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OBJECTIVES: There is a gap in knowledge about the effects of smoking on overall infection risk in otherwise healthy populations, possibly leading to underestimation of the dangers of smoking. The present study aimed to examine the association of smoking with the risk of infections in a large cohort of healthy blood donors.METHODS: This cohort study used questionnaire and health register data from 127 831 Danish blood donors. Multivariable Cox proportional hazards analysis was applied to estimate the association of current smoking with the risk of all-cause infection defined as hospital-based treatment for infection or filled prescriptions of antimicrobials stratified for age and adjusted for relevant confounders.RESULTS: Among 18 272 current smokers, 12 272 filled an antimicrobial prescription and 2035 received hospital-based treatment for infections. Among 101 974 non-smokers, 65 117 filled a prescription and 8501 received hospital-based treatment for infections. Smokers had a higher risk of all-cause infection than non-smokers (hazard ratio estimates were 1.27 in males and 1.33 in females for hospital-based treatment and 1.11 in males and up to 1.20 in females for filled prescriptions). Smoking was most strongly associated with an increased incidence of respiratory tract infection, abscesses, skin infection, and prescriptions for these ailments (hazard ratio up to 2.29). Furthermore, smokers' risk of filled prescriptions of broad-spectrum penicillin was increased (hazard ratio up to 1.96).CONCLUSIONS: Current smoking was strongly associated with the risk of hospital-based treatment of infection and filled prescriptions of antimicrobials in a large cohort of healthy individuals. These findings warrant an increased focus on infectious disease risk among smokers.

ObjectivesTo examine the level of loneliness experienced during the COVID-19 pandemic in Denmark and to identify associated behavioural patterns and demographic factors.DesignCross-sectional cohort study.SettingIncludes Danish active and former blood donors.ParticipantsA questionnaire was sent to 124 307 active and former blood donors, of these a total of 50 968 participants completed the study questionnaire (response rate=41%).Primary and secondary outcome measuresSubjective experience of loneliness was measured using the 3-item University of California, Los Angeles Loneliness Scale (UCLA-3). Besides the UCLA-3, the respondents answered items on sociodemographic and economic characteristics, items on precautionary measures taken to avoid COVID-19 infection as well as on COVID-19 anxiety.ResultsThe participants indicated their experienced level of loneliness both before and during the pandemic. Comparing the two reports yielded a mean increase in loneliness scores of 14.1% (pwell-being, which comprised three questionnaire items related to emotional heath, physical health and happiness. A high score on the factorwell-beingwas associated with reduced levels of loneliness (coefficient=−0.47, 95% CI −0.49 to −0.46)). Furthermore, women were more likely than men to have experienced increased levels of loneliness during the pandemic (coefficient=0.27, 95% CI 0.25 to 0.29). Furthermore, a negative correlation between higher age and change in loneliness score was observed.ConclusionsThe findings document an increase in the level of experienced loneliness during the COVID-19 pandemic, particularly affecting individuals with low well-being, women and younger individuals.

Familial clustering of the skin disease primary hyperhidrosis suggests a genetic component to the disease. The human leucocyte antigen (HLA) is implicated in a range of diseases, including many comorbidities to hyperhidrosis. No study has investigated whether the HLA genes are involved in the pathogenesis of hyperhidrosis. We, therefore, compared HLA alleles in individuals with and without hyperhidrosis in this study of 65 000 blood donors. In this retrospective cohort study, we retrieved information on individuals with and without hyperhidrosis using self-reported questionnaires, the Danish National Patient Registry and the Danish National Prescription Registry on participants recruited to the Danish Blood Donor Study between 2010 and 2019. Association tests using logistic regression were conducted for each HLA allele corrected for sex, age, body mass index, smoking and principal components. Overall, 145 of 65 795 (0.2%) participants had hospital diagnosed hyperhidrosis. Similarly, 1379 of 15 530 (8.9%) participants had moderate-severe self-reported hyperhidrosis, of whom 447 (2.9%) had severe self-reported hyperhidrosis. Altogether, 28 participants had both hospital diagnosed and moderate-severe self-reported hyperhidrosis. Severe self-reported hyperhidrosis was associated with HLA-A*80:01 (adjusted odds ratio 26.97; 95% confidence interval 5.32-136.70; n = 7; P

Background Studies presenting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) for healthy individuals are warranted. We estimate IFR by age and comorbidity status using data from a large serosurvey among Danish blood donors and nationwide data on coronavirus disease 2019 (COVID-19) mortality. Methods Danish blood donors aged 17–69 years donating blood October 2020–February 2021 were tested with a commercial SARS-CoV-2 total antibody assay. IFR was estimated for weeks 11 to 42, 2020 and week 43, 2020 to week 6, 2021, representing the first 2 waves of COVID-19 epidemic in Denmark. Results In total, 84944 blood donors were tested for antibodies. The seroprevalence was 2% in October 2020 and 7% in February 2021. Among 3898039 Danish residents aged 17–69 years, 249 deaths were recorded. The IFR was low for people, The COVID-19 infection fatality rate was low for citizens younger than 51 years without comorbidity (3.36 per 100000 infections). The infection fatality rate increased with age and comorbidity but declined from the first to second wave of the epidemic.

