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.

Conceptualizing the reporting of living systematic reviews.

OBJECTIVES: As part of an effort to develop an extension of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement for living systematic reviews (LSRs), we discuss conceptual issues relevant to the reporting of LSRs and highlight a few challenges. METHODS: Discussion of conceptual issues based on a scoping review of the literature and discussions among authors. RESULTS: We first briefly describe aspects of the LSR production process relevant to reporting. The production cycles differ by whether the literature surveillance identifies new evidence and whether newly identified evidence is judged to be consequential. This impacts the timing, content, and format of LSR versions. Second, we discuss four types of information that are specific to the reporting of LSRs: justification for adopting the living mode, LSR specific methods, changes between LSR versions, and LSR updating status. We also discuss the challenge of conveying changes between versions to the reader. Third, we describe two commonly used reporting formats of LSRs: full and partial reports. Although partial reports are easier to produce and publish, they lead to the scattering of information across different versions. Full reports ensure the completeness of reporting. We discuss the implications for the extension of the PRISMA 2020 statement for LSRs. CONCLUSION: We argue that a dynamic publication platform would facilitate complete and timely reporting of LSRs.

Reporting guideline for overviews of reviews of healthcare interventions: development of the PRIOR statement.

OBJECTIVE: To develop a reporting guideline for overviews of reviews of healthcare interventions. DESIGN: Development of the preferred reporting items for overviews of reviews (PRIOR) statement. PARTICIPANTS: Core team (seven individuals) led day-to-day operations, and an expert advisory group (three individuals) provided methodological advice. A panel of 100 experts (authors, editors, readers including members of the public or patients) was invited to participate in a modified Delphi exercise. 11 expert panellists (chosen on the basis of expertise, and representing relevant stakeholder groups) were invited to take part in a virtual face-to-face meeting to reach agreement (≥70%) on final checklist items. 21 authors of recently published overviews were invited to pilot test the checklist. SETTING: International consensus. INTERVENTION: Four stage process established by the EQUATOR Network for developing reporting guidelines in health research: project launch (establish a core team and expert advisory group, register intent), evidence reviews (systematic review of published overviews to describe reporting quality, scoping review of methodological guidance and author reported challenges related to undertaking overviews of reviews), modified Delphi exercise (two online Delphi surveys to reach agreement (≥70%) on relevant reporting items followed by a virtual face-to-face meeting), and development of the reporting guideline. RESULTS: From the evidence reviews, we drafted an initial list of 47 potentially relevant reporting items. An international group of 52 experts participated in the first Delphi survey (52% participation rate); agreement was reached for inclusion of 43 (91%) items. 44 experts (85% retention rate) completed the second Delphi survey, which included the four items lacking agreement from the first survey and five new items based on respondent comments. During the second round, agreement was not reached for the inclusion or exclusion of the nine remaining items. 19 individuals (6 core team and 3 expert advisory group members, and 10 expert panellists) attended the virtual face-to-face meeting. Among the nine items discussed, high agreement was reached for the inclusion of three and exclusion of six. Six authors participated in pilot testing, resulting in minor wording changes. The final checklist includes 27 main items (with 19 sub-items) across all stages of an overview of reviews. CONCLUSIONS: PRIOR fills an important gap in reporting guidance for overviews of reviews of healthcare interventions. The checklist, along with rationale and example for each item, provides guidance for authors that will facilitate complete and transparent reporting. This will allow readers to assess the methods used in overviews of reviews of healthcare interventions and understand the trustworthiness and applicability of their findings.

Accuracy and Efficiency of Machine Learning-Assisted Risk-of-Bias Assessments in "Real-World" Systematic Reviews : A Noninferiority Randomized Controlled Trial.

BACKGROUND: Automation is a proposed solution for the increasing difficulty of maintaining up-to-date, high-quality health evidence. Evidence assessing the effectiveness of semiautomated data synthesis, such as risk-of-bias (RoB) assessments, is lacking. OBJECTIVE: To determine whether RobotReviewer-assisted RoB assessments are noninferior in accuracy and efficiency to assessments conducted with human effort only. DESIGN: Two-group, parallel, noninferiority, randomized trial. (Monash Research Office Project 11256). SETTING: Health-focused systematic reviews using Covidence. PARTICIPANTS: Systematic reviewers, who had not previously used RobotReviewer, completing Cochrane RoB assessments between February 2018 and May 2020. INTERVENTION: In the intervention group, reviewers received an RoB form prepopulated by RobotReviewer; in the comparison group, reviewers received a blank form. Studies were assigned in a 1:1 ratio via simple randomization to receive RobotReviewer assistance for either Reviewer 1 or Reviewer 2. Participants were blinded to study allocation before starting work on each RoB form. MEASUREMENTS: Co-primary outcomes were the accuracy of individual reviewer RoB assessments and the person-time required to complete individual assessments. Domain-level RoB accuracy was a secondary outcome. RESULTS: Of the 15 recruited review teams, 7 completed the trial (145 included studies). Integration of RobotReviewer resulted in noninferior overall RoB assessment accuracy (risk difference, -0.014 [95% CI, -0.093 to 0.065]; intervention group: 88.8% accurate assessments; control group: 90.2% accurate assessments). Data were inconclusive for the person-time outcome (RobotReviewer saved 1.40 minutes [CI, -5.20 to 2.41 minutes]). LIMITATION: Variability in user behavior and a limited number of assessable reviews led to an imprecise estimate of the time outcome. CONCLUSION: In health-related systematic reviews, RoB assessments conducted with RobotReviewer assistance are noninferior in accuracy to those conducted without RobotReviewer assistance. PRIMARY FUNDING SOURCE: University College London and Monash University.