Deep immune cell phenotyping and induced immune cell responses at admission stratified by BMI in patients hospitalized with COVID-19: An observational multicenter cohort pilot study.

INTRODUCTION: Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients. METHODS AND RESULTS: This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese). Inflammation was assessed using TruCulture® and immune cell profiles by flow cytometry with a customized antibody panel (DuraClone®). Patients with obesity had a more pro-inflammatory phenotype with increased TNF-α, IL-8, IL-17, and IL-10 levels post-T cell stimulation, and altered B cell profiles. Patients with obesity showed higher concentrations of naïve, transitional, and non-isotype switched memory B cells, and plasmablasts compared to normal weight patients and healthy controls. CONCLUSIONS: Obesity in hospitalized COVID-19 patients may correlate with elevated pro-inflammatory cytokines, anti-inflammatory IL-10, and increased B cell subset activation, highlighting the need for further studies.

Immune cell populations and induced immune responses at admission in patients hospitalized with vaccine breakthrough SARS-CoV-2 infections.

Background: Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19. Methods: A nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission. Results: In total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015). Conclusion: We observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results.

Where Birth Month, Sex and Age Matters: The Burden of Severe Respiratory Disease in Danish Children <5 Years, 2016-2022.

BACKGROUND: In light of the substantial impact that respiratory diseases in young children poses on healthcare systems globally, and in the wake of the recent COVID-19 pandemic, there is a growing urgency to obtain reliable estimates on the burden of respiratory disease. OBJECTIVES: The aim of this study is to quantify the overall burden of respiratory disease requiring hospitalizations and explore the trends in these admissions in Danish children <5 years, January 1, 2016-October 31, 2022. METHODS: The number of hospitalizations attributed to respiratory infections in children <5 years, was extracted from the Danish National Patient Register, and stratified into subgroups based on age, gender and birth month, and presented on a month-to-month basis. RESULTS: A total of 48,194 children under the age of 5, were hospitalized due to respiratory infections within the study period and the annual hospitalization incidence exhibited a noteworthy variation. Risk factors associated with the highest hospitalization incidence were young age, male gender and in children under 1-year-old, birth months falling in the period of November to January. Younger age and admission during the winter months were linked to longer hospital stays. The seasonal pattern of hospitalizations and the distribution of hospitalizations across various subgroups were greatly influenced by the COVID-19 pandemic. CONCLUSION: This study describes and quantifies the importance of factoring in specific child demographics and seasonal variations in hospitalizations when devising preventive healthcare strategies such as the use of monoclonal antibody therapy and vaccines.

Transforming health care: Investigating Influenzer, a novel telemedicine-supported early discharge program for patients with lower respiratory tract infection: A non-randomized feasibility study.

BACKGROUND: The COVID-19 pandemic has posed unprecedented challenges to healthcare systems globally, necessitating innovative care models like hospital-at-home and virtual care programs. The Influenzer telemedicine program aims to deliver hospital-led monitoring and treatment to patients at home. Integrating telemedicine technology with domestic visits provides an alternative to traditional hospitalization, with the aim of easing the burden on healthcare facilities without compromising patient safety. To evaluate the effectiveness of the Influenzer program, a randomized controlled trial is proposed. This study aimed to assess the feasibility of the proposed clinical trial design. METHODS: A non-randomized feasibility study was conducted at the Department of Pulmonary and Infectious Diseases at Nordsjaellands Hospital offering a telemedicine-supported early discharge program to patients with lower respiratory tract infections, including COVID-19. The feasibility of trial procedures, including recruitment, adherence, and retention, was analyzed. Also, participants' characteristics and trajectory during the intervention, including telemedicine and domestic services, were assessed. RESULTS: Nineteen patients were enrolled from June 2022 to April 2023 and treated at home. Forty patients were not enrolled as 15 (25%) were non-eligible according to study protocol, 15 (25%) refused to participate and 10 (17%) had not been approached. Subjects treated at home had comparable clinical outcomes to those treated in the acute hospital, no major safety incidences occurred and patients were highly satisfied. Participants demonstrated 99% adherence to planned daily monitoring activities. In total, 63% completed all survey assessments at least partially including baseline, at discharge, and 3 months post-discharge, while 89% participated in a follow-up interview. No participants withdrew their consent. CONCLUSIONS: The feasibility study documented that the Influenzer home-hospital program was feasible and well accepted in a Scandinavian setting in terms of no withdrawals and excellent participant adherence to the planned daily monitoring activities. Challenges in the organizational structures including patient recruitment and data collection required resolution prior to our randomized clinical trial. Insights from this feasibility study have led to the improved design of the final Influenzer program evaluation trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05087082. Registered on 18 August 2021.

