Association between SARS-CoV-2 vaccination and healthcare contacts for menstrual disturbance and bleeding in women before and after menopause: nationwide, register based cohort study.

OBJECTIVES: To evaluate the risks of any menstrual disturbance and bleeding following SARS-CoV-2 vaccination in women who are premenopausal or postmenopausal. DESIGN: A nationwide, register based cohort study. SETTING: All inpatient and specialised outpatient care in Sweden from 27 December 2020 to 28 February 2022. A subset covering primary care for 40% of the Swedish female population was also included. PARTICIPANTS: 2 946 448 Swedish women aged 12-74 years were included. Pregnant women, women living in nursing homes, and women with history of any menstruation or bleeding disorders, breast cancer, cancer of female genital organs, or who underwent a hysterectomy between 1 January 2015 and 26 December 2020 were excluded. INTERVENTIONS: SARS-CoV-2 vaccination, by vaccine product (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 (AZD1222)) and dose (unvaccinated and first, second, and third dose) over two time windows (one to seven days, considered the control period, and 8-90 days). MAIN OUTCOME MEASURES: Healthcare contact (admission to hospital or visit) for menstrual disturbance or bleeding before or after menopause (diagnosed with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes N91, N92, N93, N95). RESULTS: 2 580 007 (87.6%) of 2 946 448 women received at least one SARS-CoV-2 vaccination and 1 652 472 (64.0%) 2 580 007 of vaccinated women received three doses before the end of follow-up. The highest risks for bleeding in women who were postmenopausal were observed after the third dose, in the one to seven days risk window (hazard ratio 1.28 (95% confidence interval 1.01 to 1.62)) and in the 8-90 days risk window (1.25 (1.04 to 1.50)). The impact of adjustment for covariates was modest. Risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with BNT162b2 and mRNA-1273 after the third dose, but the association with ChAdOx1 nCoV-19 was less clear. For menstrual disturbance or bleeding in women who were premenopausal, adjustment for covariates almost completely removed the weak associations noted in the crude analyses. CONCLUSIONS: Weak and inconsistent associations were observed between SARS-CoV-2 vaccination and healthcare contacts for bleeding in women who are postmenopausal, and even less evidence was recorded of an association for menstrual disturbance or bleeding in women who were premenopausal. These findings do not provide substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.

The burden of disease due to COVID-19 in Sweden 2020-2021: A disability-adjusted life years (DALYs) study.

BACKGROUND: The burden of COVID-19 disease can be measured in terms of disability-adjusted life years (DALYs), which is composed of two components: the years of life lost through premature death (YLL) and the number of years lived with disability (YLD), adjusted for level of disability. This study measured DALYs due to COVID-19 in Sweden and compared it to the burden of other diseases. METHODS: The methodology used in the calculation of DALYs was based on the Global Burden of Disease guidelines. The number of patients diagnosed with mild/moderate, severe or critical COVID-19 and/or post-COVID-19 condition between March 2020 and October 2021 was extracted from national registries and used for YLD calculations. In addition, the numbers of death due to COVID-19 in different age groups were used for the YLL calculation. RESULTS: During the study period, 152,877 DALYs were lost to COVID-19 in Sweden, 99.3% of which was attributed to YLL. Loss of DALYs occurred mainly among the elderly, with 66.8% of DALYs attributed to individuals >70 years old. Compared to other diseases, the burden of COVID-19 in 2020 ranked as the eighth leading cause of DALY lost. CONCLUSIONS: Similar to other countries, the burden of COVID-19 in Sweden was concentrated mainly among the elderly, who contributed most of the DALY lost due to premature mortality. Yet, DALY loss remained lower for COVID-19 than for several other diseases. The contribution of YLD to DALYs lost was minimal. However empirical data on the occurrence and disability of post-COVID-19 condition are scarce, and YLD may therefore be underestimated.

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 .