Key features • COVIDMENT [www.covidment.is] is a NordForsk-funded research collaboration across six nations, with the overarching aim to significantly advance current knowledge on mental morbidity trajectories associated with the coronavirus disease 2019 (COVID-19) in the general population and in specific risk groups. • From March 2020 through August 2021, 392 817 individuals have been recruited to the seven COVIDMENT cohorts: the Danish Blood Donor Study (N ¼ 71 562), the Estonian Biobank COVID-19 and Mental Health Data Collection cohorts (N ¼ 13 329 and N ¼ 86 116, respectively), the Icelandic COVID-19 National Resilience Cohort (N ¼ 22 849), the Norwegian BRY.DEG2020 (N ¼ 19 343), the Norwegian Mother, Father and Child Cohort Study (N ¼ 132 486), the Scottish Generation Scotland/CovidLife (N ¼ 18 518) and the Swedish Omtanke2020 (N ¼ 28 614). Semi-harmonized questionnaire data have been collected across all COVIDMENT cohorts with longitudinal data available, e.g. through linkage to the national registers. • The average age of participants ranged from 31.8 to 58.5 years across cohorts. The prevalence of depressive symptoms above cut-off point varied considerably across cohorts (4.2–20.8%). The prevalence of depressive symptoms was highest at COVID-19 incidence of 30 cases per week per 100 000 persons, i.e. 14.3% [95% confidence interval (CI): 9.4–21.8%], which was 61.0% (95% CI: 34.0–94.1%) higher than the prevalence at COVID-19 incidence of 0 cases per week per 100 000 persons (P ¼ 1.1 x 10 ^( 6)). •

Background The objective of this study was to perform a seroprevalence survey on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among Danish healthcare workers to identify high-risk groups. Methods All healthcare workers and administrative personnel at the 7 hospitals, prehospital services, and specialist practitioner clinics in the Central Denmark Region were invited to be tested by a commercial SARS-CoV-2 total antibody enzyme-linked immunosorbent assay (Wantai Biological Pharmacy Enterprise Co, Ltd, Beijing, China). Results A total of 25 950 participants were invited. Of these, 17 971 had samples available for SARS-CoV-2 antibody testing. After adjustment for assay sensitivity and specificity, the overall seroprevalence was 3.4% (95% confidence interval [CI], 2.5%–3.8%). The seroprevalence was higher in the western part of the region than in the eastern part (11.9% vs 1.2%; difference: 10.7 percentage points [95% CI, 9.5–12.2]). In the high-prevalence area, the emergency departments had the highest seroprevalence (29.7%), whereas departments without patients or with limited patient contact had the lowest seroprevalence (2.2%). Among the total 668 seropositive participants, 433 (64.8%) had previously been tested for SARS-CoV-2 RNA, and 50.0% had a positive reverse-transcription polymerase chain reaction (PCR) result. Conclusions We found large differences in the prevalence of SARS-CoV-2 antibodies in staff working in the healthcare sector within a small geographical area of Denmark. Half of all seropositive staff had been tested positive by PCR prior to this survey. This study raises awareness of precautions that should be taken to avoid in-hospital transmission. Regular testing of healthcare workers for SARS-CoV-2 should be considered to identify areas with increased transmission., Severe acute respiratory syndrome coronavirus 2 seroprevalence among healthcare workers in the Central Denmark Region showed large geographical differences (1%–12%). The risk of infection was associated with workplace, rather than location of residence.

Natural environments have been associated with mental health benefits, but globally access to these benefits is threatened by urban development and densification. However, it remains unclear how natural environments relate to mental health and how consistent the association is across populations. Here we use a life-course approach with a population consisting of 66 194 individuals from the Danish Blood Donor Study (DBDS) to investigate the association between green and blue space (e.g. parks and lakes) and self-evaluated mental well-being. Green and blue space was identified from remotely-sensed images from the Landsat program, while mental well-being was based on the mental component score (MCS) calculated using the 12-item short form health survey. We use multivariate linear regression models and logistic regression models to quantify the associations. We adjust for additional environmental (urbanization, and air pollution) and lifestyle factors (smoking, body mass index, socioeconomic status, and physical activity) and specifically evaluate the role of physical activity and air pollution as possible mediating factors. We found a positive association between the MCS and current and childhood green space, and a non-significant association for current and childhood blue space. Adjusting for environmental and the other factors attenuated the effect sizes indicating that a broad range of factors determine mental well-being. Physical activity and air pollution were both associated with the MCS as possible mediators of green space associations. In addition, the odds for successfully completing tasks’, seeing others, and feeling less downhearted increased with higher levels of green space, and the odds of feeling calm increased with higher levels of blue space. In conclusion, we found support for an association between green and, to less degree, blue space and mental well-being throughout different life stages. In addition, we found a positive association with individual indicators of mental well-being such as being productive, feeling less downhearted and calmer, and being social. The healthy blood donor effect and the bias towards urban residency may explain why we found smaller effect sizes between green and blue space and mental well-being for this generally healthy and resourceful cohort compared to previous studies.

