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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

Abstract Background Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood. Methods In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51–72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections. Results We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified. Conclusions SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

As solid organ transplant (SOT) recipients remain at risk of severe outcomes after SARS-CoV-2 infections, vaccination continues to be an important preventive measure. In SOT recipients previously vaccinated with at least three doses of BNT162b2, we investigated humoral responses to BNT162b2 booster doses. Anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G (IgG) was measured using an in-house ELISA. Linear mixed models were fitted to investigate the change in the geometric mean concentration (GMC) of anti-SARS-CoV-2 RBD IgG after vaccination in participants with intervals of more or less than six months between the last two doses of vaccine. We included 107 SOT recipients vaccinated with a BNT162b2 vaccine. In participants with an interval of more than six months between the last two vaccine doses, we found a 1.34-fold change in GMC per month (95% CI 1.25–1.44), while we found a 1.09-fold change in GMC per month (95% CI 0.89–1.34) in participants with an interval of less than six months between the last two vaccine doses, resulting in a rate ratio of 0.82 (95% CI 0.66 to 1.01, p = 0.063). In conclusion, the administration of identical COVID-19 mRNA vaccine boosters within six months to SOT recipients may result in limited humoral immunogenicity of the last dose.

Summary: Background: We investigated long-term durability of humoral and cellular immune responses to third dose of BNT162b2 in people with HIV (PWH) and controls. Methods: In 378 PWH with undetectable viral replication and 224 matched controls vaccinated with three doses of BNT162b2, we measured IgG-antibodies against the receptor binding domain of SARS-CoV-2 spike protein three months before third dose of BNT162b2, and four and eleven months after. In 178 PWH and 135 controls, the cellular response was assessed by interferon-γ (IFN-γ) release in whole blood four months after third dose. Differences in antibody or IFN-γ concentrations were assessed by uni- and multivariable linear regressions. Findings: Before the third dose the concentration of SARS-CoV-2 antibodies was lower in PWH than in controls (unadjusted geometric mean ratio (GMR): 0.68 (95% CI: 0.54–0.86, p = 0.002). We observed no differences in antibody concentrations between PWH and controls after four (0.90 (95% CI: 0.75–1.09), p = 0.285) or eleven months (0.89 (95% CI: 0.69–1.14), p = 0.346) after the third dose. We found no difference in IFN-γ concentrations four months after the third dose between PWH and controls (1.06 (95% CI: 0.71–1.60), p = 0.767). Interpretation: We found no differences in antibody concentrations or cellular response between PWH and controls up to eleven months after third dose of BNT162b2. Our findings indicate that PWH with undetectable viral replication and controls have comparable immune responses to three doses of the BNT162b2 vaccine. Funding: This work was funded by the Novo Nordisk Foundation (NFF205A0063505, NNF20SA0064201), the Carlsberg Foundation (CF20-476 0045), the Svend Andersen Research Foundation (SARF2021), and Bio- and Genome Bank Denmark.

To accommodate waning COVID-19 vaccine immunity to emerging SARS-CoV-2 variants, variant-adapted mRNA vaccines have been introduced. Here, we examine serological responses to the BA.1 and BA.4-5 Omicron variant-adapted BNT162b2 COVID-19 vaccines in people with lymphoid malignancies. We included 233 patients with lymphoid malignancies (chronic lymphocytic B-cell leukemia: 73 (31.3%), lymphoma: 89 (38.2%), multiple myeloma/amyloidosis: 71 (30.5%)), who received an Omicron-adapted mRNA-based COVID-19 vaccine. IgG and neutralizing antibodies specific for the receptor-binding domain (RBD) of SARS-CoV-2 were measured using ELISA-based methods. Differences in antibody concentrations and neutralizing capacity and associations with risk factors were assessed using mixed-effects models. Over the period of vaccination with an Omicron-adapted COVID-19 vaccine, the predicted mean concentration of anti-RBD IgG increased by 0.09 log10 AU/mL/month (95% CI: 0.07; 0.11) in patients with lymphoid malignancies across diagnoses. The predicted mean neutralizing capacity increased by 0.9 percent points/month (95% CI: 0.2; 1.6). We found no associations between the increase in antibody concentration or neutralizing capacity and the variant included in the adapted vaccine. In conclusion, a discrete increase in antibody concentrations and neutralizing capacity was found over the course of Omicron-adapted vaccination in patients with lymphoid malignancies regardless of the adapted vaccine variant, indicating a beneficial effect of Omicron-adapted booster vaccination in this population.

