Findings in Danish long-term care facilities in the first year of the SARS-CoV-2 pandemic.

PURPOSE: To describe the occurrence of SARS-CoV-2 infections, deaths and outbreaks among residents in Danish long-term care facilities (LTCFs) from February 2020 to February 2021. METHODS: Danish COVID-19 national register data from a newly implemented automated surveillance system was used to describe incidence rate and deaths (per 1000 residents' years), number of tests, SARS-CoV-2 infections and outbreaks among LTCF residents. A case was defined as a LTCF resident with a positive SARS-CoV-2 PCR test. An outbreak was defined as two or more cases in one LTCF within a 14-day period, and considered closed if no new cases had occurred within 28 days. Death was defined as occurring within 30-days of a positive test. RESULTS: A total of 55,359 residents living in 948 LTCFs were included. The median age of the residents was 85 years and 63% were female. There was a total of 3712 cases found among residents across 43% of all LTCFs. Nearly all (94%) cases were linked to outbreaks. Higher numbers of cases and outbreaks were seen in Denmark's Capital Region compared to other regions. Overall, 22 SARS-CoV-2 deaths and 359 deaths (non-SARS-CoV-2) per 1000 resident years were identified in the study period. CONCLUSION: Less than half of LTCFs identified any cases. The majority of cases were linked to outbreaks, emphasizing the importance of preventing introductions of SARS-CoV-2 into the facilities. Furthermore, it highlights the need to invest efforts into infrastructures, routine procedures and monitoring of SARS-CoV-2 in LTCFs to limit the introduction and the spread of SARS-CoV-2.

When schools were open for in-person teaching during the COVID-19 pandemic - the nordic experience on control measures and transmission in schools during the delta wave.

BACKGROUND: Extensive measures to control spread of SARS-CoV-2 have led to limited access to education for millions of children and adolescents during the COVID-19 pandemic. Education and access to schools is vital for children and adolescents' learning, health, and wellbeing. Based on high vaccine uptake and low incidence levels, the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) decided to start the academic year 2021/22 with schools open for in-person teaching and moderate mitigation measures. We describe trends in SARS-CoV-2 infections and vaccination coverage among students during the first 12 weeks of the fall semester. METHODS: In this multinational, retrospective, observational study, we have used surveillance and registry data from each of the Nordic countries to describe vaccine uptake (≥12 years), infection incidence (whole population) and transmission of SARS-CoV-2 among students. The study period, week 30 to 41 (Jul 26th - Oct 17th), represents the autumn semester from immediately before school started until fall break. In addition, we collected information on mitigation measures applied by the respective countries. RESULTS: There were slight variations between the countries regarding existing infection prevention and control (IPC) measures, testing strategies and vaccination start-up among adolescents. All countries had high vaccine uptake in the adult population, while uptake varied more in the younger age groups. Incidence in the school-aged population differed between countries and seemed to be influenced by both vaccine uptake and test activity. Infection clusters among school-aged children were described for Denmark and Norway, and the number of clusters per week reflected the incidence trend of the country. Most events consisted of only 1-2 cases. Larger clusters appeared more frequently in the higher grades in Norway and in lower grades in Denmark. CONCLUSION: Data from the Nordic countries indicate that vaccination of adults and adolescents, in addition to mitigation measures, enabled full in-person learning. As SARS-CoV-2 infection does not represent a severe medical risk for most children as previously thought, measures targeting this group should be carefully adjusted and kept at a minimum. Our data add to the evidence on incidence and transmission of SARS-CoV-2 among students in schools open for in-person teaching, and may be valuable for decision makers worldwide.

Seroprevalence of SARS-CoV-2 Antibodies in Denmark: Results of Two Nationwide Population-Based Surveys, February and May 2021.