Background Although the vast majority of individuals succumbing to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are elderly, infection fatality rate (IFR) estimates for the age group ≥70 years are still scarce. To this end, we assessed SARS-CoV-2 seroprevalence among retired blood donors and combined it with national coronavirus disease 2019 (COVID-19) survey data to provide reliable population-based IFR estimates for this age group. Methods We identified 60 926 retired blood donors aged ≥70 years in the rosters of 3 regionwide Danish blood banks and invited them to fill in a questionnaire on COVID-19–related symptoms and behaviors. Among 24 861 (40.8%) responders, we invited a random sample of 3200 individuals for blood testing. Overall, 1201 (37.5%) individuals were tested for SARS-CoV-2 antibodies (Wantai) and compared with 1110 active blood donors aged 17–69 years. Seroprevalence 95% confidence intervals (CIs) were adjusted for assay sensitivity and specificity. Results Among retired (aged ≥70 years) and active (aged 17–69 years) blood donors, adjusted seroprevalences were 1.4% (95% CI, .3–2.5%) and 2.5% (95% CI, 1.3–3.8%), respectively. Using available population data on COVID-19–related fatalities, IFRs for patients aged ≥70 years and for 17–69 years were estimated at 5.4% (95% CI, 2.7–6.4%) and .083% (95% CI, .054–.18%), respectively. Only 52.4% of SARS-CoV-2–seropositive retired blood donors reported having been sick since the start of the pandemic. Conclusions COVID-19 IFR in the age group >69 years is estimated to be 65 times the IFR for people aged 18–69 years.

Background and aims Allergic rhinitis (AR), allergic conjunctivitis (AC), and asthma are characterized by activation of the immune system. The aim of this study was to explore the long-term association between AR, AC, asthma, and specific immunoglobulin E (IgE) and blood platelet and leukocyte differential counts. Material and methods In the Danish Blood Donor Study, 14,440 participants from Central Denmark Region had platelet and leukocyte differential counts available and completed a questionnaire regarding AR, AC, and asthma. Of these participants, 8485 were tested for IgE to inhalation allergens. Results The prevalence of AR, AC, asthma, and IgE sensitization was 19%, 15%, 9%, and 29%, respectively. AR, AC, asthma, wheeze, and IgE sensitization was associated with increased blood eosinophil concentration even in IgE sensitized participants who did not report any allergy or asthma. The strongest associations were observed for participants with current disease. We found no differences in eosinophil concentration between months without symptoms and months with symptoms of AR and asthma. Conclusion AR, AC, asthma, wheezing, and IgE sensitization to inhalation allergens are associated with increased eosinophil concentration. This may reflect a persistent inflammation even in periods without symptomatic disease.

BACKGROUND: The distribution and nature of symptoms among SARS-CoV-2 infected individuals need to be clarified.METHODS: Between May and August 2020, 11,138 healthcare and administrative personnel from Central Denmark Region were tested for SARS-CoV-2 antibodies and subsequently completed a questionnaire. Symptom prevalence and overall duration for symptoms persisting for more than 30 days were calculated. Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: In total, 447 (4%) of the participants were SARS-CoV-2-seropositive. Loss of sense of smell and taste was reported by 50% of seropositives compared with 3% of seronegatives. Additionally, seropositives more frequently reported fever, dyspnoea, muscle or joint ache, fatigue, cough, headache and sore throat, and they were more likely to report symptoms persisting for more than 30 days. In adjusted models, they had a higher risk of reporting symptoms with the strongest association observed for loss of sense of taste and smell (OR = 35.6; 95% CI: 28.6-44.3).CONCLUSION: In this large study, SARS-CoV-2-seropositive participants reported COVID-19-associated symptoms more frequently than those who were seronegative, especially loss of sense of taste and smell. Overall, their symptoms were also more likely to persist for more than 30 days.

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.

Objective: Our study aimed to compare symptoms day by day for non-hospitalized individuals testing positive and negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In total, 210 positive-test and 630 negative-test healthcare workers in the Central Denmark Region were followed for up to 90 days after testing, between April and June, 2020. Their daily reported COVID-19-related symptoms were compared graphically and by logistic regression. Results: Thirty per cent of the positive-test and close to 0% of the negative-test participants reported a reduced sense of taste and smell during all 90 days (adjusted odds ratio [aOR] 86.07, 95% CI 22.86–323). Dyspnea was reported by an initial 20% of positive-test participants, declining to 5% after 30 days, without ever reaching the level of the negative-test participants (aOR 6.88, 95% CI 2.41–19.63). Cough, headache, sore throat, muscle pain, and fever were temporarily more prevalent among the positive-test participants; after 30 days, no increases were seen. Women and older participants were more susceptible to long-lasting COVID-19 symptoms. Conclusion: The prevalence of long-lasting reduced sense of taste and smell is highly increased in mild COVID-19 patients. This pattern is also seen for dyspnea at a low level, but not for cough, sore throat, headache, muscle pain, or fever.

