Establishing and characterising large COVID-19 cohorts after mapping the Information System for Research in Primary Care in Catalonia to the OMOP Common Data Model

BackgroundFew datasets have been established that capture the full breadth of COVID-19 patient interactions with a health system. Our first objective was to create a COVID-19 dataset that linked primary care data to COVID-19 testing, hospitalisation, and mortality data at a patient level. Our second objective was to provide a descriptive analysis of COVID-19 outcomes among the general population and describe the characteristics of the affected individuals. MethodsWe mapped patient-level data from Catalonia, Spain, to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). More than 3,000 data quality checks were performed to assess the readiness of the database for research. Subsequently, to summarise the COVID-19 population captured, we established a general population cohort as of the 1st March 2020 and identified outpatient COVID-19 diagnoses or positive test results for SARS-CoV-2, hospitalisations with COVID-19, and COVID-19 deaths during follow-up, which went up until 30th June 2021. FindingsMapping data to the OMOP CDM was performed and high data quality was observed. The mapped database was used to identify a total of 5,870,274 individuals, who were included in the general population cohort as of 1st March 2020. Over follow up, 604,472 had either an outpatient COVID-19 diagnosis or positive test result, 58,991 had a hospitalisation with COVID-19, 5,642 had an ICU admission with COVID-19, and 11,233 had a COVID-19 death. 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 in general and those who died. InterpretationWe have established a comprehensive dataset that captures COVID-19 diagnoses, test results, hospitalisations, and deaths in Catalonia, Spain. Extensive data checks have shown the data to be fit for use. From this dataset, a general population cohort of 5.9 million individuals was identified and their COVID-19 outcomes over time were described. FundingGeneralitat de Catalunya and European Health Data and Evidence Network (EHDEN).

The impact of the COVID-19 pandemic on diagnoses of common mental health disorders in adults in Catalonia, Spain

ObjectivesTo investigate how incidence trends of anxiety and depressive disorders have been affected by the COVID-19 pandemic. DesignPopulation-based cohort study. SettingObservational cohort study from 2018 to 2021 using the Information System for Research in Primary Care (SIDIAP) database in Catalonia, Spain. Participants4,255,847 individuals aged 18 or older in SIDIAP on 1 March, 2018 with no prior history of anxiety and depressive disorders. Primary and secondary outcomes measuresIncidence of anxiety and depressive disorders prior to COVID-19 (March, 2018 to February, 2020), during the COVID-19 lockdown (March to June, 2020) and post-lockdown periods (from July, 2020 to March, 2021) were calculated. Forecasted rates over COVID-19 periods were estimated using negative binomial regression models based on previous data. The percentage reduction was estimated by comparing forecasted versus observed events, overall and by age, sex and socioeconomic status. ResultsThe incidence rates per 100,000 person-months of anxiety and depressive disorders were 171.0 (95%CI: 170.2-171.8) and 46.6 (46.2-47.0), respectively, during the pre-lockdown period. We observed an increase of 39.7% (95%PI: 26.5 to 53.3) in incident anxiety diagnoses compared to the expected in March, 2020, followed by a reduction of 16.9% (8.6 to 24.5) during the post-lockdown periods. A reduction of incident depressive disorders occurred during the lockdown and post-lockdown periods (46.6% [38.9 to 53.1] and 23.2% [12.0 to 32.7], respectively). Reductions were higher among adults aged 18 to 34 and individuals living in most deprived areas. ConclusionsThe COVID-19 pandemic in Catalonia was associated with an initial increase in anxiety disorders diagnosed in primary care, but a reduction in cases as the pandemic continued. Diagnoses of depressive disorders were lower than expected throughout the pandemic. Summary boxO_ST_ABSWhat is already known on this topicC_ST_ABS- While previous self-reported studies have provided evidence of increased mental health burden during the initial phase of the COVID-19 pandemic, a number of studies observed that fewer diagnoses were made in primary care settings than would have been expected during the initial stages of the pandemic. - Population data that examine the impact of COVID-19 on temporal trends of incident cases of common mental health disorders are lacking in Catalonia, Spain. What this study adds- This study has quantified the impact of the COVID-19 pandemic on trends of incidence of anxiety and depressive disorders among adults living in Catalonia. - Reductions in incident cases of anxiety and depressive disorders were higher for young adults and people living in most deprived areas. - Incident diagnoses of anxiety and depressive disorders have not been fully recovered to what would have been expected.

