Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust.

BACKGROUND: We 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. METHODS: HCWs 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. FINDINGS: As 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. INTERPRETATION: HCWs 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 CONTEXT: Evidence before this study: We 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 study: In 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 evidence: There 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.

Risk factors for SARS-CoV-2 seroprevalence following the first pandemic wave in UK healthcare workers in a large NHS Foundation Trust.

Background: We 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. Methods: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust were prospectively enrolled and sampled at two time points. We developed an in-house ELISA for testing participant serum for SARS-CoV-2 IgG and IgA reactivity against Spike and Nucleoprotein. Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. Results: Our in-house assay had a sensitivity of 99·47% and specificity of 99·56%. We found that 24·4% (n=311/1275) of HCWs were seropositive as of 12th June 2020. 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. Conclusions:  HCWs in acute medical units and those 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 severe COVID-19 cases.

Hepatitis B: report of prevalence and access to healthcare among Chinese residents in Sheffield UK.

UNLABELLED: Overall prevalence of hepatitis B (HBV) in the UK is low. However, among migrants from endemic areas, prevalence has been shown to be high. Furthermore, timely diagnosis and/or referral are required prevent serious health consequences through early institution of treatment. METHODS: We identified locations that would be familiar to Chinese members of the community with the objective of facilitating testing. Dried blood spot samples were collected from 229 Chinese subjects and tested for HBV and also for hepatitis C virus (HCV) infection--offering complete chronic viral hepatitis screening. RESULTS: HBsAg was positive in 20/229 (8.7%) participants, (10 F, 10 M). Five women and one man were aware of their condition, but only one man and none of the women were under specialist care. The average length of residence in the UK for positive patients was 15 years (range 2-40). Evidence of HBV past infection, HBcAb(+)/HBsAg(-), was seen in 28/229 participants (12.2%). HCV antibody testing produced negative results in all participants. The methodology of testing was well accepted, 139/144 (95%) responded to a feedback questionnaire declaring no discomfort and 100% finding the information session useful. CONCLUSION: This model of outreach testing is helpful for addressing health inequalities afflicting the UK's Chinese community.

Management of herpesvirus infections.

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.

Clinical features of viral meningitis in adults: significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections.

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.

BD ProbeTec ET assay for the diagnosis of gonorrhoea in a high-risk population: a protocol for replacing traditional microscopy and culture techniques.

OBJECTIVES: To evaluate the Neisseria gonorrhoeae Becton Dickinson (BD) ProbeTec strand displacement assay (SDA) on female endocervical swab and male first void urine against culture for Neisseria gonorrhoeae on female endocervical and urethral swab for the diagnosis of N gonorrhoeae infection in genitourinary medicine (GUM) attendees. To determine an algorithm for implementation of N gonorrhoeae infection screening by SDA in these patients taking account of the desirability of having a N gonorrhoeae isolate in people with N gonorrhoeae infection. METHODS: Initially, 1582 patients attending the GUM clinic were tested for N gonorrhoeae infection by SDA and routine microscopy, and culture. On the basis of the results, a protocol for diagnosis of N gonorrhoeae infection by SDA, with culture specimens only from patients with a listed risk factor for acquiring N gonorrhoeae infection, was devised and implemented. A post implementation audit was done to assess the effectiveness of this protocol for routine service use. RESULTS: There was good concurrence between the N gonorrhoeae SDA and culture results with a N gonorrhoeae infection prevalence rate of 3.4% by both methods. All men and 85% of women with N gonorrhoeae infection had an identifiable risk factor for acquiring infection. Overall, 38% men and 60% women attending the GUM clinic had this listed risk factor for acquiring N gonorrhoeae. Post implementation audit confirmed the initial findings. CONCLUSION: Nucleic acid amplification techniques like the SDA are sensitive and specific for diagnosis of N gonorrhoeae. We were able to list certain risk factors, which were predictive of those patients most likely to have N gonorrhoeae infection. To obtain timely sensitivity data, a culture specimen should also be submitted at the same time from patients deemed to have a listed risk factor for acquiring Neisseria gonorrhoeae infection.

Screening for genital Chlamydia trachomatis in teenagers attending a family planning youth clinic: a prevalence study using a strand displacement assay on urine samples.

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 'chlamydia' as a concept. PARTICIPANTS: Attendees at our youth clinic between October 2001 and March 2002. METHODS: 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. RESULT: 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. CONCLUSION: Initial results show a high prevalence of C. trachomatis. There is a low condom usage despite a reasonable level of awareness of 'chlamydia'. 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.