Occupational role and COVID-19 among foreign-born healthcare workers in Sweden: a registry-based study.

BACKGROUND: Many studies report that foreign-born healthcare workers (HCWs) in high-income countries have an elevated risk of COVID-19. However, research has not yet specifically evaluated the distribution of COVID-19 among foreign-born workers in different healthcare work groups. We examined the risk of COVID-19 infection and hospitalization among foreign-born HCWs in different occupational roles in Sweden. METHODS: We linked occupational data (2019) of 783 950 employed foreign-born workers (20-65 years) to COVID-19 data registered between 1 January 2020 and 30 September 2021. We used Cox proportional hazards regression to estimate the hazard ratio (HR) with 95% confidence intervals (95% CIs) of COVID-19 infection and hospitalization in eight healthcare occupational groups vs. non-HCWs and assessed whether region of birth modified the association between healthcare occupations and COVID-19. RESULTS: All HCWs had a higher risk of COVID-19 outcomes than non-HCWs, but the risk differed by occupational role. Hospital-based assistant nurses had the highest risk (infection: HR 1.78; 95% CI 1.72-1.85; hospitalization: HR 1.79; 95% CI 1.52-2.11); allied HCWs had the lowest risk (infection: HR 1.22; 95% CI 1.10-1.35; hospitalization: HR 0.98; 95% CI 0.59-1.63). The relative hazard of the outcomes varied across foreign-born workers from different regions. For example, the relative risk of COVID-19 infection associated with being a physician compared to a non-HCW was 31% higher for African-born than European-born workers. CONCLUSIONS: The risk of COVID-19 among foreign-born HCWs differed by occupational role and immigrant background. Public health efforts that target occupational exposures as well as incorporate culturally responsive measures may help reduce COVID-19 risk among foreign-born HCWs.

Short-term improvement of mental health after a COVID-19 vaccination.

INTRODUCTION: The role of COVID-19 vaccination on the mental health of the general population remains poorly understood. This study aims to assess the short-term change in depressive and anxiety symptoms in relation to COVID-19 vaccination among Swedish adults. METHODS: A prospective study of 7,925 individuals recruited from ongoing cohort studies at the Karolinska Institutet, Stockholm, Sweden, or through social media campaigns, with monthly data collections on self-reported depressive and anxiety symptoms from December 2020 to October 2021 and COVID-19 vaccination from July to October 2021. Prevalence of depressive and anxiety symptoms (defined as a self-reported total score of ≥10 in PHQ-9 and GAD-7, respectively) was calculated one month before, one month after the first dose, and, if applicable, one month after the second dose. For individuals not vaccinated or choosing not to report vaccination status (unvaccinated individuals), we selected three monthly measures of PHQ-9 and GAD-7 with 2-month intervals in-between based on data availability. RESULTS: 5,079 (64.1%) individuals received two doses of COVID-19 vaccine, 1,977 (24.9%) received one dose, 305 (3.9%) were not vaccinated, and 564 (7.1%) chose not to report vaccination status. There was a lower prevalence of depressive and anxiety symptoms among vaccinated, compared to unvaccinated individuals, especially after the second dose. Among individuals receiving two doses of vaccine, the prevalence of depressive and anxiety symptoms was lower after both first (aRR = 0.82, 95%CI 0.76-0.88 for depression; aRR = 0.81, 95%CI 0.73-0.89 for anxiety) and second (aRR = 0.79, 95%CI 0.73-0.85 for depression; aRR = 0.73, 95%CI 0.66-0.81 for anxiety) dose, compared to before vaccination. Similar results were observed among individuals receiving only one dose (aRR = 0.76, 95%CI 0.68-0.84 for depression; aRR = 0.82, 95%CI 0.72-0.94 for anxiety), comparing after first dose to before vaccination. CONCLUSIONS: We observed a short-term improvement in depressive and anxiety symptoms among adults receiving COVID-19 vaccines in the current pandemic. Our findings provide new evidence to support outreach campaigns targeting hesitant groups.

