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Background: Because long‐term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well‐described, we studied effectiveness over 18 years in Denmark. Methods: A register‐based cohort study using data on filled prescriptions, 1995–2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non‐treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti‐allergic nasal inhaler during the pollen season in the treated versus non‐treated group by years since baseline. Results: Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0–5 years after baseline was reduced when compared with 15,520 non‐treated AR individuals (0–2 years, OR 0.84 (0.81–0.88); 3–5 years, OR 0.88 (0.84–0.92)), but was close to unity or higher thereafter (6–9 years, OR 1.03 (0.97–1.08); 10–18 years, OR 1.18 (1.11–1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0–2 years, OR 0.76 (0.72–0.79); 3–5 years OR 0.86 (0.81–0.93); 6–9 years, OR 0.94 (0.87–1.02); 10–18 years, OR 0.94 (0.86–1.04)) as opposed to no such use. Conclusions: Patients treated with pollen AIT in routine care to a higher degree stopped using anti‐allergic nasal inhaler 0–5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR. [ABSTRACT FROM AUTHOR]

Many individuals who refuse COVID-19 vaccination have concerns about long-term side effects. Here, we report findings on self-reported symptoms from a Danish survey- and register study. The study included 34,868 vaccinated primary course recipients, 95.8% of whom received mRNA vaccines, and 1,568 unvaccinated individuals. Participants had no known history of SARS-CoV-2 infection. Using g-computation on logistic regression, risk differences (RDs) for symptoms between vaccinated and unvaccinated persons were estimated with adjustments for possible confounders. Within six weeks after vaccination, higher risks were observed for physical exhaustion (RD 4.9%, 95% CI 1.1% to 8.4%), fever or chills (RD 4.4%, 95% CI 2.1% to 6.7%), and muscle/joint pain (RD 7.0%, 95% CI 3.1% to 10.7%), compared to unvaccinated individuals. Beyond twenty-six weeks, risks were higher among the vaccinated for sleeping problems (RD 3.0, 95% 0.2 to 5.8), fever or chills (RD 2.0, 95% CI 0.4 to 3.6), reduced/altered taste (RD 1.2, 95% CI 0.2 to 2.3) and shortness of breath (RD 2.6, 95% CI 0.9 to 4.0). However, when examining pre-omicron responses only, the difference for reduced/altered taste was significant. As expected, the risk of experiencing physical exhaustion, fever or chills, and muscle/joint pain was higher among persons who responded within six weeks of completing the primary course. No significant differences were observed for the 7-25-week period after vaccination. Associations for the period beyond 26 weeks must be interpreted with caution and in the context of undetected SARS-CoV-2 infection, wide confidence intervals, and multiple testing. Overall, we observe no concerning signs of long-term self-reported physical, cognitive, or fatigue symptoms after vaccination. [ABSTRACT FROM AUTHOR]

Post-acute sick leave is an underexplored indicator of the societal burden of SARS-CoV-2. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which include 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index- and alpha-dominant waves. We observe that 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 is defined as >1 month of sick leave within the period 1–9 months after the RT-PCR test date. Being female, 50–65 years, or having certain pre-existing health conditions such as obesity, chronic lung diseases, and fibromyalgia each increase risk for taking substantial sick leave. Altogether, these results may help motivate improved diagnostic and treatment options for persons living with post-Covid conditions. Authors utilise a questionnaire-based approach to survey self-reported, post-acute sick leave and risk factors in cases of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

A considerable number of individuals infected with SARS-CoV-2 continue to experience symptoms after the acute phase. Here, we report findings from a nationwide questionnaire study in Denmark including 61,002 RT-PCR confirmed SARS-CoV-2 cases and 91,878 test-negative controls aged 15-years or older. Six to twelve months after the test, the risks of 18 out of 21 symptoms were elevated among test-positives. The largest adjusted risk differences (RD) 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%). During the period from the test and until completion of the questionnaire, 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. Even in a population where the majority of test-positives were not hospitalized, a considerable proportion experiences symptoms up to 12 months after infection. Being female or middle-aged increases risks. The health impacts associated with SARS-CoV-2 infection are still not well understood. Here, the authors report findings from a survey of ~150,000 people in Denmark, and identify elevated risks associated with testing positive for SARS-CoV-2 for a range of acute and post-acute symptoms and new diagnoses. [ABSTRACT FROM AUTHOR]

Background: The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages.Methods: We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion.Findings: Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72-0·87; p<0·0001) and an adjusted RR of 1·42 (95% CI 1·25-1·60; p<0·0001). The adjusted RR was increased in all strata of age and calendar period-the two covariates with the largest contribution to confounding of the crude RR.Interpretation: Infection with SARS-CoV-2 lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with that of other lineages in an analysis adjusted for covariates. The overall effect on hospitalisations in Denmark was lessened due to a strict lockdown, but our findings could support hospital preparedness and modelling of the projected impact of the epidemic in countries with uncontrolled spread of B.1.1.7.Funding: None. [ABSTRACT FROM AUTHOR]

