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Purpose: Infective endocarditis (IE) can be complicated by vertebral osteomyelitis (VO). This study investigates risk factors associated with VO in patients with infective endocarditis, and 6-month mortality and relapse rates in patients with IE and concomitant VO., Methods: We performed a observational study in two hospitals between September 2016 and October 2022. Patients with possible or definite IE according European Society of Cardiology (2015) modified criteria were retrieved from the local endocarditis team registries. The VO diagnosis was based on radiological signs, irrespective of clinical symptoms. Multivariable logistic regression analysis was performed to identify risk factors for vertebral osteomyelitis., Results: We included 633 consecutive patients with IE. A total of 229 (36.2%) patients had prosthetic valves and 127 (20.1%) had cardiac implantable electronic devices. The most frequent causative micro-organism was Streptococcus species (217, 34.3%), followed by Staphylococcus aureus (167, 26.4%). VO was diagnosed in 73 patients (11.5%, 95% CI 9.0%-14.0%). Enterococcus spp.(OR 2.48, 95% CI 1.31-4.52) and age (OR 1.04 per year, 95% CI 1.02-1.06) were independently associated with concomitant VO. The 6-month mortality risk did not differ between patients with (16/73, 21.9%) or without (110/560, 19.6%) VO (HR 1.13, 95% CI 0.67-1.91). Relapse rate was higher in patients with VO but the difference was not statistically significant (16.1 vs. 7.5%, OR 3.62, 95% CI 0.94-13.34)., Conclusions: Twelve percent of patients with IE also had VO. Among older patients and patients with IE caused by enterococci, there should be a higher index of suspicion for vertebral infection., Competing Interests: Declarations. Ethical approval: This study is an observational study. The study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Amsterdam UMC (Date 12-10-2023./No METC2023.0424). In the Noordwest Hospital the Research Ethics Committee has confirmed that no ethical approval is required. Competing interests: Dr. van Werkhoven has received grants from DaVolterra, bioMerieux and LimmaTech which were paid to the institution. Dr. van Werkhoven has received consulting fees from Merck/MSD and Sanofi-Pasteur in regards to pneumococcal vaccines. These payments were made to the institution., (© 2025. The Author(s).)

Background: Many trials, reviews, and meta-analyses have been performed on the comparison of short versus long antibiotic treatment in respiratory tract infections, generally supporting shorter treatment. The aim of this umbrella review is to assess the soundness of the current evidence base for optimal antibiotic treatment duration., Methods: A search in Ovid MEDLINE, Embase, and Clarivate Analytics Web of Science Core Collection was performed on May 1, 2024, without date and language restrictions. Systematic reviews addressing treatment durations in community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), hospital-acquired pneumonia (HAP), acute sinusitis, and streptococcal pharyngitis, tonsillitis, or pharyngotonsillitis were included. Studies from inpatient and outpatient settings were included; reviews in paediatric populations were excluded. Outcomes of interest were clinical and bacteriological cure, microbiological eradication, mortality, relapse rate, and adverse events. The quality of the reviews was assessed using the AMSTAR 2 tool, risk of bias of all included randomised controlled trials (RCTs) using the Cochrane risk-of-bias tool (version 1), and overall quality of evidence according to GRADE., Findings: We identified 30 systematic reviews meeting the criteria; they were generally of a low to critically low quality. 21 reviews conducted a meta-analysis. For CAP outside the intensive care unit (ICU; 14 reviews, of which eight did a meta-analysis) and AECOPD (eight reviews, of which five did a meta-analysis), there was sufficient evidence supporting a treatment duration of 5 days; evidence for shorter durations is scarce. Evidence on non-ventilator-associated HAP is absent, despite identifying three reviews (of which one did a meta-analysis), since no trials were conducted exclusively in this population. For sinusitis the evidence appears to support a shorter regimen, but more evidence is needed in the population who actually require antibiotic treatment. For pharyngotonsillitis (eight reviews, of which six did a meta-analysis), sufficient evidence exists to support short-course cephalosporin but not short-course penicillin when dosed three times a day., Interpretation: The available evidence for non-ICU CAP and AECOPD supports a short-course treatment duration of 5 days in patients who have clinically improved. Efforts of the scientific community should be directed at implementing this evidence in daily practice. High-quality RCTs are needed to underpin even shorter treatment durations for CAP and AECOPD, to establish the optimal treatment duration of HAP and acute sinusitis, and to evaluate shorter duration using an optimal penicillin dosing schedule in patients with pharyngotonsillitis., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: To estimate risk factors for acute kidney injury (AKI) and the effect of AKI on mortality in Staphylococcus aureus bacteraemia, while taking into account recurrent AKI