Parechovirus A Circulation and Testing Capacities in Europe, 2015-2021.

Parechovirus infections usually affect neonates and young children; manifestations vary from asymptomatic to life-threatening. We describe laboratory capacity in Europe for assessing parechovirus circulation, seasonality, and epidemiology. We used retrospective anonymized data collected from parechovirus infection case-patients identified in Europe during January 2015-December 2021. Of 21 laboratories from 18 countries that participated in the study, 16 (76%) laboratories with parechovirus detection capacity reported 1,845 positive samples; 12/16 (75%) with typing capability successfully identified 517 samples. Parechovirus A3 was the most common type (n = 278), followed by A1 (153), A6 (50), A4 (13), A5 (22), and A14 (1). Clinical data from 1,269 participants highlighted correlation of types A3, A4, and A5 with severe disease in neonates. We observed a wide capacity in Europe to detect, type, and analyze parechovirus data. To enhance surveillance and response for PeV outbreaks, sharing typing protocols and data on parechovirus-positive cases should be encouraged.

Respiratory Syncytial Virus-Associated Hospitalization in Adults With Comorbidities in 2 European Countries: A Modeling Study.

BACKGROUND: Individuals with comorbidities are at increased risk of severe respiratory syncytial virus (RSV) infection. We estimated RSV-associated respiratory hospitalization among adults aged ≥45 years with comorbidities in Denmark and Scotland. METHODS: By analyzing national hospital and virologic data, we estimated annual RSV-associated hospitalizations by 7 selected comorbidities and ages between 2010 and 2018. We estimated rate ratios of RSV-associated hospitalization for adults with comorbidity than the overall population. RESULTS: In Denmark, annual RSV-associated hospitalization rates per 1000 adults ranged from 3.1 for asthma to 19.4 for chronic kidney disease (CKD). In Scotland, rates ranged from 2.4 for chronic liver disease to 9.0 for chronic obstructive pulmonary disease (COPD). In both countries, we found a 2- to 4-fold increased risk of RSV hospitalization for adults with COPD, ischemic heart disease, stroke, and diabetes; a 1.5- to 3-fold increased risk for asthma; and a 3- to 7-fold increased risk for CKD. RSV hospitalization rates among adults aged 45 to 64 years with COPD, asthma, ischemic heart disease, or CKD were higher than the overall population. CONCLUSIONS: This study provides important evidence for identifying risk groups and assisting health authorities in RSV vaccination policy making.

Implementation of Intelligent Physical Exercise Training at a Danish Hospital-A Qualitative Study of Employees' Barriers and Facilitators for Participation.

BACKGROUND: Exercise training at work has the potential to improve employees' productivity, health, and well-being. However, exercise interventions for healthcare workers in hospitals may be challenged by time pressure and the ongoing workflow with patient care. OBJECTIVE: The aim was to identify barriers and facilitators for participation in exercise training during work in a hospital department. METHODS: Eight semi-structured interviews of 13 individuals were conducted with hospital employees from different staff groups who participated in 12 weeks of exercise twice weekly. The data analysis was a thematic approach based on the Theoretical Domains Framework and the COM-B factors in the Behavior Change Wheel. RESULTS: Barriers and facilitators varied between different groups. Barriers included limited structure, busyness, and a discouraging culture. Facilitators included gaining a feeling of community and psychological and physical well-being. Seven contextual subthemes were vital for successful implementation of exercise in a hospital setting: sharing of knowledge and information; involvement; administration and structure; culture; individualization; purpose and objective; and incentives. CONCLUSIONS: The informants appreciated exercise training during work. Inpatient departments' informants found it difficult to participate in the intervention, whilst those with more administrative tasks found it easier. This study identified barriers and facilitators vital for a successful implementation of an exercise training intervention in a hospital department. The study explains how future interventions can improve reach, adoption, and implementation of exercise training interventions to hospital staffs.

