Patterns of testing in the extensive Danish national SARS-CoV-2 test set-up.

BACKGROUND: The Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in relation to the three waves of SARS-CoV-2 transmission in Denmark. METHODS: We included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above. Descriptive statistics and Poisson regression models were used to analyse characteristics of individuals tested for SARS-CoV-2 using a national cohort study design. RESULTS: A total of 63.7 million PCR-tests and 60.0 million rapid antigen-tests were performed in the study period, testing 90.9% and 78.8% of the Danish population at least once by PCR or antigen, respectively. Female sex, younger age, Danish heritage and living in the capital area were all factors positively associated with the frequency of PCR-testing. The association between COVID-19 vaccination and PCR-testing changed from negative to positive over time. CONCLUSION: We provide details of the widely available, free-of-charge, national SARS-CoV-2 test system, which served to identify infected individuals, assist isolation of infectious individuals and contact tracing, and thereby mitigating the spread of SARS-CoV-2 in the Danish population. The test system was utilized by nearly the entire population at least once, and widely accepted across different demographic groups. However, demographic differences in the test uptake did exist and should be considered in order not to cause biases in studies related to SARS-CoV-2, e.g., studies of transmission and vaccine effectiveness.

Associations of body fat mass and fat-free mass with breast cancer incidence in postmenopausal women: A Danish prospective cohort study.

PURPOSE: Previous studies have established associations between body mass index and breast cancer, but fat mass is a more direct measure of the amount of fat tissue in the body than body mass index. This study examined the association between body fat mass, fat-free mass, and other anthropometric measures and breast cancer in postmenopausal women according to use of hormone replacement therapy (HRT). METHODS: From the Danish Diet, Cancer and Health cohort established during 1993-1997, 24,219 postmenopausal women were included who had anthropometric and bioimpedance measurements performed by a laboratory technician at baseline. Information on breast cancer incidence (outcome), other cancer diagnoses, and vital status (censoring variables) through 2016 was obtained from nationwide registers. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) while adjusting for known breast cancer risk factors and stratifying by HRT use and running age. RESULTS: During a total of 431,104 person-years, 1919 women developed breast cancer. Among never-users of HRT, the HR for breast cancer at or after age 65 years was 1.06 (95% CI, 1.03-1.08) per 1 kg/m2 higher body fat mass index (BFMI), and 1.30 (95% CI, 1.14-1.47) per 10% higher body fat percentage. The corresponding HRs for breast cancer before age 65 years were close to unity. The HRs were 1.11 (95% CI, 1.02-1.21) and 1.17 (95% CI, 1.10-1.23) for each 1 kg/m2 increase in fat-free mass index, respectively, for breast cancer below and above age 65 years. Mutual adjustment attenuated the HRs for BFMI and body fat percentage, whereas the HRs for fat-free mass index were largely unaffected. Among ever-users of HRT, there was no statistical significant association between any of the body composition measures and breast cancer incidence in the two age groups. CONCLUSIONS: Among postmenopausal women who never used HRT, BFMI was associated with breast cancer in women aged 65 years or older. Fat-free mass index was found to be more strongly associated with postmenopausal breast cancer incidence than BFMI independently of age in never-users of HRT.

Sociodemographic differences in Covid-19 vaccine uptake in Denmark: a nationwide register-based cohort study.

BACKGROUND: Covid-19 vaccination is the main strategy to reduce SARS-CoV-2 transmission, mortality and morbidity. This study aimed to examine sociodemographic differences in Covid-19 vaccine uptake among all individuals invited for Covid-19 vaccination in Denmark. METHODS: This study was designed as a nationwide register-based cohort study. The study population included all Danish residents aged 12 years or above in Denmark between December 27, 2020 and October 20, 2021. Individuals who died during the study period before receiving an invitation for Covid-19 vaccination were excluded. Associations between sociodemographic factors and Covid-19 vaccination uptake were analyzed using logistic regression models adjusting for age, sex, immigration status, educational level, disposable income and history of SARS-CoV-2 infection. RESULTS: The study population included 5,164,558 individuals. The overall vaccination coverage was 87.1% by October 20, 2021. In the full adjusted logistic regression models, the highest ORs for non-vaccination were observed among individuals aged 12-24 years (OR: 8.99 (95% CI: 8.76-9.23)), descendants of non-western immigrants (OR: 5.26 (95% CI: 5.18-5.33)), individuals who never had a PCR-test performed (OR: 2.93 (95% CI: 2.90-2.96)), individuals with primary school as highest completed educational level (OR: 2.87 (95% CI: 2.83-2.91)) and individuals with disposable income < 33,605 EUR (OR: 3.72 (95% CI: 3.52-3.93)). CONCLUSION: Overall, the Covid-19 vaccine uptake was high in Denmark. However, large sociodemographic differences in the vaccine uptake exist. The youngest age groups had the lowest vaccination coverage. Furthermore, the impact of the sociodemographic factors was more pronounced in the youngest age groups. The identified determinants may be used to design policies to help maximize the vaccination coverage.

