Impact of COVID-19 pre-test probability on positive predictive value of high cycle threshold SARS-CoV-2 real-time reverse transcription PCR test results

  1. Jonathan B. Gubbay
  2. Heather Rilkoff
  3. Heather L. Kristjanson
  4. Jessica D. Forbes
  5. Michelle Murti
  6. AliReza Eshaghi
  7. George Broukhanski
  8. Antoine Corbeil
  9. Nahuel Fittipaldi
  10. Jessica P. Hopkins
  11. Erik Kristjanson
  12. Julianne V. Kus
  13. Liane Macdonald
  14. Anna Majury
  15. Gustavo V Mallo
  16. Tony Mazzulli
  17. Roberto G. Melano
  18. Romy Olsha
  19. Stephen J. Perusini
  20. Vanessa Tran
  21. Vanessa G Allen
  22. Samir N Patel
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Abstract

Background

Performance characteristics of SARS-CoV-2 nucleic acid detection assays are understudied within contexts of low pre-test probability, including screening asymptomatic persons without epidemiological links to confirmed cases, or asymptomatic surveillance testing. SARS-CoV-2 detection without symptoms may represent resolved infection with persistent RNA shedding, presymptomatic or asymptomatic infection, or a false positive test. This study assessed clinical specificity of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) assays by retesting positive specimens from five pre-test probability groups ranging from high to low with an alternate assay.

Materials and Methods

A total of 122 rRT-PCR positive specimens collected from unique patients between March and July 2020 were retested using a laboratory-developed nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene followed by Sanger sequencing.

Results

Significantly less positive results in the lowest pre-test probability group (facilities with institution-wide screening having ≤ 3 positive asymptomatic cases) were reproduced with the nested RdRp gene RT-PCR assay than in all other groups combined (5/32, 15·6% vs 61/90, 68%; p <0·0001), and in each subgroup with higher pre-test probability (individual subgroup range 50·0% to 85·0%).

Conclusions

A higher proportion of false-positive test results are likely with lower pre-test probability. Positive SARS-CoV-2 PCR results should be interpreted within the context of patient history, clinical setting, known exposure, and estimated community disease prevalence. Large-scale SARS-CoV-2 screening testing initiatives among low pre-test probability populations should be evaluated thoroughly prior to implementation given the risk of false positives and consequent potential for harm at the individual and population level.

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