Background: Seroprevalence studies can be used to measure the progression of national COVID-19 epidemics. The Danish National Seroprevalence Survey of SARS-CoV-2 infections (DSS) was conducted as five separate surveys between May 2020 and May 2021. Here, we present results from the two last surveys conducted in February and May 2021. Methods: Persons aged 12 or older were randomly selected from the Danish Population Register and those having received COVID-19 vaccination subsequently excluded. Invitations to have blood drawn in local test centers were sent by mail. Samples were analyzed for whole Immunoglobulin by ELISA. Seroprevalence was estimated by sex, age and geography. Comparisons to vaccination uptake and RT-PCR test results were made. Results: In February 2021, we found detectable antibodies in 7.2% (95% CI: 6.3-7.9%) of the invited participants (participation rate 25%) and in May 2021 in 8.6% (95% CI: 7.6-9.5%) of the invited (participation rate: 14%). Seroprevalence did not differ by sex, but by age group, generally being higher among the <50 than 50+ year-olds. In May 2021, levels of seroprevalence varied from an estimated 13% (95% CI: 12-15%) in the capital to 5.2% (95% CI: 3.4-7.4%) in rural areas. Combining seroprevalence results with vaccine coverage, estimates of protection against infection in May 2021 varied from 95% among 65+ year-olds down to 10-20% among 12-40 year-olds. In March-May 2021, an estimated 80% of all community SARS-CoV-2 infections were diagnosed by RT-PCR and captured by surveillance. Conclusion: Seroprevalence estimates doubled during the 2020-21 winter wave of SARS-CoV-2 infections and then stabilized as vaccinations were rolled out. The epidemic affected large cities and younger people the most. Denmark saw comparatively low infections rates, but high test coverage; an estimated four out of five infections were detected by RT-PCR in March-May 2021.

Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) occurs after infection with SARS-CoV-2 and its incidence is likely to depend on multiple factors, including the variant of the preceding SARS-CoV-2 infection and vaccine effectiveness. We aimed to estimate the incidence of MIS-C, and describe the clinical phenotype, following the delta variant of SARS-CoV-2 (B.1.617.2 and sublineages) according to vaccination status. We aimed to compare the incidence and clinical phenotype of MIS-C from our cohort during the pre-delta era. METHODS: This prospective, population-based cohort study included patients aged 0-17 years hospitalised with MIS-C in Denmark, according to the US Centers for Disease Control and Prevention case definition, from Aug 1, 2021, to Feb 1, 2022, a period dominated by the delta variant. We identified MIS-C cases via a nationwide research collaboration involving real-time data collection from all 18 paediatric departments. Aggregated number of SARS-CoV-2 infections by vaccination status was obtained from the Danish COVID-19 surveillance registries. The incidence of MIS-C was calculated using the estimated number of infected individuals by vaccination status. We calculated the incidence of MIS-C per 1 000 000 vaccinated and unvaccinated person-years, and estimated vaccine effectiveness as 1-incidence rate ratio using Poisson regression. Incidence and phenotype of MIS-C were compared with MIS-C cases from the first year of the pandemic. This study is registered at ClinicalTrials.gov, NCT05186597. FINDINGS: We identified 51 MIS-C cases among unvaccinated individuals and one in a fully vaccinated adolescent. The incidence of MIS-C was one in 3400 unvaccinated individuals (95% CI 2600-4600) with the delta variant and one in 9900 vaccinated individuals (95% CI 1800-390 000) with breakthrough infection. The estimated vaccine effectiveness against MIS-C after the delta variant was 94% (95% CI 55-99; p=0·0061) in individuals aged 5-17 years. The clinical phenotype during the delta wave was comparable to the pre-delta era. INTERPRETATION: We found the incidence and phenotype of MIS-C in unvaccinated children during the delta wave to be similar to the incidence during the first year of the pandemic. We found vaccine effectiveness to be high against MIS-C, which we suggest was due to protection from infection and, possibly, a decreased incidence of MIS-C after breakthrough infection. Knowledge of the incidence of MIS-C after different SARS-CoV-2 variants and the effect of vaccination might contribute to the elucidation of the extent to which MIS-C is a vaccine-preventable disease. FUNDING: National Ministry of Higher Education and Science and Innovation Fund Denmark.

Case-control study of activities associated with SARS-CoV-2 infection in an adult unvaccinated population and overview of societal COVID-19 epidemic counter measures in Denmark.