Wastewater Surveillance in Europe for Non-Polio Enteroviruses and Beyond.

Wastewater surveillance (WWS) was developed in the early 1960s for the detection of poliovirus (PV) circulation in the population. It has been used to monitor several pathogens, including non-polio enteroviruses (NPEVs), which are increasingly recognised as causes of morbidity in children. However, when applying WWS to a new pathogen, it is important to consider the purpose of such a study as well as the suitability of the chosen methodology. With this purpose, the European Non-Polio Enterovirus Network (ENPEN) organised an expert webinar to discuss its history, methods, and applications; its evolution from a culture-based method to molecular detection; and future implementation of next generation sequencing (NGS). The first simulation experiments with PV calculated that a 400 mL sewage sample is sufficient for the detection of viral particles if 1:10,000 people excrete poliovirus in a population of 700,000 people. If the method is applied correctly, several NPEV types are detected. Despite culture-based methods remaining the gold standard for WWS, direct methods followed by molecular-based and sequence-based assays have been developed, not only for enterovirus but for several pathogens. Along with case-based sentinel and/or syndromic surveillance, WWS for NPEV and other pathogens represents an inexpensive, flexible, anonymised, reliable, population-based tool for monitoring outbreaks and the (re)emergence of these virus types/strains within the general population.

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 COVID-19 and Development of Type 1 Diabetes: A Danish Nationwide Register Study.

OBJECTIVE: To compare the incidence of type 1 diabetes (T1D) before and during the coronavirus disease 2019 (COVID-19) pandemic and determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with T1D development. RESEARCH DESIGN AND METHODS: All Danish residents aged <30 years free of diabetes from 2015 to 2021 were included. Individuals were followed from 1 January 2015 or birth until the development of T1D, the age of 30, the end of the study (31 December 2021), emigration, development of type 2 diabetes, onset of any cancer, initiation of immunomodulating therapy, or development of any autoimmune disease. We compared the incidence rate ratio (IRR) of T1D using Poisson regression models. We matched each person with a SARS-CoV-2 infection with three control individuals and used a cause-specific Cox regression model to estimate the hazard ratio (HR). RESULTS: Among 2,381,348 individuals, 3,579 cases of T1D occurred. The adjusted IRRs for T1D in each quarter of 2020 and 2021 compared with 2015-2019 were as follows: January-March 2020, 1.03 (95% CI 0.86; 1.23); January-March 2021, 1.01 (0.84; 1.22), April-June 2020, 0.98 (0.80; 1.20); April-June 2021, 1.34 (1.12; 1.61); July-September 2020, 1.13 (0.94; 1.35); July-September 2021, 1.21 (1.01; 1.45); October-December 2020, 1.09 (0.91; 1.31); and October-December 2021, 1.18 (0.99; 1.41). We identified 338,670 individuals with a positive SARS-CoV-2 test result and matched them with 1,004,688 control individuals. A SARS-2-CoV infection was not significantly associated with the risk of T1D development (HR 0.90 [95% CI 0.60; 1.35]). CONCLUSIONS: There was an increase in T1D incidence during April-June 2021 compared with April-June 2015-2019, but this could not be attributed to SARS-CoV-2 infection.

