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Invasive fungal disease (IFD) is a recognised and potentially life-threatening complication of chronic graft-versus-host disease (cGVHD) and its treatment. Invasive aspergillosis (IA), most often due to the species Aspergillus fumigatus, is the leading IFD in this setting. IA can occur during the early weeks following allogeneic haematopoietic stem cell transplantation (HSCT) coinciding with profound neutropenia, but increasingly, cases of IA occur after engraftment, coinciding with the occurrence of cGVHD. Immunomodulatory treatments of cGVHD can impair innate immune responses to inhaled Aspergillus conidia, increasing the risk of developing IA. Here, in a pilot study, we present an analysis of the phenotypic characteristics (phagocytic efficiency, fungal killing, and cytokine release) of circulating monocytes derived from patients with cGVHD compared to healthy volunteers. We found that there was no statistically significant difference in their ability to phagocytose A. fumigatus conidia, and while there was a trend in their reduced ability to kill conidia, this was not significant when compared to the ability of volunteers’ monocytes to do so. Although we could not demonstrate in this small cohort of patients with cGVHD that monocytes may be a factor in the increased susceptibility to IA, further investigation of larger numbers of study subjects is warranted so that in vitro biomarkers may be developed for immune responses to Aspergillus in patients with cGVHD.

The prevention of SARS-CoV-2 acquisition and transmission among healthcare workers is an ongoing challenge. Vaccination has been introduced to mitigate these risks. Vaccine uptake varies among healthcare workers in the absence of vaccine mandates. We investigated engagement with SARS-CoV-2 vaccination among healthcare workers and identified characteristics associated with lower vaccine uptake. This multi-site cross-sectional study recruited n = 1260 healthcare workers in both clinical and non-clinical roles over a three-month period from November 2022. Participants reported their engagement with the primary SARS-CoV-2 vaccination programme and subsequent booster programmes, as well as providing demographic, occupational and personal medical history information. Multivariable linear regression identified characteristics associated with vaccine uptake. Engagement with vaccination programmes was high, with 88% of participants receiving at least one booster dose after primary vaccination course. Younger age and female sex were associated with reduced vaccine uptake. Healthcare workers in non-clinical roles also had reduced vaccine uptake. These findings should inform vaccination strategies across healthcare settings and target populations with reduced vaccine uptake directly, in particular young, female, and non-clinical healthcare workers, both for SARS-CoV-2 and other healthcare-associated vaccine-preventable infections.

The PRECISE Study, a multi-phase cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers (HCW) investigated: (1) risk factors for SARS-CoV-2 seropositivity, (2) the durability of antibody responses in a highly vaccinated HCW cohort, and (3) the neutralisation capacity of detected antibodies, prior to booster COVID-19 vaccination. Serology samples were collected across two hospital sites in November 2021 and analysed using the Roche Elecsys Anti-SARS-CoV-2/Elecsys-S Anti-SARS-CoV-2 assays to detect anti-nucleocapsid (N) and anti-spike (S) antibodies respectively. Paired serology results from prior study phases were used to analyse changes in individual HCW serostatus over time. Risk-factors for SARS-CoV-2 infection were assessed for demographic and work-related factors. Antibody neutralisation capacity was assessed in a subset of samples an ACE2 binding enzyme-linked immunosorbent assay. 2,344 HCW samples were analysed. Median age was 43 years (IQR 33-50) with 80.5% ( = 1,886) female participants. Irish (78.9%, = 1,850) and Asian (12.3%, = 288) were the most commonly reported ethnicities. Nursing/midwifery (39.3%, = 922) was the most common job role. 97.7% of participants were fully vaccinated, with Pfizer (81.1%, = 1,902) and AstraZeneca (16.1%, = 377) the most common vaccines received. Seroprevalence for anti-SARS-CoV-2 antibodies indicating prior infection was 23.4%, of these 33.6% represented previously undiagnosed infections. All vaccinated participants demonstrated positive anti-S antibodies and in those with paired serology, no individual demonstrated loss of previously positive anti-S status below assay threshold for positivity. Interval loss of anti-N antibody positivity was demonstrated in 8.8% of previously positive participants with paired results. Risk factors for SARS-CoV-2 seropositivity suggestive of previous infection included age 18-29 years (aRR 1.50, 95% CI 1.19-1.90, < 0.001), India as country of birth (aRR 1.35, 95% CI 1.01-1.73, = 0.036), lower education level (aRR 1.35, 95% CI 1.11-1.66, = 0.004) and HCA job role (aRR 2.12, 95% CI 1.51-2.95, < 0.001). Antibody neutralisation varied significantly by anti-SARS-CoV-2 antibody status, with highest levels noted in those anti-N positive, in particular those with vaccination plus previous SARS-CoV-2 infection. All vaccinated HCWs maintained anti-S positivity prior to COVID-19 booster vaccination, however anti-N positivity was more dynamic over time. Antibody neutralisation capacity was highest in participants with COVID-19 vaccination plus prior SARS-CoV-2 infection.