Measures to restrict physical inter-personal contact in the community have been widely implemented during the COVID-19 pandemic. We studied determinants for infection with SARS-CoV-2 with the aim of informing future public health measures. We conducted a national matched case-control study among unvaccinated not previously infected adults aged 18-49 years. Cases were selected among those testing positive for SARS-CoV-2 by RT-PCR over a five-day period in June 2021. Controls were selected from the national population register and were individually matched on age, sex and municipality of residence. Cases and controls were interviewed via telephone about contact with other persons and exposures in the community. We determined matched odds ratios (mORs) and 95% confidence intervals (95%CIs) by conditional logistical regression with adjustment for household size and immigration status. For reference, we provide a timeline of non-pharmaceutical interventions in place in Denmark from February 2020 to March 2022. We included 500 cases and 529 controls. We found that having had contact with another individual with a known infection was the main determinant for SARS-CoV-2 infection: reporting close contact with an infected person who either had or did not have symptoms resulted in mORs of 20 (95%CI:9.8-39) and 8.5 (95%CI 4.5-16) respectively. Community exposures were generally not associated with disease; several exposures were negatively associated. Consumption of alcohol in restaurants or cafés, aOR = 2.3 (95%CI:1.3-4.2) and possibly attending fitness centers, mOR = 1.4 (95%CI:1.0-2.0) were weakly associated with SARS-CoV-2 infection. Apart from these two factors, no community activities were more common amongst cases under the community restrictions in place during the study. The strongest risk factor for transmission was contact to an infected person. Results were in agreement with findings of our similar study conducted six month earlier.

Seroprevalence and infection fatality rate of the SARS-CoV-2 Omicron variant in Denmark: A nationwide serosurveillance study.

Background: Introduction of the Omicron variant caused a steep rise in SARS-CoV-2 infections despite high vaccination coverage in the Danish population. We used blood donor serosurveillance to estimate the percentage of recently infected residents in the similarly aged background population with no known comorbidity. Methods: To detect SARS-CoV-2 antibodies induced due to recent infection, and not vaccination, we assessed anti-nucleocapsid (anti-N) immunoglobulin G (IgG) in blood donor samples. Individual level data on SARS-CoV-2 RT-PCR results and vaccination status were available. Anti-N IgG was measured fortnightly from January 18 to April 3, 2022. Samples from November 2021 were analysed to assess seroprevalence before introduction of the Omicron variant in Denmark. Findings: A total of 43 088 donations from 35 309 Danish blood donors aged 17-72 years were screened. In November 2021, 1·2% (103/8 701) of donors had detectable anti-N IgG antibodies. Adjusting for test sensitivity (estimates ranging from 74%-81%) and November seroprevalence, we estimate that 66% (95% confidence intervals (CI): 63%-70%) of the healthy, similarly aged Danish population had been infected between November 1, 2021, and March 15, 2022. One third of infections were not captured by SARS-CoV-2 RT-PCR testing. The infection fatality rate (IFR) was 6·2 (CI: 5·1-7·5) per 100 000 infections. Interpretation: Screening for anti-N IgG and linkage to national registers allowed us to detect recent infections and accurately assess assay sensitivity in vaccinated or previously infected individuals during the Omicron outbreak. The IFR was lower than during previous waves. Funding: The Danish Ministry of Health.

Disability adjusted life years associated with COVID-19 in Denmark in the first year of the pandemic.

BACKGROUND: Burden of disease studies measure the public health impact of a disease in a society. The aim of this study was to quantify the direct burden of COVID-19 in the first 12 months of the epidemic in Denmark. METHODS: We collected national surveillance data on positive individuals for SARS-CoV-2 with RT-PCR, hospitalization data, and COVID-19 mortality reported in the period between 26th of February, 2020 to 25th of February, 2021. We calculated disability adjusted life years (DALYs) based on the European Burden of Disease Network consensus COVID-19 model, which considers mild, severe, critical health states, and premature death. We conducted sensitivity analyses for two different death-registration scenarios, within 30 and 60 days after first positive test, respectively. RESULTS: We estimated that of the 211,823 individuals who tested positive to SARS-CoV-2 by RT-PCR in the one-year period, 124,163 (59%; 95% uncertainty interval (UI) 112,782-133,857) had at least mild symptoms of disease. The total estimated disease burden was 30,180 DALYs (95% UI 30,126; 30,242), corresponding to 520 DALYs/100,000. The disease burden was higher in the age groups above 70 years of age, particularly in men. Years of life lost (YLL) contributed with more than 99% of total DALYs. The results of the scenario analysis showed that defining COVID-19-related fatalities as deaths registered up to 30 days after the first positive test led to a lower YLL estimate than when using a 60-days window. CONCLUSION: COVID-19 led to a substantial public health impact in Denmark in the first full year of the epidemic. Our estimates suggest that it was the the sixth most frequent cause of YLL in Denmark in 2020. This impact will be higher when including the post-acute consequences of COVID-19 and indirect health outcomes.