episodes, competing risks, time-varying variables, and time-varying effects., Methods: We performed an unplanned analysis using data from a multicentre cohort study of patients with Staphylococcus aureus bacteraemia (SAB). The primary outcome was cumulative incidence of AKI, according to Kidney Disease Improving Global Outcomes definitions., Results: We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (hazard ratio (HR) 1.013, 95% CI 1.001-1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01-1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28-2.42), septic shock (HR 3.28, 95% CI 2.31-4.66), persistent bacteraemia (HR 1.53, 95% CI 1.08-2.17), and vancomycin therapy (HR 1.80, 95% CI 1.05-3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin, and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91-6.23)., Discussion: The incidence of AKI in SAB is high and a substantial proportion of patients develop recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. The clinical outcome of patients with SAB complicated by AKI is worse than previously estimated., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite being the leading cause of mortality from bloodstream infections worldwide, little is known about regional variation in treatment practices for Staphylococcus aureus bacteremia (SAB). The aim of this study was to identify global variation in management, diagnostics, and definitions of SAB., Methods: During a 20-day period in 2022, physicians throughout the world were surveyed on SAB treatment practices. The survey was distributed through listservs, e-mails, and social media., Results: In total, 2031 physicians from 71 different countries on 6 continents (North America [701, 35%], Europe [573, 28%], Asia [409, 20%], Oceania [182, 9%], South America [124, 6%], and Africa [42, 2%]) completed the survey. Management-based responses differed significantly by continent for preferred treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia, use of adjunctive rifampin for prosthetic material infection, and use of oral antibiotics (P < .01 for all comparisons). The 18F-FDG PET/CT scans were most commonly used in Europe (94%) and least frequently used in Africa (13%) and North America (51%; P < .01). Although most respondents defined persistent SAB as 3-4 days of positive blood cultures, responses ranged from 2 days in 31% of European respondents to 7 days in 38% of Asian respondents (P < .01)., Conclusions: Large practice variations for SAB exist throughout the world, reflecting the paucity of high-quality data and the absence of an international standard of care for the management of SAB., Competing Interests: Potential conflicts of interest. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio, Akagera, Aridis, Roche; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio, honoraria from Infectious Diseases of America for his service as Associate Editor of Clinical Infectious Diseases, and a patent sepsis diagnostics pending. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Hospital health care workers (HCW) are at increased risk of contracting SARS-CoV-2. We investigated whether certain behavioral and physical features, e.g. nose picking and wearing glasses, are associated with infection risk., Aim: To assess the association between nose picking and related behavioral or physical features (nail biting, wearing glasses, and having a beard) and the incidence of SARS-CoV-2-infection., Methods: In a cohort study among 404 HCW in two university medical centers in the Netherlands, SARS-CoV-2-specific antibodies were prospectively measured during the first phase of the pandemic. For this study HCW received an additional retrospective survey regarding behavioral (e.g. nose picking) and physical features., Results: In total 219 HCW completed the survey (response rate 52%), and 34/219 (15.5%) became SARS-CoV-2 seropositive during follow-up from March 2020 till October 2020. The majority of HCW (185/219, 84.5%) reported picking their nose at least incidentally, with frequency varying between monthly, weekly and daily. SARS-CoV-2 incidence was higher in nose picking HCW compared to participants who refrained from nose picking (32/185: 17.3% vs. 2/34: 5.9%, OR 3.80, 95% CI 1.05 to 24.52), adjusted for exposure to COVID-19. No association was observed between nail biting, wearing glasses, or having a beard, and the incidence of SARS-CoV-2 infection., Conclusion: Nose picking among HCW is associated with an increased risk of contracting a SARS-CoV-2 infection. We therefore recommend health care facilities to create more awareness, e.g. by educational sessions or implementing recommendations against nose picking in infection prevention guidelines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lavell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response and mortality in patients with COVID-19., Methods: We determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort., Results: 464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumour necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1 and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively)., Conclusions: Ageing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19., Competing Interests: Conflicts of interest: The authors declare no potential conflicts of interest., (Copyright ©The authors 2023.)

