Common Data Model and Its Use for COVID-19 Research.

Purpose: The primary aim of this work was to convert the Information System for Research in Primary Care (SIDIAP) from Catalonia, Spain, to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Our second aim was to provide a descriptive analysis of COVID-19-related outcomes among the general population. Patients and Methods: We mapped patient-level data from SIDIAP to the OMOP CDM and we performed more than 3,400 data quality checks to assess its readiness for research. We established a general population cohort as of the 1st March 2020 and identified outpatient COVID-19 diagnoses or tested positive for, hospitalised with, admitted to intensive care units (ICU) with, died with, or vaccinated against COVID-19 up to 30th June 2022. Results: After verifying the high quality of the transformed dataset, we included 5,870,274 individuals in the general population cohort. Of those, 604,472 had either an outpatient COVID-19 diagnosis or positive test result, 58,991 had a hospitalisation, 5,642 had an ICU admission, and 11,233 died with COVID-19. A total of 4,584,515 received a COVID-19 vaccine. People who were hospitalised or died were more commonly older, male, and with more comorbidities. Those admitted to ICU with COVID-19 were generally younger and more often male than those hospitalised and those who died. Conclusion: We successfully transformed SIDIAP to the OMOP CDM. From this dataset, a general population cohort of 5.9 million individuals was identified and their COVID-19-related outcomes over time were described. The transformed SIDIAP database is a valuable resource that can enable distributed network research in COVID-19 and beyond.

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

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.

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.

Are we leaving someone behind? A critical discourse analysis on the understanding of public participation among people with experiences of participatory research.

Participatory research (PR) is on the rise. In Spain, PR is scarce in the field of health, although there is an increasing interest in the matter. A comprehensive understanding of the meanings and practical implications of "public participation" is essential to promote participation in health research. The aim of the study is to explore the discursive positions on PR among individuals with experience in participatory processes in different areas and how this understanding translates into practice. We conducted a critical discourse analysis of 21 individuals with experience in PR and participatory processes (13 women, 8 men), mainly from the field of health and other areas of knowledge. Sixteen were Spanish and the rest were from the United Kingdom (3), United States (1), and Canada (1). Interviews were conducted in person or by telephone. The fieldwork was conducted between March 2019 and November 2019. The dominant discourses on public participation are situated along two axes situated on a continuum: the purpose of public participation and how power should be distributed in public participation processes. The first is instrumental public participation, which sees participatory research as a tool to improve research results and focuses on institutional interests and power-decision making is hold by researchers and institutions. The second, is transformative public participation, with a focus on social change and an equitable sharing of decision-making power between the public and researchers. All discursive positions stated that they do not carry out specific strategies to include the most socially disadvantaged individuals or groups. A shift in the scientific approach about knowledge, along with time and resources, are required to move towards a more balanced power distribution in the processes involving the public.

Association between covid-19 vaccination, SARS-CoV-2 infection, and risk of immune mediated neurological events: population based cohort and self-controlled case series analysis.