Cancer and the risk of COVID-19 diagnosis, hospitalisation, and death: a population-based multi-state cohort study including 4,618,377 adults in Catalonia, Spain

ObjectivesTo investigate the associations between cancer and risk of outpatient COVID-19 diagnosis, hospitalisation, and COVID-19-related death, overall and by years since cancer diagnosis (<1-year, 1-5-years, >5-years), sex, age, and cancer type. DesignPopulation-based cohort study SettingPrimary care electronic health records including [~]80% of the population in Catalonia, Spain, linked to hospital and mortality records between 1 March and 6 May 2020. ParticipantsIndividuals aged [≥]18 years with at least one year of prior medical history available from the general population. Cancer was defined as any prior diagnosis of a primary invasive malignancy excluding non-melanoma skin cancer. Main outcome measuresCause-specific hazard ratios (aHR) with 95% confidence intervals for each outcome. Estimates were adjusted by age, sex, deprivation, smoking status, and comorbidities. ResultsWe included 4,618,377 adults, of which 260,667 (5.6%) had a history of cancer. Patients with cancer were older and had more comorbidities than cancer-free patients. A total of 98,951 individuals (5.5% with cancer) were diagnosed and 6,355 (16.4% with cancer) were directly hospitalised (no prior diagnosis) with COVID-19. Of those diagnosed, 6,851 were subsequently hospitalised (10.7% with cancer) and 3,227 died without being hospitalised (18.5% with cancer). Among those hospitalised, 1,963 (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 a COVID-19 hospitalisation (1.12 [1.01-1.25]). These associations were stronger for patients recently diagnosed with cancer, aged <70 years, and with haematological cancers. ConclusionsPatients recently diagnosed with cancer, aged <70 years, or with haematological cancers are a high-risk population for COVID-19 diagnosis and severity. These patients should be prioritised in COVID-19 vaccination campaigns and continued non-pharmaceutical interventions. What is already known on this subjectO_LIPrior studies addressing the relationship between cancer and COVID-19 infection and adverse outcomes have found conflicting results C_LIO_LIThe majority of these studies had small sample sizes, were not population-based (i.e. restricted to hospitalised patients), thus increasing the risks of selection and collider bias. C_LIO_LIIn addition, they used different definitions for cancer (i.e. some included only patients with active cancer, while others focused on specific cancer types, etc.), which limits the comparability of their findings, and only a few analysed the effect of cancer across different patient subgroups. C_LI What this study addsO_LIWe conducted a population-based cohort study to analyse the associations between having a prior diagnosis of cancer and the risks of COVID-19 diagnosis, hospitalisation and COVID-19-related deaths from 1 March to 6 May 2020. C_LIO_LIIn a population of 4,618,377 adults, we found that 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 a COVID-19 hospitalisation (1.12 [1.01-1.25]). C_LIO_LIThese risks were higher for patients recently diagnosed with cancer (within the last year), younger than 70 years, or with haematological cancers. We also found a particularly high risk of COVID-19 hospitalisation and death among patients with lung and bladder cancer. C_LI

Background rates of five thrombosis with thrombocytopenia syndromes of special interest for COVID-19 vaccine safety surveillance: incidence between 2017 and 2019 and patient profiles from 20.6 million people in six European countries

