SARS-CoV-2 vaccines are crucial in controlling COVID-19, but knowledge of which factors determine waning immunity is limited. We examined antibody levels and T-cell gamma-interferon release after two ...doses of BNT162b2 vaccine or a combination of ChAdOx1-nCoV19 and BNT162b2 vaccines for up to 230 days after the first dose. Generalized mixed models with and without natural cubic splines were used to determine immunity over time. Antibody responses were influenced by natural infection, sex, and age. IgA only became significant in naturally infected. A one-year IgG projection suggested an initial two-phase response in those given the second dose delayed (ChAdOx1/BNT162b2) followed by a more rapid decrease of antibody levels. T-cell responses correlated significantly with IgG antibody responses. Our results indicate that IgG levels will drop at different rates depending on prior infection, age, sex, T-cell response, and the interval between vaccine injections. Only natural infection mounted a significant and lasting IgA response.
Abstract
Background
The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19).
Methods
A cohort of 46 112 healthcare ...workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination.
Results
The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56–1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found.
Conclusions
The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.
This cohort study of 46 112 healthcare workers examined the effect of influenza vaccination on hospitalization and symptoms due to COVID-19 and development of antibodies against SARS-CoV-2. Influenza vaccination had no effect on the specified outcomes.
Part of the pathophysiology in septic shock is a progressive activation of the endothelium and platelets leading to widespread microvascular injury with capillary leakage, microthrombi and ...consumption coagulopathy. Modulating the inflammatory response of endothelium and thrombocytes might attenuate this vicious cycle and improve outcome.
The CO-ILEPSS trial was a randomised, placebo-controlled, double-blind, pilot trial. Patients admitted to the intensive care unit with septic shock were randomised and allocated in a 2:1 ratio to active treatment with dual therapy of iloprost 1 ng/kg/min and eptifibatide 0.5 μg/kg/min for 48 h or placebo. The primary outcomes were changes in biomarkers reflecting endothelial activation and disruption, platelet consumption and fibrinolysis. We compared groups with mixed models, post hoc Wilcoxon signed-rank test and Mann-Whitney U test.
We included 24 patients of which 18 (12 active, 6 placebo) completed the full 7-day trial period and were included in the per-protocol analyses of the primary outcomes. Direct comparison between groups showed no differences in the primary outcomes. Analyses of within-group delta values revealed that biomarkers of endothelial activation and disruption changed differently between groups with increasing levels of thrombomodulin (p = 0.03) and nucleosomes (p = 0.02) in the placebo group and decreasing levels of sE-Selectin (p = 0.007) and sVEGFR1 (p = 0.005) in the active treatment group. Platelet count decreased the first 48 h in the placebo group (p = 0.049) and increased from baseline to day 7 in the active treatment group (p = 0.023). Levels of fibrin monomers declined in the active treatment group within the first 48 h (p = 0.048) and onwards (p = 0.03). Furthermore, there was a significant reduction in SOFA score from 48 h (p = 0.024) and onwards in the active treatment group. Intention-to-treat analyses of all included patients showed no differences in serious adverse events including bleeding, use of blood products or mortality.
Our results could indicate benefit from the experimental treatment with reduced endothelial injury, reduced platelet consumption and ensuing reduction in fibrinolytic biomarkers along with improved SOFA score. The results of the CO-ILEPSS trial are exploratory and hypothesis generating and warrant further investigation in a large-scale trial.
Clinicaltrials.com, NCT02204852 (July 30, 2014); EudraCT no. 2014-002440-41.
Abstract
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.
OBJECTIVES
To investigate the prevalence of preoperative hypercoagulability assessed by thromboelastography (TEG), to identify patient characteristics associated with hypercoagulability and to ...explore whether hypercoagulability is associated with a greater risk for myocardial infarction (MI), stroke and mortality 30 days after coronary artery bypass grafting (CABG) surgery.
METHODS
This is a prospective, observational study of 200 consecutive CABG surgery patients. Hypercoagulability was defined as TEG maximum amplitude >69 mm.
RESULTS
Eighty-seven out of 200 (43.5%) CABG patients were TEG-hypercoagulable. In univariate regression analysis, age, female gender, hypertension, severe chronic obstructive pulmonary disease, platelet count and fibrinogen level were significantly associated with TEG-hypercoagulability. Multivariate regression analysis revealed higher age, platelet count and fibrinogen levels as variables independently associated with TEG-hypercoagulability. Thirty-day outcome data: MI (TEG-hypercoagulable 6.9% vs. TEG-normocoagulable 3.7%, NS), stroke (8.0 vs. 2.8%, NS) and mortality (4.6 vs. 0.9%, NS). There was a significant difference in 30-day combined event rate of MI, stroke and mortality (17.2 vs. 6.6%, P = 0.019). In univariate analysis, only female gender and TEG-hypercoagulability were significantly associated with 30-day combined event rate. In multivariate analysis, only female gender was significantly associated with 30-day outcome (P = 0.014), whereas TEG-hypercoagulability demonstrated a trend (P = 0.065).
