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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: Travellers visiting rabies-endemic countries are at risk of rabies infection. Assessing travellers’ knowledge and risk perception of rabies and risk behaviour during travel can help identify knowledge gaps and improve pre-travel risk education. Methods: Cohort study in Dutch adult travellers, using two surveys: one before travel to assess knowledge and perception of rabies, and one after return to identify risk behaviour during travel. Results: The pre-travel and post-travel survey were completed by 301 and 276 participants, respectively. 222 participants had travelled to a high-risk rabies-endemic country. 21.6 % of the participants scored their rabies knowledge as poor. Some participants were unaware cats or bats can transmit rabies (26.6 % and 13.6 %, respectively), or that post-exposure prophylaxis (PEP) is required for certain exposures such as skin abrasions without bleeding or licks on damaged skin (35.5 % and 18.9 %, respectively), while 27.9 % of participants did not know PEP needs to be administered within one day. 115 participants (51.8 %) reported any form of contact with any animal during travel. Two participants reported animal exposure, of which one took adequate PEP measures. Risk factors for animal contact abroad were regularly touching cats or dogs at home or abroad, longer travel duration, having pets during childhood and being an animal lover. Conclusions: Pre-travel rabies risk education currently does not meet travellers’ needs, which is reflected in knowledge gaps and engagement in risk behaviour during travel. During pre-travel health advice, avoiding animal contact abroad should be emphasized, and additional education is required about indications for PEP.

The goal of the study was to describe the population pharmacokinetics of trimethoprim, sulfamethoxazole, and N-acetyl sulfamethoxazole in hospitalized patients. Furthermore, this study used the model to optimize dosing regimens of cotrimoxazole for Pneumocystis jirovecii pneumonia and in patients with renal insufficiency or with continuous renal replacement therapy (CRRT). This was a retrospective multicenter observational cohort study based on therapeutic drug monitoring (TDM) data from hospitalized patients treated with cotrimoxazole. We developed two population pharmacokinetic (POPPK) models: a model of trimethoprim and an integrated model with both sulfamethoxazole and N-acetyl sulfamethoxazole concentrations. Monte Carlo simulations were performed to determine the optimal dosing regimen. A total of 348 measurements from 168 patients were available. The estimated glomerular filtration rate (eGFR) and CRRT were included as covariates on the clearance of all three compounds. Cotrimoxazole TID 1,920 mg and b.i.d. 2,400 mg led to sufficient exposure for infections with P. jirovecii in patients without renal insufficiency. To reach equivalent exposure, a dose reduction of 33.3% is needed in patients with an eGFR of 10 mL/minute/1.73 m2 and of 16.7% for an eGFR of 30 mL/minute/1.73 m2. N-acetyl sulfamethoxazole accumulates in patients with a reduced eGFR. CRRT increased the clearance of sulfamethoxazole, but not trimethoprim or N-acetyl sulfamethoxazole, compared with the median clearance in the population. Doubling the sulfamethoxazole dose is needed for patients on CRRT to reach equivalent exposure.

Introduction: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. Methods: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. Results: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79–1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48–1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (< 7 days) (OR 2.84, 95% CI 1.07–7.56). Conclusion: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.

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

Introduction: In 2020, the first Dutch West Nile virus (WNV) infected birds were detected through risk-targeted surveillance of songbirds. Retrospective testing of patients with unexplained neurological disease revealed human WNV infections in July and August 2020. Bird ringers are highly exposed to mosquito bites and possibly avian excrements during ringing activities. This study therefore investigates whether bird ringers are at higher risk of exposure to WNV and Usutu virus (USUV). Methods: Dutch bird ringers were asked to provide a single serum sample (May – September 2021) and to fill out a survey. Sera were screened by protein microarray for presence of specific IgG against WNV and USUV non-structural protein 1 (NS1), followed by focus reduction virus neutralization tests (FRNT). Healthcare workers (2009–2010), the national immunity cohort (2016–2017) and blood donors (2021) were used as control groups without this occupational exposure. Results: The majority of the 157 participating bird ringers was male (132/157, 84%) and the median age was 62 years. Thirty-seven participants (37/157, 23.6%) showed WNV and USUV IgG microarray signals above background, compared to 6.4% (6/94) in the community cohort and 2.1% (2/96) in blood donors (p < 0.01). Two seroreactive bird ringers were confirmed WNV or USUV positive by FRNT. The majority of seroreactive bird ringers travelled to EU countries with reported WNV human cases (30/37, 81%) (p = 0.07). No difference was observed between bird ringers with and without previous yellow fever vaccination. Discussion: The higher frequency of WNV and/or USUV IgG reactive bird ringers indicates increased flavivirus exposure compared to the general population, suggesting that individuals with high-exposure professions may be considered to complement existing surveillance systems. However, the complexity of serological interpretation in relation to location-specific exposure (including travel), and antibody cross-reactivity, rem

Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration and amount of postoperative wound drainage in patients with and without prosthetic joint infection (PJI) are currently absent. Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files. Results: Of the 1019 included patients, 16 patients (1.6g %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50g % to 3g %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95g % confidence interval (CI) 26.08 to 408.57, OR 80.71, 95g % CI 9.12 to 714.52, respectively). The positive predictive value (PPV) for PJI was 83g % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were strongly associated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI.

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.