Purpose Staphylococcus aureus carriage poses an increased risk of S. aureus infection. The aim of this study was to investigate the colonization of S. aureus among healthy individuals and to establish a prospective cohort and biobank for research in the health consequences of colonization. Population and methods The Danish Blood Donor S. aureus Carriage Study (DBDSaCS) was established in 2014. So far, a total of 6082 healthy participants have been included with nasal swabs and repeated swabs are performed at subsequent donations. Samples from the first 2217 participants were cultured using a two-step method to evaluate the effect of using enrichment broth. Furthermore, 262 participants were sampled from both the nares and the throat. All participants completed a questionnaire with self-reported health, anthropometric measurements, current smoking status, and physical activity. Plasma samples, nasal swab transport media, and S. aureus isolates were stored. Results The prevalence of S. aureus nasal colonization was 41%. The prevalence of colonization was higher in men (46%) than women (34%), lower for smokers, and decreased with increasing age ( 55 years: 35%). In participants swabbed from the nose and throat, the prevalence of S. aureus colonization after enrichment was 55% with significantly higher prevalence in the throat (45%) than in the nose (40%). The use of an enrichment broth increased the proportion of S. aureus colonization. Conclusion We describe a large and growing cohort of healthy individuals established to investigate predictors for S. aureus carriage and the health consequences of carriage. Multiple projects using data from DBDSaCS linked with Danish health registers, biomarkers, and genetic markers are ongoing. Results will be published in the coming years.

Background Blood donors are at increased risk of developing iron deficiency, and several studies have recommended iron supplementation for this group. The aim of this study was to investigate the effect of oral iron supplementation on risk of infections among healthy blood donors. Study design and methods We included 82,062 participants from the Danish Blood Donor Study who completed a questionnaire on health-related items including use of oral iron supplementation. Infection outcomes were ascertained by using ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis was used as the statistical model. Risk estimates are presented as crude hazard ratios (HRs) with 95% confidence intervals (CIs). Results During 19,978 person-years of observation, 6983 donors redeemed at least one prescription of antimicrobials. Similarly, during 19,829 person-years of observation, 242 donors were treated for infection at a hospital. Use of oral iron supplementation was not associated with redeemed prescriptions of antimicrobials in any strata: premenopausal women-HR 1.00, 95% CI 0.91-1.10; postmenopausal women-HR 1.07, 95% CI 0.87-1.32; and men-HR 1.01, 95% CI 0.84-1.21. In addition, use of oral iron supplementation was not associated with risk of hospital-based treatment for infection. Conclusion In a large cohort of blood donors, use of oral iron supplementation was not associated with subsequent short-term risk of infection. These findings are important to help understanding the safety of using oral iron supplementation among blood donors and the general population.

BackgroundLittle is known about the long-term course of symptoms for mild coronavirus disease 2019 (COVID-19) when accounting for symptoms due to other causes. We aimed to compare symptoms day by day for non-hospitalised individuals who tested positive and negative with polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsWe followed 210 test-positive and 630 individually matched test-negative health-care workers of the Central Denmark Region up to 90 days after the test, April-June 2020. They daily reported seven COVID-19 related symptoms. Symptom courses were compared graphically and by conditional multivariable logistic regression.ResultsThirty % of test-positive and close to zero of test-negative participants reported a reduced sense of taste and smell during all 90 days of follow-up (adjusted odds ratio [aOR] 86.07, 95% CI 22.86-323). Dyspnoea was reported by an initial 20% of test-positive with a gradual decline to about 5% after 30 days without ever reaching the level of the test-negative participants (aOR 6.88, 95% CI 2.41-19.63). Cough, headache, sore throat, muscle aches, and fever were temporarily more prevalent among the test positive participants, but after 30 days, no increases were seen. Women and participants aged 45 years or older tended to be more susceptible to SARS-CoV-2 infection.ConclusionPrevalence of long-lasting reduced sense of taste and smell is highly increased after being diagnosed with mild COVID-19. This pattern is also seen for dyspnoea at a low level but not for cough, sore throat, headache, muscle ache or pain, or fever.Key messagesReduced sense of taste and smell is present at a highly increased level of 30% during 90 days after testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2).Test-positive participants experience dyspnoea persistently more often than test-negative participants but affect only few.The prevalence of cough, sore throat, headache, muscle ache or pain, and fever following a positive test reach the level seen after a negative test within 30 days.Women and participants aged 45 years or older tend to be more susceptible to symptoms following SARS-CoV-2 infection.

