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Background: Healthcare workers were at a high risk of infection early in the SARS-CoV-2 pandemic. It is uncertain to what extent occupational, household and community factors contributed, and how this changed over time. We aimed to characterise the risk factors for infection over four successive waves of the pandemic in a large, UK healthcare worker cohort (SIREN)., Methods: Participants underwent fortnightly SARS-CoV-2 PCR testing and symptom/exposure questionnaire. Attack rates and adjusted OR of infection were calculated according to participant characteristics and exposures for each wave between 1st October 2020 and 30th August 2022., Findings: 19,427 participants were included in the second wave, 20,260 in the third, 11,937 in the fourth, and 6503 in the fifth. The attack rates of infection were 9.1% (alpha), 6.6% (delta), 36.6% (omicron BA.1/2) and 15.9% (omicron BA.4/5), respectively. Occupational risk factors were only apparent in the second wave, during which significant social distancing measures were in place. These were identified as working as a healthcare assistant, nurse or bedside therapist, and working on an inpatient ward. Occupational exposure requiring personal protective equipment was also a risk. In subsequent waves, without social restrictions, occupational characteristics were not risk factors. Instead, living with others compared to living alone was a risk, particularly children. During the third wave (winter 2021-2022), having a colleague with COVID-19 was identified as a risk for the first time., Interpretation: Our findings highlight clinical areas and occupational groups in which there may be scope to prevent healthcare-associated infections, particularly during winter pressures. Prospective studies targeting these are essential to establish which interventions are most effective. This study also underscores the importance of community circulation and exposures when considering healthcare workforce protection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2025. Published by Elsevier Ltd. All rights reserved.)

Objectives: Bivalent original/BA.4-5 and monovalent XBB.1.5 mRNA boosters were offered to UK healthcare workers (HCWs) in the autumn of 2023. We aimed to estimate booster vaccine effectiveness (VE) and post-infection immunity among the SIREN HCW cohort over the subsequent 6-month period of XBB.1.5 and JN.1 variant circulation., Methods: Between October 2023 to March 2024, 2867 SIREN study participants tested fortnightly for SARS-CoV-2 and completed symptoms questionnaires. We used multi-state models, adjusted for vaccination, prior infection, and demographic covariates, to estimate protection against mild/asymptomatic and moderate SARS-CoV-2 infection., Results: Half of the participants (1422) received a booster during October 2023 (280 bivalent, 1142 monovalent), and 536 (19%) had a PCR-confirmed infection over the study period. Bivalent booster VE was 15.1% (-55.4 to 53.6%) at 0-2 months and 4.2% (-46.4 to 37.3%) at 2-4 months post-vaccination. Monovalent booster VE was 44.2% (95% CI 21.7 to 60.3%) at 0-2 months, and 24.1% (-0.7 to 42.9%) at 2-4 months. VE was greater against moderate infection than against mild/asymptomatic infection, but neither booster showed evidence of protection after 4 months. Controlling for vaccination, compared to an infection >2 years prior, infection within the past 6 months was associated with 58.6% (30.3 to 75.4%) increased protection against moderate infection and 38.5% (5.8 to 59.8%) increased protection against mild/asymptomatic infection., Conclusions: Monovalent XBB.1.5 boosters provided short-term protection against SARS-CoV-2 infection, particularly against moderate symptoms. Vaccine formulations that target the circulating variant may be suitable for inclusion in seasonal vaccination campaigns among HCWs., Competing Interests: Declaration of Competing Interest All authors have completed the ICJME uniform disclosure form at: https://www.icmje.org/disclosure-of-interest/ and declare: CSB and SH report grant funding from the NIHR HPRU; CSB reports participation in an ad-hoc one-off market research advisory on a variety of infection topics; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Introduction: Following SARS-CoV-2 infection, some patients experience a range of long-lasting symptoms, with a specific burden on their lives and ability to work., Aim: We describe the prevalence and impact of persistent symptoms pre-/post-vaccination in SIREN study participants., Methods: A cross-sectional study of SARS-CoV-2 positive participants was carried out within SIREN, a frequently tested UK healthcare worker cohort with vaccination and demographic data available. Participants with a SARS-CoV-2 positive PCR or anti-SARS-CoV-2 sample between 01 March 2020 and 31 September 2022 were asked via a questionnaire about symptoms and days absent from work following infection. Responses were excluded if infection dates were inconsistent with study records or missing key data. Symptom type/duration and whether infection occurred pre-/post-vaccination and during which variant period were described. Logistic regression was used to estimate factors associated with persistent symptoms (>12 weeks), adjusting for vaccination and demographic factors. The median days absent from work were also determined., Results: Of 16,599 invitations, 6677 participants responded, and 5053 were included in the analysis. The prevalence of persistent symptoms (symptoms lasting over 12 weeks) differed by infection episode; highest for first infections (32.7%; 1557/4767) compared to second (21.6%; 214/991) and third infections (21.6%; 16/74). Most frequently reported symptoms were fatigue, tiredness, shortness of breath and difficulty concentrating. A higher prevalence of persistent symptoms was reported during the Wild-type variant period compared to the other variant periods (52.9% Wild-type vs. 20.7% Omicron, for any symptom reported during their first infection). Overall, persistent symptoms were higher among unvaccinated participants (unvaccinated 38.1% vs vaccinated 22.0%). Multivariable analysis showed that participants were less likely to report persistent symptoms in infections occurring after vaccination compared to those with an infection before vaccination in the Alpha/Delta and Omicron periods (Alpha/Delta: adjusted Odds Ratio (aOR) 0.66, CI 95% 0.51-0.87, p = aOR 0.07, CI 95% 0.01-0.65, p = 0.02). About half of participants reported that their persistent symptoms impacted their day-to-day (51.8%) and work-related (42.1%) activities 'a little', and 24.0% and 14.4% reported that the impact was 'A lot'. 8.9% reported they had reduced their working hours, and 13.9% had changed their working pattern., Discussion: Persistent symptoms were frequent in our cohort, and there was a reduction in symptom duration in those with multiple infection episodes during later variant periods and post-vaccination. The impact of persistent symptoms resulting in reducing working hours or adjusting working patterns has important implications for workforce resilience. UK healthcare workers were highly exposed during the pandemic, demonstrating a significant burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of Competing Interest None of the authors declare a competing interest.