Tendon injury is a considerable problem affecting both physically active and sedentary people. The aim of this study was to examine the relationship between markers for metabolic disorders (hyperglycemia, hypercholesterolemia, and metabolic syndrome) and the risk of developing tendon injuries requiring referral to a hospital. The Copenhagen City Heart Study is a prospective study of diabetic and non‐diabetic individuals from the Danish general population with different physical activity levels. The cohort was followed for 3 years via national registers with respect to tendon injuries. Data from 5856 individuals (median age 62 years) were included. The overall incidence of tendon injury in both upper and lower extremities that required an out‐patient or in‐house visit to a hospital was ~5.7/1000 person years. Individuals with elevated HbA1c (glycated hemoglobin) even in the prediabetic range (HbA1c>5.7%) had a ~3 times higher risk of tendon injury in the lower extremities only, as compared to individuals with normal HbA1C levels. Hypercholesterolemia (total cholesterol>5 mmol/L) increased risk of tendon injury in the upper extremities by ~1.5 times, and individuals with metabolic syndrome had ~2.5 times higher risk of tendon injury in both upper and lower extremities. In conclusion, these data demonstrate for the first time in a large cohort with different physical activity levels that the indicators for metabolic syndrome are a powerful systemic determinant of tendon injury, and two of its components, hyperglycemia and hypercholesterolemia, each independently make tendons susceptible for damage and injury. [ABSTRACT FROM AUTHOR]

Few studies have addressed the possible association between age at menarche and multiple sclerosis (MS), and results are conflicting. We studied this issue in a large prospective cohort study. The study cohort comprised 77,330 women included in the Danish National Birth Cohort (1996-2002). Information on menarcheal age was ascertained at the first interview, which took place in the 16th week of pregnancy. Women were followed for MS from the first interview to December 31, 2011. Associations between age at menarche and risk of MS were evaluated with hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Overall, 226 women developed MS during an average follow-up period of 11.7 years. Age at menarche among women with MS was generally lower than that among women without MS (Wilcoxon rank-sum test; P = 0.002). We observed an inverse association between age at menarche and MS risk. For each 1-year increase in age at menarche, risk of MS was reduced by 13% (hazard ratio = 0.87, 95% confidence interval: 0.79, 0.96). Early age at menarche appears to be associated with an increased risk of MS. The mechanisms behind this association remain to be established. [ABSTRACT FROM AUTHOR]

Background. As carriers of filaggrin gene ( FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer. Methods. We genotyped 586 cervical cancer patients for the two most common FLG mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic regression with adjustment for age at blood sampling, and weighted by the genotype-specific inverse probability of death between diagnosis and sampling. Hazard ratios (HR) were estimated by Cox regression with time since diagnosis as underlying time, and with adjustment for age at diagnosis and stratification by cancer stage. Results. The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased mortality due to cervical cancer (HR 4.55, 95% CI 1.70-12.2), however, the association was reduced after stratification by cancer stage (HR 2.53, 95% CI 0.84-7.59). Conclusion. Carriage of FLG mutations was not associated with the risk of cervical cancer. [ABSTRACT FROM AUTHOR]

The article presents a nationwide register-based cohort study which assesses the association between cesarean section (C-section) delivery and the risk of developing multiple sclerosis (MS) in people born from 1973-2005 in Denmark. The registered-based data were analyzed by means of MS incidence rate ratios with 95% confidence intervals obtained in log-linear Poisson regression analyses. The results indicate no significant association between C-section and the risk of developing MS.

In a national cohort comprising 1.5 million Danes born from 1966 to 1992, we studied the association between childhood socioeconomic status (SES) and the risk of multiple sclerosis (MS) from 1981 to 2007 using information about household income and parental educational levels at the person's 15th birthday. The association between childhood SES and MS was evaluated using MS incidence rate ratios with 95% confidence intervals obtained in log-linear Poisson regression analyses. We found no strong association between childhood SES and MS but did observe a tendency toward a reduced risk of MS among children from households with more highly educated parents, particularly mothers. Children whose mothers had a secondary (rate ratio = 0.95, 95% confidence interval: 0.86, 1.04) or higher (rate ratio = 0.86, 95% confidence interval: 0.76, 0.97) education had reduced risks of MS (5% and 14%, respectively) compared with children of mothers with a basic education (P for trend = 0.02). Results were practically unchanged in an analysis restricted to persons aged 15–29 years, among whom the possible effect of own SES on MS risk is considered limited. Overall, SES in childhood seems of no major importance for the subsequent risk of MS; however, offspring of well-educated mothers may be at a slightly reduced risk of MS. [ABSTRACT FROM PUBLISHER]