Background Allergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed. Objectives The objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen-specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors. Methods From the nationwide population-based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop). Results The prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants. Conclusion Birth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self-reported ARC represent a primarily sIgE-positive phenotype, while those with either AR or AC represent more diverse phenotypes. Background: Allergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed. Objectives: The objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen-specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors. Methods: From the nationwide population-based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop). Results: The prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants. Conclusion: Birth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self-reported ARC represent a primarily sIgE-positive phenotype, while those with either AR or AC represent more diverse phenotypes.

Background Restless Legs Syndrome (RLS) is a neurological sensorimotor disorder that occurs in the evening and night, thereby impacting quality of sleep in sufferers. The pathophysiology of RLS is poorly understood but inflammation has been proposed as possibly being involved. The neutrophil-to-lymphocyte ratio (NLR) can be used as an inflammation marker but results from small studies have been inconclusive in determining whether NLR is associated with RLS. We aimed to assess whether an association between NLR and RLS exists in a large cohort of healthy individuals. Methods Neutrophils and lymphocytes were measured in blood samples of 13,055 individuals from the Danish Blood Donor Study, all of whom completed the validated Cambridge-Hopkins RLS-questionnaire for RLS assessment. Results In the sample, 661 individuals were determined as current RLS cases (5.1%). A higher proportion of individuals with RLS were females (62.5% vs 47.5%; P Conclusion We found no association between RLS and NLR among Danish blood donors after adjusting for sex, age, alcohol consumption, smoking status and BMI. Further studies are needed to determine whether inflammation is a risk factor for RLS.

ObjectivesThe objective of this study was to perform a large seroprevalence survey on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among Danish healthcare workers to identify high risk groups.DesignCross-sectional survey.SettingAll healthcare workers and administrative personnel at the seven hospitals, pre-hospital services and specialist practitioner clinics in the Central Denmark Region were invited by e-mail to be tested for antibodies against SARS-CoV-2 by a commercial SARS-CoV-2 total antibody enzyme-linked immunosorbent assay (ELISA, Wantai Biological Pharmacy Enterprise Co., Ltd., Beijing, China).ParticipantsA total of 25,950 participants were invited. Of these, 17,987 (69%) showed up for blood sampling, and 17,971 had samples available for SARS-CoV-2 antibody testing.Main outcome measures1) Prevalence of SARS-CoV-2 antibodies; 2) Risk factors for seropositivity; 3) Association of SARS-CoV-2 RNA and antibodies.ResultsAfter adjustment for assay sensitivity and specificity, the overall seroprevalence was 3.4% (CI: 2.5%-3.8%). The seroprevalence was higher in the western part of the region than in the eastern part (11.9% vs 1.2%, difference: 10.7 percentage points, CI: 9.5-12.2). In the high prevalence area, the emergency departments had the highest seroprevalence (29.7%) while departments without patients or with limited patient contact had the lowest seroprevalence (2.2%). Multivariable logistic regression analysis with age, sex, and profession as the predictors showed that nursing staff, medical doctors, and biomedical laboratory scientists had a higher risk than medical secretaries, who served as reference (OR = 7.3, CI: 3.5–14.9; OR = 4., CI: 1.8–8.9; and OR = 5.0, CI: 2.1–11.6, respectively).Among the total 668 seropositive participants, 433 (64.8%) had previously been tested for SARS-CoV-2 RNA, and 50.0% had a positive RT-PCR result. A total of 98% of individuals who had a previous positive viral RNA test were also found to be seropositive.ConclusionsWe found large differences in the prevalence of SARS-CoV-2 antibodies in staff working in the healthcare sector within a small geographical area of Denmark and signs of in-hospital transmission. Half of all seropositive staff had been tested positive by PCR prior to this survey. This study raises awareness of precautions which should be taken to avoid in-hospital transmission. Additionally, regular testing of healthcare workers for SARS-CoV-2 should be considered to identify areas with increased transmission.Trial registrationThe study is approved by the Danish Data Protection Agency (1-16-02-207-20).

BACKGROUND Low hemoglobin (Hb) is associated with poor general health and adverse outcomes in a wide range of diseases. However, a link between Hb levels and the risk of infection among healthy individuals has yet to be investigated. STUDY DESIGN AND METHODS Using data from the Scandinavian Donations and Transfusions database, 497,390 donors were followed after 5,458,499 donations in health registers. With 1,339,362 person-years of follow-up, Andersen-Gill Cox regression was used to study the association of Hb levels below deferral thresholds, very low Hb levels (in the lowest 0.1 percentile), and declining Hb levels with the risk of infection as measured by hospital or outpatient contact for infection and filling of prescription for antimicrobials, respectively, within 3 months of donation. Analyses were stratified by sex, menopausal status, and frequency of donation. RESULTS Hb levels below deferral thresholds were not associated with a risk of hospital contact for infection among premenopausal women (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.95-1.14), postmenopausal women (HR, 0.77; 95% CI, 0.54-1.11), or men (HR, 0.97; 95% CI, 0.81-1.16), nor was there any association with hospital contact for very low Hb levels or patterns of declining Hb levels. However, subthreshold Hb levels were associated with a reduced risk of antimicrobial prescriptions among premenopausal women (HR, 0.92; 95% CI, 0.91-0.93), postmenopausal women (HR, 0.93; 95% CI, 0.89-0.97), and men (HR, 0.91; 95% CI, 0.88-0.94). CONCLUSIONS Neither Hb levels below deferral thresholds nor very low or declining Hb levels were associated with an increased risk of infection. This is reassuring, because blood donation can lead to lower Hb levels.