BackgroundThrombosis with thrombocytopenia syndrome (TTS) has been reported among individuals vaccinated with adenovirus-vectored COVID-19 vaccines. In this study we describe the background incidence of TTS in 6 European countries. MethodsElectronic medical records from France, Netherlands, Italy, Germany, Spain, and the United Kingdom informed the study. Incidence rates of cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke, all with concurrent thrombocytopenia, were estimated among the general population between 2017 to 2019. A range of additional adverse events of special interest for COVID-19 vaccinations were also studied in a similar manner. FindingsA total of 25,432,658 individuals were included. Background rates ranged from 1.0 (0.7 to 1.4) to 8.5 (7.4 to 9.9) per 100,000 person-years for DVT with thrombocytopenia, from 0.5 (0.3 to 0.6) to 20.8 (18.9 to 22.8) for PE with thrombocytopenia, from 0.1 (0.0 to 0.1) to 2.5 (2.2 to 2.7) for SVT with thrombocytopenia, and from 0.2 (0.0 to 0.4) to 30.9 (28.6 to 33.3) for stroke with thrombocytopenia. CVST with thrombocytopenia was only identified in one database, with incidence rate of 0.1 (0.1 to 0.2) per 100,000 person-years. The incidence of TTS increased with age, with those affected typically having more comorbidities and greater medication use than the general population. TTS was also more often seen in men than women. A sizeable proportion of those affected were seen to have been taking antithrombotic and anticoagulant therapies prior to their TTS event. InterpretationAlthough rates vary across databases, TTS has consistently been seen to be a very rare event among the general population. While still very rare, rates of TTS are typically higher among older individuals, and those affected were also seen to generally be male and have more comorbidities and greater medication use than the general population. FundingThis study was funded by the European Medicines Agency (EMA/2017/09/PE Lot 3).

Alpha-1 blockers and susceptibility to COVID-19 in benign prostate hyperplasia patients : an international cohort study

Alpha-1 blockers, often used to treat benign prostate hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storms release. We conducted a prevalent-user active-comparator cohort study to assess association between alpha-1 blocker use and risks of three COVID-19 outcomes: diagnosis, hospitalization, and hospitalization requiring intensive services. Our study included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH therapy during the period between November 2019 and January 2020, found in 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 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 found no differential risk for any of COVID-19 outcome, pointing to the need for further research on potential COVID-19 therapies.

Characteristics and outcomes of 118,155 COVID-19 individuals with a history of cancer in the United States and Spain

PurposeWe aimed to describe the demographics, cancer subtypes, comorbidities and outcomes of patients with a history of cancer with COVID-19 from March to June 2020. Secondly, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. MethodsWe conducted a cohort study using eight routinely-collected healthcare databases from Spain and the US, 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 2017-2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. ResultsWe included 118,155 patients with a cancer history in the COVID-19 diagnosed and 41,939 in the COVID-19 hospitalized cohorts. The most frequent cancer subtypes were prostate and breast cancer (range: 5-19% and 1-14% in the diagnosed cohort, respectively). Hematological malignancies were also frequent, with non-Hodgkins lymphoma being among the 5 most common cancer subtypes in the diagnosed cohort. Overall, patients were more frequently aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 8% to 14% and from 18% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n=242,960) had a similar distribution of cancer subtypes, sex, age and comorbidities but lower occurrence of adverse events. ConclusionPatients with a history of cancer and COVID-19 have advanced age, multiple comorbidities, and a high occurence of COVID-19-related events. Additionaly, hematological malignancies were frequent in these patients.This observational study provides epidemiologic characteristics that can inform clinical care and future etiological studies.

Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a population-based multi-state cohort analysis including 2,524,926 people in Catalonia, Spain