A comprehensive characterisation of patients diagnosed with post-COVID-19 condition in Sweden 16 months after the introduction of the ICD-10 diagnosis code (U09.9): a population-based cohort study.

BACKGROUND: The objective of this study was to provide a comprehensive characterisation of patients diagnosed with post-COVID-19 condition (PCC) during the first 16 months of usage of the International Classification of Diseases revision 10 (ICD-10) diagnosis code U09.9 in Sweden. METHODS: We used data from national registers and primary healthcare databases for all adult inhabitants of the two largest regions in Sweden, comprising 4.1 million inhabitants (approximately 40% of the Swedish population). We present the cumulative incidence and incidence rate of PCC overall and among subgroups and describe COVID-19 patients with or without PCC regarding sociodemographic characteristics, comorbidities, subsequent diseases, COVID-19 severity, and virus variants. FINDINGS: Of all registered COVID-19 cases available for PCC diagnosis (n=506,107), 2.0% (n=10,196) had been diagnosed with PCC using ICD-10 code U09.9 as of 15 February 2022 in the two largest regions in Sweden. The cumulative incidence was higher among women compared to men (2.3% vs 1.6%, p<0.001). The majority of PCC cases (n=7,162, 70.2%) had not been hospitalised for COVID-19. This group was more commonly female (69.9% vs 52.9%, p<0.001), had a tertiary education (51.0% vs 44.1%, p<0.001), and was older (median age difference 5.7 years, p<0.001) compared to non-hospitalised COVID-19 patients without PCC. INTERPRETATION: This characterisation furthers the understanding of patients diagnosed with PCC and could support policymakers with appropriate societal and healthcare resource allocation.

A population-based, retrospective cohort study of the association between ABO blood group and risk of COVID-19.

BACKGROUND: Several studies have investigated associations between ABO blood group and risk of COVID-19, with inconsistent results. OBJECTIVE: To study associations between ABO blood group and risk of different stages of COVID-19. METHODS: The study was based on nationwide registers encompassing all blood-grouped persons in Sweden, and all of their COVID-19-related outcomes. Associations between ABO blood group and COVID-19 outcomes were estimated using Poisson regression models. Analyses were conducted overall and stratified by vaccination status. RESULTS: A total of 4,986,878 individuals were included. The incidence rate ratios of testing positive for COVID-19 were 1.08 (95% confidence interval [CI], 1.07-1.08), 1.06 (95% CI, 1.05-1.07), and 1.01 (95% CI, 1.00-1.01) for blood groups A, AB, and B, respectively, as compared to O. Similar associations were seen for risk of hospital admissions, intensive care unit admissions, and risk of death. For most outcomes, associations with ABO blood group were much attenuated or even reversed in vaccinated individuals. CONCLUSIONS: Individuals with blood groups A, AB, and B are at increased risk of contracting COVID-19 as well as developing more severe forms of the disease.

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.

Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden.

BACKGROUND: Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population. METHODS: COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19. RESULTS: Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD. CONCLUSIONS: The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.

Effectiveness of COVID-19 Vaccines over 13 Months Covering the Period of the Emergence of the Omicron Variant in the Swedish Population.

BACKGROUND: We estimated real-world vaccine effectiveness (VE) against COVID-19 infection, hospitalization, ICU admission, and death up to 13 months after vaccination. VE before and after the emergence of Omicron was investigated. METHODS: We used registered data from the entire Swedish population above age 12 (n = 9,153,456). Cox regression with time-varying exposure was used to estimate weekly/monthly VE against COVID-19 outcomes from 27 December 2020 to 31 January 2022. The analyses were stratified by age, sex, and vaccine type (BNT162b2, mRNA-1273, and AZD1222). RESULTS: Two vaccine doses offered good long-lasting protection against infection before Omicron (VE were above 85% for all time intervals) but limited protection against Omicron infection (dropped to 43% by week four and no protection by week 14). For severe COVID-19 outcomes, higher VE was observed during the entire follow-up period. Among individuals above age 65, the mRNA vaccines showed better VE against infection than AZD1222 but similar high VE against hospitalization. CONCLUSIONS: Our findings provide strong evidence for long-term maintained protection against severe COVID-19 by the basic two-dose schedule, supporting more efforts to encourage unvaccinated persons to get the basic two doses, and encourage vaccinated persons to get a booster to ensure better population-level protection.