Because parvovirus B19 infection during pregnancy has been associated with increased risk of fetal loss in small or selected study populations, the authors evaluated the risk in a population-based study. A nested case-control study was conducted by using a population-based screening for syphilis in 3 regions in Denmark from 1992 to 1994. Cases of women with fetal loss were identified in the National Patient Register (n = 2,918), and control women with live-born children were identified in the Medical Birth Register (n = 8,429) by matching on age and sampling week. First-trimester serum samples were tested for parvovirus B19 immunoglobulin M positivity. Parvovirus B19 immunoglobulin M positivity was associated with a 71% increased risk of fetal loss (odds ratio = 1.71, 95% confidence interval: 1.02, 2.86). Adjustment for number of children or stratifying for gestational age at loss did not change the risk estimate. Assuming causality, only 0.1% of fetal losses were attributable to parvovirus B19 positivity, a proportion which could increase to approximately 1% during epidemic periods. In conclusion, acute parvovirus B19 infection during the first trimester of pregnancy was associated with an increased risk of fetal loss. However, the impact on the overall burden of fetal losses appeared small even during epidemics. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. There was no funding source for this study. [ABSTRACT FROM AUTHOR]

It has been hypothesized that age at infection with a common microbial agent may be associated with the risk of multiple sclerosis (MS). The authors addressed this hypothesis by using number of older siblings and other sibship characteristics as an approximation of age at exposure to common infections. Data on family characteristics and vital status from the Danish Civil Registration System were used to establish a cohort of all Danes whose mothers had been born in Denmark since 1935. Persons diagnosed with MS during the period 1968–1998 were identified through linkage with the Danish Multiple Sclerosis Register. The cohort of 1.9 million Danes was followed for 28.1 million person-years; during that time, 1,036 persons developed MS. Overall, there was no association between number of older siblings, number of younger siblings, total number of siblings, age distance from the nearest younger sibling, or exposure to younger siblings under 2 years of age and risk of MS later in life. There was no association of MS risk with multiple birth (vs. singleton birth) or with the age of the mother or father at birth. These results do not lend support to the hypothesis that number of older siblings or any of the other sibship characteristics studied is associated with risk of MS. [ABSTRACT FROM AUTHOR]

Importance: Fatigue remains one of the most common and debilitating symptoms of post-COVID-19 condition; however, existing studies are limited to select populations and often lack noninfected controls. It also remains unclear to what extent severity of infection and psychiatric conditions, which are often linked to chronic fatigue, modify the risk of post-COVID-19 condition fatigue symptoms., Objective: To evaluate the impact of SARS-CoV-2 infection on self-reported fatigue and postexertional malaise over time and to explore possible risk factors, such as the impact of acute SARS-CoV-2 hospitalization and preexisting psychiatric conditions on postacute fatigue., Design, Setting, and Participants: In this cohort study, Danish residents aged 15 years and older were invited to participate in the EFTER-COVID survey, which used repeated, self-reported online questionnaires that collected information on fatigue (Fatigue Assessment Scale) and postexertional malaise scores (DePaul Symptom Questionnaire) after individuals' index SARS-CoV-2 polymerase chain reaction test. Participants were included if they completed a baseline and at least 1 follow-up questionnaire 2 to 18 months after testing for SARS-CoV-2., Exposure: Testing for SARS-CoV-2 infection., Main Outcomes and Measures: The primary outcomes were fatigue and postexertional malaise 2 to 18 months after testing. Mixed-effects models were used to compare scores between SARS-CoV-2 test-positive and test-negative individuals (testing period April 2021 to February 2023)., Results: Of a total of 50 115 participants (median [IQR] age at test date, 57 [46-67] years; 29 774 female [59.4%]), 25 249 were test positive and 24 866 were test negative. Most participants were vaccinated with at least 2 doses (21 164 test-negative participants [85.1%] and 22 120 test-positive participants [87.6%]) before their SARS-CoV-2 index test and fatigue reporting. In the period 2 to 18 months after testing, SARS-CoV-2 infection was associated with a small but significant 3% increase in self-reported fatigue scores (score ratio [SR], 1.03; 95% CI, 1.03-1.04) and higher odds of self-reported postexertional malaise (odds ratio, 2.04; 95% CI, 1.81-2.30), compared with test-negative participants. In the same period, hospitalization with SARS-CoV-2 increased fatigue scores by 23% (SR, 1.23; 95% CI, 1.20-1.26) compared with test-negative participants. Preexisting psychiatric conditions did not significantly modify postacute fatigue scores., Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with a subtle increase in self-reported fatigue and postexertional malaise symptoms 2 to 18 months after mild infection. In contrast, individuals hospitalized with acute SARS-CoV-2 experienced a more substantial increase in postacute symptoms. Preexisting psychiatric conditions did not significantly modify the risk of postacute fatigue symptoms. The findings largely captured symptoms following first-time infections in a population where most had been vaccinated. Persons who experienced severe acute infection may benefit from clinical follow-up for fatigue.