BACKGROUND: Health-Related Quality of Life (HRQL) represent individuals' subjective assessment of their mental and physical well-being, and is highly predictive of future health. C-reactive protein (CRP) is a well-established marker of inflammation. Low-grade inflammation (LGI), defined as slightly increased CRP levels, is associated with increased risk of several diseases. LGI may reflect subclinical pathology, which could affect individual's subjective health assessment. This study aimed to examine whether LGI has an independent impact on self-reported health or rather is a mediator of a confounder in a large population of healthy individuals.METHODS: Plasma CRP levels were measured in 17,024 participants from the Danish Blood Donor Study (DBDS). All participants completed a standard questionnaire including smoking status, and the 12-item short-form health survey (SF-12), which is a widely used scale for HRQL. SF-12 is reported as a mental (MCS) and physical (PCS) score. The relationship between LGI (defined as a plasma CRP level between 3 mg/L and 10 mg/L) and MCS or PCS was explored by mediation analysis and adjusted multivariable linear regression analysis. Multiple imputation modelling was used to remedy missing values. The analyses were stratified according to sex and use of combined oral contraception (OC).RESULTS: In the study, 1,542 (10.3%) participants had LGI. PCS was associated with LGI in all strata, i.e. women using OC: RC = -0.36 points lower PCS in participants with LGI vs no LGI, CI: -0.94 to -0.19, women not using OC: RC = -0.63, CI: -1.05 to -0.21 and men: RC = -0.76, CI: -1.10 to -0.42. But LGI had no impact on MCS. Predictors of lower PCS included obesity, current smoking, and waist circumference in all strata. Physical activity in leisure time was the only factor positively associated with PCS. Age and physical activity in leisure time was associated with increased MCS in all strata whereas current smoking was the only strong predictor of a reduction in MCS. Only a small effect of smoking on PCS was mediated through LGI.CONCLUSION: In this population of healthy individuals, LGI had independent impact on lower self-rated physical health score in HRQL in both sexes, but was not associated with self-rated mental health score. A small and significant effect of smoking on physical health score was mediated through LGI.

Blood donors are at increased risk of developing iron deficiency, and several studies have recommended iron supplementation for this group. The aim of this study was to investigate the effect of oral iron supplementation on risk of infections among healthy blood donors.We included 82,062 participants from the Danish Blood Donor Study who completed a questionnaire on health-related items including use of oral iron supplementation. Infection outcomes were ascertained by using ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis was used as the statistical model. Risk estimates are presented as crude hazard ratios (HRs) with 95% confidence intervals (CIs).During 19,978 person-years of observation, 6983 donors redeemed at least one prescription of antimicrobials. Similarly, during 19,829 person-years of observation, 242 donors were treated for infection at a hospital. Use of oral iron supplementation was not associated with redeemed prescriptions of antimicrobials in any strata: premenopausal women-HR 1.00, 95% CI 0.91-1.10; postmenopausal women-HR 1.07, 95% CI 0.87-1.32; and men-HR 1.01, 95% CI 0.84-1.21. In addition, use of oral iron supplementation was not associated with risk of hospital-based treatment for infection.In a large cohort of blood donors, use of oral iron supplementation was not associated with subsequent short-term risk of infection. These findings are important to help understanding the safety of using oral iron supplementation among blood donors and the general population.

The clinical importance of immunoglobulin A (IgA) deficiency in otherwise healthy individuals is not well described. We aimed to investigate the self-reported mental and physical health and the risk of infection in IgA-deficient blood donors compared to healthy control blood donors. Infectious events, recorded in public health registries either as prescriptions filled of any antimicrobial medicine or as hospital infections, were compared between 177 IgA-deficient blood donors and 1770 control blood donors. A subset of the IgA-deficient donors were further characterized by self-reported health (Short Form-12, n = 28) and circulating C-reactive protein (CRP) (n = 10). IgA-deficient individuals had lower self-reported mental health (p = 0.01) and higher CRP (p < 0.05). A strong trend was found regarding prescription of antimicrobial medicine (hazard ratio = 1.19, p = 0.05). No association was found with hospital infections (hazard ratio = 1.02, p = 0.95) or self-reported physical health (p = 0.86). IgA-deficient blood donors have impaired self-reported mental health, enhanced inflammation and possibly an increased risk of infection. Despite these findings, this study does not provide sufficient evidence to warrant specific health precautions for donors with IgA deficiency.

BACKGROUND: It is well known that obesity complicates the course of several diseases. However, it is unknown whether obesity affects the risk of infection among healthy individuals.METHODS: We included 37,808 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. Obesity was defined as a body mass index ≥ 30 kg/m. Infections among participants were identified by relevant ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical (ATC) codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis with age as the underlying timescale was used as the statistical model.RESULTS: During 113,717 person-years of observation, 1,233 participants were treated for infection at a hospital. Similarly, during 58,411 person-years of observation, 15,856 participants filled at least one prescription of antimicrobials. Obesity was associated with risk of hospital-based treatment for infection (women: hazard ratio [HR] = 1.5, 95% confidence interval [CI] = 1.1, 1.9; men: HR = 1.5, 95% CI = 1.2, 1.9). For specific infections, obesity was associated with increased risk of abscesses (both sexes), infections of the skin and subcutaneous tissue (men), and respiratory tract infections and cystitis (women). Similarly, obesity was associated with filled prescriptions of antimicrobials overall (women: HR = 1.22, 95% CI = 1.14, 1.30; men: HR = 1.23, 95% CI: 1.15, 1.33) and particularly with phenoxymethylpenicillin, macrolides, dicloxacillin and flucloxacillin, and broad-spectrum penicillins.CONCLUSIONS: In a large cohort of healthy individuals, obesity was associated with risk of infection. This result warrants further studies of metabolism and the immune response.

INTRODUCTION: The aim of this study was to examine whether low-grade inflammation (LGI) is associated with a subsequently increased risk of infection.METHODS: We included 15,754 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. LGI was defined as a C-reactive protein level between 3 and 10 mg/L. Infections were identified by ICD-10 codes in the Danish National Patient Register and ATC-codes in the Danish Prescription Register. Multivariable Cox proportional hazard analysis was used as the statistical model.RESULTS: During 53,302 person-years of observation, 571 participants were hospitalized for infection. Similarly, during 26,125 person-years of observation, 7,276 participants filled a prescription of antimicrobials. LGI was associated with increased risk of hospital-based treatment for infection only among men (hazard ratio = 1.60, 95% confidence interval (CI): 1.10-2.34) and specifically infections were abscesses and infections of the skin and subcutaneous tissue. Similarly, LGI was associated with the overall use of antimicrobials among men, and particularly with phenoxymethylpenicillin and broad-spectrum antimicrobials for treatment of urinary tract infections. The difference between men and women was not statistically significant.CONCLUSIONS: In a large cohort of healthy individuals, LGI was associated with an increased risk of infection among healthy male blood donors.

Low hemoglobin (Hb) is associated with poor general health and adverse outcomes in a wide range of diseases. However, a link between Hb levels and the risk of infection among healthy individuals has yet to be investigated.Using data from the Scandinavian Donations and Transfusions database, 497,390 donors were followed after 5,458,499 donations in health registers. With 1,339,362 person-years of follow-up, Andersen-Gill Cox regression was used to study the association of Hb levels below deferral thresholds, very low Hb levels (in the lowest 0.1 percentile), and declining Hb levels with the risk of infection as measured by hospital or outpatient contact for infection and filling of prescription for antimicrobials, respectively, within 3 months of donation. Analyses were stratified by sex, menopausal status, and frequency of donation.Hb levels below deferral thresholds were not associated with a risk of hospital contact for infection among premenopausal women (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.95-1.14), postmenopausal women (HR, 0.77; 95% CI, 0.54-1.11), or men (HR, 0.97; 95% CI, 0.81-1.16), nor was there any association with hospital contact for very low Hb levels or patterns of declining Hb levels. However, subthreshold Hb levels were associated with a reduced risk of antimicrobial prescriptions among premenopausal women (HR, 0.92; 95% CI, 0.91-0.93), postmenopausal women (HR, 0.93; 95% CI, 0.89-0.97), and men (HR, 0.91; 95% CI, 0.88-0.94).Neither Hb levels below deferral thresholds nor very low or declining Hb levels were associated with an increased risk of infection. This is reassuring, because blood donation can lead to lower Hb levels.

BACKGROUND AND PURPOSE: The C-C chemokine receptor 5-Δ32 deletion (CCR5-Δ32) has been associated with lower levels of C-reactive protein (CRP), but the effect on cardiovascular diseases is uncertain. This study addresses the impact of CCR5-Δ32 on the risk of low-grade inflammation and hospitalization with cardiovascular diseases in a large cohort of blood donors.METHODS: Genotyping of 15,206 healthy participants from The Danish Blood Donor Study for CCR5-Δ32 was performed and combined with CRP measurements and questionnaire data. Cardiovascular disease diagnoses were identified by ICD-10 codes in the Danish National Patient Registry.RESULTS: CCR5-Δ32-carriers had a higher risk of hospitalization for cardiovascular diseases when compared with wild-type homozygotes (hazard ratio = 1.35, 95%-confidence interval: 1.00-1.87). CRP levels were unaffected by the CCR5-Δ32 deletion.CONCLUSION: In this cohort, carriers of the CCR5-Δ32 deletion had normal CRP levels but a borderline significant increased risk of cardiovascular diseases.