Objectives: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia., Methods: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses., Results: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]., Conclusions: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB., Methods and Analysis: The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study., Ethics and Dissemination: This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal., Trial Registration Number: NL8347 (the Netherlands Trial Register)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Potential conflicts of interest. K. C. E. S. has received funding to study the optimal treatment duration for Staphylococcus aureus bacteremia from The Netherlands Organization for Health Research and Development (grant 848018006). The remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Antibodies against seasonal human coronaviruses (HCoVs) are known to cross-react with SARS-CoV-2, but data on cross-protective effects of prior HCoV infections are conflicting. In a prospective cohort of healthcare workers (HCWs), we studied the association between seasonal HCoV (OC43, HKU1, 229E and NL63) nucleocapsid protein IgG and SARS-CoV-2 infection during the first pandemic wave in the Netherlands (March 2020 - June 2020), by 4-weekly serum sampling. HCW with HCoV-OC43 antibody levels in the highest quartile, were less likely to become SARS-CoV-2 seropositive when compared with those with lower levels (6/32, 18.8%, versus 42/97, 43.3%, respectively: p = 0.019; HR 0.37, 95% CI 0.16-0.88). We found no significant association with HCoV-OC43 spike protein IgG, or with antibodies against other HCoVs. Our results indicate that the high levels of HCoV-OC43-nucleocapsid antibodies, as an indicator of a recent infection, are associated with protection against SARS-CoV-2 infection; this supports and informs efforts to develop pancoronavirus vaccines., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Objectives: To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB)., Methods: A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021., Results: A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks., Conclusions: This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Infants may develop severe viral respiratory tract infections because their immune system is still developing in the first months after birth. Human milk provides passive humoral immunity during the first months of life. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to the preventative measures resulting in reduced maternal exposure. Therefore, we hypothesized that this might result in lower antibody levels in human milk during the pandemic and, subsequently, decreased protection of infants against viral respiratory tract infections. We assessed antibody levels against respiratory syncytial virus (RSV), Influenza virus, and several seasonal coronaviruses in different periods of the COVID-19 pandemic in serum and human milk using a Luminex assay. IgG levels against RSV, Influenza, HCoV-OC43, HCoV-HKU1, and HCoV-NL63 in human milk were reduced with a factor of 1.7 ( P < 0.001), 2.2 ( P < 0.01), 2.6 ( P < 0.05), 1.4 ( P < 0.01), and 2.1 ( P < 0.001), respectively, since the introduction of the COVID-19 restrictions. Furthermore, we observed that human milk of mothers that experienced COVID-19 contained increased levels of IgG and IgA binding to other respiratory viruses. Passive immunity via human milk against common respiratory viruses was reduced during the COVID-19 pandemic, which may have consequences for the protection of breastfed infants against respiratory infections. IMPORTANCE Passive immunity derived from antibodies in human milk is important for protecting young infants against invading viruses. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to preventative measures. In this study, we observed a decrease in human milk antibody levels against common respiratory viruses several months into the COVID-19 pandemic. This waning of antibody levels might partially explain the previously observed surge of hospitalizations of infants, mostly due to RSV, when preventative hygiene measures were lifted. Knowledge of the association between preventative measures, antibody levels in human milk and subsequent passive immunity in infants might help predict infant hospital admissions and thereby enables anticipation to prevent capacity issues. Additionally, it is important in the consideration for strategies for future lockdowns to best prevent possible consequences for vulnerable infants.