Epidemiological characterisation of the first 785 SARS-CoV-2 Omicron variant cases in Denmark, December 2021.

By 9 December 2021, 785 SARS-CoV-2 Omicron variant cases have been identified in Denmark. Most cases were fully (76%) or booster-vaccinated (7.1%); 34 (4.3%) had a previous SARS-CoV-2 infection. The majority of cases with available information reported symptoms (509/666; 76%) and most were infected in Denmark (588/644; 91%). One in five cases cannot be linked to previous cases, indicating widespread community transmission. Nine cases have been hospitalised, one required intensive care and no deaths have been registered.

Societal activities associated with SARS-CoV-2 infection: a case-control study in Denmark, November 2020.

Identification of societal activities associated with SARS-CoV-2 infection may provide an evidence base for implementing preventive measures. Here, we investigated potential determinants for infection in Denmark in a situation where society was only partially open. We conducted a national matched case-control study. Cases were recent RT-PCR test-positives, while controls, individually matched on age, sex and residence, had not previously tested positive for SARS-CoV-2. Questions concerned person contact and community exposures. Telephone interviews were performed over a 7-day period in December 2020. We included 300 cases and 317 controls and determined odds ratios (ORs) and 95% confidence intervals (95% CI) by conditional logistical regression with adjustment for household size and country of origin. Contact (OR 4.9, 95% CI 2.4-10) and close contact (OR 13, 95% CI 6.7-25) with a person with a known SARS-CoV-2 infection were main determinants. Contact most often took place in the household or work place. Community determinants included events with singing (OR 2.1, 95% CI 1.1-4.1), attending fitness centres (OR 1.8, 95% CI 1.1-2.8) and consumption of alcohol in a bar (OR 10, 95% CI 1.5-65). Other community exposures appeared not to be associated with infection, these included shopping at supermarkets, travel by public transport, dining at restaurants and private social events with few participants. Overall, the restrictions in place at the time of the study appeared to be sufficient to reduce transmission of disease in the public space, which instead largely took place following direct exposures to people with known SARS-CoV-2 infections.

Prevalence of SARS-CoV-2 antibodies in Denmark: nationwide, population-based seroepidemiological study.

Seroprevalence studies have proven an important tool to monitor the progression of the coronavirus disease 2019 (COVID-19) pandemic. We present results of consecutive population-based seroprevalence surveys performed in Denmark in 2020. In spring, late summer and autumn/winter of 2020, invitation letters including a questionnaire covering symptoms were sent to representative samples of the population above 12 years and to parents of children below 18 years in the sample. Blood samples were analysed for total Ig and seroprevalence estimates per population segment were calculated and compared to other surveillance parameters. Based on 34 081 participants (participation rate 33%), seroprevalence estimates increased from 1.2% (95%CI: 0.3-1.9%) in May to 4.1% (95%CI: 3.1-4.9%) in December 2020. Seroprevalence estimates were roughly three times higher in those aged 12-29 years compared to 65 + and higher in metropolitan municipalities. By December 2020, 1.5% of the population had tested positive by RT-PCR. Infected individuals in older age groups were hospitalised several fold more often than in younger. Amongst seropositives, loss of taste/smell were the more specific symptoms, 32-56% did not report any symptoms. In more than half of seroconverted families, we did not see evidence of transmission between generations. Seroprevalence increased during 2020; adolescents were primarily infected in the autumn/winter. Denmark has a high per capita test rate; roughly one undiagnosed infection of SARS-CoV-2 were estimated to occur for each diagnosed case. Approximately half were asymptomatically infected. The epidemic appears to have progressed relatively modestly during 2020 in Denmark.