ObjectiveTo investigate associations between body mass index (BMI) and risk of COVID-19 diagnosis, hospitalisation with COVID-19, and COVID-19-related death, accounting for potential effect modification by age and sex. DesignPopulation-based cohort study. SettingPrimary care records covering >80% of the Catalonian population (Spain), linked to region-wide testing, hospital, and mortality records from March to May 2020. ParticipantsPeople aged [≥]18 years with at least one measurement of weight and height from the general population and with at least one year of prior medical history available. Main outcome measuresCause-specific hazard ratios (HR) with 95% confidence intervals for each outcome. ResultsOverall, 2,524,926 participants were followed up for a median of 67 days. A total of 57,443 individuals were diagnosed with COVID-19, 10,862 were hospitalised with COVID-19, and 2,467 had a COVID-19-related death. BMI was positively associated with being diagnosed as well as hospitalised with COVID-19. Compared to a BMI of 22kg/m2, the HR (95%CI) of a BMI of 31kg/m2 was 1.22 (1.19-1.24) for COVID-19 diagnosis, and 1.88 (1.75-2.03) and 2.01 (1.86-2.18) for hospitalisation without and with a prior outpatient diagnosis, respectively. The relation between BMI and risk of COVID-19 related death was J-shaped. There was a modestly higher risk of death among individuals with BMIs[≤]19 kg/m2 and a more pronounced increasing risk for BMIs [≥]37 kg/m2 and [≥]40 kg/m2 among those who were previously hospitalised with COVID-19 and diagnosed with COVID-19 in outpatient settings, respectively. The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients. ConclusionsThere is a monotonic association between BMI and COVID-19 infection and hospitalisation risks, but a J-shaped one with mortality. More research is needed to unravel the mechanisms underlying these relationships. Summary boxesO_ST_ABSSection 1: What is already known on this topicC_ST_ABSO_LIA high body mass index (BMI) has previously been associated in a linear and non-linear fashion with an increased risk of multiple health outcomes; these associations may vary by individual factors such as age and sex. C_LIO_LIObesity has been identified as a risk factor for COVID-19 severity and mortality. However, the role of general adiposity in relation to COVID-19 outcomes has mostly been studied by dichotomizing BMI (below or above 30 kg/m2) or by a diagnostic code indicating obesity. C_LIO_LITwo studies have investigated BMI (as a continuous variable) in relation to COVID-19 outcomes, accounting for non-linearity: one conducted in a tested population sample of the UK Biobank found BMI is related in a dose-response manner with the risk of testing positive for COVID-19; another conducted in a hospital setting in New York reported a J-shaped association between BMI and the risk of intubation or death. These studies were limited in sample size and were prone to collider bias due to the participants restriction to tested and hospitalised patients. No studies have described the association between BMI and COVID-19 outcomes across the natural history of the disease (from no disease to symptomatic disease, hospitalisation, and mortality) using data from diverse health settings. C_LI Section 2: What this study addsO_LIWe provide a comprehensive analysis of the association between BMI and the course of the COVID-19 disease in the general population of a Spanish region during the first wave of the pandemic, using linked data capturing outpatient clinical diagnoses, RT-PCR test results, hospitalisations, and mortality (inside and outside of the hospital setting). C_LIO_LIWe found that BMI is positively associated with being diagnosed as well as hospitalised with COVID-19, and is linked in a J-shaped fashion with the risk of COVID-19 related death. C_LIO_LIThe association between BMI and COVID-19 related outcomes is modified by age and sex; particularly, the risk of COVID-19 outcomes related to increased BMI is higher for those aged between 18 and 59 years, compared to those in older age groups. C_LI

Characteristics, outcomes, and mortality amongst 133,589 patients with prevalent autoimmune diseases diagnosed with, and 48,418 hospitalised for COVID-19: a multinational distributed network cohort analysis

ObjectivePatients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. DesignMultinational network cohort study SettingElectronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea). ParticipantsAll patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included. Main outcome measures30-day complications during hospitalisation and death ResultsWe studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 with prevalent autoimmune diseases. The majority of participants were female (60.5% to 65.9%) and aged [≥]50 years. The most prevalent autoimmune conditions were psoriasis (3.5 to 32.5%), rheumatoid arthritis (3.9 to 18.9%), and vasculitis (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis in HIRA (18.9%), and psoriasis in SIDIAP-H (26.4%). Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%). ConclusionsPatients with autoimmune diseases had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19. Compared to influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 patients with autoimmune diseases. What is already known about this topicO_LIPatients with autoimmune conditions may be at increased risk of COVID-19 infection andcomplications. C_LIO_LIThere is a paucity of evidence characterising the outcomes of hospitalised COVID-19 patients with prevalent autoimmune conditions. C_LI What this study addsO_LIMost people with autoimmune diseases who required hospitalisation for COVID-19 were women, aged 50 years or older, and had substantial previous comorbidities. C_LIO_LIPatients who were hospitalised with COVID-19 and had prevalent autoimmune diseases had higher prevalence of hypertension, chronic kidney disease, heart disease, and Type 2 diabetes as compared to those with prevalent autoimmune diseases who were diagnosed with COVID-19. C_LIO_LIA variable proportion of 6% to 25% across data sources died within one month of hospitalisation with COVID-19 and prevalent autoimmune diseases. C_LIO_LIFor people with autoimmune diseases, COVID-19 hospitalisation was associated with worse outcomes and 30-day mortality compared to admission with influenza in the 2017-2018 season. C_LI