The genetics of the mating-type (MAT) locus have been studied extensively in Saccharomyces cerevisiae, but relatively little is known about how this complex system evolved. We compared the organization of MAT and mating-type-like (MTL) loci in nine species spanning the hemiascomycete phylogenetic tree. We inferred that the system evolved in a two-step process in which silent HMR/HML cassettes appeared, followed by acquisition of the Ho endonuclease from a mobile genetic element. Ho-mediated switching between an active MAT locus and silent cassettes exists only in the Saccharomyces sensu stricto group and their closest relatives: Candida glabrata, Kluyveromyces delphensis, and Saccharomyces castellii. We identified C. glabrata MTL1 as the ortholog of the MAT locus of K. delphensis and show that switching between C. glabrata MTL1a and MTL1{alpha} genotypes occurs in vivo. The more distantly related species Kluyveromyces lactis has silent cassettes but switches mating type without the aid of Ho endonuclease. Very distantly related species such as Candida albicans and Yarrowia lipolytica do not have silent cassettes. In Pichia angusta, a homothallic species, we found MAT{alpha}2, MAT{alpha}1, and MATa1 genes adjacent to each other on the same chromosome. Although some continuity in the chromosomal location of the MAT locus can be traced throughout hemiascomycete evolution and even to Neurospora, the gene content of the locus has changed with the loss of an HMG domain gene (MATa2) from the MATa idiomorph shortly after HO was recruited.

BackgroundReports of monozygotic HD twins are rare (Panas et al, 2008) and phenotypic concordance reported as the rule (Sudarsky et al, 1973). Reports are of twins with the same number of trinucleotide repeats, with different clinical behavioral difficulties but not significant motor differences (Gómed-Esteban et al, 2007). Such phenotypic discordance was reported as very rare (Friedman et al, 2005) and thus be used to explore environmental factors (Ketelaar, Hofstra and Hayden, 2012).Case HistoryTwo female monozygotic twins with HD were born 6 weeks premature and raised in the same environment. Voluntary predictive testing for HD was done when both (Heimler and Zanko, 1995) were aged 21 years. We will report on motor, neuropsychological and psychiatric manifestations along with MRI findings. Twin 2 required admission in 2015 while Twin 1 required admission in 2020.Twin 1 (first born): Referred to Liaison Psychiatry with Eating disorder and low mood aged 23, followed by two suicide attempts and aggressive impulsive behavior. Neurocognitive difficulties included memory impairment, dysarthria and balance difficulties, poor levels of motivation and self-care. OT assessment found a sensory level of activities and exploratory activities were required. MRI: Generalised and bifrontal cerebral atrophy appeared was unusual given the patient‘s age. There was no acute area of infarction on diffusion weighted imaging. Generalised cerebral and bifrontal cerebral atrophy noted.Twin 2: Diagnosed with a heart murmur aged 4 years and surgery aged 10 years. Presented at 18 years with low mood and history of OCD symptoms. Multiple episodes of self-harm and becoming more aggressive and violent. Irritability, impulsivity, and aggressive behavior has continued with word funding difficulties. OT assessment recommended exploratory level of activities. MRI: There was parenchymal atrophy reported, most marked in the frontal and temporal lobes with prominence of sulci and ventricles. Signal return from grey-white matter was normal.ConclusionA detailed comparison of motor, cognitive, and behavioural profile is currently in progress.