The SARS-CoV-2 Omicron variant is associated with high rates of vaccine breakthrough infections, but the immunological basis for this is not well characterised. Here, the authors show that increased anti-Spike IgG antibody levels are associated with a reduced risk of infection with the Delta variant, but not with Omicron.

Abstract Background Valve surgery guidelines for infective endocarditis (IE) are unchanged over decades and nationwide data about the use of valve surgery do not exist. Methods We included patients with first-time IE (1999–2018) using Danish nationwide registries. Proportions of valve surgery were reported for calendar periods (1999–2003, 2004–2008, 2009–2013, 2014–2018). Comparing calendar periods in multivariable analyses, we computed likelihoods of valve surgery with logistic regression and rates of 30 day postoperative mortality with Cox regression. Results We included 8804 patients with first-time IE; 1981 (22.5%) underwent surgery during admission, decreasing by calendar periods (N = 360 [24.4%], N = 483 [24.0%], N = 553 [23.5%], N = 585 [19.7%], P =

Abstract Background People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with “Severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. Design and methods In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. Results We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9–59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1–55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p = 0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p

Abstract Background Early stages of heart failure (HF) are associated with an increased risk of hospitalization and increased mortality, however the course of progression and the impact of non-cardiovascular comorbidities on adverse events in elderly high-risk patients are unknown. Aim To examine the risk of future cardiovascular (CV) and non-CV events in early stages of HF in a cohort of elderly patients (age ≥ 60 with ≥ 1 risk factor for HF and without known or clinically suspected HF). Methods A total of 400 patients (American Heart Association HF stage A: N = 177; stage B: N = 150; stage C: N = 73) from the Copenhagen Heart Failure Risk Study were identified and followed for the main composite outcome of a HF hospitalization (HFH), ischemic heart disease (IHD), stroke, and all-cause death, recorded within the Danish nationwide registries. Non-CV hospitalization was a secondary outcome. Absolute risk was calculated by the Aalen-Johansen estimator. Results The median follow-up time was 3.3 years, total number of events were 83, and the 3-year risk (95% confidence interval) of the main outcome was 12.8% (7.8–17.9), 22.8% (16.1–29.6) and 31.8% (21.0–42.6) for patients with stage A, B, and C, respectively. 1.1% (0.0–2.7), 3.4% (1.0–6.3) and 10.0% (2.8–16.3) experienced HFH as their first event, whereas 37.3% (30.2–44.4), 49.7% (41.6–57.8) and 54.8% (43.4–66.2) were admitted for non-CV causes as their first event. Conclusion The risk of HFH, IHD, stroke and all-cause death increased with severity of HF stage, and 10% of patients with undiagnosed HF stage C were admitted for HF within 3 years. However, the risk of non-CV hospitalizations was greater compared to the risk of experiencing HFH.

Abstract Background COVID-19 is thought to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas. Methods We conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning risk factors associated with COVID-19. As a proxy for the general Danish population we accessed data on seroprevalence from Danish blood donors (total Ig ELISA assay) in same time period. Results Of the 13,279 included participants, 2296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78–3.16, p > 0.001). Seropositivity was higher among males (RR 1.1, 95% CI 1.05–1.22%, p = 0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00–1.06, p = 0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among household members (OR 5.0, 95% CI 4.1–6.2 p

ABSTRACT 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.

IntroductionWe investigated humoral and T-cell responses within 12 months after first BNT162b2 vaccine in solid organ transplant (SOT) recipients and controls who had received at least three vaccine doses. Furthermore, we compared the immune response in participants with and without previous SARS-CoV-2 infection.MethodsWe included adult liver, lung, and kidney transplant recipients, and controls were selected from a parallel cohort of healthcare workers.ResultsAt 12th-month, the IgG geometric mean concentrations (GMCs) (P