Background: During the 2023 Danish COVID-19 vaccination campaign, an updated monovalent mRNA vaccine targeting the SARS-CoV-2 omicron XBB.1.5 subvariant was administered. However, the rapid spread of a genetically divergent omicron BA.2.86 subvariant, JN.1, since September, 2023, poses potential challenges due to its rapid dominance and possible immune escape. Using national electronic health registry data from all regions of Denmark, we aimed to investigate whether the SARS-CoV-2 subvariant BA.2.86, and its descendant JN.1, differed from other circulating variants in terms of their ability to escape vaccine protection, the risk of infection leading to severe disease, and self-reported symptoms among infected people., Methods: In this observational study, we included all residents of Denmark aged 65 years and older who tested positive for SARS-CoV-2 by PCR between Oct 1 and Dec 31, 2023, and for whom genomic data on the SARS-CoV-2 variant that had caused their infection were available. Data from clinical testing, sentinel, and self-sampling-based surveillance were linked with national electronic civil, vaccination, and hospitalisation registers. The relative protection of the XBB.1.5 updated COVID-19 vaccine against BA.2.86 infections versus infections with other variants was analysed in a case-only study, and the relative risk of hospitalisation in people infected with BA.2.86 versus other variants was analysed in a case-control study. Both analyses were adjusted for time, comorbidities, and previous vaccination history, among other potential confounders. Additionally, prevalence patterns in self-reported symptoms among people of all ages infected with SARS-CoV-2 were reported separately by subvariant., Findings: Of the 7581 people in Denmark aged 65 years or older who tested positive for SARS-CoV-2 by PCR during the study period, 5882 (78%) samples were eligible for sequencing. 3862 (66%) of these passed quality control, were successfully sequenced, and the SARS-CoV-2 variant and subvariant identified, and these individuals were included in the study. Of these 3862 people, 2184 (57%) were infected with the BA.2.86 subvariant, including 1615 JN.1 infections. Participants infected with BA.2.86 had 1·52 (95% CI 1·25-1·86) times the odds, and those infected with JN.1 had 1·60 (1·27-2·02) times the odds, of having received the XBB.1.5 vaccine at least 7 days before their infection compared with participants infected with a non-BA.2.86 variant. The severity analysis showed no evidence of association between the infecting variant and the risk of COVID-19 hospitalisation (odds ratio 1·04 [95% CI 0·86-1·26] for BA.2.86 and 1·07 [0·85-1·34] for JN.1). Similarly, there was no evidence of differences in self-reported symptoms by variant strain., Interpretation: Compared with other SARS-CoV-2 variants, BA.2.86 and the JN.1 sublineage were less sensitive to vaccine-induced immune protection from the XBB.1.5 updated COVID-19 vaccine; however, we found no evidence that infection with BA.2.86 or JN.1 resulted in increased disease severity or different symptom profiles. Although less effective against the new variants, XBB.1.5 vaccination remains protective and reduces the risk of infection and COVID-19 disease., Funding: The Danish Government and the EU's EU4Health programme., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Postacute symptoms are not uncommon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with pre-Omicron variants. How the Omicron variant and coronavirus disease 2019 (COVID-19) booster vaccination influence the risk of postacute symptoms is less clear. We analyzed data from a nationwide Danish questionnaire study, EFTER-COVID, comprising 36 109 individuals aged ≥15 years who were tested between July 2021 and January 2022, to evaluate the associations of the Omicron variant and COVID-19 booster vaccination with postacute symptoms and new-onset general health problems 4 months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron cases with controls, comparing Omicron cases with Delta cases, and comparing Omicron cases vaccinated with 3 doses with those vaccinated with 2 doses, adjusting for age, sex, body mass index, self-reported chronic diseases, Charlson comorbidity index, health-care occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial postacute symptoms and new-onset health problems in comparison with controls; the largest RD was observed for memory issues (RD = 7.4%; 95% CI, 6.4-8.3). However, risks were generally lower than those in the Delta period, particularly for dysosmia (RD = -15.0%; 95% CI, -17.0 to -13.2) and dysgeusia (RD = -11.2%; 95% CI, -13.2 to -9.5). Booster vaccination was associated with fewer postacute symptoms and new-onset health problems 4 months after Omicron infection as compared with 2 doses of COVID-19 vaccine., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern. Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes when compared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study included hospitalized patients in Denmark with Enterococcus faecium -positive blood cultures collected between 2010 and 2019 identified in the Danish Microbiology Database. We estimated 30-day hazard ratio (HR) of death or discharge among VRE compared to VSE patients adjusted for age, sex, and comorbidity. The cohort included 6071 patients with E. faecium BSI (335 VRE, 5736 VSE) among whom VRE increased (2010-13, 2.6%; 2014-16, 6.3%; 2017-19; 9.4%). Mortality (HR 1.08, 95%CI 0.90-1.29; 126 VRE, 37.6%; 2223 VSE, 37.0%) or discharge (HR 0.89, 95%CI 0.75-1.06; 126 VRE, 37.6%; 2386 VSE, 41.6%) was not different between VRE and VSE except in 2014 (HR 1.87, 95% CI 1.18-2.96). There was no interaction between time from admission to BSI (1-2, 3-14, and >14 days) and HR of death ( P  = 0.14) or discharge ( P  = 0.45) after VRE compared to VSE, despite longer time for VRE patients (17 vs. 10 days for VSE, P  < 0.0001). In conclusion, VRE BSI was not associated with excess morbidity and mortality. The excess mortality in 2014 only may be attributed to improved diagnostic- and patient-management practices after 2014, reducing time to appropriate antibiotic therapy. The high level of mortality after E. faecium BSI warrants further study.

