Covid-19 and post-acute sick leave: a hybrid register and questionnaire study in the adult Danish population (preprint)

Long covid follows 10-20% of first-time SARS-CoV-2 infections, but the societal burden of long covid and risk factors for the condition are not well-understood. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which included 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index and alpha waves. An additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave was defined as >1 month of sick leave within the period 1-9 months after the RT-PCR test date. Being female, [≥]50 years, and having certain pre-existing conditions such as fibromyalgia increased risks for taking substantial sick leave. Further research exploring this heterogeneity is urgently needed and may provide important evidence for more targeted preventative strategies.

Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study (preprint)

ObjectivesTo evaluate the effects of the Omicron variant on the post-acute symptoms, four months after infection with SARS-CoV-2. DesignA nationwide questionnaire study. SettingDenmark. Participants44,004 individuals aged 15 years or older with either a SARS-CoV-2 RT-PCR positive test result from the period of Delta dominance (July to November 2021), or a positive or negative RT-PCR test result from the period of Omicron dominance (December 2021 to January 2022). MethodsA questionnaire based cohort study with outcomes on post-acute physical, fatigue, cognitive, mental health symptoms, and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing cases and controls during the Omicron period, cases during the Delta and Omicron periods, and vaccinated cases with two and three doses during the Omicron period, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation and vaccination status. ResultsFour months after testing for SARS-CoV-2 during the Omicron period, cases experienced higher risk of 18 out of 26 post-acute symptoms and five out of five new-onset general health problems, compared to controls. Cases during the Omicron period experienced lower risks of 8 of the 18 symptoms and of all five new-onset general health problems, compared to Delta cases. The most prominent RDs estimated when comparing Omicron cases to controls were: memory issues (RD=5.4%, 95% CI 4.8 to 6.1), post-exertional malaise (RD=5.3%, 95% CI 3.1 to 7.7), fatigue/exhaustion (RD=5.2%, 95% CI 3.7 to 6.9), substantial fatigue (RD=5.0%, 95% CI 2.7 to 7.5), and dyspnea (RD=4.8%, 95% CI 3.8 to 5.9). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute altered/reduced sense of smell (dysosmia) (RD=-15.1%, 95% CI -17.0 to -12.9) and -taste (dysgeusia) (RD=-11.6%, 95% CI -13.6 to -9.7). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13 of the 26 post-acute symptoms and of three of the five new-onset general health problems, compared to those vaccinated with two doses. ConclusionsA considerable amount of cases infected during the Omicron period experienced post-acute symptoms and new-onset health problems, four months after testing, although milder compared to Delta cases. During the Omicron period, a booster vaccination dose was associated with fewer post-acute symptoms and new-onset health problems, four months after infection, compared to two doses of COVID-19 vaccine.

Post-acute symptoms, new onset diagnoses and health problems 6 to 12 months after SARS-CoV-2 infection: a nationwide questionnaire study in the adult Danish population (preprint)

Background. A considerable number of individuals infected with SARS-CoV-2 continue to experience symptoms after the acute phase. More information on duration and prevalence of these symptoms in non-hospitalized populations is needed. Methods. We conducted a nationwide cross-sectional study including 152 880 individuals aged 15-years or older, consisting of RT-PCR confirmed SARS-CoV-2 cases between September 2020-April 2021 (N=61 002) and a corresponding test-negative control group (N=91 878). Data were collected 6, 9 or 12 months after the test using web-based questionnaires. The questionnaire covered acute and post-acute symptoms, selected diagnoses, sick leave and general health, together with demographics and life style at baseline. Risk differences (RDs) between test-positives and -negatives were reported, adjusted for age, sex, single comorbidities, Charlson comorbidity score, obesity and healthcare-occupation. Findings. Six to twelve months after the test date, the risks of 18 out of 21 physical symptoms were elevated among test-positives and one third (29.6%) of the test-positives experienced at least one physical post-acute symptom. The largest risk differences were observed for dysosmia (RD = 10.92%, 95%CI 10.68-11.21%), dysgeusia (RD=8.68%, 95%CI 8.43-8.93%), fatigue/exhaustion (RD=8.43%, 95%CI 8.14-8.74%), dyspnea (RD=4.87%, 95%CI 4.65-5.09%) and reduced strength in arms/legs (RD=4.68%, 95%CI 4.45-4.89%). More than half (53.1%) of test-positives reported at least one of the following conditions: concentration difficulties (RD=28.34%, 95%CI 27.34-28.78%), memory issues (RD=27.25%, 95%CI 26.80-27.71%), sleep problems (RD=17.27%, 95%CI 16.81-17.73%), mental (RD=32.58%, 95%CI 32.11-33.09%) or physical exhaustion (RD=40.45%, 95%CI 33.99-40.97%), compared to 11.5% of test-negatives. New diagnoses of anxiety (RD=1.15%, 95%CI 0.95-1.34%) or depression (RD=1.00%, 95%CI 0.81-1.19%) were also more common among test-positives. Interpretation. At the population-level, where the majority of test-positives (96.0%) were not hospitalized during acute infection, a considerable proportion experience post-acute symptoms and sequelae 6-12 months after infection. Funding. None