ABSTRACT The majority of long coronavirus disease (COVID) symptoms are not specific to COVID-19 and could be explained by other conditions. The present study aimed to explore whether Danish individuals with a perception that they suffer from long COVID have antibodies against the nucleocapsid antigen, as a proxy for detecting previous infection. The study was conducted in February and March 2021, right after the second surge of the COVID-19 pandemic in Denmark. All members of the social media group on Facebook “Covidramte med senfølger” (“long COVID sufferers'') above the age of 17 years and living in Denmark were invited to participate in a short electronic questionnaire about long COVID risk factors and symptoms. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein was detected in blood samples as a proxy for natural SARS-CoV-2 infection. The final study population comprised 341 participants (90.6% females) who completed blood sampling and answered the questionnaire. A total of 232 (68%) were seropositive (median age, 49.5 years; interquartile range [IQR], 41 to 55 years; 90.1% females). There was no significant difference between sexes and serostatus. Seronegative and seropositive individuals had a similar burden of symptoms that could be attributed to long COVID. Time since perceived COVID-19 was significantly longer in the group of seronegative individuals than the seropositive ones (P

Background COVID‐19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID‐19. We hypothesized that GWI was associated with disease severity and all‐cause death in patients with COVID‐19. Methods and Results In a multicenter study of patients admitted with COVID‐19 (n=305), 249 underwent pressure‐strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), disease severity (oxygen requirement and CRP [C‐reactive protein]), and all‐cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT‐proBNP was observed, with increasing NT‐proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100–mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow‐up (median, 58 days). In multivariable Cox regression, GWI was associated with all‐cause death (hazard ratio, 1.08 [95% CI, 1.01–1.15], per 100–mm Hg% decrease), but did not increase C‐statistics when added to clinical parameters. Conclusions In patients admitted with COVID‐19, our findings indicate that NT‐proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all‐cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Summary: Introduction: Diagnostic confirmation of SARS-CoV-2 by self-collection of specimens is a reliable method compared with healthcare worker collected samples. Citizens’ preferences for collection methods are unknown, but at-home collection could have several advantages. Methods: This study investigated the preference for guided at-home self-collection versus at-hospital specimen collection by healthcare workers. Results: Among the 3709 participants, at-home swab collection was the preferred setting for 2362 (63.7%) compared with 1347 (36.3%) reporting a preference for an at-hospital swabbing procedure. Conclusion: A high preference for guided at-home self-collection of oropharyngeal/nasal SARS-CoV-2 specimens exists and could be a future norm beyond COVID-19.

Background Monitoring of microbiological cause of infective endocarditis (IE) remains key in the understanding of IE; however, data from large, unselected cohorts are sparse. We aimed to examine temporal changes, patient characteristics, and in‐hospital and long‐term mortality, according to microbiological cause in patients with IE from 2010 to 2017. Methods and Results Linking Danish nationwide registries, we identified all patients with first‐time IE. In‐hospital and long‐term mortality rates were assessed according to microbiological cause and compared using multivariable adjusted logistic regression analysis and Cox proportional hazard analysis, respectively. A total of 4123 patients were included. Staphylococcus aureus was the most frequent cause (28.1%), followed by Streptococcus species (26.0%), Enterococcus species (15.5%), coagulase‐negative staphylococci (6.2%), and “other microbiological causes” (5.3%). Blood culture–negative IE was registered in 18.9%. The proportion of blood culture–negative IE declined during the study period, whereas no significant changes were seen for any microbiological cause. Patients with Enterococcus species were older and more often had a prosthetic heart valve compared with other causes. For Streptococcus species IE, in‐hospital and long‐term mortality (median follow‐up, 2.3 years) were 11.1% and 58.5%, respectively. Compared with Streptococcus species IE, the following causes were associated with a higher in‐hospital mortality: S aureus IE (odds ratio [OR], 3.48 [95% CI, 2.74–4.42]), Enterococcus species IE (OR, 1.48 [95% CI, 1.11–1.97]), coagulase‐negative staphylococci IE (OR, 1.79 [95% CI, 1.21–2.65]), “other microbiological cause” (OR, 1.47 [95% CI, 0.95–2.27]), and blood culture–negative IE (OR, 1.99 [95% CI, 1.52–2.61]); and the following causes were associated with higher mortality following discharge (median follow‐up, 2.9 years): S aureus IE (hazard ratio [HR], 1.39 [95% CI, 1.19–1.62]), Enterococcus species IE (HR, 1.31 [95% CI, 1.11–1.54]), coagulase‐negative staphylococci IE (HR, 1.07 [95% CI, 0.85–1.36]), “other microbiological cause” (HR, 1.45 [95% CI, 1.13–1.85]), and blood culture–negative IE (HR, 1.05 [95% CI, 0.89–1.25]). Conclusions This nationwide study showed that S aureus was the most frequent microbiological cause of IE, followed by Streptococcus species and Enterococcus species. Patients with S aureus IE had the highest in‐hospital mortality.

Objective: Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation. Design: Prospective longitudinal cohort study. Materials and methods: We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n = 16), urosepsis (n = 28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n = 5). Correlations between C-reactive protein (CRP), a marker of systemic inflammat ion, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1 ng/kg) in nine healthy young males. Results: Glucagon and CRP were positively and significantly correlated ( r = 0.27; P = 0.0003), whereas no significant association between GLP-1 and CRP was found (r = 0.08, P = 0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P < 0.05) but not GLP-1. Conclusions: Systemic inflammation caused by bacterial infections or develop ed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.

Here the authors generate a capsid-like particle based vaccine candidate displaying the receptor-binding domain of the SARS-CoV-2 spike protein and show induction of neutralizing antibodies after intramuscular prime-boost immunization in mice.

Abstract Aims The present study had two aims: (i) compare echocardiographic parameters in COVID‐19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID‐19 related death. Methods and results In this prospective multicentre cohort study, 214 consecutive hospitalized COVID‐19 patients underwent an echocardiographic examination (by pre‐determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID‐19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P

Abstract Background Infective endocarditis (IE) is associated with high mortality. Surgery may improve survival and reduce complications, but the balance between benefit and harm is difficult and may be closely related to age and type of surgical intervention. We aimed to examine how age and type of left-sided surgical intervention modified mortality in patients undergoing surgery for IE. Methods By crosslinking nationwide Danish registries we identified patients with first-time IE undergoing surgical treatment 2000–2017. Patients were grouped by age 75 years, respectively. Mortality at 90 days were 7.5, 13.9, and 22.3% (p

Abstract Background Cardiovascular disease is the most common cause of death in patients with end-stage kidney disease on haemodialysis. The potential clinical consequence of systematic echocardiographic assessment is however not clear. In an unselected, contemporary population of patients on maintenance haemodialysis we aimed to assess: the prevalence of structural and functional heart disease, the potential therapeutic consequences of echocardiographic screening and whether left-sided heart disease is associated with prognosis. Methods Adult chronic haemodialysis patients in two large dialysis centres had transthoracic echocardiography performed prior to dialysis and were followed prospectively. Significant left-sided heart disease was defined as moderate or severe left-sided valve disease or left ventricular ejection fraction (LVEF) ≤40%. Results Among the 247 included patients (mean 66 years of age [95%CI 64–67], 68% male), 54 (22%) had significant left-sided heart disease. An LVEF ≤40% was observed in 31 patients (13%) and severe or moderate valve disease in 27 (11%) patients. The findings were not previously recognized in more than half of the patients (56%) prior to the study. Diagnosis had a potential impact on management in 31 (13%) patients including for 18 (7%) who would benefit from initiation of evidence-based heart failure therapy. After 2.8 years of follow-up, all-cause mortality among patients with and without left-sided heart disease was 52 and 32% respectively (hazard ratio [HR] 1.95 (95%CI 1.25–3.06). A multivariable adjusted Cox proportional hazard analysis showed that left-sided heart disease was an independent predictor of mortality with a HR of 1.60 (95%CI 1.01–2.55) along with age (HR per year 1.05 [95%CI 1.03–1.07]). Conclusion Left ventricular systolic dysfunction and moderate to severe valve disease are common and often unrecognized in patients with end-stage kidney failure on haemodialysis and are associated with a higher risk of death. For more than 10% of the included patients, systematic echocardiographic assessment had a potential clinical consequence.

Patients with infective endocarditis (IE) form a heterogeneous group by age, co-morbidities and severity ranging from stable patients to patients with life-threatening complications with need for intensive care. A large proportion need surgical intervention. In-hospital mortality is 15-20%. The concept of using hyperbaric oxygen therapy (HBOT) in other severe bacterial infections has been used for many decades supported by various preclinical and clinical studies. However, the availability and capacity of HBOT may be limited for clinical practice and we still lack well-designed studies documenting clinical efficacy. In the present review we highlight the potential beneficial aspects of adjunctive HBOT in patients with IE. Based on the pathogenesis and pathophysiological conditions of IE, we here summarize some of the important mechanisms and effects by HBOT in relation to infection and inflammation in general. In details, we elaborate on the aspects and impact of HBOT in relation to the host response, tissue hypoxia, biofilm, antibiotics and pathogens. Two preclinical (animal) studies have shown beneficial effect of HBOT in IE, but so far, no clinical study has evaluated the feasibility of HBOT in IE. New therapeutic options in IE are much needed and adjunctive HBOT might be a therapeutic option in certain IE patients to decrease morbidity and mortality and improve the long-term outcome of this severe disease.

BackgroundPrevious studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls.MethodsWe measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose.ResultsIn SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08–1.24 to 11.97 AU/ml, 95% CI 7.73–18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70–385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95–83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p < 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11–1.35, p < 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30–1.85, p < 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09–2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10–1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25–2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16–2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26–1.82, p < 0.001).ConclusionImmune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.

Patients with severe mental illness (SMI) i.e. schizophrenia, schizoaffective disorder, and bipolar disorder are at increased risk of severe outcomes if infected with coronavirus disease 2019 (COVID-19). Whether patients with SMI are at increased risk of COVID-19 is, however, sparsely investigated. This important issue must be addressed as the current pandemic could have the potential to increase the existing gap in lifetime mortality between this group of patients and the background population. The objective of this study was to determine whether a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder is associated with an increased risk of COVID-19. A cross-sectional study was performed between January 18th and February 25th, 2021. Of 7071 eligible patients with schizophrenia, schizoaffective disorder, or bipolar disorder, 1355 patients from seven psychiatric centres in the Capital Region of Denmark were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. A total of 1258 unvaccinated patients were included in the analysis. The mean age was 40.5 years (SD 14.6), 54.3% were female. Fifty-nine of the 1258 participants had a positive SARS-CoV-2 antibody test, corresponding to a adjusted seroprevalence of 4.96% (95% CI 3.87–6.35). No significant difference in SARS-CoV-2-risk was found between female and male participants (RR = 1.32; 95% CI 0.79–2.20; p = .290). No significant differences in seroprevalences between schizophrenia and bipolar disease were found (RR = 1.12; 95% CI 0.67–1.87; p = .667). Seroprevalence among 6088 unvaccinated blood donors from the same region and period was 12.24% (95% CI 11.41–13.11). SARS-CoV-2 seroprevalence among included patients with SMI was significantly lower than among blood donors (RR = 0.41; 95% CI 0.31–0.52; p < .001). Differences in seroprevalences remained significant when adjusting for gender and age, except for those aged 60 years or above. The study is registered at ClinicalTrails.gov (NCT04775407). https://clinicaltrials.gov/ct2/show/NCT04775407?term=NCT04775407&draw=2&rank=1.

ABSTRACT “Testing Denmark” is a national, large-scale, epidemiological surveillance study of SARS-CoV-2 in the Danish population. Between September and October 2020, approximately 1.3 million people (age >15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by point-of care rapid test (POCT) distributed to participants’ home addresses. In total, 318,552 participants (24.5% invitees) completed the study and 2,519 (0.79%) were seropositive. Of the participants with a prior positive PCR test (n = 1,828), 29.1% were seropositive in the POCT. Although seropositivity increased with age, participants 61 years and over reported fewer symptoms and were tested less frequently. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (risk ratio [RR] 7.43, 95% CI: 6.57–8.41), particular in household members (RR 17.70, 95% CI: 15.60–20.10). A greater risk of seropositivity was seen in home care workers (RR 2.09, 95% CI: 1.58–2.78) compared to office workers. A high degree of adherence with national preventive recommendations was reported (e.g., >80% use of face masks), but no difference were found between seropositive and seronegative participants. The seroprevalence result was somewhat hampered by a lower-than-expected performance of the POCT. This is likely due to a low sensitivity of the POCT or problems reading the test results, and the main findings therefore relate to risk associations. More emphasis should be placed on age, occupation, and exposure in local communities. IMPORTANCE To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants’ homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested individuals, type of occupation, as well as exposure in local communities and households. To meet the challenge that broad nationwide information can be difficult to gather. This study design sets the stage for a novel way of conducting studies. Additionally, this study design can be used as a supplementary model in future general test strategy for ongoing monitoring of COVID-19 immunity in the population, both from past infection and from vaccination against SARS-CoV-2, however, with attention to the complexity of performing and reading the POCT at home.