Introduction: Repeated COVID-19 booster vaccination was recommended in healthcare workers (HCWs) to maintain protection. We measured the relative vaccine effectiveness (rVE) of the second booster dose of COVID-19 vaccine compared to the first booster, against laboratory-confirmed SARS-CoV-2 infection in HCWs. Methods: In a prospective cohort study among HCWs from 12 European hospitals, we collected nasopharyngeal or saliva samples at enrolment and during weekly/fortnightly follow-up between October 2022 and May 2023. We estimated rVE of the second versus first COVID-19 vaccine booster dose against SARS-CoV-2 infection, overall, by time since second booster and restricted to the bivalent vaccines only. Using Cox regression, we calculated the rVE as (1-hazard ratio)*100, adjusting for hospital, age, sex, prior SARS-CoV-2 infection and at least one underlying condition. Results: Among the 979 included HCWs eligible for a second booster vaccination, 392 (40 %) received it and 192 (20 %) presented an infection during the study period. The rVE of the second versus first booster dose was −5 % (95 %CI: −46; 25) overall, 3 % (−46; 36) in the 7–89 days after receiving the second booster dose. The rVE was 11 % (−43; 45) when restricted to the use of bivalent vaccines only. Conclusion: The bivalent COVID-19 could have reduced the risk of SARS-CoV-2 infection among HCWs by 11 %. However, we note the limitation of imprecise rVE estimates due to the proportion of monovalent vaccine used in the study, the small sample size and the study being conducted during the predominant circulation of XBB.1.5 sub-lineage. COVID-19 vaccine effectiveness studies in HCWs can provide important evidence to inform the optimal timing and the use of updated COVID-19 vaccines.

Background Healthcare workers (HCWs) face high occupational exposure to SARS-CoV-2 and are a priority group for vaccination. Both natural infection and vaccination—individually or combined as hybrid immunity—confer protection against SARS-CoV-2 infection. This study aimed to evaluate the protection conferred by hybrid, infection-induced, and booster vaccine-induced immunity against laboratory-confirmed SARS-CoV-2 infections in HCWs during the circulation of three pandemic and one post-pandemic Omicron sublineages. Methods We conducted a prospective cohort study of HCWs from 18 hospitals across nine European countries. Participants underwent RT-PCR testing at enrolment and during weekly or fortnightly follow-ups. The study period was divided based on dominant Omicron sublineage circulation: BA.1/2 (Dec 16, 2021–Jun 1, 2022), BA.4/5/BQ.1 (Jun 2–Dec 31, 2022), BA.2/XBB (Jan 1–May 2, 2023), and post-pandemic XBB.1.5/BA.2.86 (Sep 1, 2023–May 21, 2024). Participants were classified into four groups: hybrid (prior infection and recent booster vaccination 7–179 days), infection-induced (prior infection, no recent vaccination), vaccine-induced immunity (recent booster vaccination, no prior infection), and a reference group (no prior infection, no recent booster vaccination). Adjusted hazard ratios (aHRs) for infection were estimated using Cox regression, adjusting for hospital, age, sex, chronic condition, and patient-facing role. Results A total of 3 133 HCWs were included: 2572 (82%) female, 1734 (55%) aged 40–59, and 563 (29%) with ≥ 1 chronic condition. Hybrid immunity showed significant protection during BA.1/2 (aHR = 0.37, 95%CI 0.21–0.63), BA.4/5/BQ.1 (aHR = 0.36, 95%CI 0.22–0.58), and XBB.1.5/BA.2.86 (aHR = 0.53, 95%CI 0.37–0.74) periods. Infection-induced immunity was protective across all periods, most during BA.1/2 (aHR = 0.26, 95%CI 0.12–0.53), and least during BA.2/XBB (aHR = 0.66, 95%CI 0.36–1.22). Vaccine-induced immunity alone offered limited protection during BA.1/2 (aHR = 0.72, 95%CI 0.49–1.06) and BA.4/5/BQ.1 (aHR = 0.77, 95%CI 0.50–1.19), with wide confidence intervals suggesting low statistical significance. Conclusions Hybrid and infection-induced immunity groups were more protected against infection caused by earlier Omicron sub-lineages and more protected than vaccination alone, which had no significant protective effect. These findings highlight the need for adaptive public health strategies, including timely vaccine updates and understanding of prior SARS-CoV-2 infection to inform COVID-19 vaccination policies for HCWs in the post-pandemic era.

Acute coronary syndrome (ACS) in pregnancy has traditionally been considered to be a rare event, but the combination of normal physiological changes of pregnancy and more prevalent cardiovascular risk factors are increasing its incidence in this population. The present report describes a 39 year-old woman that is seven weeks pregnant presenting with a non ST elevation myocardial infarction. The incidence, risk factors, pathophysiology and management of ACS in pregnancy are discussed.

Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May–6 September 2021), Delta (7 September–14 December 2021), and Omicron (15 December 2021–2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: −25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7–90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs.