Clinical Sensitivity and Interpretation of PCR and Serological COVID-19 Diagnostics for Patients Presenting to the Hospital

Abstract

Introduction: The diagnosis of COVID-19 requires integration of clinical and laboratory data. SARS-CoV-2 diagnostic assays play a central role in diagnosis and have fixed technical performance metrics. Interpretation becomes challenging because the clinical sensitivity changes as the virus clears and the immune response emerges. Our goal was to examine the clinical sensitivity of two most common SARS-CoV-2 diagnostic test modalities, polymerase chain reaction (PCR) and serology, over the disease course to provide insight into their clinical interpretation in patients presenting to the hospital. Methods: A single-center, retrospective study. To derive clinical sensitivity of PCR, we identified 209 PCR-positive SARS-CoV-2 patients with multiple PCR test results (624 total PCR tests) and calculated daily sensitivity from date of symptom onset or first positive test. To calculate daily clinical sensitivity by serology, we utilized 157 PCR-positive patients with a total of 197 specimens tested by enzyme-linked immunosorbent assay for IgM, IgG, and IgA anti-SARS-CoV-2 antibodies. Results: Clinical sensitivity of PCR decreased with days post symptom onset with >90% clinical sensitivity during the first 5 days after symptom onset, 70-71% from days 9-11, and 30% at day 21. In contrast, serological sensitivity increased with days post symptom onset with >50% of patients seropositive by at least one antibody isotype after day 7, >80% after day 12, and 100% by day 21. Conclusion: PCR and serology are complimentary modalities that require time-dependent interpretation. Superimposition of sensitivities over time indicate that serology can function as a reliable diagnostic aid indicating recent or prior infection.

Routine saliva testing for the identification of silent coronavirus disease 2019 (COVID-19) in healthcare workers

“…In our analysis, we only included individuals who went on to develop a symptomatic course of disease. To estimate case detection percentages, we first constructed a sensitivity function to map the infectiousness profile of symptomatic COVID-19 cases 14,15 to the reported percent positivity of NP RT-PCR tests post-symptom onset 16 . The infectiousness profile (Appendix: Figure A1) was extracted from computer code provided in previous studies that utilized maximum likelihood and optimization methods 14,15 .…”

“…This research was based on publicly available data [14][15][16] and therefore did not require ethics approval.…”

Buyer beware: inflated claims of sensitivity for rapid COVID-19 tests

“…For example, the BD Veritor EUA study had 31 positive cases (PPA 83·9%, 95% CI 66·3–94·5). Combining the effect of small sample size with the reported sensitivity that is typical of RT-PCR (92·1%, 95% CI 86·6–95·9; over the first 7 days after symptom onset) 4 would correspond to diagnostic sensitivities of 89·4% (81·7–94·7) for BinaxNOW and 77·3% (63·5–87·8) for BD Veritor.…”

“…The PPA is measured relative to an RT-PCR test, which is imperfect itself. 4 Due to variation in the diagnostic sensitivity of different RT-PCR tests, which are evaluated by the Foundation for Innovative New Diagnostics (FIND) , understanding the accuracy of a rapid antigen test requires knowledge of the exact RT-PCR test that is selected as the comparator. However, manufacturers of most rapid antigen tests have not specified the test comparator.…”

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“…werden sich jedoch auch echte Fälle von Covid-19 befunden haben, die bei den Kennzahlen des QKK e. V. unter Annahme einer überwiegenden Fehlkodierung keine Berücksichtigung fanden. Diese Annahme wird durch die erreichte hohe Güte des Virusnachweises getragen [7]. Im Vergleich mit den beim Robert Koch-Institut gemeldeten Covid-19-Fällen waren die in den Krankenhäusern stationär versorgten Patienten älter (s. https://corona.rki.de/).…”