Abstract
BackgroundCovid-19 healthcare worker testing, isolation and quarantine policies had to balance risks to patients from the virus and from staff absence. The emergence of the Omicron variant led to dangerous levels of key-worker absence globally.We evaluated whether using two manufacturers' lateral flow tests (LFTs) concurrently improved SARS-CoV-2 Omicron detection and was acceptable to hospital staff. In a nested study, to understand risks of return to work after a 5-day isolation/quarantine period, we examined virus culture 5-7 days after positive test or significant exposure.MethodsFully-vaccinated Liverpool (UK) University Hospitals staff participated (February-May 2022) in a random-order, open-label trial testing whether dual LFTs improved SARS-CoV2 detection, and whether dual swabbing was acceptable to users. Participants used nose-throat swab Innova and nose-only swab Orient Gene LFTs in daily randomised order for 10 days. A user-experience questionnaire was administered on exit. Selected participants gave swabs for viral culture on Days 5-7. Cultures were considered positive if cytopathic effect was apparent or SARs-COV2 N gene sub-genomic RNA was detected.Results226 individuals reported 1466 pairs of LFT results. Tests disagreed in 127 cases (8.7%). Orient Gene was more likely (78 cf. 49, P=0.03) to be positive. Orient Gene positive Innova negative result-pairs became more frequent over time (P<0.001). If Innova was swabbed second, it was less likely to agree with a positive Orient Gene result (P=0.005); swabbing first with Innova made no significant difference (P=0.85).Of 311 individuals completing the exit questionnaire, 90.7% reported dual swabbing was easy, 57.1% said it was no barrier to their daily routine and 65.6% preferred dual testing. Respondents had more confidence in dual c.f. single test results (P<0.001).Viral cultures from Days 5-7 were positive for 6/31 (19.4%, 7.5%-37.5%) and indeterminate for 11/31 (35.5%, 19.2%-54.6%) LFT-positive participants, indicating they were likely still infectious.ConclusionsDual brand testing increased LFT detection of SARS-CoV-2 antigen by a small but meaningful margin and was acceptable to hospital workers. Viral cultures demonstrated that policies recommending safe return to work ~5 days after Omicron infection/exposure were flawed. Key-workers should be prepared for dynamic self-testing protocols in future pandemics.
Competing Interest Statement
All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest and declare: funding from the Department of Health and Social Care, Economic and Social Research Council, and National Institute for Health and Care Research; no support from any organisation for the submitted work; 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. IB, TF and MGS were members of the UK Covid-19 Testing Initiatives Evaluation Board but did not take part in sessions where this study was adjudicated. The City of Liverpool received a donation from Innova Medical Group towards the foundation of the Pandemic Institute but neither Innova Medical Group or any other commercial entity gave any support to this study or had any participation in it. Lateral Flow Test supply and company interactions was handled independently by the UK Health Security Agency. LT has received consulting fees from MHRA; and from AstraZeneca and Synairgen, paid to the University of Liverpool; speakers' fees from Eisai Ltd, and support for conference attendance from AstraZeneca.
Clinical Trial
ISRCTN47058442
Clinical Protocols
https://github.com/iain-buchan/cipha/blob/master/SMART_Release_Return.pdf
Funding Statement
This research was commissioned and funded by the UK Health Security Agency and carried out independently by the University of Liverpool. The work was also supported by the Economic and Social Research Council (grant No ES/L011840/1). IB is supported by the National Institute for Health and Care Research (NIHR) as senior investigator award NIHR205131. IB and XZ are also supported by the NIHR Health Protection Research Unit in Gastrointestinal Infections, a partnership between UKHSA, the University of Liverpool, and the University of Warwick (NIHR200910). MGS and LT are supported by the NIHR Health Protection Unit in Emerging and Zoonotic Infections, a partnership between UKHSA, The University of Liverpool and The University of Oxford (NIHR200907). The NIHR had no role in the study design, data collection and analysis, decision to publish, or preparation of the article. LT, RPR and XD are supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085. The funders had no role in considering the study design or in the collection, analysis, or interpretation of data, writing of the report, or decision to submit the article for publication. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, NIHR, or Department of Health and Social Care.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The study protocol was developed with the UK Covid-19 Testing Initiatives Evaluation Board (TIEB) and approved by UK Health Security Agency (UKHSA) Urgent Studies Ethics Committee. TIEB was part of the UK Covid-19 testing initiatives evaluation programme, which included academics and public health professionals independent of this study. The motivation for the study came from a request by Merseyside Resilience Forum to UKHSA and NHS England to vary Covid-19 testing policies in response to dangerous levels of NHS staff absence in December 2021. TIEB signed off the study protocol on 4th January 2022 and UKHSA Research Support and Governance Office approved the study on 25th January 2022 as NR0308. The sponsor code for this study is UoL001685 and trial registration code IRAS ID 311842; https://www.isrctn.com/ISRCTN47058442.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Footnotes
Expanded discussion section with a conclusion paragraph. Restructured abstract. Expanded data availability statement to include recent upload of anonymised study data to trials registration site. No differences in results or interpretation from the original version.
Data Availability
The study required person identifiable data and the main analyses were conducted on a de-identified extract. The fully anonymised data for reproducing the results are available from https://www.isrctn.com/ISRCTN47058442. The study protocol can be downloaded from https://github.com/iain-buchan/cipha/blob/master/SMART_Release_Return.pdf and statistical analysis plan from https://github.com/iain-buchan/cipha/blob/master/SMART_RR_SAP.pdf.