Third doses of COVID-19 vaccines were widely deployed following the primary vaccine course waning and the emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2), by primary series vaccination type. Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021t o 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (3rd dose) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). The relative VE of 3rd dose (heterologous BNT162b2) was greater for primary course ChAdOX1 recipients, with VE 0-2 months post-3rd dose over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with the potential emergence of immune-escape variants and the importance of continued monitoring., Competing Interests: Declaration of Competing Interest We declare no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK., Methods: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to nationwide NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms., Results: We analysed WGS data of 838 S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005 and 2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer., Conclusions: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection., Methods: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models., Results: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40)., Conclusions: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect., Trial Registration Number: ISRCTN11041050., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread., Methods: Cross-sectional 'snapshot' survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples., Findings: Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42-37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38-8.67; p = 0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month., Interpretation: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests., Funding: Public Health England., Competing Interests: Declaration of Competing Interest Eight of the authors have either substantive or honorary contracts with PHE, the study funder., (Copyright © 2020. Published by Elsevier Ltd.)

Depressive and anxiety disorders are common problems facing obstetrician-gynecologists. Although psychiatric disorders are equally common in men and women, women are at least twice as likely to present with depressive disorders and most anxiety disorders. The depressive disorders include major depression, dysthymia, seasonal affective disorder, and premenstrual dysphoric disorder. The anxiety disorders are panic disorder (with and without agoraphobia), generalized anxiety disorder, social phobia, obsessive compulsive disorder, and PTSD. One must diagnose and manage depressive and anxiety disorders during pregnancy, the purpureum, and while breastfeeding. General treatment principles include assessing suicide risk, psychotherapy, pharmacologic treatment, and an appropriate medical work-up for depressive and anxiety disorders. The SSRIs are the first-line treatment for most depressive and anxiety disorders because of data supporting their efficacy, the minimal need for dosage titration, the overall favorable side-effect profile, and the length of available clinical experience. Newer antidepressants, such as venlafaxine, bupropion, nefazodone, and mirtazapine, are options for patients unresponsive to, or intolerant of, the SSRIs. Treatment considerations include acute, maintenance, and continuation therapy, dosage regimens, adverse effects, and drug interactions. Specific guidelines are available for referring patients to a mental health specialist.