Protective effects of statins on COVID-19 risk, severity and fatal outcome: a nationwide Swedish cohort study.

The impact of statins on COVID-19 remains unclear. This study aims to investigate whether statin exposure assessed both in the population and in well-defined cohorts of COVID-19 patients may affect the risk and severity of COVID-19 using nationwide Swedish population-based register data. A population ≥ 40 years was selected by age/sex-stratified random sampling from the Swedish population on 1 Jan 2020. COVID-19 outcomes were identified from the SmiNet database, the National Patient Register and/or Cause-of-Death Register and linked with the National Prescribed Drug Register and sociodemographic registers. Statin exposure was defined as any statin prescriptions in the year before index date. In Cox regressions, confounding was addressed using propensity score ATT (Average Treatment effect in the Treated) weighting. Of 572,695 individuals in the overall cohort, 22.3% had prior statin treatment. After ATT weighting, protective effects were observed among statin user for hospitalization and COVID-19 death in the overall cohort and onset cohort. In the hospitalized cohort, statin use was only associated with lower risk for death (HR = 0.86, 95% CI 0.79-0.95), but not ICU admission. Statin-treated individuals appear to have lower COVID-19 mortality than nonusers, whether assessed in the general population, from COVID-19 onset or from hospitalization.

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

PURPOSE: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. METHODS: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. RESULTS: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. CONCLUSIONS: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.

Initiation of antihypertensive drugs to patients with confirmed COVID-19-A population-based cohort study in Sweden.

PURPOSE: Hypertension is an important risk factor for severe outcomes in patients with COVID-19, and antihypertensive drugs may have a protective effect. However, the pandemic may have negatively impacted health care services for chronic diseases. The aim of this study was to assess initiations of antihypertensive medicines in patients infected by COVID-19. METHODS: A cohort study including all Swedish residents 20-80 years old with a COVID-19 positive test compared with an unexposed group without COVID-19 matched for age, sex, and index date (date of confirmed COVID-19). Data were collected within SCIFI-PEARL, a study including linked data on COVID tests, hospital diagnoses, dispensed prescriptions, and socioeconomic data from Swedish national registers. Initiations of different antihypertensive drugs were studied from March 2020 until October 2020. Associations between COVID-19 and initiation of antihypertensives were assessed by a multivariable Cox proportional hazards model. RESULTS: A total of 224 582 patients (exposed and unexposed) were included. After adjusting for cardiovascular comorbidities and education level, ACEi was the most commonly initiated antihypertensive agent to patients with COVID-19. Hazard ratio and 95% confidence interval for initiation of drug therapy was 1.83 [1.53-2.19] for ACEi, followed by beta-blockers 1.74 [1.55-1.95], calcium channel blockers 1.61 [1.41-1.83], angiotensin receptor blockers 1.61 [1.40-1.86], and diuretics 1.53 [1.32-1.77]. CONCLUSION: All antihypertensive medicines were initiated more frequently in COVID-19 patients. This can either be associated with hypertension caused by the COVID-19 infection, more frequent diagnosis of hypertension among people with COVID-19 since they consult health care, or residual confounding factors not adjusted for in the study.

Uncontrolled asthma predicts severe COVID-19: a report from the Swedish National Airway Register.

