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

Abstract

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.

Fig 1. Public health measures and restrictions (February 2020 to March 2022).

^a: As of 16 March 2020, all schoolchildren and students were sent home. As of 15 April 2020, schoolchildren in grades 0–5 and final year students in upper secondary school returned to in–person learning. As of 18 May 2020, schoolchildren in grades 6–10 and all students in upper secondary school returned to in–person learning. As of 27 May 2020, institutions for higher education reopened for in–person learning when physical attendance were essential. As of 22 June 2020, academic institutions facilities for higher education students were allowed to open. As of 29 October 2020, primary school staff were allowed to wear face masks. Within upper secondary school and higher education, face masks were partially mandatory. As of 16 December 2020, all schoolchildren from grade 5, upper secondary and higher education underwent remote learning. Staff for grades 0–4 were allowed to wear face masks. As of 21 December 2021, schoolchildren and students not already on holiday were sent home. As of 8 February 2021, schoolchildren in grades 0–4 returned to in–person learning. As of 1 March 2021, final year students were allowed to return to 50% in–person learning in North–and West Jutland and all students at all education levels in Bornholm were allowed to return to 100% in–person learning. As of 15 March 2021, schoolchildren in grades 5–8 and graduating students who had not returned to 50% in–person learning in were allowed to attend outdoor classes once a week. Final year students were allowed to return to 50% in–person learning in Jutland, Funen, Vest and South Zealand and offshore islands. In offshore islands, primary and lower secondary school students returned 100% to in–person learning. For staff and students over 12 years of age, biweekly tests were recommended. For upper secondary schools and higher education, testing twice a week for students and staff was mandatory. As of 22 March 2021, students in the Capital Region were allowed to return to in–person learning in line with the rest of Denmark. As of 6 April 2021, schoolchildren in grades 5–8 were allowed to return to 50% in–person learning. Students within higher education with practical components to their studies were allowed return to 50% in–person learning and all other students were allowed return to 20% in–person learning. It was mandatory to get tested two times a week. As of 21 April 2021, 80% of learning was in–person for final year students and 30% for students in higher education (with the exception of the Capital Region) and there was the option for outdoor learning. Teaching for grades 5–8 was allowed to resume in–person if held outdoors during the weeks were in–person learning could not take place indoors. As of 6 May 2021, final year students and grades 5–8 returned to 100% in–person learning. Higher education in the Capital Region was allowed to take place in–person outdoors. As of 21 May 2021, all students were allowed to return to 100% learning in–person with the condition of getting tested twice a week. As of 29 November 2021, a valid coronapas was required within upper secondary and higher education. As of 15 December 2021, all schoolchildren in primary and lower secondary school underwent online learning. As of 19 December 2021, it was mandatory to wear face masks in upper secondary and higher education. As of 3 January 2022, it was recommended that those in upper secondary and higher education get tested twice a week. As of 5 January 2022, primary and lower secondary schools were allowed to return to 100% in–person learning, with the condition of students and staff getting tested twice a week. As of 1 February 2022, all restrictions were lifted. Primary and lower secondary school: 0–3 grade (schoolchildren age 5 to 10 years), 4–5 grade (schoolchildren age 9 to 13 years) 6–10 grade (schoolchildren in the age of 12 to 17 years). ^b: As of 13 March 2020, all employees were sent home. As of 14 April 2020, employees of private workplaces were allowed to return to work in–person. However, it was recommended that employees of private workplaces worked from home if possible. As of 27 May 2020, public workplaces in Jutland and Funen were allowed to return to office. As of 15 June 2020, public workplaces in Zealand were allowed to return to office. However, working from home and staggered working hours were recommended. As of 19 September 2020, employees of private and public workplaces were encouraged to work from home. As of 21 May 2021, 20% of the workforce from both public and private workplaces were allowed to return to office. As of 14 June 2021, 20% of the workforce from both public and private workplaces were allowed to return to office, with