OBJECTIVE: To study the association between covid-19 vaccines, SARS-CoV-2 infection, and risk of immune mediated neurological events. DESIGN: Population based historical rate comparison study and self-controlled case series analysis. SETTING: Primary care records from the United Kingdom, and primary care records from Spain linked to hospital data. PARTICIPANTS: 8 330 497 people who received at least one dose of covid-19 vaccines ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, or Ad.26.COV2.S between the rollout of the vaccination campaigns and end of data availability (UK: 9 May 2021; Spain: 30 June 2021). The study sample also comprised a cohort of 735 870 unvaccinated individuals with a first positive reverse transcription polymerase chain reaction test result for SARS-CoV-2 from 1 September 2020, and 14 330 080 participants from the general population. MAIN OUTCOME MEASURES: Outcomes were incidence of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. Incidence rates were estimated in the 21 days after the first vaccine dose, 90 days after a positive test result for SARS-CoV-2, and between 2017 and 2019 for background rates in the general population cohort. Indirectly standardised incidence ratios were estimated. Adjusted incidence rate ratios were estimated from the self-controlled case series. RESULTS: The study included 4 376 535 people who received ChAdOx1 nCoV-19, 3 588 318 who received BNT162b2, 244 913 who received mRNA-1273, and 120 731 who received Ad26.CoV.2; 735 870 people with SARS-CoV-2 infection; and 14 330 080 people from the general population. Overall, post-vaccine rates were consistent with expected (background) rates for Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome. Self-controlled case series was conducted only for Bell's palsy, given limited statistical power, but with no safety signal seen for those vaccinated. Rates were, however, higher than expected after SARS-CoV-2 infection. For example, in the data from the UK, the standardised incidence ratio for Bell's palsy was 1.33 (1.02 to 1.74), for encephalomyelitis was 6.89 (3.82 to 12.44), and for Guillain-Barré syndrome was 3.53 (1.83 to 6.77). Transverse myelitis was rare (<5 events in all vaccinated cohorts) and could not be analysed. CONCLUSIONS: No safety signal was observed between covid-19 vaccines and the immune mediated neurological events of Bell's palsy, encephalomyelitis, Guillain-Barré syndrome, and transverse myelitis. An increased risk of Bell's palsy, encephalomyelitis, and Guillain-Barré syndrome was, however, observed for people with SARS-CoV-2 infection.

Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.

Purpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services. Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed. Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.

SARS-CoV2 hospital surveillance and control system with contact tracing for patients and health care workers at a large reference hospital in Spain during the first wave: An observational descriptive study.

BACKGROUND AND AIMS: During the first peak of the COVID-19 pandemic, the Preventive Medicine Department and the Occupational Health Department at Hospital Clinic de Barcelona (HCB), a large Spanish referral hospital, developed an innovative comprehensive SARS-CoV2 Surveillance and Control System (CoSy-19) in order to preserve patients' and health care workers' (HCWs) safety. We aim to describe the CoSy-19 and to assess the impact in the number of contacts that new cases generated along this time. METHODS: Observational descriptive study of the findings of the activity of contact tracing of all cases received at the HCB during the first peak of COVID-19 in Spain (February 25th-May 3rd, 2020). RESULTS: A team of 204 professionals and volunteers performed 384 in-hospital contact-tracing studies which generated contacts, detecting 298 transmission chains which suggested preventive measures, generated around 22 000 follow-ups and more than 30 000 days of work leave. The number of contacts that new cases generated decreased during the study period. CONCLUSION: Coordination between Preventive Medicine and Occupational Health departments and agile information systems were necessary to preserve non-COVID activity and workers safety.

Cancer and the risk of coronavirus disease 2019 diagnosis, hospitalisation and death: A population-based multistate cohort study including 4 618 377 adults in Catalonia, Spain.

The relationship between cancer and coronavirus disease 2019 (COVID-19) infection and severity remains poorly understood. We conducted a population-based cohort study between 1 March and 6 May 2020 describing the associations between cancer and risk of COVID-19 diagnosis, hospitalisation and COVID-19-related death. Data were obtained from the Information System for Research in Primary Care (SIDIAP) database, including primary care electronic health records from ~80% of the population in Catalonia, Spain. Cancer was defined as any primary invasive malignancy excluding non-melanoma skin cancer. We estimated adjusted hazard ratios (aHRs) for the risk of COVID-19 (outpatient) clinical diagnosis, hospitalisation (with or without a prior COVID-19 diagnosis) and COVID-19-related death using Cox proportional hazard regressions. Models were estimated for the overall cancer population and by years since cancer diagnosis (<1 year, 1-5 years and ≥5 years), sex, age and cancer type; and adjusted for age, sex, smoking status, deprivation and comorbidities. We included 4 618 377 adults, of which 260 667 (5.6%) had a history of cancer. A total of 98 951 individuals (5.5% with cancer) were diagnosed, and 6355 (16.4% with cancer) were directly hospitalised with COVID-19. Of those diagnosed, 6851 were subsequently hospitalised (10.7% with cancer), and 3227 died without being hospitalised (18.5% with cancer). Among those hospitalised, 1963 (22.5% with cancer) died. Cancer was associated with an increased risk of COVID-19 diagnosis (aHR: 1.08; 95% confidence interval [1.05-1.11]), direct COVID-19 hospitalisation (1.33 [1.24-1.43]) and death following hospitalisation (1.12 [1.01-1.25]). These associations were stronger for patients recently diagnosed with cancer, aged <70 years, and with haematological cancers. These patients should be prioritised in COVID-19 vaccination campaigns and continued non-pharmaceutical interventions.

Characteristics and outcomes of patients with COVID-19 with and without prevalent hypertension: a multinational cohort study.

OBJECTIVE: To characterise patients with and without prevalent hypertension and COVID-19 and to assess adverse outcomes in both inpatients and outpatients. DESIGN AND SETTING: This is a retrospective cohort study using 15 healthcare databases (primary and secondary electronic healthcare records, insurance and national claims data) from the USA, Europe and South Korea, standardised to the Observational Medical Outcomes Partnership common data model. Data were gathered from 1 March to 31 October 2020. PARTICIPANTS: Two non-mutually exclusive cohorts were defined: (1) individuals diagnosed with COVID-19 (diagnosed cohort) and (2) individuals hospitalised with COVID-19 (hospitalised cohort), and stratified by hypertension status. Follow-up was from COVID-19 diagnosis/hospitalisation to death, end of the study period or 30 days. OUTCOMES: Demographics, comorbidities and 30-day outcomes (hospitalisation and death for the 'diagnosed' cohort and adverse events and death for the 'hospitalised' cohort) were reported. RESULTS: We identified 2 851 035 diagnosed and 563 708 hospitalised patients with COVID-19. Hypertension was more prevalent in the latter (ranging across databases from 17.4% (95% CI 17.2 to 17.6) to 61.4% (95% CI 61.0 to 61.8) and from 25.6% (95% CI 24.6 to 26.6) to 85.9% (95% CI 85.2 to 86.6)). Patients in both cohorts with hypertension were predominantly >50 years old and female. Patients with hypertension were frequently diagnosed with obesity, heart disease, dyslipidaemia and diabetes. Compared with patients without hypertension, patients with hypertension in the COVID-19 diagnosed cohort had more hospitalisations (ranging from 1.3% (95% CI 0.4 to 2.2) to 41.1% (95% CI 39.5 to 42.7) vs from 1.4% (95% CI 0.9 to 1.9) to 15.9% (95% CI 14.9 to 16.9)) and increased mortality (ranging from 0.3% (95% CI 0.1 to 0.5) to 18.5% (95% CI 15.7 to 21.3) vs from 0.2% (95% CI 0.2 to 0.2) to 11.8% (95% CI 10.8 to 12.8)). Patients in the COVID-19 hospitalised cohort with hypertension were more likely to have acute respiratory distress syndrome (ranging from 0.1% (95% CI 0.0 to 0.2) to 65.6% (95% CI 62.5 to 68.7) vs from 0.1% (95% CI 0.0 to 0.2) to 54.7% (95% CI 50.5 to 58.9)), arrhythmia (ranging from 0.5% (95% CI 0.3 to 0.7) to 45.8% (95% CI 42.6 to 49.0) vs from 0.4% (95% CI 0.3 to 0.5) to 36.8% (95% CI 32.7 to 40.9)) and increased mortality (ranging from 1.8% (95% CI 0.4 to 3.2) to 25.1% (95% CI 23.0 to 27.2) vs from 0.7% (95% CI 0.5 to 0.9) to 10.9% (95% CI 10.4 to 11.4)) than patients without hypertension. CONCLUSIONS: COVID-19 patients with hypertension were more likely to suffer severe outcomes, hospitalisations and deaths compared with those without hypertension.

