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Background: Electronic informed consent (eConsent) usage has expanded in recent years in Europe, especially during the pandemic. Slow recruitment rate and limitations in participant outreach are the challenges often faced in clinical research. Given the benefits of eConsent and group counselling reported in the literature, group eConsent was implemented in recruitment for the SWITCH-ON study. We aim to explore the experience of participants who attended group eConsent for the SWITCH-ON study and evaluate its potential for future use. Methods: SWITCH-ON study aims to analyse the immunogenicity of a healthy population following bivalent COVID-19 booster vaccination. Four hundred thirty-four healthcare workers aged 18–65 were successfully recruited and sent a questionnaire about their experience with group eConsent. Out of 399 completed questionnaires (response rate 92%), 39 participants did not join group eConsent. The remaining 360 responses were included in the final analysis. Quantitative and qualitative data were reported using descriptive statistical analysis and thematic analysis respectively. Results: Participants found that group eConsent was an efficient method that it allowed them to hear each other’s questions and concerns and created a sense of togetherness. However, limited privacy, barriers to asking questions in a group, and peer pressure can limit the use of group eConsent. One hundred sixty-five (46%) participants thought that group eConsent was suitable to recruit participants with diseases or conditions, while 87 (24%) reported limitations with this method. The remaining participants suggested that applicability of group eConsent depended on the diseases or conditions of the study population, and one-to-one conversation should always be available. Participants who had experienced both one-to-one and group eConsent shared different preferred consent formats for future studies. Concl

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.

Background: Bivalent mRNA-based COVID-19 vaccines encoding the ancestral and omicron spike (S) protein were developed as a countermeasure against antigenically distinct SARS-CoV-2 variants. We aimed to assess the (variant-specific) immunogenicity and reactogenicity of mRNA-based bivalent omicron (BA.1) vaccines in individuals who were primed with adenovirus-based or mRNA-based vaccines encoding the ancestral spike protein. Methods: We analysed results of the direct boost group of the SWITCH ON study, an open-label, multicentre, randomised controlled trial. Health-care workers from four academic hospitals in the Netherlands aged 18–65 years who had completed a primary COVID-19 vaccination regimen and received one booster of an mRNA-based vaccine, given no later than 3 months previously, were eligible. Participants were randomly assigned (1:1) using computer software in block sizes of 16 and 24 to receive an omicron BA.1 bivalent booster straight away (direct boost group) or a bivalent omicron BA.5 booster, postponed for 90 days (postponed boost group), stratified by priming regimen. The BNT162b2 OMI BA.1 boost was given to participants younger than 45 years, and the mRNA-1273.214 boost was given to participants 45 years or older, as per Dutch guidelines. The direct boost group, whose results are presented here, were divided into four subgroups for analysis: (1) Ad26.COV2.S (Johnson & Johnson) prime and BNT162b2 OMI BA.1 (BioNTech–Pfizer) boost (Ad/P), (2) mRNA-based prime and BNT162b2 OMI BA.1 boost (mRNA/P), (3) Ad26.COV2.S prime and mRNA-1273.214 (Moderna) boost (Ad/M), and (4) mRNA-based prime and mRNA-1273.214 boost (mRNA/M). The primary outcome was fold change in S protein S1 subunit-specific IgG antibodies before and 28 days after booster vaccination. The primary outcome and safety were assessed in all participants except those who withdrew, had a SARS-CoV-2 breakthrough infection, or had a missing blood sample at day 0 or day 28. This tria

OBJECTIVES: Renal sympathetic denervation (RDN) reduces blood pressure (BP). However, one out of three patients does not exhibit a significant BP response to the therapy. This study investigates the association between noninvasive vascular stiffness indices and RDN-mediated BP reduction.METHODS: In this prospective, single-arm pilot study, patients with systolic office BP at least 140 mmHg, mean 24-h systolic ambulatory blood pressure (ABP) at least 130 mmHg and at least three prescribed antihypertensive drugs underwent radiofrequency RDN. The primary efficacy endpoint was temporal evolution of mean 24-h systolic ABP throughout 1-year post RDN (measured at baseline and 3-6-12 months). Effect modification was studied for baseline ultrasound carotid-femoral and magnetic resonance (MR) pulse wave velocity (PWV), MR aortic distensibility, cardiac MR left ventricular parameters and clinical variables. Statistical analyses were performed using linear mixed-effects models, and effect modification was assessed using interaction terms.RESULTS: Thirty patients (mean age 62.5 ± 10.7 years, 50% women) with mean 24-h ABP 146.7/80.8 ± 13.7/12.0 mmHg were enrolled. Following RDN, mean 24-h systolic ABP changed with -8.4 (95% CI: -14.5 to -2.3) mmHg/year (P = 0.007). Independent effect modifiers were CF-PWV [+2.7 (0.3 to 5.1) mmHg/year change in outcome for every m/s increase in CF-PWV; P = 0.03], daytime diastolic ABP [-0.4 (-0.8 to 0.0) mmHg/year per mmHg; P = 0.03], age [+0.6 (0.2 to 1.0) mmHg/year per year of age; P = 0.006], female sex [-14.0 (-23.1 to -5.0) mmHg/year as compared with men; P = 0.003] and BMI [+1.2 (0.1 to 2.2) mmHg/year per kg/m2; P = 0.04].CONCLUSION: Higher CF-PWV at baseline was associated with a smaller reduction in systolic ABP following RDN. These findings could contribute to improve identification of RDN responders.