BACKGROUND: Severe asthma increases the risk of severe COVID-19 outcomes such as hospitalization and death. However, more studies are needed to understand the association between asthma and severe COVID-19. METHODS: A cohort of 150,430 adult asthma patients were identified in the Swedish National Airway Register (SNAR) from 2013 to December 2020. Data on body mass index, smoking habits, lung function, and asthma control test (ACT) were obtained from SNAR, and uncontrolled asthma was defined as ACT ⩽19. Patients with severe COVID-19 were identified following hospitalization or in death certificates based on ICD-10 codes U07.1 and U07.2. The Swedish Prescribed Drug register was used to identify comorbidities and data from Statistics Sweden for educational level. Multivariate logistic regression analyses were used to estimate associations with severe COVID-19. RESULTS: Severe COVID-19 was identified in 1067 patients (0.7%). Older age (OR = 1.04, 95% CI = 1.03-1.04), male sex (1.42, 1.25-1.61), overweight (1.56, 1.27-1.91), obesity (2.12, 1.73-2.60), high-dose inhaled corticosteroids in combination with long-acting ß-agonists (1.40, 1.22-1.60), dispensed oral corticosteroids ⩾2 (1.48, 1.25-1.75), uncontrolled asthma (1.64, 1.35-2.00), cardiovascular disease (1.20, 1.03-1.40), depression (1.47, 1.28-1.68), and diabetes (1.52, 1.29-1.78) were associated with severe COVID-19, while current smoking was inversely associated (0.63, 0.47-0.85). When comparing patients who died from COVID-19 with those discharged alive from hospital until 31 December 2020, older age, male sex, and current smoking were associated with COVID-19 death. CONCLUSION: Patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, should be identified as risk patients for severe COVID-19. Furthermore, current smoking is strongly associated with COVID-19 death in asthma.

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.

The social patterning of Covid-19 vaccine uptake in older adults: A register-based cross-sectional study in Sweden.

BACKGROUND: A broad vaccination coverage is crucial for preventing the spread of Covid-19 and reduce serious illness or death. The aim of this study was to examine social inequalities in Covid-19 vaccination uptake as of 17th May 2021 among Swedish adults aged ≥ 60 years. METHODS: The study population comprised a general population cohort aged 60 years or older (n = 350,805), representative of the Swedish population. Data were collected through the nationwide linked multi-register observational study SCIFI-PEARL, and associations between sociodemographic determinants and Covid-19 vaccination uptake were analysed using logistic regression. Intersectional analyses of sociodemographic heterogeneity were performed by taking several overlapping social dimensions into account. Data availability extended to 17 May 2021. FINDINGS: The overall vaccination coverage was 87·2% by 17th May 2021. Younger age, male sex, lower income, living alone, and being born outside Sweden, were all associated with a lower uptake of vaccination. The lowest Covid-19 vaccination uptake was seen in individuals born in low-or middle-income countries, of which only 60% had received vaccination, with an odds ratio (OR) of not being vaccinated of 6·05 (95% CI: 5·85-6·26) compared to individuals born in Sweden. These associations persisted after adjustments for possible confounding factors. The intersectional analyses showed even larger variations in vaccination in cross-classified sociodemographic subgroups (ranging from 44% to 97%) with marked differences in uptake of vaccination within sociodemographic groups. INTERPRETATION: The uptake of Covid-19 vaccine during the spring of 2021 in Sweden varied substantially both between and within sociodemographic groups. The use of an intersectional approach, taking several overlapping social dimensions into account at the same time rather than only using one-dimensional measures, contributes to a better understanding of the complexity in the uptake of vaccination. FUNDING: SciLifeLab / Knut & Alice Wallenberg Foundation, Swedish Research Council, Swedish government ALF-agreement, FORMAS.

Seek COVER: using a disease proxy to rapidly develop and validate a personalized risk calculator for COVID-19 outcomes in an international network.

BACKGROUND: We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient's risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. METHODS: We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. RESULTS: Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. CONCLUSIONS: This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use.