Purpose: To follow SARS-CoV-2-infected persons up to 18 months after a positive test in order to assess the burden and nature of post acute symptoms and health problems., Participants: Persons in Denmark above 15 years of age, who were tested positive for SARS-CoV-2 during 1 September 2020 to 21 February 2023 using a RT-PCR test. As a reference group, three test-negative individuals were selected for every two test-positive individuals by matching on test date., Findings to Date: In total, 2 427 913 invitations to baseline questionnaires have been sent out and 839 528 baseline questionnaires (34.5%) have been completed. Females, the age group 50-69 years, Danish-born and persons, who had received at least one SARS-CoV-2 vaccination booster dose were more likely to participate. Follow-up questionnaires were sent at 2, 4, 6, 9, 12 and 18 months after the test, with response rates at 42%-54%., Future Plans: New participants have been recruited on a daily basis from 1 August 2021 to 23 March 2023. Data collection will continue until the last follow-up questionnaires (at 18 months after test) have been distributed in August 2024., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

It is not well-described how the acute symptoms of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ by variant, vaccination, sex and age. A cross-sectional questionnaire study linked to national testing- and registry data was conducted among 148,874 SARS-CoV-2 first time reverse transcription polymerase chain reaction (RT-PCR) test-positive individuals and corresponding date-matched symptomatic test-negative controls. Major SARS-CoV-2 variants (Index/wild type, Alpha, Delta and Omicron) were defined using periods of predominance. Risk differences (RDs) were estimated for each of 21 predefined acute symptoms comparing: (1) test-positive and -negative individuals, by variant period, (2) vaccinated and unvaccinated test-positives, by variant period, (3) individuals tested positive during the Omicron and Delta periods, by vaccination status, and (4) vaccinated Omicron test-positive and -negative individuals, by age and sex. Compared to pre-Omicron, RDs between test-positive and test-negative individuals during the Omicron period were lower for most symptoms. RDs for altered sense of smell (dysosmia) and taste (dysgeusia) were highest for Delta (RD = 50.8 (49.4-52.0) and RD = 54.7 (53.4-56.0), respectively) and lowest for Omicron (RD = 12.8 (12.1-13.5) and RD = 11.8 (11.1-12.4), respectively). Across variants, vaccinated individuals reported fewer symptoms. During Omicron, females and 30-59 year-old participants reported more symptoms., (© 2023. The Author(s).)

Background: Estimates of the severity of the SARS-CoV-2 omicron variant (B.1.1.529) are crucial to assess the public health impact associated with its rapid global dissemination. We estimated the risk of SARS-CoV-2-related hospitalisations after infection with omicron compared with the delta variant (B.1.617.2) in Denmark, a country with high mRNA vaccination coverage and extensive free-of-charge PCR testing capacity., Methods: In this observational cohort study, we included all RT-PCR-confirmed cases of SARS-CoV-2 infection in Denmark, with samples taken between Nov 21 (date of first omicron-positive sample) and Dec 19, 2021. Individuals were identified in the national COVID-19 surveillance system database, which included results of a variant-specific RT-PCR that detected omicron cases, and data on SARS-CoV-2-related hospitalisations (primary outcome of the study). We calculated the risk ratio (RR) of hospitalisation after infection with omicron compared with delta, overall and stratified by vaccination status, in a Poisson regression model with robust SEs, adjusted a priori for reinfection status, sex, age, region, comorbidities, and time period., Findings: Between Nov 21 and Dec 19, 2021, among the 188 980 individuals with SARS-CoV-2 infection, 38 669 (20·5%) had the omicron variant. SARS-CoV-2-related hospitalisations and omicron cases increased during the study period. Overall, 124 313 (65·8%) of 188 980 individuals were vaccinated, and vaccination was associated with a lower risk of hospitalisation (adjusted RR 0·24, 95% CI 0·22-0·26) compared with cases with no doses or only one dose of vaccine. Compared with delta infection, omicron infection was associated with an adjusted RR of hospitalisation of 0·64 (95% CI 0·56-0·75; 222 [0·6%] of 38 669 omicron cases admitted to hospital vs 2213 [1·5%] of 150 311 delta cases). For a similar comparison by vaccination status, the RR of hospitalisation was 0·57 (0·44-0·75) among cases with no or only one dose of vaccine, 0·71 (0·60-0·86) among those who received two doses, and 0·50 (0·32-0·76) among those who received three doses., Interpretation: We found a significantly lower risk of hospitalisation with omicron infection compared with delta infection among both vaccinated and unvaccinated individuals, suggesting an inherent reduced severity of omicron. Our results could guide modelling of the effect of the ongoing global omicron wave and thus health-care system preparedness., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Following emergence of the SARS-CoV-2 variant Omicron in November 2021, the dominant BA.1 sub-lineage was replaced by the BA.2 sub-lineage in Denmark. We analysed the first 2,623 BA.2 cases from 29 November 2021 to 2 January 2022. No epidemiological or clinical differences were found between individuals infected with BA.1 versus BA.2. Phylogenetic analyses showed a geographic east-to-west transmission of BA.2 from the Capital Region with clusters expanding after the Christmas holidays. Mutational analysis shows distinct differences between BA.1 and BA.2.