Objectives: [18F]FDG-PET/CT is used for diagnosing metastatic infections in Staphylococcus aureus bacteremia (SAB) and guidance of antibiotic treatment. The impact of [18F]FDG-PET/CT on outcomes remains to be determined. The aim of this systematic review was to summarize the effects of [18F]FDG-PET/CT on all-cause mortality and new diagnostic findingsin SAB., Methods: We systematically searched PubMed, EMBASE.com, Web of Science, and Wiley's Cochrane library from inception to 29 January 2021. Eligible studies were randomized controlled trials, clinically controlled trials, prospective and retrospective cohort studies, and case-control studies investigating the effects of [18F]FDG-PET/CT in hospitalized adult patients with SAB. We excluded studies lacking a control group without [18F]FDG-PET/CT. Risk of bias was assessed using the ROBINS-I tool and certainty of evidence using the GRADE approach by two independent reviewers., Results: We identified 1956 studies, of which five were included in our qualitative synthesis, including a total of 880 SAB patients. All studies were non-randomized and at moderate or serious risk of bias. Four studies, including a total of 804 patients, reported lower mortality in SAB patients that underwent [18F]FDG-PET/CT. One study including 102 patients reported more detected metastatic foci in the participants in whom [18F]FDG-PET/CT was performed., Discussion: We found low certainty of evidence that [18F]FDG-PET/CT reduces mortality in patients with SAB. This effect is possibly explained by a higher frequency of findings guiding optimal antibiotic treatment and source control interventions., (© 2022. The Author(s).)

Background: We defined the frequency of respiratory community-acquired bacterial co-infection in patients with COVID-19, i.e. patients with a positive SARS-CoV-2 PCR or a COVID-19 Reporting and Data System (CO-RADS) score ≥ 4, based on a complete clinical assessment, including prior antibiotic use, clinical characteristics, inflammatory markers, chest computed tomography (CT) results and microbiological test results., Methods: Our retrospective study was conducted within a cohort of prospectively included patients admitted for COVID-19 in our tertiary medical centres between 1-3-2020 and 1-6-2020. A multidisciplinary study team developed a diagnostic protocol to retrospectively categorize patients as unlikely, possible or probable bacterial co-infection based on clinical, radiological and microbiological parameters in the first 72 h of admission. Within the three categories, we summarized patient characteristics and antibiotic consumption., Results: Among 281 included COVID-19 patients, bacterial co-infection was classified as unlikely in 233 patients (82.9%), possible in 35 patients (12.4%) and probable in 3 patients (1.1%). Ten patients (3.6%) could not be classified due to inconclusive data. Within 72 h of hospital admission, 81% of the total study population and 78% of patients classified as unlikely bacterial co-infection received antibiotics., Conclusions: COVID-19 patients are unlikely to have a respiratory community-acquired bacterial co-infection. This study underpins recommendations for restrictive use of antibacterial drugs in patients with COVID-19., (© 2021. The Author(s).)

Importance: It is unclear when, where, and by whom health care workers (HCWs) working in hospitals are infected with SARS-CoV-2., Objective: To determine how often and in what manner nosocomial SARS-CoV-2 infection occurs in HCW groups with varying exposure to patients with COVID-19., Design, Setting, and Participants: This cohort study comprised 4 weekly measurements of SARS-CoV-2-specific antibodies and collection of questionnaires from March 23 to June 25, 2020, combined with phylogenetic and epidemiologic transmission analyses at 2 university hospitals in the Netherlands. Included individuals were HCWs working in patient care for those with COVID-19, HCWs working in patient care for those without COVID-19, and HCWs not working in patient care. Data were analyzed from August through December 2020., Exposures: Varying work-related exposure to patients infected with SARS-CoV-2., Main Outcomes and Measures: The cumulative incidence of and time to SARS-CoV-2 infection, defined as the presence of SARS-CoV-2-specific antibodies in blood samples, were measured., Results: Among 801 HCWs, there were 439 HCWs working in patient care for those with COVID-19, 164 HCWs working in patient care for