Testing Denmark: A Danish nationwide surveillance study of COVID-19 (preprint)

BackgroundNational data on the spread of SARS-CoV-2 infection and knowledge on associated risk factors are important for understanding the course of the pandemic. "Testing Denmark" is a national large-scale epidemiological surveillance study of SARS-CoV-2 in the Danish population. MethodsBetween September and October 2020, approximately 1.3 million of 5.8 million Danish citizens (age > 15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by Point-of Care rapid Test (POCT) distributed to participants home addresses. FindingsIn total 318,552 participants (24.5% invitees) completed the questionnaire and provided the result of the POCT. Of these, 2,519 (0.79%) were seropositive (median age 55 years) and women were more often seropositive than men, interquartile range (IQR) 42-64, 40.2% males. Of participants with a prior positive Polymerase Chain Reaction (PCR) test (n=1,828), 29.1% were seropositive in the POCT. Seropositivity increased with age irrespective of sex. Elderly participants (>61 years) reported less symptoms and had less frequently been tested for SARS-CoV-2 compared to younger participants. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (Risk ratio (RR) 7.43, 95% CI: 6.57-8.41) and in particular household members (RR 17.70, 95% CI: 15.60-20.10). Home care workers had a higher risk of seropositivity (RR 2.09 (95% CI: 1.58-2.78) as compared to office workers. Geographic population density was not associated to seropositivity. A high degree of compliance with national preventive recommendations was reported (e.g., > 80% use of face masks), but no difference was found between seropositive and seronegative participants. InterpretationThis study provides insight into the immunity of the Danish population seven to eight months after the first COVID-19 case in Denmark. The seroprevalence was lower than expected probably due to a low sensitivity of the POCT used or due to challenges relating to the reading of test results. Occupation or exposure in local communities were major routes of infection. As elderly participants were more often seropositive despite fewer symptoms and less PCR tests performed, more emphasis should be placed on testing this age group.

Seroprevalence of SARS-CoV-2 antibodies in social housing areas in Denmark (preprint)

Background COVID-19 is suggested to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas . Methods As part of Testing Denmark, a nationwide sero-epidemiological surveillance survey, we conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas in Denmark. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning previous testing (viral throat- and nasopharyngeal swab or antibody test), test results for COVID-19, demographics, household characteristics, employment, risk factors for SARS-CoV-2 infection and history of symptoms associated with COVID-19. Data on seroprevalence from Danish blood donors in same period using a total Ig ELISA assay were used as a proxy for the general Danish population. Findings Of the 13,279 included participants, 2,296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78-3.16, p>0.001). Seropositivity was higher among males than females (RR 1.1, 95% CI 1.05-1.22%, p=0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00-1.06, p=0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among members of the same households (OR 5.0, 95% CI 4.1-6.2 p<0,001). Adjusted for age, gender and region living at least 4 people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.1-1.6, p=0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1-1.5, p=0.007). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. Anosmia (RR 3.2 95% CI 2.8-3.7, p<0.001) and ageusia (RR 3.3, 95% CI 2.9-3.8, p<0.001) were strongest associated with seropositivity. Interpretation Danish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased with age. Living in multiple generations or more than four persons in a household was an independent risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.

SARS-CoV-2 antibody prevalence among homeless people, sex workers and shelter workers in Denmark: a nationwide cross-sectional study (preprint)

Background People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with 'Severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. Design and methods In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. Results We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9-59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1-55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p=0.87); and 12% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2,9%, p <0.001). Participants engaging in sex work had a significantly increased risk of seropositivity compared to other participants (95% CI: 0.86-2.36, p=0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively). Interpretations The prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. The subset of the study participants who were also sex workers were at particularly high risk of COVID-19 infection. Funding Tryg and HelseFonden.