Experience with sotrovimab treatment of SARS-CoV-2-infected patients in Denmark.

AIMS: To evaluate the experience with use of sotrovimab following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in high-risk groups. METHODS: In a nationwide, population-based cohort study, we identified all individuals treated with sotrovimab (N = 2933) and stratified them by 4 high-risk groups: (A) malignant haematological disease, (B) solid organ transplantation, (C) anti-CD20 therapy ≤1 year and (D) other risks. Cox regression analysis was used to calculate hazard ratios for hospitalization, death and associated prognostic factors. RESULTS: Of 2933 sotrovimab-treated individuals, 83% belonged to high-risk groups (37.6% haematological malignancy, 27.4% solid organ transplantation and 17.5% treatment with anti-CD20 ≤1 year). Only 17.8% had other risks (11.8% were pregnant, 10.7% primary immunodeficiency, 21.2% other malignancy, 4.3% received anti-CD20 >1 year and 52.0% other/unknown causes). Within 90 days of infusion, 30.2% were hospitalized and 5.3% died. The main prognostic factors were the predefined high-risk groups, mainly malignant haematological disease and age ≥65 years. Number of COVID-19 vaccines (≥3) was associated with a decreased risk of hospitalization. The Delta but not the Omicron BA.2 variant was associated with a higher risk of death compared to the BA.1 variant. CONCLUSION: More than 90% of the patients treated with sotrovimab belonged to the very high-risk groups as described in the Danish guidelines. Sotrovimab-treated individuals remained at a high risk of hospitalization and death which was strongly associated with the underlying immunocompromised state and age. Having received >3 COVID-19 vaccines was association with decreased risk of death and hospitalization.

Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark.

BACKGROUND: Estimates of immunity and severity for the SARS-CoV-2 omicron subvariant BA.5 are important to assess the public health impact associated with its rapid global spread despite vaccination. We estimated natural and vaccine immunity and severity of BA.5 relative to BA.2 in Denmark, a country with high mRNA-vaccination coverage and free-of-charge RT-PCR testing. METHODS: This nation-wide population-based study in Denmark included residents aged 18 years or older who had taken an RT-PCR test between 10 April and 30 June, 2022 (ie, the outcome period), and who the national COVID-19 surveillance system identified as having information since February 2020 on RT-PCR tests, whole-genome sequencing, vaccinations, and hospitalisation with a positive RT-PCR test and COVID-19 as the main diagnosis. First, we used a case-control design, in which cases were people infected with BA.5 or BA.2 during the outcome period and controls were people who tested negative for SARS-CoV-2 infection during the outcome period. We calculated the protection provided by a previous PCR-confirmed omicron infection against BA.5 and BA.2 infection and hospitalisation among triple-vaccinated individuals. Second, we compared vaccination status in people infected with BA.5 versus BA.2 and estimated relative vaccine protection against each subvariant. Third, we compared rates of hospitalisation for COVID-19 among people infected with BA.5 versus BA.2. We estimated effects using logistic regression with adjustment for sex, age, region, PCR-test date, comorbidity and, as appropriate, vaccination and previous infection status. FINDINGS: A total of 210 (2·4%) of 8678 of BA.5 cases, 192 (0·7%) of 29 292 of BA.2 cases, and 33 972 (19·0%) of 178 669 PCR-negative controls previously had an omicron infection, which was estimated in the adjusted analyses to offer 92·7% (95% CI 91·6-93·7) protection against BA.5 infection and 97·1% (96·6-97·5) protection against BA.2 infection. We found similarly high amounts of protection against hospitalisation owing to infection with BA.5 (96·4% [95% CI 74·2-99·5]) and BA.2 (91·2% [76·3-96·7]). Vaccine coverage (three mRNA doses vs none) was 9307 (94·2%) of 9878 among BA.5 cases and 30 581 (94·8%) of 32 272 among BA.2 cases, although in the adjusted analysis, there was a trend towards slightly higher vaccination coverage among BA.5 cases than BA.2 cases (OR 1·18 [95% CI 0·99-1·42]; p=0·064), possibly suggesting marginally poorer vaccine protection against BA.5. The rate of hospitalisation due to COVID-19 was higher among the BA.5 cases (210 [1·9%] of 11 314) than among the BA.2 cases (514 [1·4%] of 36 805), with an OR of 1·34 (95% CI 1·14-1·57) and an adjusted OR of 1·69 (95% CI 1·22-2·33), despite low and stable COVID-19 hospitalisation numbers during the study period. INTERPRETATION: The study provides evidence that a previous omicron infection in triple-vaccinated individuals provides high amounts of protection against BA.5 and BA.2 infections. However, protection estimates greater than 90% might be too high if individuals with a previous infection were more likely than those without one to come forward for a test for reasons other than suspicion of COVID-19. Our analysis also showed that vaccine protection against BA.5 infection was similar to, or slightly weaker than, protection against BA.2 infection. Finally, there was evidence that BA.5 infections were associated with an increased risk of hospitalisation compared with BA.2 infections. FUNDING: There was no funding source for this study.

Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha, Delta, or Omicron dominance: A Danish nationwide study.

BACKGROUND: Individuals with a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, Coronavirus Disease 2019 (COVID-19)-related hospitalization, and COVID-19-related death, in individuals with prior SARS-CoV-2 infection, and to assess the effect of time since vaccination during periods with different dominant SARS-CoV-2 variants. METHODS AND FINDINGS: This study used a nationwide cohort design including all individuals with a confirmed SARS-CoV-2 infection, who were alive, and residing in Denmark between 1 January 2020 and 31 January 2022. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, COVID-19 vaccination, age, sex, comorbidity, staying at hospital, and country of origin. The study population included were individuals with prior SARS-CoV-2 infection. Estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using a Poisson regression model and adjusted for age, sex, country of origin, comorbidity, staying at hospital, calendar time, and test incidence using a Cox regression model. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference. In total, 148,527 person-years and 44,192 SARS-CoV-2 infections were included for the analysis regarding reinfections. The study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period, and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%), and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 71% (95% CI: -Inf to 100%) at 104 days or more after vaccination during the Alpha period, 94% (95% CI: 92% to 96%) 14 to 43 days after vaccination during the Delta period, and 60% (95% CI: 58% to 62%) 14 to 43 days after vaccination during the Omicron period. Waning immunity following vaccination was observed and was most pronounced during the Omicron period. Due to too few events, it was not possible to estimate VE for hospitalization and death. Study limitations include potentially undetected reinfections, differences in health-seeking behavior, or risk behavior between the compared groups. CONCLUSIONS: This study shows that in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods.

Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha, Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study.

BACKGROUND: The continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period. METHODS AND FINDINGS: A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: -0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals. CONCLUSIONS: Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.

Vaccine effectiveness against SARS-CoV-2 infection, hospitalization, and death when combining a first dose ChAdOx1 vaccine with a subsequent mRNA vaccine in Denmark: A nationwide population-based cohort study.

BACKGROUND: The recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines. METHODS AND FINDINGS: All individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19-related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19-related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results. CONCLUSIONS: In this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.

The influence of marital status and partner concordance on participation in colorectal cancer screening.

BACKGROUND: Colorectal cancer screening program using a fecal immunochemical test aims to reduce morbidity and mortality through early detection. Although screening participation is free-of-charge, almost 40% of the invited individuals choose not to participate. To bring new insight into how non-participation can be identified and targeted, we examined the association between marital status and screening participation; with a focus on partner concordance in participation and sex differences. METHODS: This nationwide cross-sectional study included all Danish citizens aged 50-74 years, who were invited to colorectal cancer screening between 2014 and 2017. Logistic regression analysis was used to estimate odds ratio (OR) of participation while adjusting for sociodemographic variables. RESULTS: A total of 1 909 662 individuals were included in the analysis of which 62.7% participated in the screening program. Participation was highest among women. Stratified by marital status, screening participation was markedly lower in widowed (61.5%), divorced (54.8%) and single (47.3%), while participation reached 68.4% in married individuals. This corresponded to ORs of 0.59 (95% CI 0.58-0.59) for widowed, 0.56 (95% CI 0.55-0.56) for divorced and 0.47 (95% CI 0.47-0.48) for single, compared to married individuals. Individuals married to a participating partner were five times more likely to participate than married individuals with a non-participating partner, regardless of gender. CONCLUSIONS: Marital status was strongly associated with participation in colorectal cancer screening, and participation was even higher in married individuals with a participating partner. Future efforts to increase participation in colorectal cancer screening could potentially benefit from considering the role of partner concordance.