Infective endocarditis (IE) is a life-threatening infective disease with increasing incidence worldwide. From early on, in the antibiotic era, it was recognized that high-dose and long-term antibiotic therapy was correlated to improved outcome. In addition, for several of the common microbial IE etiologies, the use of combination antibiotic therapy further improves outcome. IE vegetations on affected heart valves from patients and experimental animal models resemble biofilm infections. Besides the recalcitrant nature of IE, the microorganisms often present in an aggregated form, and gradients of bacterial activity in the vegetations can be observed. Even after appropriate antibiotic therapy, such microbial formations can often be identified in surgically removed, infected heart valves. Therefore, persistent or recurrent cases of IE, after apparent initial infection control, can be related to biofilm formation in the heart valve vegetations. On this background, the present review will describe potentially novel non-antibiotic, antimicrobial approaches in IE, with special focus on anti-thrombotic strategies and hyperbaric oxygen therapy targeting the biofilm formation of the infected heart valves caused by Staphylococcus aureus. The format is translational from preclinical models to actual clinical treatment strategies.

Abstract Introduction Soluble urokinase plasminogen activator receptor (suPAR) is a prognostic and nonspecific biomarker associated with short-term mortality in emergency department (ED) patients. Therefore, the blood level of suPAR might be usable for identification of patients at high- and low risk, shortly after arrival at the ED. Here, we investigate the value of adding suPAR to triage and how this may impact on risk stratification regarding mortality. Methods The analyses were performed on the TRIAGE III cohort. Patients were triaged in four groups: Red, Orange, Yellow, and Green. Outcome was all-cause mortality within seven days. Discriminative abilities of triage and suPAR on mortality were assessed using the area under the curve (AUC) for receiver operating characteristics (ROC) curves. A suPAR cut-off value was generated using the Youden’s index. Patients were subsequently reclassified one triage level up if the suPAR level was above this cut-off and one level down if the suPAR level was below that value. Results The study included 4420 patients with an available triage category and suPAR measurement. suPAR was significantly better in predicting mortality than triage; AUC (95% confidence interval): 0.85 (0.80–0.89) vs. 0.71 (0.64–0.78), P

Objective: To describe the clinical trial “Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest” (VAM-IHCA). Methods: The VAM-IHCA trial is an investigator-initiated, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial of vasopressin and methylprednisolone during adult in-hospital cardiac arrest. The study drugs consist of 40 mg methylprednisolone and 20 IU of vasopressin given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU).The primary outcome is return of spontaneous circulation and key secondary outcomes include survival and survival with a favorable neurological outcome at 30 days. 492 patients will be enrolled. The trial was registered at the EU Clinical Trials Register (EudraCT Number: 2017-004773-13) on Jan. 25, 2018 and ClinicalTrials.gov (Identifier: NCT03640949) on Aug. 21, 2018. Results: The trial started in October 2018 and the last patient is anticipated to be included in January 2021. The primary results will be reported after 3-months follow-up and are, therefore, anticipated in mid-2021. Conclusion: The current article describes the design of the VAM-IHCA trial. The results from this trial will help clarify whether the combination of vasopressin and methylprednisolone when administered during in-hospital cardiac arrest improves outcomes.