those without COVID-19, and 198 HCWs not working in patient care. There were 580 (72.4%) women, and the median (interquartile range) age was 36 (29-50) years. The incidence of SARS-CoV-2 was increased among HCWs working in patient care for those with COVID-19 (54 HCWs [13.2%; 95% CI, 9.9%-16.4%]) compared with HCWs working in patient care for those without COVID-19 (11 HCWs [6.7%; 95% CI, 2.8%-10.5%]; hazard ratio [HR], 2.25; 95% CI, 1.17-4.30) and HCWs not working in patient care (7 HCWs [3.6%; 95% CI, 0.9%-6.1%]; HR, 3.92; 95% CI, 1.79-8.62). Among HCWs caring for patients with COVID-19, SARS-CoV-2 cumulative incidence was increased among HCWs working on COVID-19 wards (32 of 134 HCWs [25.7%; 95% CI, 17.6%-33.1%]) compared with HCWs working on intensive care units (13 of 186 HCWs [7.1%; 95% CI, 3.3%-10.7%]; HR, 3.64; 95% CI, 1.91-6.94), and HCWs working in emergency departments (7 of 102 HCWs [8.0%; 95% CI, 2.5%-13.1%]; HR, 3.29; 95% CI, 1.52-7.14). Epidemiologic data combined with phylogenetic analyses on COVID-19 wards identified 3 potential HCW-to-HCW transmission clusters. No patient-to-HCW transmission clusters could be identified in transmission analyses., Conclusions and Relevance: This study found that HCWs working on COVID-19 wards were at increased risk for nosocomial SARS-CoV-2 infection with an important role for HCW-to-HCW transmission. These findings suggest that infection among HCWs deserves more consideration in infection prevention practice.

Background: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to what extent this association is influenced by total body fat. Therefore, we aimed to examine the association between serum leptin and blood coagulation while taking total body fat into account in a population-based cohort study., Methods: We performed a cross-sectional analysis with baseline measurements of 5797 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort of middle-aged men and women. We examined associations between serum leptin concentration and coagulation factor concentrations and parameters of platelet activation in linear regression analyses. All analyses were adjusted for multiple covariates, including total body fat., Results: In multivariable adjusted analyses a 1 μg/L higher serum leptin concentration was associated with a 0.22 IU/dL (95% CI: 0.11, 0.32) higher FVIII concentration and a 0.20 IU/dL (95% CI: 0.14, 0.27) higher FIX concentration (3.5 IU/dL FVIII and 3.2 IU/dL FIX per SD leptin). Serum leptin concentration was not associated with FXI, fibrinogen, platelet count, mean platelet volume and platelet distribution width in multivariable adjusted analyses., Discussion: This study showed that serum leptin concentration was associated with higher concentrations of FVIII and FIX in an observational study, which could be clinically relevant., Competing Interests: Declaration of competing interest The authors state that they have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The heterozygous DQ2/8 (DQA1*05:01-DQB1*02:01/DQA1*03:01-DQB1*03:02) genotype confers the highest risk in type 1 diabetes (T1D), whereas the DQ6/8 (DQA1*02:01-DQB1*06:02/DQA1*03:01-DQB1*03:02) genotype is protective. The mechanism of dominant protection by DQ6 (DQB1*06:02) is unknown. We tested the hypothesis that DQ6 interferes with peptide binding to DQ8 by competition for islet epitope ("epitope stealing") by analysis of the islet ligandome presented by HLA-DQ6/8 and -DQ8/8 on dendritic cells pulsed with islet autoantigens preproinsulin (PPI), GAD65, and IA-2, followed by competition assays using a newly established "epitope-stealing" HLA/peptide-binding assay. HLA-DQ ligandome analysis revealed a distinct DQ6 peptide-binding motif compared with the susceptible DQ2/8 molecules. PPI and IA-2 peptides were identified from DQ6, of DQ6/8 heterozygous dendritic cells, but no DQ8 islet peptides were retrieved. Insulin B6-23, a highly immunogenic CD4 T-cell epitope in patients with T1D, bound to both DQ6 and DQ8. Yet, binding of InsB6-23 to DQ8 was prevented by DQ6. We obtained first functional evidence of a mechanism of dominant protection from disease, in which HLA molecules associated with protection bind islet epitopes in a different, competing, HLA-binding register, leading to "epitope stealing" and conceivably diverting the immune response from islet epitopes presented by disease-susceptible HLA molecules in the absence of protective HLA., (© 2019 by the American Diabetes Association.)