Background: Atopic dermatitis (AD) normally onsets in childhood and mostly resolves before adolescences. Disease persistence is known to be difficult to study properly, and current predictors are insufficient to identify more than a small fraction of patients at risk., Objective: To study personal AD medicine history as a retrospective marker of persistent AD., Methods: The study population included all Danish first hospital contacts with a diagnosis of AD (ICD-10, L20) between 1995 and 2012. National register data following the diagnosis were used to define persistent AD activity until 2017 according to personal AD medicine history before diagnosis. Activity was defined as filled prescriptions for topical corticosteroids (TCS) or calcineurin inhibitors (TCI), dermatologist contacts or hospital re-contacts for AD. Risk ratios (RR) for persistent activity (defined as activity >4 of the most recent 5 years) were estimated according to AD medicine history (prescriptions filled prior to diagnosis) adjusted for age at onset, parental AD and basic covariates., Results: A total of 13 628 patients were diagnosed at ages 0-16 years and had up to 21 years of follow-up. 10 years after diagnosis, 67% showed activity (9.5% persistent). Among prior TCS users (69%), the RR 10y of persistent activity increased 1- to 6-fold with increasing strength of strongest TCS/TCI ever, and with number of TCS courses. Prior use of antibiotics (RR 10y 1.32, 95% CI 1.09-1.59) and antihistamines (RR 10y 1.65, 95% CI 1.42-1.91) increased the RR 10y in a dose-dependent manner. In >90% of patients, prior medication use occurred <4 years before diagnosis., Conclusions and Clinical Relevance: The strength and type of AD medication used in the previous 4 years may predict 10-year persistence of AD. Since children may be misjudged as having milder disease when seen between flares of skin lesions, this information may improve physicians' ability to determine the correct prognosis independently of current AD severity., (© 2019 John Wiley & Sons Ltd.)

Background: The possible etiologic link between tonsillectomy and inflammatory bowel diseases remains unclear. To investigate the hereditary component, we assessed the risk of inflammatory bowel disease after own tonsillectomy as well as after tonsillectomy among family members., Methods: A nationwide Danish cohort of 7,045,288 individuals was established and linked to comprehensive national registers with data on kinship, tonsillectomy surgery, and diagnosis of inflammatory bowel disease from all health sectors. We used Poisson regression models to estimate hospital contact rate ratios (RR) for Crohn's disease and ulcerative colitis, with 95% confidence intervals (CI), between individuals with or without tonsillectomy, as well as between individuals with or without tonsillectomized relatives., Results: During 189 million person-years of follow-up between 1977 and 2014, 276,673 individuals were tonsillectomized, 22,015 developed Crohn's disease, and 49,550 developed ulcerative colitis. Rates of inflammatory bowel disease were elevated up to 20 years after own tonsillectomy (Crohn's disease: RR 1.52 [95% CI = 1.43, 1.61]; ulcerative colitis: RR 1.24 [95% CI = 1.18, 1.29]). RRs for Crohn's disease was 1.22 (95% CI = 1.17, 1.27) after first-degree relatives' tonsillectomy, 1.14 (95% CI = 1.08, 1.19) after second-degree relatives' tonsillectomy, and 1.08 (95% CI = 1.01, 1.15) after third-degree relatives' tonsillectomy. Corresponding RRs for ulcerative colitis were 1.10 (95% CI = 1.07, 1.13), 1.05 (95% CI = 1.01, 1.08), and 1.03 (95% CI = 0.98, 1.09)., Conclusions: Even individuals with tonsillectomized family members were at increased risk of inflammatory bowel disease. These findings call into question a direct influence of tonsillectomy on gastrointestinal inflammation and point instead toward shared hereditary or environmental factors. See video abstract at, http://links.lww.com/EDE/B464.