Estimation of the Number of Respiratory Syncytial Virus-Associated Hospitalizations in Adults in the European Union.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in adults that can result in hospitalizations. Estimating RSV-associated hospitalization is critical for planning RSV-related healthcare across Europe. METHODS: We gathered RSV-associated hospitalization estimates from the RSV Consortium in Europe (RESCEU) for adults in Denmark, England, Finland, Norway, Netherlands, and Scotland from 2006 to 2017. We extrapolated these estimates to 28 European Union (EU) countries using nearest-neighbor matching, multiple imputations, and 2 sets of 10 indicators. RESULTS: On average, 158 229 (95% confidence interval [CI], 140 865-175 592) RSV-associated hospitalizations occur annually among adults in the EU (≥18 years); 92% of these hospitalizations occur in adults ≥65 years. Among 75-84 years, the annual average is estimated at 74 519 (95% CI, 69 923-79 115) at a rate of 2.24 (95% CI, 2.10-2.38) per 1000. Among ≥85 years, the annual average is estimated at 37 904 (95% CI, 32 444-43 363) at a rate of 2.99 (95% CI, 2.56-3.42). CONCLUSIONS: Our estimates of RSV-associated hospitalizations in adults are the first analysis integrating available data to provide the disease burden across the EU. Importantly, for a condition considered in the past to be primarily a disease of young children, the average annual hospitalization estimate in adults was lower but of a similar magnitude to the estimate in young children (0-4 years): 158 229 (95% CI, 140 865-175 592) versus 245 244 (95% CI, 224 688-265 799).

Persistent Symptoms and Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection Not Requiring Hospitalization: Results From Testing Denmark, a Danish Cross-sectional Survey.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms ("long COVID"). We assessed the burden of long COVID among nonhospitalized adults with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Methods: In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)-associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score-weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome. Results: In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval [CI], 22.2-27.4). Compared to controls, cases reported worse general health (OR, 5.9 [95% CI, 5.0-7.0]) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 [95% CI, 9.5-14.6]) and smell (OR, 11.2 [95% CI, 9.1-13.9]). Physical and Mental Component Summary scores were also significantly reduced with differences of -2.5 (95% CI, -3.1 to -1.8) and -2.0 (95% CI, -2.7 to -1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID. Conclusions: Nonhospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.

A cohort study of wastewater treatment plant workers: Association between levels of biomarkers of systemic inflammation and exposure to bacteria and fungi, and endotoxin as measured using two methods.

Work in wastewater treatment plants (WWTPs) can be associated with exposure to airborne microorganisms and endotoxin from the working environment. The aim of this study was to obtain knowledge about whether serum levels of the markers of systemic inflammation, C-reactive protein (CRP) and serum amyloid A (SAA), are associated with personal exposure to endotoxin, measured using the Limulus (endotoxinLimulus) and the rFC (endotoxinrFC) assays, as well as bacteria and fungi in a cohort of WWTP workers. Exposure and blood samples were collected for 11 workers over one year. Exposure to endotoxinLimulus-day and endotoxinrFC-day correlated significantly (r = 0.80, p<0.0001, n = 104), but endotoxinLimulus-day was 4.4 (Geometric mean (GM) value) times higher than endotoxinrFC-day (p<0.0001). The endotoxinLimulus-day, endotoxinrFC-day, bacteria, and fungal exposure as well as serum levels of CRP-day (GM=1.4 mg/l) and SAA-day (GM=12 mg/l) differed between workers. Serum levels of SAAday correlated significantly with CRPday (r = 0.30, p = 0.0068). The serum levels of CRPday were associated significantly with exposure to endotoxinLimulus-day. Exposure, SAA and CRP data were also analyzed as av. of each season, and SAAseason was associated positively and significantly with endotoxinLimulus-season and endotoxinrFC-season and negatively with fungalseason exposure. In conclusion, CRPday was associated with the endotoxinLimulus-day and SAAseason with endotoxinLimulus-season and endotoxinrFC-season exposure. Thus, we hereby document that WWTP workers are exposed to airborne endotoxin which seems to have a negative impact on their health.

High titers of neutralizing SARS-CoV-2 antibodies six months after symptom onset are associated with increased severity in COVID-19 hospitalized patients.

