Omicron Variant-Specific Serological Imprinting Following BA.1 or BA.4/5 Bivalent Vaccination and Previous SARS-CoV-2 Infection: A Cohort Study.

BACKGROUND: Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. METHODS: In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. RESULTS: Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05-7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09-1.57) and BA.3 (1.32, 1.09-1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76-0.98), BA.4 (0.85, 0.75-0.97), and BA.5 (0.87, 0.76-0.99) antigens in individuals with a prior infection. CONCLUSIONS: Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants.

Prevalence and predictors of maternal smoking prior to and during pregnancy in a regional Danish population: a cross-sectional study.

BACKGROUND: Maternal smoking is still a major public health problem posing the risk of several negative health outcomes for both the pregnant woman and her offspring. The prevalence of maternal smoking in Denmark and other high-income countries has decreased continuously since the 1980s, and a prevalence below 10% of women who continue to smoke during pregnancy has been reported in studies after 2010. Previous studies have shown that low socioeconomic status is associated with maternal smoking. Information from the Danish Birth Register about maternal smoking shows that the prevalence of women who report to smoke in pregnancy has decreased continuously with 23.3% who reported ever smoking in pregnancy in 2000, 12.9% in 2010 and 9.0% in 2017. The aim of this study was to estimate the prevalence of maternal smoking at the time of conception and at 20 weeks of gestation in a regional Danish population, to describe differences in maternal characteristics among smokers, quitters and never-smokers, and to estimate predictors of smoking at the time of conception. METHODS: A cross-sectional study was conducted among pregnant women receiving antenatal care at the Department of Obstetrics, Zealand University Hospital, Denmark from August 2015 to March 2016 (n = 566). The main outcome was smoking at the time of conception and at 20 weeks of gestation. The questionnaire also collected information about maternal, health-related and sociodemographic characteristics. Descriptive analysis was conducted, and multivariate logistic regression analysis was used to assess the potential associated predictors (adjusted odds ratio). RESULTS: The prevalence of self-reported smoking at the time of conception was 16% (n = 90) and 6% smoked at 20 weeks of gestation (n = 35), as 61% of smokers quit smoking during early pregnancy. Multiple logistic regression analysis showed that significant predictors for smoking at conception were the socioeconomic factors; ≤12 years of education, shift work and being unemployed. CONCLUSION: The prevalence of self-reported maternal smoking in this regional Danish population of pregnant women is lower than seen in previous studies. However, predictors for smoking at the time of conception remain to be factors of low socioeconomic status confirming a social inequality in maternal smoking. Women at risk of smoking during pregnancy must be identified in early pregnancy or even before pregnancy and be offered interventions to help them quit smoking.

Not now but later - a qualitative study of non-exercising pregnant women's views and experiences of exercise.

BACKGROUND: Evidence has shown that there are several physical and mental advantages of exercise during pregnancy. Despite this, the recommendations for exercise during pregnancy are poorly fulfilled. The aim of this study was to illuminate non-exercising pregnant women's views and experiences concerning exercise before and during pregnancy. METHOD: The study had a qualitative design with an inductive approach and was analysed by content analysis. A total of 16 individual and face-to-face interviews were conducted with healthy pregnant women, mainly in the third trimester and living in Sweden. The participating women had not been exercising 3 months before pregnancy or during pregnancy. RESULTS: The main category "Insurmountable now, but possible in the future" was based on the four categories: "Lost and lack of routines", "Feelings of inadequacy", "Having a different focus" and "Need for support". The women experienced that their lack of routines was a major barrier that prevented them from exercising. Other factors that contributed were, for example, pregnancy-related problems, long working days and prioritizing family life. The women described it as difficult to combine exercise with their focus on the pregnancy and they missed continuous support from the antenatal care provider. The women expressed a need for suggestions concerning exercise during pregnancy and follow-up on previous counselling, especially when pregnancy-related issues arose. Information about easily accessible alternatives or simple home exercises was requested. They felt immobile and were not satisfied with their inactivity and tried to partly compensate with everyday activities. The women identified the postpartum period as an important possibility for becoming more active, for their own sake, but also because they wanted to become role models for their children. CONCLUSION: Continuous support during pregnancy is needed concerning exercise. Pregnancy is mostly a barrier that prevents exercise for this group of women but, at the same time, may be a motivator and a possibility for better health. As the result showed that these women were highly motivated to a life-style change post-pregnancy, it may be crucial to support previously non-exercising women postpartum.

Alcohol consumption and binge drinking in early pregnancy. A cross-sectional study with data from the Copenhagen Pregnancy Cohort.

BACKGROUND: Since 2007 the Danish Health and Medicines Authority has advised total alcohol abstinence from the time of trying to conceive and throughout pregnancy. The prevalence of binge drinking among pregnant Danish women has nevertheless been reported to be up to 48 % during early pregnancy. Since the introduction of the recommendation of total abstinence, no studies have examined pre-pregnancy lifestyle and reproductive risk factors associated with this behaviour in a Danish context. The aims of this study were therefore to describe the prevalence of weekly alcohol consumption and binge drinking in early pregnancy among women living in the capital of Denmark. Secondly to identify pre-pregnancy lifestyle and reproductive risk factors associated with binge drinking during early pregnancy. METHODS: Data were collected from September 2012 to August 2013 at the Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark. Self-reported information on each woman's socio-demographic characteristics, medical history, and lifestyle factors including alcohol habits was obtained from an electronic questionnaire filled out as part of the individual medical record. Descriptive analysis was conducted and multivariate logistic regression analysis was used to assess the potential associated risk factors (adjusted odds ratio (aOR)). RESULTS: Questionnaires from 3,238 women were included. A majority of 70 %, reported weekly alcohol consumption before pregnancy. The prevalence decreased to 3 % during early pregnancy. The overall proportion of women reporting binge drinking during early pregnancy was 35 % (n = 1,134). The following independent risk factors for binge drinking in early pregnancy were identified: lower degree of planned pregnancy, smoking and alcohol habits before pregnancy ((1 unit/weekly aOR 4.48, CI: 3.14 - 6.40), (2-7 units aOR 10.23, CI: 7.44-14.06), (≥8 units aOR 33.18, CI: 19.53-56.36)). Multiparity and the use of assisted reproductive technology were associated with lower odds of binge drinking in early pregnancy. CONCLUSION: The prevalence of weekly alcohol consumption decreased considerably during early pregnancy compared with pre-pregnancy levels. Nevertheless one third of the pregnant women engaged in binge drinking. Identification of risk factors for this behaviour renders it possible not only to design prevention strategies, but also to target those most at risk.

Nutritional risk predicts readmission within 30 and 180 days after discharge among older adult patients across a broad spectrum of diagnoses.

BACKGROUND AND AIMS: Hospital readmissions can have negative consequences for older adult patients, their relatives, the hospital, and society. Previous studies indicate that older adult patients who are at nutritional risk during hospital admission are at higher risk of readmission. There is a lack of studies investigating this relationship across different older adult patient groups while using recommended instruments and adjusting for relevant confounders. Thus, the aim of the present study was to investigate whether nutritional status according to the Nutrition Risk Screening 2002 during hospitalization predicted readmission among older adult patients within 30 and 180 days across a broad spectrum of wards and diagnoses when adjusting for age, sex, length-of-stay, diagnosis, and discharge destination. MATERIALS AND METHODS: The present study is a retrospective cohort study based on registry data and included 21,807 older adult patients (≥65 years) hospitalized during a 5-year period. In order to investigate the relationship between nutritional risk and readmission, hierarchical logistic regression analyses with readmission within 30 days (n = 8371) and 180 days (n = 7981) as the dependent variable were performed. RESULTS: Older adult patients at nutritional risk during the index admission were 1.44 times more likely to be readmitted within 30 days after discharge (P < 0.001), and 1.47 times more likely to be readmitted within 180 days after discharge (P < 0.001), compared to older adult patients who were not at nutritional risk during index admission when adjusting for age, sex, discharge destination, diagnosis group, and length-of-stay. CONCLUSIONS: Our results highlight the importance of focusing on nutritional status in older adults as a factor in the prevention of readmissions, including ensuring that practices, resources, and guidelines support appropriate screening procedures. Because nutritional risk predicts readmission both in a 30-days and 180-days perspective, the results point to the importance of ensuring follow-up on the screening result, both in the hospital context and after discharge.

Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

OBJECTIVES: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. METHODS: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day 365, PCR+ after Day 365) on anti-spike IgG trajectories. RESULTS: A total of 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day 251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, P<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. CONCLUSION: Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.

SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection.

SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection. The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73-0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48-0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30-0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males. High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.

Association of Self-reported Systemic Reactions Following SARS-CoV-2 Vaccination With Immunological Response in the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE).

Background: Side effects to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are a key concern contributing to vaccine hesitancy, but more individuals may be encouraged if SARS-CoV-2 vaccines were known to lead to a stronger immune response. Methods: Included were adult participants from the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE) who completed a questionnaire to assess systemic reactions following SARS-CoV-2 vaccination (BTN162b2, mRNA-1273, ChAdOx1) and had SARS-CoV-2 spike immunoglobulin G (IgG) levels measured at baseline and post-vaccine. A symptom score was developed to measure severity of systemic adverse reactions (+1 for each moderate, +2 for each severe). Post-vaccination SARS-CoV-2 spike IgG levels were compared between participants with different scores using multivariable linear regression. Results: A total of 6528 participants were included (56.3% females; median age [interquartile range], 64 [54-75] years). After the first vaccination, no association was found between symptom score and post-vaccine dose spike IgG level (P = .575). Following the second vaccination, significantly higher spike IgG levels were observed according to higher symptom scores (P < .001); adjusted geometric mean ratios were 1.16 (95% CI, 1.04-1.30), 1.24 (95% CI, 1.09-1.41), 1.25 (95% CI, 1.06-1.46), and 1.21 (95% CI, 1.08-1.35), for scores of 2, 3, 4, and ≥5, respectively, compared with a score of 0. After adjustment for pre-vaccine dose spike IgG, this association was attenuated. Conclusions: An association was found between more severe adverse reactions and stronger antibody response after the second vaccination but not the first, likely attributed to higher levels of preexisting immunity gained from response to first vaccination. Regardless of side effects, most people experienced an effective immune response following vaccination.

Cohort Profile:The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE).

PURPOSE: The ENFORCE cohort is a national Danish prospective cohort of adults who received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination programme. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark. PARTICIPANTS: A total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 vaccination programme were enrolled in the study prior to their first vaccination. Participants will be followed for a total of 2 years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 PCR results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53-75), 56.6% were women and 23% were individuals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline. FINDINGS TO DATE: Results have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant and on the antibody neutralising capacity against different SARS-CoV-2 variants following primary and booster vaccinations. FUTURE PLANS: The ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines. TRIAL REGISTRATION NUMBER: NCT04760132.

Characteristics associated with serological COVID-19 vaccine response and durability in an older population with significant comorbidity: the Danish Nationwide ENFORCE Study.

OBJECTIVES: To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and the durability of vaccine-induced antibodies. METHODS: Adults without history of SARS-CoV-2 infection from the Danish population scheduled for SARS-CoV-2 vaccination were enrolled in this parallel group, phase 4 study. SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibodies were measured at days 0, 21, 90, and 180. Vaccine responsiveness was categorized according to Spike IgG and Spike-ACE2-receptor-blocking levels at day 90 after first vaccination. Nondurable vaccine response was defined as day-90 responders who no longer had significant responses by day 180. RESULTS: Of 6544 participants completing two vaccine doses (median age 64 years; interquartile range: 54-75), 3654 (55.8%) received BTN162b2, 2472 (37.8%) mRNA-1273, and 418 (6.4%) ChAdOx1 followed by an mRNA vaccine. Levels of both types of antibodies increased from baseline to day 90 and then decreased to day 180. The decrease was more pronounced for levels of Spike-ACE2-receptor-blocking antibodies than for Spike IgG. Proportions with vaccine hyporesponsiveness and lack of durable response were 5.0% and 12.1% for Spike IgG and 12.7% and 39.6% for Spike-ACE2-receptor-blocking antibody levels, respectively. Male sex, vaccine type, and number of comorbidities were associated with all four outcomes. Additionally, age ≥75 years was associated with hyporesponsiveness for Spike-ACE2-receptor-blocking antibodies (adjusted odds ratio: 1.59; 95% confidence interval: 1.25-2.01) but not for Spike IgG. DISCUSSION: Comorbidity, male sex, and vaccine type were risk factors for hyporesponsiveness and nondurable response to COVID-19 vaccination. The functional activity of vaccine-induced antibodies declined with increasing age and had waned to pre-second-vaccination levels for most individuals after 6 months.

Levels of SARS-CoV-2 antibodies among fully vaccinated individuals with Delta or Omicron variant breakthrough infections.

SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21-28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15-0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.

Experiences managing pregnant hospital staff members using an active management policy-A qualitative study.

BACKGROUND AND OBJECTIVE: During pregnancy, absence from work increases significantly. Job adjustments have been shown to decrease absences; however, studies show only half of pregnant women who need job adjustments receive them. Little is known about the viewpoints of managers and possible challenges in the management of pregnant employees. The aim of this study was to investigate the experiences and considerations of managers in relation to managing pregnant hospital staff members and to describe the experiences of an active management policy for pregnant individuals. METHODS: A qualitative study based on five focus group interviews was conducted at five public hospitals in Zealand, Denmark with participation of 19 hospital managers, from 17 different wards, representing six different medical specialties. The interviews took place from February to May 2019. Thematic analysis was used to analyze the data. RESULTS: Four themes were identified: (1) The everyday management, (2) Managerial dilemmas, (3) Acknowledging the workplace culture, and (4) Dialogue as a means for the working relationship. The managers' experiences revolved around investing a lot of effort into the working relationship with pregnant staff members by adjusting job tasks and work schedules while balancing work tasks between all staff members. The dialogue was considered central in order to identify the needs of the individual staff member. CONCLUSIONS: Overall, management dialogue constituted a central tool in order to identify the needs of the individual staff member. A proactive and open approach increased the chances of a fruitful dialogue. The individual staff member, the influence of the workplace culture, and the everyday management of the workplace all shaped the experiences of the managers. The concept of an active management policy for pregnant individuals was perceived to entail useful elements, but also as replicating what managers already did.

Danish women's experiences of the rebozo technique during labour: A qualitative explorative study.

OBJECTIVE: The study aimed to explore women's experiences of the rebozo technique during labour. METHODS: This was a qualitative study based on individual telephone interviews, analysed by means of qualitative content analysis and inspired by interpretive description. 17 participants were recruited from two different-sized Danish hospitals and identified by applying a purposeful sample strategy. RESULTS: The main theme expressed the women's overall experience with the rebozo: "Joined movements in a harmless effort towards a natural birth". The women experienced that the technique created bodily sensations, which reduced their pain, and furthermore they expressed that it interrelated the labour process and produced mutual involvement and psychological support from the midwife and the women's partner. The rebozo technique was in most situations carried out because the midwife suspected a foetus malposition. CONCLUSION: The experiences of the rebozo technique were overall positive and both of a physical and psychological nature. The results indicate that health professionals should view rebozo as an easy accessible clinical tool with high user acceptance and possible positive psychological and clinical implications. The study contributes with a deeper and more nuanced understanding of a topic where only limited knowledge exists, however, efficacy studies are warranted.