The emergence of novel SARS-CoV-2 variants led to the recommendation of booster vaccinations after Ad26.COV2.S priming. It was previously shown that heterologous booster vaccination induces high antibody levels, but how heterologous boosters affect other functional aspects of the immune response remained unknown. Here, we performed immunological profiling of Ad26.COV2.S-primed individuals before and after homologous or heterologous (mRNA-1273 or BNT162b2) booster. Booster vaccinations increased functional antibodies targeting ancestral SARS-CoV-2 and emerging variants. Especially heterologous booster vaccinations induced high levels of functional antibodies. In contrast, T-cell responses were similar in magnitude following homologous or heterologous booster vaccination and retained cross-reactivity towards variants. Booster vaccination led to a minimal expansion of SARS-CoV-2-specific T-cell clones and no increase in the breadth of the T-cell repertoire. In conclusion, we show that Ad26.COV2.S priming vaccination provided a solid immunological base for heterologous boosting, increasing humoral and cellular responses targeting emerging variants of concern.

The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous boosters after Ad26.COV2.S-priming. We found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies, and T cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed.

Vaccination against coronavirus disease 2019 (COVID-19) has contributed greatly to providing protection against severe disease, thereby reducing hospital admissions and deaths. Several studies have reported reduction in vaccine effectiveness over time against the Omicron sub-lineages. However, the willingness to receive regular booster doses in the general population is declining. To determine the need for repeated booster vaccinations in healthy individuals and to aid policymakers in future public health interventions for COVID-19, we aim to gain insight into the immunogenicity of the additional bivalent booster vaccination in a representative sample of the healthy Dutch population. The SWITCH ON study was initiated to investigate three main topics: i) immunogenicity of bivalent vaccines after priming with adenovirus- or mRNA-based vaccines, ii) immunological recall responses and reactivity with relevant variants after booster vaccination, and iii) the necessity of booster vaccinations for the healthy population in the future. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05471440.

INTRODUCTION: Hypertension is a modifiable risk factor in patients at the highest risk for cardiovascular events. New invasive treatment options are becoming available that might be particularly appealing for high-risk patients. Therefore, the aim of this study was to determine the prevalence of high-risk patients on routine therapy that do not meet guideline recommended ambulatory blood pressure (ABP) targets.METHODS: This single-center, cross-sectional study was conducted at the Erasmus University Medical Center (Rotterdam, The Netherlands). Inclusion criteria were: (1) age 18-80 years, (2) drugs prescribed for hypertension or history of hypertension and (3) high cardiovascular risk as defined according to the European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines. Patients underwent standardized office blood pressure (OBP) and same-day 24-h ABP measurements. Blood pressure (BP) control was defined according to the 2018 ESC/ESH and 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines.RESULTS: A total of 100 patients were enrolled (median age 71 years, 35% female). Mean OBP was 142.2/81.9 ± 18.6/12.6 mmHg and mean 24-h ABP was 126.1/70.1 ± 14.3/9.2 mmHg. Patients were on 2.0 [25th-75th percentile: 1.0-3.3] Defined Daily Doses of antihypertensive drugs. ESC/ESH guideline 24-h ABP and OBP targets were not met in 41.8% (95%CI: 31.5-52.6%) and 52.7% (95%CI: 42.0-63.3%), respectively. ACC/AHA guideline 24-h ABP and OBP targets were not met in 59.3% (95%CI: 48.5-69.5%) and 79.1% (95%CI: 69.3-86.9%), respectively.CONCLUSIONS: BP remains uncontrolled in 40-60% of high-risk hypertensive patients despite routine use of guideline-recommended therapy. Our findings support the search towards novel invasive BP lowering treatment options.

Background: During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe. Methods: This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS 1–3), mildly frail (CFS 4–5), or frail (CFS 6–9). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities). Findings: Between March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55–77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS 6–9 vs CFS 1–3 odds ratio [OR] 2·71 [95% CI 2·04–3·60], p<0·0001 and CFS 4–5 vs CFS 1–3 OR 1·54 [1·16–2·06], p=0·0030; age

Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARS-CoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19.