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BackgroundWe aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity.MethodsHCWs at Sheffield Teaching Hospitals NHS Foundation Trust (STH) were prospectively enrolled and sampled at two time points. SARS-CoV-2 antibodies were tested using an in-house assay for IgG and IgA reactivity against Spike and Nucleoprotein (sensitivity 99·47%, specificity 99·56%). Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model.FindingsAs of 12th June 2020, 24·4% (n=311/1275) HCWs were seropositive. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0–52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4–56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years.InterpretationHCWs in acute medical units working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more symptomatic individuals.Research in contextEvidence before this studyWe searched PubMed for studies published up to March 6th 2021, using the terms “COVID”, “SARS-CoV-2”, “seroprevalence”, and “healthcare workers”, and in addition for articles of antibody titres in different age groups against coronaviruses using “coronavirus”, “SARS-CoV-2, “antibody”, “antibody tires”, “COVID” and “age”. We included studies that used serology to estimate prevalence in healthcare workers. SARS-CoV-2 seroprevalence has been shown to be greater in healthcare workers working on acute medical units or within domestic services. Antibody levels against seasonal coronaviruses, SARS-CoV and SARS-CoV-2 were found to be higher in older adults, and patients who were hospitalised.Added value of this studyIn this healthcare worker seroprevalence modelling study at a large NHS foundation trust, we confirm that those working on acute medical units, COVID-19 “Red Zones” and within domestic services are most likely to be seropositive. Furthermore, we show that physiotherapists and occupational therapists have an increased risk of COVID-19 infection. We also confirm that antibody titres are greater in older individuals, even in the context of non-hospitalised cases. Importantly, we demonstrate that this can result in age-specific sensitivity in serological assays, where lower antibody titres in younger individuals results in lower assay sensitivity.Implications of all the available evidenceThere are distinct occupational roles and locations in hospitals where the risk of COVID-19 infection to healthcare workers is greatest, and this knowledge should be used to prioritise infection prevention control and other measures to protect healthcare workers. Serological assays may have different sensitivity profiles across different age groups, especially if assay validation was undertaken using samples from older and/or hospitalised patients, who tend to have higher antibody titres. Future seroprevalence studies should consider adjusting for age-specific assay sensitivities to estimate true seroprevalence rates.Author Contributions

Management of human herpesviruses remains a considerable clinical challenge, in part due to their ability to cause both lytic and latent disease. Infection with the Herpesviridae results in lifelong infection, which can reactivate at any time. Control of herpesviruses is by the innate and adaptive immune systems. Herpesviruses must evade the host innate immune system to establish infection. Once infected, the adaptive immune response, primarily CD8 + T-cells, is crucial in establishing and maintaining latency. Latent herpesviruses are characterised by the presence of viral DNA in infected cells and limited or no viral replication. These characteristics provide a challenge to clinicians and those developing antiviral agents. The scope of this review is two-fold. First, to provide an overview of all antivirals used against herpesviruses, including their mechanism of action, pharmacokinetics, side effects, resistance and clinical uses. And second, to address the management of each of the eight herpesviruses both in the immunocompetent and immunocompromised host, providing evidence for clinical management and therapeutic options, which is important to the clinician engaged in the management of these infections.

Herpes viruses are a common cause of viral skin infection ranging from chickenpox in children to shingles in older patients. Our Drug review discusses current management of herpes simplex and varicella-zoster infections, followed by a review of prescription data and sources of further information. Copyright © 2011 Wiley Interface Ltd

Background In this retrospective study, our objective was to review the epidemiology of viral meningitis and to compare clinical features associated with enterovirus, herpes simplex virus (HSV), and varicella zoster virus (VZV) infections in immunocompetent adults. Methods Data on cerebrospinal fluid (CSF) samples submitted to the Trust Virology Laboratory (Sheffield, UK) from April 2004 through April 2007 were reviewed. Notes on immunocompetent adults who were polymerase chain reaction (PCR) positive for enterovirus, HSV type 2, or VZV and who had presented to local clinical departments were scrutinized (4 patients were positive for HSV type 1 and did not meet the inclusion criteria). Results A total of 2045 samples were analyzed for viral pathogens during the 3-year period. Of the 109 PCR-positive samples, 38 (35%) were from immunocompetent adults, of whom 22 were infected with enterovirus, 8 were infected with HSV type 2, and 8 were infected with VZV. The median ages were 32 years (range, 16-39 years), 39 years (range, 22-53 years), and 47.5 years (range, 26-80 years), respectively. Rash occurred after the meningitis symptoms in 5 patients infected with VZV (median time from meningitis symptoms to rash, 6 days). Protein levels were significantly higher in CSF samples from patients infected with HSV type 2 (median, 1205 mg/L) and in samples from those infected with VZV (median, 974 mg/L) than in samples from those infected with enterovirus (median, 640 mg/L; P = .001 and P = .01, respectively). White blood cell counts were significantly higher in CSF samples from patients infected with HSV type 2 (median, 240 x 10(6) cells/L) than in samples from those infected with enterovirus (median, 51 x 10(6) cells/L; P = .01). Conclusions Enterovirus infection was the most common cause of viral meningitis in immunocompetent adults in this study. White blood cell counts and protein levels were significantly higher in CSF samples from patients infected with HSV type 2 than in samples from patients with enterovirus infection. Zoster rash often occurs after meningitis. PCR testing provides a rapid and specific etiological diagnosis.