the recommendation of weekly testing. As of 1 August 2021, 100% of public and private* employees were allowed to return to office. As of 26 November 2021, valid coronapas was mandatory at public workplaces. As of 10 December 2021, employees of private and public workplaces were encouraged to work from home. As of 1 February 2022, all COVID–19 restrictions were lifted. Recommendations, rather than restrictions, were provided for all private workplaces. For public workplaces, restrictions were provided for non–essential employees. ^c Shops: As of 18 March 2020, shopping malls and non–essential shops were required to close. As of 11 May 2020, shopping malls were allowed to reopen with guidelines about space requirements. As of 29 October 2020, the use of face masks when shopping was mandatory, the sale of alcohol was prohibited after 10 PM, and shops larger than 2.000 m² had space requirements and supervisory guards. As of 17 December 2020, shopping malls and non–essentials shops larger than 5 000 m² had to close. As of 25 December 2020, all non–essential shops were required to close. As of 1 March 2021, non–essential shops were allowed to reopen with restrictions (booking and space requirements). As of 13 April 2021, shopping malls smaller than 15.000 m2 were allowed to reopen. As of 21 April 2021, all shopping malls and non–essential shops were allowed to reopen. As of 14 June 2021, face masks were no longer mandatory in shopping malls or non–essential shops. As of 29 November 2021, use of face masks was mandatory for customers (not employees) when shopping. As of 19 December 2021, the use of face masks was mandatory for employees and valid coronapas and further space requirements were introduced. As of 1 February 2022, all COVID–19 restrictions were lifted. Restaurants and bar/night clubs: As of 18 March 2020, restaurants and bar/night clubs were required to close. As of 18 May 2020, restaurants and bars were allowed to reopen (restrictions on space requirements and opening hours). As of August 2020 opening hours for restaurants and bars were extended. As of 19 August 2020 opening hours were limited and the use of face masks was mandatory (except when seated). As of 16 December 2020, restaurants and bars were required to close. As of 21 April 2021, restaurants and bars were allowed to reopen (05 AM to 11 PM), with restrictions (booking, valid corona pas and space requirements). As of 11 June 2021, opening hours at restaurants were extended to 12 AM. As of 14 June 2021, no longer mandatory to use face masks indoor. As of 15 July 2021, opening hours were extended to 2 AM. As of 1 September 2021, all restrictions for restaurants were lifted and night clubs were allowed to reopen with valid coronapas. As of 12 November 2021, a valid coronapas was required at restaurants and bars. As of 10 December 2021, night clubs were required to close and restrictions on opening hours (12 AM) and mandatory use of face masks (only for customers) at restaurants were put in place. As of 19 December 2021, further restrictions were put in place regarding opening hours (11 PM) and mandatory use of face masks for employees and space requirements. As of 1 February 2022, all COVID–19 restrictions were lifted. Public transport: As of 16 March 2020, limited use of public transport was recommended and seat reservation was required (regional trains). As of 31 July 2020, the Danish Health Authority recommended face masks during rush hour. As of 22 August 2020, it was mandatory to use face masks on public transport. As of 14 June 2021, it was mandatory to use face masks while standing in public transport. As of 1 September 2021, it was no longer mandatory to use face masks in public transport. As of 29 November 2021, it was mandatory to use face masks on public transport. As of 19 December 2021, it was mandatory for passengers to have a valid coronapas on long–distance buses and trains. As of 1 February 2022, all COVID–19 restrictions were lifted. Library, cultural activities, church and other religious communities: As of 13 March 2020, the lockdown suspended all public cultural and religious activities. As of 18 May 2020, libraries were allowed to open for the loan of books and churches were allowed to reopen. As of 1 March 2021, outdoor cultural activities were allowed to resume. As of 22 March 2021, a maximum of 50 persons were allowed to gather at religious activities. As of 19 December 2021, restrictions on space requirements and face masks were implemented. As of 24 December 2021, a valid coronapas was required to attend public cultural activities. As of 16 January 2022, indoor cultural facilities were allowed to resume with mandatory use of face masks. No space requirements within the church and other religious communities. As of 1 February 2022, all COVID–19 restrictions were lifted. ^d As of 18 March 2020, the lockdown suspended