RT-PCR testing to detect a COVID-19 outbreak in Austria: rapid, accurate and early diagnosis in primary care (The REAP study)

  1. Werner Leber
  2. Oliver Lammel
  3. Monika Redlberger-Fritz
  4. Maria Elisabeth Mustafa-Korninger
  5. Karin Stiasny
  6. Reingard Christina Glehr
  7. Eva-Maria Hochstrasser
  8. Christian Hoellinger
  9. Andrea Siebenhofer
  10. Chris Griffiths
  11. Jasmina Panovska-Griffiths

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Abstract

Background

Delay in COVID-19 detection has led to a major pandemic. We report rapid early detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR), comparing it to the serostatus of convalescent infection, at an Austrian National Sentinel Surveillance Practice in an isolated ski-resort serving a population of 22,829 people.

Methods

Retrospective dataset of all 73 patients presenting with mild to moderate flu-like symptoms to a sentinel practice in the ski-resort of Schladming-Dachstein, Austria, between 24 February and 03 April, 2020. We split the outbreak in two halves, by dividing the period from the first to the last case by two, to characterise the following three cohorts of patients with confirmed infection: people with reactive RT-PCR presenting during the first half (early acute infection) vs. those presenting in the second half (late acute), and people with non-reactive RT-PCR (late convalescent). For each cohort we report the number of cases detected, the accuracy of RT-PCR and the duration of symptoms. We also report multivariate regression of 15 clinical symptoms as covariates, comparing all people with convalescent infection to those with acute infection.

Findings

All 73 patients had SARS-CoV-2 RT-PCR testing. 22 patients were diagnosed with COVID-19, comprising: 8 patients presenting early acute, and 7 presenting late acute and 7 late convalescent respectively; 44 patients tested SARS-COV-2 negative, and 7 were excluded. RT-PCR sensitivity was high (100%) among acute presenters, but dropped to 50% in the second half of the outbreak; specificity was 100%. The mean duration of symptoms was 2 days (range 1-4) among early acute presenters, and 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent presenters respectively. Convalescent infection was only associated with loss of taste (ORs=6.02;p=0.047). Acute infection was associated with loss of taste (OR=571.72;p=0.029), nausea and vomiting (OR=370.11;p=0.018), breathlessness (OR=134.46;p=0.049), and myalgia (OR=121.82;p=0.032); but not loss of smell, fever or cough.

Interpretation

RT-PCR rapidly and reliably detects early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. RT-PCR testing in primary care should be prioritised for effective COVID-19 prevention and control.

Research in Context

Evidence before this study

A comprehensive and effective test-trace-isolate (TTI) strategy is necessary to keep track of current and future COVID-19 infection in the UK and avoid a secondary wave later this year, as society reopens. As part of a wider TTI strategy, it is important to assess the feasibility of COVID-19 testing in primary care. We searched PubMed for implementation of SARS-CoV-2 testing in primary care using the following search terms: (“SARS-CoV-2” OR “COVID-19”) AND “testing” AND (“primary care” OR “general practice”). We did not find any studies that met these criteria.

Added value of this study

To our knowledge, our study provides first evidence that extension of a National Influenza Surveillance Programme to include SARS-CoV-2 RT-PCR testing in primary care leads to viral detection among patients presenting with mild to moderate flu-like illness during a local outbreak of COVID-19. We show that the sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR), the technique to detect viral RNA, is high (100%) in the initial phase of the outbreak and among patients who were acutely unwell. Acute infection was associated with multiply symptoms: loss of taste, nausea and vomiting, breathlessness, myalgia and sore throat; but not loss of smell, fever or cough. We also show high correlation between reactive RT-PCR and seropositivity.

Implications of all available evidence

Our findings suggest that RT-PCR can rapidly and reliably detect early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. Furthermore RT-PCR testing in primary care can effectively detect new COVID-19 clusters in the community and should be included in any strategy for prevention and control of the disease.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.13.20152439: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics approval: The study used secondary anonymised data for which approval was granted by the University of Graz Research Ethics Committee, Austria (reference number: 32-429 ex 19/20).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Outcome measures: We characterise the outbreak using the following testing and clinical outcomes: A) As first outcome we report the diagnostic accuracy (using sensitivity and specificity) of SARS-CoV-2 RT-PCR testing among patients with mild to moderate flu-like symptoms at presentation by comparing it with anti-SARS-CoV-2 antibody during convalescence.
    anti-SARS-CoV-2
    suggested: None
    It is a total antibody assay not differentiating between IgA, IgM or IgG but detecting IgG predominantly.
    IgM
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The mixture was added to Vero E6 (ATCC ® CRL-1586) cell monolayers and incubation was continued for two to three days.
    Vero E6
    suggested: None

    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:
    There are some limitations of our study. Firstly, we used a relatively small patient cohort from a single sentinel practice, potentially limiting conclusions on causality and generalisability of our finding to other areas and secondly, we excluded seven patients for whom COVID-19 serostatus were not available. Lack of association with high fever and cough in our COVID-19 cohort, may be due to the National health hotline 1450 directing patients with more severe disease to attend emergency service. Therefore, people with these symptoms might have preferred to attend acute services rather than general practice. Although we collected data prospectively, recall bias cannot be excluded. This could be suggested by the lack of association of symptoms of acute infection (nausea and vomiting, breathless and myalgia) among all people confirmed with infection (when including those with negative RT-PCR), compared to those people presenting early (reactive RT-PCR). Specific recall bias of taste is less likely, as it featured in both groups and data collection was completed prior to publication of the first systematic review of altered taste and smell in the media.3 To our knowledge, this is the first study to show that primary care can contribute to early case detection and termination of a SARS-CoV-2 outbreak in the community. Our study has important implications for patients, public health, and health systems; nationally and internationally for outbreak epidemiology and control. Strict a...

    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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  2. Version published to 10.1101/2020.07.13.20152439v1 on medRxiv