Herpes viruses are a common cause of viral skin infection seen in general practice ranging from minor skin lesions to life-threatening illness. Our Drug Review considers the recommended management of herpes simplex and varicella-zoster infections, followed by a review of prescription data, sources of further information and details of the treatments available in the Datafile. Copyright © 2008 Wiley Interface Ltd

A simple absorption step using blocking fluid prepared from a selected campylobacter strain was introduced in parallel with routine legionella serology tests. Over 12 months, 2716 patients were tested for legionella antibodies by the Indirect Fluorescent Antibody Test of whom 58 (2.1%) had a positive titre (or = 16) in one or more sera. Campylobacter blocking fluid significantly reduced the legionella titres in 17 of these patients (29%) including four patients with diagnostic serology results (two of whom had pneumonia) and 13 patients with non-diagnostic titres. Absorption with campylobacter however had no effect on the legionella titres in 10 patients with positive serology, in whom legionnaires' disease had been confirmed by culture of Legionella pneumophila from sputum or detection of legionella urinary antigen by ELISA. These results indicate that the serological cross-reaction between legionella and campylobacter is encountered in routine legionella serology tests. The important implications for the diagnosis of legionnaires' disease are discussed.

Post-transplant lymphoproliferative disorder (PTLD) is the most common non-cutaneous malignancy in solid organ transplant recipients and is associated with significant mortality. In renal transplant recipients the incidence has been estimated to be between 0.2 and 2.3% [1,2]. Most PTLD is driven by Epstein–Barr virus (EBV) infection. The risk of lymphoma in transplant recipients is up to 40 times that of the general population [1]. A spectrum of severity is seen and this reflects the degree of additional oncogene activation and the associated transition from a polyclonal to a monoclonal disease [3]. Extra-nodal disease is common and as a consequence the presentation is often subtle and the diagnosis delayed. There are two principle risk factors for the development of PTLD: the intensity of immunosuppression and the EBV status of the donor and recipient. High dose immunosuppression with ciclosporin, tacrolimus, or anti-lymphocyte antibodies are all associated with increased risk [1]. EBV naive recipients receiving EBV positive grafts are at greatly increased risk [4,5]. Such patients acquire a primary infection in the context of high dose immunosuppression during the early posttransplant period when cytotoxic T-cell responses to EBV are undetectable [6]. This report describes a minimally immunosuppressed patient who developed PTLD very early in the posttransplant period. The clinical presentation was catastrophic and to the best of our knowledge has not been described before. Case

Background Chlamydia trachomatis is the most common bacterial sexually transmitted infection. Rates are highest in the 16-24-year-old age group. Untreated it can be a significant cause of morbidity. At least 50% of men and 70% of women with C. trachomatis are asymptomatic. Study aims The aims of the study were: To determine the prevalence of C. trachomatis . To determine the success of our referral policy to genitourinary medicine (GU clinic). To determine the characteristics of the population with C. trachomatis . To estimate the level of recognition of 9chlamydia9 as a concept. Participants Attendees at our youth clinic between October 2001 and March 2002. Method Ethical approval was obtained for this ongoing study. All attendees who were sexually active were asked to participate. An information leaflet was provided. Those who agreed to participate answered a questionnaire, which included a number of lifestyle questions, and provided a urine sample for C. trachomatis testing using a strand displacement assay. Positive results were forwarded to the GU clinic, which provided antibiotic therapy, contact tracing and follow-up. Results The ongoing study has yielded 616 results with 73 positive (11.9%). To date 66 individuals (90%) have attended the GU clinic and 41 (50%) of the possible 82 partners have responded to contact tracing. Conclusions Initial results show a high prevalence of C. trachomatis . There is a low condom usage despite a reasonable level of awareness of 9chlamydia9. Contact tracing has not been as successful as anticipated. When the study is complete, various service provision questions will need to be answered, such as the ability to treat the disease in a dedicated youth clinic, making urine testing for C. trachomatis by strand displacement assay (SDA) more widespread, the problem of follow-up, screening for associated sexually transmitted infections (STIs) and contact tracing in a relatively less mobile and less empowered population.

Objective To appraise the inter-agency protocol used in sudden unexpected death in infancy (SUDI) cases in South Yorkshire, UK. Design A retrospective audit of 121 postmortems carried out over a 3-year period was completed to assess adherence to local guidelines introduced in 2005 specifying the required microbiological specimen set to be collected at postmortem in cases of SUDI. Data on organisms isolated was also collated and assessed for significance. Setting Sheffield Children9s Hospital Histopathology Department is the South Yorkshire referral centre for SUDI. Post-mortem samples were processed by Sheffield Teaching Hospital9s microbiology and virology departments. Patients All postmortems of SUDI in children less than 2 years of age performed between January 2004 and December 2007. Results 116/121 cases had samples sent for microbiological and/or virological investigation: 90% of cases had a blood culture and 68% had a cerebrospinal fluid sample taken. Of the 116 cases, 49% had a potentially pathogenic organism isolated, 73% had post-mortem flora and 10% had no organisms isolated (32% had both post-mortem flora and a potential pathogen). 27% of cases were found to have middle ear exudate requiring sampling, from 48% of which a potentially pathogenic organism was isolated. Conclusions Our finding of a potential pathogen in 57/116 (49%) of our cases, although not necessarily the cause of death, confirms the relevance of performing multisite and virology investigations in all cases of SUDI. Standardised protocols with agreed definitions are necessary for a consistent approach.