all indoor and outdoor sport activities. As of 18 May 2020, outdoor sport activities were allowed to resume. As of 8 June 2020, indoor sport activities were allowed to resume. As of 26 October 2020, a maximum of 10 persons were allowed to gather. As of 16 December 2020, the lockdown suspended all indoor and outdoor sport activities. As of 1 March 2021, a maximum of 25 persons were allowed to gather outside for sport activities. As of 22 March 2021, a maximum of 50 persons were allowed to gather outside for sport activities. As of 21 May 2021, sport activities were allowed to resume with valid coronapas. As of 10 August 2021, all restrictions were lifted. As of 19 December 2021, mandatory to use face masks inside. Valid coronapas was required. As of 1 February 2022, all COVID–19 restrictions were lifted. Travel restrictions: During this period, travel restrictions were also in place. Some of the restrictions enacted by the Danish Ministry of Foreign Affairs advised against all non–essential travel worldwide, quarantine, coronapas etc. However, these restrictions were not mapped because the restrictions depended on the travel destination. Coronapas: As of 6 April 2021, coronapas was implemented as a part of the reopening of society. A valid coronapas was either: I) Completed primary vaccination. II) Negative official RT–PCR SARS–CoV–2 or antigen test: Taken within the past 72 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive test, performed at least 14 days and maximum 12 weeks prior. As of 21 April 2021, a valid coronapas was either: I) Completed primary vaccination. II) Negative official RT–PCR SARS–CoV–2 or antigen test: Taken within the past 72 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive PCR test, performed at least 14 days and maximum 6 months prior. As of 21 May 2021, a valid coronapas was either: I) Vaccination: from 14 days to 42 days after the first dose, or after the second dose (mRNA vaccines). After vaccination, the corona passport was valid for 7 months. II) Negative official RT–PCR SARS–CoV–2 or antigen test: Taken within the past 72 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive PCR test, performed at least 14 days and maximum 8 months prior. As of 28 May 2021, the Danish ‘coronapas app’ was introduced. As of 1 July 2021, a valid coronapas was either: I) Vaccination: from 14 days to 42 days after the first dose, or after the second dose (mRNA vaccines). After vaccination, the corona passport was valid for 7 months. II) Negative official RT–PCR SARS–CoV–2 test: Taken within the past 96 hours or negative official antigen test: Taken within the past 72 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive PCR test, performed at least 14 days and maximum 8 months prior. As of 7 July 2021, a valid coronapas was either: I) Vaccination: from 14 days to 42 days after the first dose, or after the second dose (mRNA vaccines). After vaccination, the corona passport was valid for 12 months. II) Negative official RT–PCR SARS–CoV–2 test: Taken within the past 96 hours or Negative official antigen test: Taken within the past 72 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive PCR test, performed at least 14 days and maximum 12 months prior. As of 29 November 2021, a valid coronapas was either: I) Vaccination: from 14 days to 42 days after the first dose, or after the second dose (mRNA vaccines). After vaccination, the corona passport was valid for 12 months. II) Negative official RT–PCR SARS–CoV–2 test: Taken within the past 72 hours or negative official antigen test: Taken within the past 48 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive PCR test, performed at least 14 days and maximum 12 months prior. As of 8 December 2021, a valid coronapas was either: I) Vaccination: from 14 days to 42 days after the first dose, or after the second dose (mRNA vaccines). After vaccination, the corona passport was valid for 7 months. After revaccination, the corona passport is valid. II) Negative official RT–PCR SARS–CoV–2 test: Taken within the past 72 hours or negative official antigen test: Taken within the past 48 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive PCR test, performed at least 14 days and maximum 12 months prior. As of 16 January 2022, a valid coronapas was either: I) Vaccination: from 14 days to 42 days after the first dose, or after the second dose (mRNA vaccines). After vaccination, the corona passport was valid for 5 months. After revaccination, the corona passport is valid. II) Negative official RT–PCR SARS–CoV–2 test: Taken within the past 72 hours or Negative official antigen test: Taken within the past 48 hours. III) Recovered after SARS–CoV–2 infection: Previously infected with SARS–CoV–2 documented by positive PCR test, performed at least 11 days and maximum 5 months prior.

Fig 2. Flow diagram illustrating inclusion of cases and control.