BACKGROUND: Viral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020-2021. MATERIALS AND METHODS: Prospective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 - 10), 37 (IQR 35 - 38), 97 (IQR 95 - 100), and 187 (IQR 185 - 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells. RESULTS: Patients with high disease severity had higher mean log2 NAb titers at day 37 (1.58, 95% CI [0.34 -2.81]), 97 (2.07, 95% CI [0.53-3.62]) and 187 (2.49, 95% CI [0.20- 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [- 0.627 - 0.728]), expressed as log10 SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission. CONCLUSIONS: We document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity. TRIAL REGISTRATION: The study is registered at https://clinicaltrials.gov/ (NCT05274373).

Hospitalisation at Home of Patients with COVID-19: A Qualitative Study of User Experiences.

Hospitalisation at Home (HaH) is a new model providing hospital-level care at home as a substitute for traditional care. Biometric monitoring and digital communication are crucial, but little is known about user perspectives. We aim to explore how in-patients with severe COVID-19 infection and clinicians engage with and experience communication and self-monitoring activities following the HaH model. A qualitative study based on semi-structured interviews of patients and clinicians participating in the early development phase of HaH were conducted. We interviewed eight clinicians and six patients. Five themes emerged from clinicians: (1) staff fear and concerns, (2) workflow, (3) virtual closeness, (4) patient relatives, and (5) future HaH models; four themes emerged from patients: (1) transition to home, (2) joint responsibility, (3) acceptability of technologies, and (4) relatives. Despite technical problems, both patients and clinicians were enthusiastic about the conceptual HaH idea. If appropriately introduced, treatment based on self-monitoring and remote communication was perceived acceptable for the patients; however, obtaining vitals at night was an overwhelming challenge. HaH is generally acceptable, perceived patient-centred, influencing routine clinical workflow, role and job satisfaction. Therefore, it calls for educational programs including more perspective than issues related to technical devices.

A Cross-Sectional Study of SARS-CoV-2 Antibodies and Risk Factors for Seropositivity in Staff in Day Care Facilities and Preschools in Denmark.

The aim of this study was to provide information about immunity against COVID-19 along with risk factors and behavior among employees in day care facilities and preschools (DCS) in Denmark. In collaboration with the Danish Union of Pedagogues, during February and March 2021, 47,810 members were offered a point-of-care rapid SARS-CoV-2 antibody test (POCT) at work and were invited to fill in an electronic questionnaire covering COVID-19 exposure. Seroprevalence data from Danish blood donors (total Ig enzyme-linked immunosorbent assay [ELISA]) were used as a proxy for the Danish population. A total of 21,018 (45%) DCS employees completed the questionnaire and reported their POCT result {median age, 44.3 years (interquartile range [IQR], [32.7 to 53.6]); females, 84.1%}, of which 20,267 (96.4%) were unvaccinated and included in analysis. A total of 1,857 (9.2%) participants tested seropositive, significantly higher than a seroprevalence at 7.6% (risk ratio [RR], 1.2; 95% confidence interval [CI], 1.14 to 1.27) among 40,541 healthy blood donors (median age, 42 years [IQR, 28 to 53]; males, 51.3%). Exposure at work (RR, 2.9; 95% CI, 2.3 to 3.6) was less of a risk factor than exposure within the household (RR, 12.7; 95% CI, 10.2 to 15.8). Less than 25% of participants reported wearing face protection at work. Most of the participants expressed some degree of fear of contracting COVID-19 both at work and outside work. SARS-CoV-2 seroprevalence was slightly higher in DCS staff than in blood donors, but possible exposure at home was associated with a higher risk than at work. DCS staff expressed fear of contracting COVID-19, though there was limited use of face protection at work. IMPORTANCE Identifying at-risk groups and evaluating preventive interventions in at-risk groups is imperative for the ongoing pandemic as well as for the control of future epidemics. Although DCS staff have a much higher risk of being infected within their own household than at their workplace, most are fearful of being infected with COVID-19 or bringing COVID-19 to work. This represents an interesting dilemma and an important issue which should be addressed by public health authorities for risk communication and pandemic planning. This study design can be used in a strategy for ongoing surveillance of COVID-19 immunity or other infections in the population. The findings of this study can be used to assess the need for future preventive interventions in DCS, such as the use of personal protective equipment.

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.