Body Mass Index and Risk of COVID-19 Diagnosis, Hospitalization, and Death: A Cohort Study of 2 524 926 Catalans.

CONTEXT: A comprehensive understanding of the association between body mass index (BMI) and coronavirus disease 2019 (COVID-19) is still lacking. OBJECTIVE: To investigate associations between BMI and risk of COVID-19 diagnosis, hospitalization with COVID-19, and death after a COVID-19 diagnosis or hospitalization (subsequent death), accounting for potential effect modification by age and sex. DESIGN: Population-based cohort study. SETTING: Primary care records covering >80% of the Catalan population, linked to regionwide testing, hospital, and mortality records from March to May 2020. PARTICIPANTS: Adults (≥18 years) with at least 1 measurement of weight and height. MAIN OUTCOME MEASURES: Hazard ratios (HR) for each outcome. RESULTS: We included 2 524 926 participants. After 67 days of follow-up, 57 443 individuals were diagnosed with COVID-19, 10 862 were hospitalized with COVID-19, and 2467 had a subsequent death. BMI was positively associated with being diagnosed and hospitalized with COVID-19. Compared to a BMI of 22 kg/m2, the HR (95% CI) of a BMI of 31 kg/m2 was 1.22 (1.19-1.24) for diagnosis and 1.88 (1.75-2.03) and 2.01 (1.86-2.18) for hospitalization without and with a prior outpatient diagnosis, respectively. The association between BMI and subsequent death was J-shaped, with a modestly higher risk of death among individuals with BMIs ≤ 19 kg/m2 and a more pronounced increasing risk for BMIs ≥ 40 kg/m2. The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients. CONCLUSIONS: There is a monotonic association between BMI and COVID-19 diagnosis and hospitalization risks but a J-shaped relationship with mortality. More research is needed to unravel the mechanisms underlying these relationships.

Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom.

BACKGROUND: A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity. METHODS: We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status. RESULTS: We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity. CONCLUSION: We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies.

Characteristics and Outcomes of Over 300,000 Patients with COVID-19 and History of Cancer in the United States and Spain.

BACKGROUND: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. METHODS: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. RESULTS: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. CONCLUSIONS: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. IMPACT: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

Thirty-Day Outcomes of Children and Adolescents With COVID-19: An International Experience.

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19.

Use of repurposed and adjuvant drugs in hospital patients with covid-19: multinational network cohort study.

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

Unraveling COVID-19: a large-scale characterization of 4.5 million COVID-19 cases using CHARYBDIS.

Background: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response [1,2]. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) [3] Characterizing Health Associated Risks, and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD. Methods: We conducted a descriptive cohort study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11 th June 2020 and are iteratively updated via GitHub [4]. Findings: We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services . All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts, and are available in an interactive website: https://data.ohdsi.org/Covid19CharacterizationCharybdis/. Interpretation: CHARYBDIS findings provide benchmarks that contribute to our understanding of COVID-19 progression, management and evolution over time. This can enable timely assessment of real-world outcomes of preventative and therapeutic options as they are introduced in clinical practice.

The natural history of symptomatic COVID-19 during the first wave in Catalonia.

The natural history of coronavirus disease 2019 (COVID-19) has yet to be fully described. Here, we use patient-level data from the Information System for Research in Primary Care (SIDIAP) to summarise COVID-19 outcomes in Catalonia, Spain. We included 5,586,521 individuals from the general population. Of these, 102,002 had an outpatient diagnosis of COVID-19, 16,901 were hospitalised with COVID-19, and 5273 died after either being diagnosed or hospitalised with COVID-19 between 1st March and 6th May 2020. Older age, being male, and having comorbidities were all generally associated with worse outcomes. These findings demonstrate the continued need to protect those at high risk of poor outcomes, particularly older people, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death were lower for younger populations, there is a need to limit their role in community transmission.