Objective: It is unclear whether psychological stress is associated with increased risk of multiple sclerosis (MS). We studied the association between major stressful life events and MS in a nationwide cohort study using death of a child or a spouse or marital dissolution as indicators of severe stress., Methods: We created two study cohorts based on all Danish men and women born 1950-1992. One cohort consisted of all persons who became parents between 1968 and 2010, and another cohort consisted of all persons who married between 1968 and 2010. Members of both cohorts were followed for MS between 1982 and 2010 using data from the National Multiple Sclerosis Registry. Associations between major stressful life events and risk of MS were evaluated by means of MS incidence rate ratios (RR) with 95% confidence interval (CI) obtained in Poisson regression analyses., Results: During approximately 30 million person-years of follow-up, bereaved parents experienced no unusual risk of MS compared with parents who did not lose a child (RR=1.12 (95% CI 0.89 to 1.38)). Likewise, neither divorced (RR=0.98 (95% CI 0.89 to 1.06)) nor widowed (RR=0.98 (95% CI 0.71 to 1.32) persons were at any unusual risk of MS compared with married persons of the same sex., Conclusions: Our national cohort study provides little evidence for a causal association between major stressful life events (as exemplified by divorce or the loss of a child or a spouse) and subsequent MS risk., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: Filaggrin proteins are expressed in the skin, oral cavity, oesophagus, and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG) reduce filaggrin expression and cause an impaired skin barrier function. We hypothesized that FLG mutation carriers would be more susceptible to human papillomavirus (HPV) infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix., Methods: We included 13,376 persons from four population-based studies conducted in the same background population in Copenhagen, Denmark. Participants were genotyped for the most common FLG mutations in Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011., Results: There were 489 cases of prevalent and 97 cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5 years). There was a statistically significant association between FLG genotype and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95% confidence intervals, CI: 1.2, 3.7) for FLG mutation carriers vs. wild types., Conclusions: FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable.

Background: Because parvovirus B19 infection in pregnancy has been associated with infant morbidity and mortality in case reports and after intrauterine transfusion, we tested the population-based association using serum and hospital data of high quality., Methods: We established a cohort of 113 228 children born to women tested for parvovirus B19 infection during pregnancy in a major diagnostic laboratory in Denmark, from 1994 to 2009. Information on 20 selected morbidity diagnoses and on mortality was obtained from the Danish National Patient Register, the Danish Cancer Register and the Danish Civil Registration System. Incidence rate ratios (IRR) were estimated by log-linear Poisson regression with adjustment for age and sex of the child, maternal age and year of maternal parvovirus B19 test., Results: A total of 1095 (1.0%) children were born to mothers who were infected with parvovirus B19 during pregnancy. During 1 million person-years of follow-up, 10 856 children experienced morbidity and 590 children died. Overall, maternal infection status was neither associated with morbidity during infancy (IRR 0.64; 95% CI: 0.40 to 1.02) or childhood (IRR 0.93; 95% CI: 0.77 to 1.14), nor with infant mortality (IRR 0.98; 95% CI: 0.44 to 2.20). Specifically, there was no association with 19 of 20 morbidities. An excess risk of cancer in the central nervous system was observed (IRR 5.88; 95% CI: 1.41 to 24.6); however, the number of exposed cases was very small (n = 2)., Conclusions: Parvovirus B19 infection during pregnancy was not associated with overall morbidity or mortality in infancy and childhood.

Background & Aims: Parasitic helminth infections can suppress symptoms of allergy, type 1 diabetes, arthritis, and inflammatory bowel disease in animal models. We analyzed data from a large, population-based cohort study to determine whether common childhood enterobiasis protects against these diseases., Methods: We collected information on individual prescriptions filled for the drug mebendazole against Enterobius vermicularis for all children born in Denmark 1995-2008 from the National Register of Medicinal Product Statistics (n = 924,749; age 0-14 years); 132,383 of these children (14%) filled a prescription for mebendazole, 102,482 of the children (11%) had a household peer who was registered with a filled mebendazole prescription, and the remaining 689,884 children (75%) comprised the reference group. Children diagnosed with asthma, type 1 diabetes, juvenile arthritis, ulcerative colitis, or Crohn's disease were identified from the National Patient Registry. We used Poisson regression to estimate confounder-adjusted incidence rate ratios for first in- or outpatient hospital diagnosis of chronic inflammatory disease according to history of mebendazole treatment prescribed to children in the study., Results: Chronic inflammatory disease was diagnosed in 10,352 children during 6.4 million person-years of follow-up. The incidence rate ratios was 1.07 for asthma (95% confidence interval [CI]: 1.00-1.13), 1.05 for type 1 diabetes (95% CI: 0.79-1.12), 1.13 for juvenile arthritis (95% CI: 0.94-1.37), 0.77 for ulcerative colitis (95% CI: 0.41-1.46), and 1.44 for Crohn's disease (95% CI: 0.82-2.53). Results were not modified by number of treatments or age at treatment., Conclusions: Based on a population-based analysis, enterobiasis does not reduce risk for asthma, type 1 diabetes, arthritis, or inflammatory bowel disease., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Enteric pathogens have been implicated in the aetiology of inflammatory bowel disease (IBD), but increased rates of stool testing of patients with unclear gastrointestinal symptoms might cause detection bias. Hence, the objective of this study was to analyse incidence rates of Crohn's disease and ulcerative colitis among patients with Salmonella- or Campylobacter-positive and negative stool tests and to study the incidence of positive and negative stool tests among patients already diagnosed with IBD., Methods: The Danish population was followed for 94.3 million person-years during 1992-2008 using national registers to identify persons with positive and negative stool tests and patients with IBD. Using Poisson regression, incidence rate ratios (IRRs) for IBD after positive or negative stool tests and, conversely, IRRs for positive and negative stool tests following IBD, were calculated., Results: IRRs for IBD were significantly high in the first year after Salmonella- or Campylobacter-positive stool tests (IRRs 5.4-9.8), and they remained moderately increased 1-10 years later (IRRs 1.6-2.2), and less so >10 years later (IRRs 0.8-1.8). However, IRRs for IBD <1 year after a negative stool test were several-fold higher (IRRs 53.2-57.5), and a decreasing incidence pattern over time was parallel to that following positive test results. Among patients with IBD, IRRs for subsequent positive and-most notably-negative stool test results were also significantly high., Conclusion: Similarities in temporal risk patterns for IBD following positive or negative stool tests indicate that the increased occurrence of Salmonella- or Campylobacter-positive results around the time of first IBD hospitalisation results from detection bias.