Baseline characteristics, management, and outcomes of 55,270 children and adolescents diagnosed with COVID-19 and 1,952,693 with influenza in France, Germany, Spain, South Korea and the United States: an international network cohort study

ObjectivesTo characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children/adolescents diagnosed or hospitalized with COVID-19. Secondly, to describe health outcomes amongst children/adolescents diagnosed with previous seasonal influenza. DesignInternational network cohort. SettingReal-world data from European primary care records (France/Germany/Spain), South Korean claims and US claims and hospital databases. ParticipantsDiagnosed and/or hospitalized children/adolescents with COVID-19 at age <18 between January and June 2020; diagnosed with influenza in 2017-2018. Main outcome measuresBaseline demographics and comorbidities, symptoms, 30-day in-hospital treatments and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome (ARDS), multi-system inflammatory syndrome (MIS-C), and death. ResultsA total of 55,270 children/adolescents diagnosed and 3,693 hospitalized with COVID-19 and 1,952,693 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were all more common among those hospitalized vs diagnosed with COVID-19. The most common COVID-19 symptom was fever. Dyspnea, bronchiolitis, anosmia and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital treatments for COVID-19 included repurposed medications (<10%), and adjunctive therapies: systemic corticosteroids (6.8% to 37.6%), famotidine (9.0% to 28.1%), and antithrombotics such as aspirin (2.0% to 21.4%), heparin (2.2% to 18.1%), and enoxaparin (2.8% to 14.8%). Hospitalization was observed in 0.3% to 1.3% of the COVID-19 diagnosed cohort, with undetectable (N<5 per database) 30-day fatality. Thirty-day outcomes including pneumonia, ARDS, and MIS-C were more frequent in COVID-19 than influenza. ConclusionsDespite negligible fatality, complications including pneumonia, ARDS and MIS-C were more frequent in children/adolescents with COVID-19 than with influenza. Dyspnea, anosmia and gastrointestinal symptoms could help differential diagnosis. A wide range of medications were used for the inpatient management of pediatric COVID-19. What is already known on this topic?O_LIMost of the early COVID-19 studies were targeted at adult patients, and data concerning children and adolescents are limited. C_LIO_LIClinical manifestations of COVID-19 are generally milder in the pediatric population compared with adults. C_LIO_LIHospitalization for COVID-19 affects mostly infants, toddlers, and children with pre-existing comorbidities. C_LI What this study adds This study comprehensively characterizes a large international cohort of pediatric COVID-19 patients, and almost 2 million with previous seasonal influenza across 5 countries. Although uncommon, pneumonia, acute respiratory distress syndrome (ARDS) and multi-system inflammatory syndrome (MIS-C) were more frequent in children and adolescents diagnosed with COVID-19 than in those with seasonal influenza. Dyspnea, bronchiolitis, anosmia and gastrointestinal symptoms were more frequent in COVID-19, and could help to differentiate pediatric COVID-19 from influenza. A plethora of medications were used during the management of COVID-19 in children and adolescents, with great heterogeneity in the use of antiviral therapies as well as of adjunctive therapies.

Baseline phenotype and 30-day outcomes of people tested for COVID-19: an international network cohort including >3.32 million people tested with real-time PCR and >219,000 tested positive for SARS-CoV-2 in South Korea, Spain and the United States

Early identification of symptoms and comorbidities most predictive of COVID-19 is critical to identify infection, guide policies to effectively contain the pandemic, and improve health systems response. Here, we characterised socio-demographics and comorbidity in 3,316,107persons tested and 219,072 persons tested positive for SARS-CoV-2 since January 2020, and their key health outcomes in the month following the first positive test. Routine care data from primary care electronic health records (EHR) from Spain, hospital EHR from the United States (US), and claims data from South Korea and the US were used. The majority of study participants were women aged 18-65 years old. Positive/tested ratio varied greatly geographically (2.2:100 to 31.2:100) and over time (from 50:100 in February-April to 6.8:100 in May-June). Fever, cough and dyspnoea were the most common symptoms at presentation. Between 4%-38% required admission and 1-10.5% died within a month from their first positive test. Observed disparity in testing practices led to variable baseline characteristics and outcomes, both nationally (US) and internationally. Our findings highlight the importance of large scale characterization of COVID-19 international cohorts to inform planning and resource allocation including testing as countries face a second wave.