Data sources

We obtained data from the Danish Microbiology Database for all individuals tested with SARS-CoV-2 by RT-PCR in Denmark^{16, 17, 18} and data from other national registers, available in the national COVID-19 surveillance system database at Statens Serum Institut (SSI; Copenhagen, Denmark), described elsewhere.¹⁹ Briefly, the surveillance system links individual-level information daily between national registers and databases by use of the unique personal identification number of all Danish citizens, thereby centralising surveillance information from the National Patient Register (inpatient and outpatient diagnoses, admission, and discharge dates),²⁰ the Civil Registration System (vital status and previous and current addresses),²¹ and viral WGS data from the Danish COVID-19 Genome Consortium,²² among others.

In Denmark, health-care personnel (who are routinely tested) and individuals with symptoms suggestive of COVID-19 who were seen by a doctor are tested for SARS-CoV-2 by RT-PCR in regional clinics connected with the ten Danish departments of clinical microbiology, which serve public and private hospitals and primary care clinics. This workflow is referred to as the health-care track. Additionally, a centralised high-throughput public COVID-19 test laboratory—the Test Center Denmark (TCDK)—was established by the end of April, 2020, at SSI. TCDK offers free RT-PCR testing to asymptomatic individuals and those with mild symptoms, which is referred to as the community track. All tests are offered as part of a universal tax-funded health-care system and provided free of cost to the citizen. Test slots at TCDK are made publicly available and can be booked online. Information on PCR cycle threshold (Ct) values were available for samples analysed in TCDK, which uses a single laboratory protocol. Information on Ct values in the health-care test track was not available, and many different protocols are used by hospitals. A laboratory-confirmed SARS-CoV-2 case was defined as a person testing positive for SARS-CoV-2 by RT-PCR. Rapid antigen testing has been used increasingly since December, 2020, but, according to national recommendations, a positive rapid antigen test has to be confirmed with a RT-PCR test.

WGS data for SARS-CoV-2 was obtained from the Danish COVID-19 Genome Consortium (DCGC). The DCGC was established in March, 2020, with the purpose of assisting public health authorities by providing rapid genomic monitoring of the spread of SARS-CoV-2. Large-scale SARS-CoV-2 sequencing capacity was initially established at Aalborg University (Aalborg, Denmark) and supported by local sequencing capacity at SSI, Aarhus University Hospital, and Hvidovre Hospital (Hvidovre, Denmark). Since June, 2020, DCGC has included local sequencing nodes across the country to increase the proportion of sequenced samples from the health-care track.

Because of an increased number of cases in the early study period and some initial restrictions in sequencing capacity, some degree of selection of samples by Ct value in both test tracks was required. Therefore, in the community track, samples with Ct values lower than 30 were prioritised from week 53, 2020, to week 3, 2021, and samples with Ct values lower than 35 were prioritised in weeks 4 to 5. Otherwise, samples in this track were picked randomly as they arrived, according to the available workforce at the time of sample arrival and with no deliberate choice taken to pick samples from any particular location, age, or demographic criteria. In the health-care track, hospitals were advised to prioritise samples with Ct value lower than 32, if and when capacity was surpassed in the studied period. However, the degree to which this recommendation was followed for the health-care track is unclear, and Ct values from the health-care track were not available for analysis. All WGS data were centrally stored at Aalborg University and transferred daily to SSI.