Background: An individual's intestinal bacterial flora is established soon after birth. Delivery by Cesarean section (c-section) deprives the newborn of colonization with maternal vaginal bacteria. We determined whether delivery by c-section is associated with an altered risk of infection with intestinal bacterial pathogens., Methods: In a cohort of 1.7 million Danes born 1973-2005 we identified cases of laboratory-confirmed non-typhoidal Salmonella species, Campylobacter species, Yersinia enterocolitica, Shigella species, and Shiga toxin-producing Escherichia coli from 1991-2005 in the National Registry of Enteric Pathogens. Using Poisson-regression we estimated confounder-adjusted incidence rate ratios (IRRs) for infection according to mode of delivery., Results: During 14.0 million person-years of follow-up, 22,486 individuals were diagnosed with 1 intestinal bacterial infection. C-section was associated with a small increase in risk at age 1 to <2 years (IRR, 1.09; 95% confidence interval, 1.00-1.18) and at age 2 to <5 years (IRR, 1.08; 95% confidence interval, 1.00-1.17), but after age 5 years, there was no significant association. Assuming causality only 0.62% of intestinal bacterial infections were attributable to c-section., Conclusions: Mode of delivery appears not to be a clinically relevant determinant of risk for intestinal bacterial infections. The possible impact of increasing frequencies of c-section on the overall burden of intestinal bacterial infections appears negligible.

Background: Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy for allergic disease, the helminth Trichuris suis has demonstrated efficacy in treatment of inflammatory bowel disease., Objective: To determine efficacy of helminth therapy for allergic rhinitis., Methods: We conducted a double-blind, placebo-controlled, parallel group trial in which 100 subjects age 18 to 65 years with grass pollen-induced allergic rhinitis were randomly assigned to ingest a total of 8 doses with 2500 live T suis ova or placebo with an interval of 21 days. The primary outcome was a change in mean daily total symptom score for runny, itchy, sneezing nose (maximum change, 9.0) or in percentage of well days during the grass pollen season., Results: Treatment with T suis ova (N = 49) compared with placebo (N = 47) caused transient diarrhea peaking at day 41 in 33% of participants (placebo, 2%), and increased eosinophil counts (P < .001) and T suis-specific IgE (P < .05), IgG (P < .001), IgG(4) (P < .003), and IgA (P < .001), whereas there was no significant change in symptom scores (0.0; 95% CI, -0.5 to 0.4; P = .87), well days (3%; 95% CI, -9% to 14%; P = .63), total histamine (P = .44), grass-specific IgE (P = .76), or diameter of wheal reaction on skin prick testing with grass (P = .85) or 9 other allergens., Conclusion: Repeated treatment with the helminth T suis induced a substantial clinical and immunologic response as evidence of infection, but had no therapeutic effect on allergic rhinitis., (Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: It has been proposed that childhood vaccinations may influence the development of allergy. Atopy and allergic diseases have increased after routine smallpox vaccination was stopped in the 1970s., Objective: We examined whether administration of smallpox vaccination during childhood was associated with a decreased risk of atopy, allergic rhinitis, and asthma., Methods: The occurrence of atopy, allergic rhinitis, and asthma was studied in nearly 2000 women participating in a national birth cohort study. Detailed information on smallpox vaccination was available from school health records. Atopic status was assessed serologically by a specific response to 11 common inhalant allergens by using serum samples obtained from the women during the period 1997 to 2001. Information on allergic rhinitis and asthma was available from telephone interviews., Results: We found no association between having been vaccinated against smallpox in childhood and risk of atopy or allergic rhinitis. Smallpox vaccination was associated with a slightly decreased risk of asthma. There was no association between age at smallpox vaccination and risk of atopy, allergic rhinitis, or asthma. Adjusting for birth cohort, sibship size, age of the woman's mother at birth, and social class in childhood did not change these results., Conclusion: Our findings do not suggest that childhood vaccination against smallpox, even if given early in life, influences the development of atopy or allergic rhinitis. The association with asthma should be interpreted with caution and needs further study.