Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection syndromes: Results from a pilot service implemented during the first pandemic wave

  1. Nicola Sweeney
  2. Blair Merrick
  3. Rui Pedro Galão
  4. Suzanne Pickering
  5. Alina Botgros
  6. Harry D. Wilson
  7. Adrian W. Signell
  8. Gilberto Betancor
  9. Mark Kia Ik Tan
  10. John Ramble
  11. Neophytos Kouphou
  12. Sam Acors
  13. Carl Graham
  14. Jeffrey Seow
  15. Eithne MacMahon
  16. Stuart J. D. Neil
  17. Michael H. Malim
  18. Katie Doores
  19. Sam Douthwaite
  20. Rahul Batra
  21. Gaia Nebbia
  22. Jonathan D. Edgeworth

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Abstract

During the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves.

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  1. Version published to 10.1371/journal.pone.0249791
  2. ScreenIT

    SciScore for 10.1101/2020.07.10.20150540: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Next, HeLa cells stably expressing the ACE2 receptor (provided by Dr James Voss, The Scripps Research Institute) were added and the plates were left for 72 hours.
    HeLa
    suggested: None
    Software and Algorithms
    SentencesResources
    The ID50 for each sera was calculated using GraphPad Prism.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The main limitation of this study is in being performed at a single-centre at a discrete time-point in the COVID-19 pandemic. It is impossible to predict precise future serology service needs, whether that be aiding acute diagnosis alongside PCR testing,(23) informing patients that they have or have not had COVID-19, helping guide infection control decisions in hospitals or helping diagnose emerging post-inflammatory syndromes. Faster, more accurate even point of care SARS-CoV-2 virus detection assays may become widely available in hospitals and the community during a second wave, reducing the number of missed or delayed diagnoses and thus reduce demand for serological testing. The second limitation, although not technology specific, is that using serology as the marker of previous SARS-CoV-2 infection will likely only identify a proportion of infected patients given emerging evidence that seronegative individuals can show T-cell specific responses.(24) Nevertheless, LFIAs are quick (10 minute test), straightforward to perform by trained operators, inexpensive and are already used in many diagnostic laboratories for example for detecting pneumococcal and legionella urinary antigens. They could also potentially be deployed outside pathology laboratories to provide more immediate results for decision making. This could include community healthcare facilities after appropriate training and mechanisms to record and disseminate the results. It should be noted however that as only ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.07.10.20150540v1 on medRxiv