CONCLUSIONS
Hypercoagulability identified by TEG was preoperatively found in 43.5% of CABG patients, and the findings of this study support the notion that TEG-hypercoagulable patients have a higher risk for a combination of thromboembolic complications and death after surgery.
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.
The real-world use of triptans in the treatment of migraine is disappointing. Only 12% of the Danish migraine population purchased a triptan between 2014 and 2019, and only 43% repurchased a triptan ...after first prescription. The aim of the present study was to assess whether physicians and patients adhere to the therapeutic guideline on acute migraine treatment. We interviewed 299 triptan experienced participants with migraine and 101 triptan naïve participants with migraine from the Danish Migraine Population Cohort, using a semi-structured questionnaire. Descriptive statistical analyses were used to study the association with triptan use and the assessed factors. Among triptan naïve participants with migraine, 64% had consulted their general practitioner about their migraine, of whom only 23% received information about the possibility of triptan treatment. Among triptan experienced participants, 77% had only tried one type of triptan. Only 12% could recall they had been informed by their general practitioner to try each triptan three times before giving up. Twenty percent were informed to try three different triptans in total, if the first did not work. In disagreement with the guideline, participants who reported a low pain reduction by a triptan had only tried one type of triptan. Our study shows a low adherence to therapeutic guideline for the attack treatment of migraine. There is a need for better education of general practitioners regarding treatment of migraine. Future campaigns should aim to inform both the public and the general practitioner about antimigraine treatments.
Abstract
The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse immune imprinting is observed in vaccinated individuals. Despite vaccination, ...following the emergence of the Omicron variant, some individuals appear more susceptible to primary infections and reinfections than others, underscoring the need to elucidate how immune responses are influenced by previous infections and vaccination. IgG, IgA, neutralizing antibodies and T-cell immune responses in 1,325 individuals (955 of which were infection-naive) were investigated before and after three doses of the BNT162b2 vaccine, examining their relation to breakthrough infections and immune imprinting in the context of Omicron. Our study shows that both humoral and cellular responses following vaccination were generally higher after SARS-CoV-2 infection compared to infection-naive. Notably, viral exposure before vaccination was crucial to achieving a robust IgA response. Individuals with lower IgG, IgA, and neutralizing antibody responses postvaccination had a significantly higher risk of reinfection and future Omicron infections. This was not observed for T-cell responses. A primary infection before Omicron and subsequent reinfection with Omicron dampened the humoral and cellular responses compared to a primary Omicron infection, consistent with immune imprinting. These results underscore the significant impact of hybrid immunity for immune responses in general, particularly for IgA responses even after revaccination, and the importance of robust humoral responses in preventing future infections.
Quantifying the contribution of genetics and environmental effects on disease initiation and progression, as well as the shared genetics of different diseases, is vital for the understanding of the ...disease etiology of multimorbidities. In this study, we leverage nationwide Danish registries to provide a granular atlas of the genetic origin of disease phenotypes for a cohort of all Danes 1978–2018 with partially known pedigree (n = 6.3 million). We estimate the heritability and genetic correlation between thousands of disease phenotypes using a novel approach that can be scaled to nationwide data. Our findings confirm the importance of genetics for a number of known associations and increase the resolution of heritability by adding numerous associations, some of which point to shared biologically origin of different phenotypes. We also establish the heritability of disease trajectories and the importance of sex-specific genetic contributions. Results can be accessed at https://h2.cpr.ku.dk/.Discovering the genetic roots of diseases is a major question in genetic research. Here, the authors shed light on pleiotropy across diseases using a new method, scaled to millions of individuals, applied to single diseases and disease trajectories.
Restless Legs Syndrome (RLS) is a neurological sensorimotor disorder that occurs in the evening and night, thereby impacting quality of sleep in sufferers. The pathophysiology of RLS is poorly ...understood but inflammation has been proposed as possibly being involved. The neutrophil-to-lymphocyte ratio (NLR) can be used as an inflammation marker but results from small studies have been inconclusive in determining whether NLR is associated with RLS. We aimed to assess whether an association between NLR and RLS exists in a large cohort of healthy individuals.
Neutrophils and lymphocytes were measured in blood samples of 13,055 individuals from the Danish Blood Donor Study, all of whom completed the validated Cambridge-Hopkins RLS-questionnaire for RLS assessment.
In the sample, 661 individuals were determined as current RLS cases (5.1%). A higher proportion of individuals with RLS were females (62.5% vs 47.5%; P<0.001) and RLS cases were older than controls (P<0.001), but no differences in body mass index (BMI), smoking or alcohol consumption were found between the two groups. An increased NLR was observed in RLS cases compared to controls (median NLR: 1.80 vs 1.72; P = 0.033). In an unadjusted logistic regression model, increased NLR was associated with RLS (OR = 1.10 per NLR unit increase 95%CI:1.01-1.20; P = 0.032); however, the association was not significant in multivariate models adjusting for sex and age (P = 0.094) or sex, age, alcohol consumption, smoking status and BMI (P = 0.107).
We found no association between RLS and NLR among Danish blood donors after adjusting for sex, age, alcohol consumption, smoking status and BMI. Further studies are needed to determine whether inflammation is a risk factor for RLS.
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