Objective To prospectively validate the CT-Valve score, a new risk score designed to identify patients with valvular heart disease at a low risk of coronary artery disease (CAD) who could benefit from multislice CT (MSCT) first instead of coronary angiography (CAG).Methods This was a prospective cohort study of patients referred for valve surgery in the Capital Region of Denmark and Odense University Hospital from the 1 February 2015 to the 1 February 2017. MSCT was implemented for patients with a CT-Valve score ≤7 at the referring physician’s discretion. Patients with a history of CAD or chronic kidney disease were excluded. The primary outcome was the proportion of patients needing reevaluation with CAG after MSCT and risk of CAD among the patients determined to be low to intermediate risk.Results In total, 1149 patients were included. The median score was 9 (IQR 3) and 339 (30%) had a score ≤7. MSCT was used for 117 patients. Of these 29 (25%) were reevaluated and 9 (7.7%) had CAD. Of the 222 patients with a score ≤7 that did not receive an MSCT, 14 (6%) had significant CAD. The estimated total cost of evaluation among patients with a score ≤7 before implementation was €132 093 compared with €79 073 after, a 40% reduction. Similarly, estimated total radiation before and after was 608 mSv and 362 mSv, a 41% reduction. Follow-up at a median of 32 months (18–48) showed no ischaemic events for patients receiving only MSCT.Conclusion The CT-Valve score is a valid method for determining risk of CAD among patients with valvular heart disease. Using a score ≤7 as a cut-off for the use of MSCT is safe and cost-effective.

Objective: This study evaluated the associations between the natriuretic peptide activity and the neurohormonal response in non-obese and obese outpatients with and without heart failure (HF). Background: Obesity-related HF may be a distinct subtype of HF. Obesity is associated with lower plasma concentrations of natriuretic peptides. The associations between obesity and neurohormonal activation estimated by mid-regional pro-adrenomedullin (MR-proADM) and copeptin in patients with HF is not elucidated. Methods: This prospective cohort-study included 392 outpatients ≥60years, plus ≥1 risk-factor(-s) for HF (hypertension, ischemic heart disease, atrial fibrillation, diabe­tes, chronic kidney disease), and without known HF. Patients were categorized ‘non-obese’ BMI = 18.5–29.9 kg/m2 (n = 273) and ‘obese’ BMI ≥ 30 kg/m2 (n = 119). The diagnosis of HF required signs, symptoms, and abnormal echocardiography. NT-proBNP, MR-proANP, MR-proADM, and copeptin were analyzed. Results: Obese patients were younger, had a higher prevalence of diabetes and chronic kidney disease, but a lower prevalence of atrial fibrillation. A total of 39 (14.3%) non-obese and 26 (21.8%) obese patients were diagnosed with HF. In obese patients, HF was not associ­ated with higher plasma concentrations of NT-proBNP (Estimate: 0.063; 95%CI: –0.037–1.300; P = 0.064), MR-proANP (Estimate: 0.207; 95%CI: –0.101–0.515; P = 0.187), MR-proADM (Estimate: 0.112; 95%CI: –0.047–0.271; P = 0.168), or copeptin (Estimate: 0.093; 95%CI: –0.333–0.518; P = 0.669). Additionally, obese patients with HF had lower plasma concentra­tions of NT-proBNP (Estimate: –0.998; 95%CI: –1.778–0.218; P = 0.012), and MR-proANP (Estimate: –0.488; 95%CI: –0.845–0.132; P = 0.007) compared to non-obese patients with HF, whereas plasma concentrations of MR-proADM (Estimate: 0.066; 95%CI: –0.119–0.250; P = 0.484) and copeptin (Estimate: 0.140; 95%CI: –0.354–0.633; P = 0.578) were comparable. Conclusions: Patients with obesity-related HF have natriuretic peptide deficiency and lack of increased plasma concentrations of MR-proADM and copeptin suggesting that patients with obesity-related HF have a blunted overall neurohormonal activity.

Abstract Background Acutely admitted medical patients are often fragile and in risk of future surgery. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is a predictor of readmission and mortality in the acute care setting. We aimed to investigate if suPAR also predicts acute surgery, which is associated with higher mortality than elective surgery, and if it predicts post-operative mortality. Methods A retrospective registry-based cohort study of 17,312 patients admitted to an acute medical unit in Denmark, from 18 November 2013 until 30 September 2015. The first admission with available suPAR was defined as the index admission, and patients were followed via national registries until 1 January 2016. The risk of acute surgery during the entire follow-up period as well as the 90-day post-operative mortality risk was modeled by Cox regression analyses adjusted for sex, age, C-reactive protein, and Charlson Comorbidity Index (Charlson Score). Results Acute surgery was carried out on 2404 patients (13.9%) after a median of 45 days (interquartile range 5–186) following the index admission. Patients receiving acute surgery had higher baseline suPAR compared with patients receiving elective- or no surgery (p

Abstract Background Prioritization of acutely ill patients in the Emergency Department remains a challenge. We aimed to evaluate whether routine blood tests can predict mortality in unselected patients in an emergency department and to compare risk prediction with a formalized triage algorithm. Methods A prospective observational cohort study of 12,661 consecutive admissions to the Emergency Department of Nordsjælland University Hospital during two separate periods in 2010 (primary cohort, n = 6279) and 2013 (validation cohort, n = 6383). Patients were triaged in five categories by a formalized triage algorithm. All patients with a full routine biochemical screening (albumin, creatinine, c-reactive protein, haemoglobin, lactate dehydrogenase, leukocyte count, potassium, and sodium) taken at triage were included. Information about vital status was collected from the Danish Central Office of Civil registration. Multiple logistic regressions were used to predict 30-day mortality. Validation was performed by applying the regression models on the 2013 validation cohort. Results Thirty-day mortality was 5.3%. The routine blood tests had a significantly stronger discriminative value on 30-day mortality compared to the formalized triage (AUC 88.1 [85.7;90.5] vs. 63.4 [59.1;67.5], p

INTRODUCTION:Triage systems with limited room for clinical judgment are used by emergency departments (EDs) worldwide. The Copenhagen Triage Algorithm (CTA) is a simplified triage system with a clinical assessment. METHODS:The trial was a non-inferiority, two-center cluster-randomized crossover study where CTA was compared to a local adaptation of Adaptive Process Triage (ADAPT). CTA involves initial categorization based on vital signs with a final modification based on clinical assessment by an ED nurse. We used 30-day mortality with a non-inferiority margin at 0.5%. Predictive performance was compared using Receiver Operator Characteristics. RESULTS:We included 45,347 patient visits, 23,158 (51%) and 22,189 (49%) were triaged with CTA and ADAPT respectively with a 30-day mortality of 3.42% and 3.43% (P = 0.996) a difference of 0.01% (95% CI: -0.34 to 0.33), which met the non-inferiority criteria. Mortality at 48 hours was 0.62% vs. 0.71%, (P = 0.26) and 6.38% vs. 6.61%, (P = 0.32) at 90 days for CTA and ADAPT. CTA triaged at significantly lower urgency level (P

The aim of this study was to compare the sensitivity of self-collected versus healthcare worker (HCW)-collected swabs for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. Symptomatic individuals referred for SARS-CoV-2 testing were invited to provide mobile-phone video-instructed self-collected oropharyngeal and nasal samples followed by a HCW-collected oropharyngeal sample. All samples were sent for analysis to the same microbiology laboratory, and the number of SARS-CoV-2-positive participants in the two tests was compared. A total of 109 participants were included, and 19 participants had SARS-CoV-2-positive results. The diagnostic sensitivity of the self-collected and HCW-collected swabs was 84.2% and 89.5%, respectively, with an acceptable agreement, Cohens kappa 0.82, p < 0.001. Further, results from a questionnaire answered by the participants found that loss of smell as a self-reported symptom was a strong predictor for a SARS-CoV-2-positive test. In conclusion, we found that self-collected oropharyngeal and nasal swabs for SARS-CoV-2 testing can be reliable compared to HCW-collected oropharyngeal samples.

BackgroundMidregional proadrenomedullin (MR‐proADM) has demonstrated prognostic potential after myocardial infarction (MI). Yet, the prognostic value of MR‐proADM at admission has not been examined in patients with ST‐segment–elevation MI (STEMI). Methods and ResultsThe aim of this substudy, DANAMI‐3 (The Danish Study of Optimal Acute Treatment of Patients with ST‐segment–elevation myocardial infarction), was to examine the associations of admission concentrations of MR‐proADM with short‐ and long‐term mortality and hospital admission for heart failure in patients with ST‐segment–elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of MR‐proADM was 0.64 nmol/L (25th–75th percentiles, 0.53–0.79). Within 30 days 23 patients (2.0%) died and during a 3‐year follow‐up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of MR‐proADM was, in adjusted models, associated with an increased risk of 30‐day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01–7.11; P=0.049), long‐term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97–5.29; P