BACKGROUND: Combined oral contraceptives (OC) are the most commonly used method of contraception among women aged 15-49 years in the Nordic countries. OC offer convenient, effective, and reversible fertility regulation.Epidemiological studies in 2011 demonstrated that OC are associated with increased risk of venous thromboembolism (VTE), thrombotic stroke, and myocardial infarction. This resulted in revised OC prescription practices, demanding renewed follow-up studies of the risk of thrombotic complications linked to OC. Indeed, unpublished data from our group reveal that OC users have a higher blood platelet level (PLT) but the association between PLT and thrombotic events remains unknown. AIMS: The aim of this study was, first, to examine the association between PLT and venous or arterial thrombotic events and, second, to investigate the risk of VTE, thrombotic stroke, and myocardial infarction associated with use of OC among healthy female blood donors.METHODS: We included 28,950 women aged 18-49 years from The Danish Blood Donor Study. Participants completed a standard questionnaire on lifestyle factors and stated their use of contraception. All participants were followed in national registers between March 2010 and December 2015: OC exposure period and type of OC were identified in the Danish National Prescription Register and venous or arterial thrombosis endpoints were identified by ICD-10 diagnosis codes in the Danish National Patient Register. PLT from each donation were measured by automated haematology analysers. The association between OC and thrombosis endpoints was explored by multivariable Cox proportional hazards regression analysis with age as underlying timescale. Adjustment for age, body mass index, smoking, education level, and duration of OC use was performed. Groups were compared by unpaired t-test or analysis of variance. Results are presented as hazard ratios (HR) with 95% confidence intervals (CI) and p-values. RESULTS: Within 209,164 person-years of observation, 135 first ever events occurred. 118 (87%) were VTE and 17 (13%) were arterial thrombotic events. Mean PLT was 262.4 (CI: 248.3 – 276.6) and 254.7 (254.0 – 255.4) in the group with thrombotic event and without event, respectively. No statistically difference in mean PLT was observed between OC users having an event compared with OC users without event (p = 0.92). The crude HR of overall thrombotic event in users of OC was 3.14 (CI: 2.10 – 4.78) compared with non-users. The adjusted HR was 3.70 (2.23 – 6.13). The adjusted HR of VTE for OC users of 2nd generation, 3rd generation, and 4th generation was 2.51 (1.21 – 5.21), 4.76 (2.68 – 8.45), and 4.41 (1.93 – 10.0), respectively, all compared with non-users of OC. Similarly, the risk of arterial thrombosis was increased among OC users compared with non-users, however not statistically significant. CONCLUSION: No difference in blood platelet levels in participants with thrombotic event compared with controls was observed. OC users had higher risk of VTE compared with non-users and the risk was highest among users of 3rd and 4th generation OC. Our findings underscores that blood donor cohorts are feasible for the study of general health risks in otherwise healthy persons.

Background Combined oral contraceptives (OC) are used by 27% of women aged 15-49 years in Denmark. OC offers convenient, effective and reversible fertility regulation, but the increased risk of venous thromboembolism, myocardial infarction, and ischemic stroke is the most important safety issues. Studies have investigated metabolic, proinflammatory, and haemostatic effects of estrogen and progestins contained in OC, meanwhile the impact of OC on blood platelet levels remains unknown. Aim: The aim of this study was to examine the impact of OC on the levels of blood platelets and haematocrit in a large cohort of blood donors. Methods Blood platelets levels in 28,950 women from The Danish Blood Donor Study giving blood in 2011-2016 in the Capital and Central Danish Regions were measured by automated haematology analysers at each donation. All participants completed a standard questionnaire on lifestyle factors and further stated their use of contraception, childbirth, and menopausal status. OC exposure period and type of OC were identified by ATC codes in the Danish National Prescription Registry. The association between OC and blood platelet levels was explored by repeated measures mixed model analysis. Adjustment for age and time since last donation was performed. Results are presented as coefficients with 95% confidence intervals (CI). Results A total of 9,327 (32.2%) participants filled an OC prescription in the study period, of whom 5,821 (20.1% of women) were intermittent OC users and 3,506 (12.1% of women) were continuous OC users. Among users, 559 (2.7%), 5,552 (26.8%), 12,447 (60.0%) and 2.172 (10.5%) were users of 1st, 2nd, 3rd, and 4th generation of OC, respectively. Blood platelet levels were higher among OC users compared to non-users (coef: 9.7 billion thrombocytes/L, CI: 9.2-10.2, p