Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
The diagnosis of COVID‐19 requires integration of clinical and laboratory data. Severe acute respiratory syndrome coronavirus 2 (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. We conducted 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. 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 to 11, and 30% at Day 21. 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. In contrast to PCR, 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. Taken together, 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.
Article activity feed
-
-
SciScore for 10.1101/2020.06.19.20135723: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was conducted with approval from the local Institutional Review Board. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Serology: An in-house enzyme-linked immunosorbent assay was used to measure IgG, IgA, and IgM antibodies that target the SARS-CoV-2 receptor binding domain (RBD) within the spike protein. IgMsuggested: NoneResults 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 …SciScore for 10.1101/2020.06.19.20135723: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was conducted with approval from the local Institutional Review Board. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Antibodies Sentences Resources Serology: An in-house enzyme-linked immunosorbent assay was used to measure IgG, IgA, and IgM antibodies that target the SARS-CoV-2 receptor binding domain (RBD) within the spike protein. IgMsuggested: NoneResults 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:Using available published data (3-7, 12, 14) and data presented here from our hospital, we offer the following five diagnostic principles for consideration: Limitations in our study include relatively small numbers, a retrospective design, and selection bias due to the specific setting and testing practice. We evaluated symptomatic, mostly hospitalized patients and we cannot derive recommendations for asymptomatic or mildly symptomatic patients from our data. Due to limited availability of tests and time constraints during an ongoing pandemic, we do not have daily samples. Date of symptom onset is not consistently available, subjective, and affected by recall biases – yet, it represents a useful anchor point for disease time course in symptomatic patients. Notably, the eclipse period ranges from 2-14 days (18-21) and some patients already mounted a serologic response at the time of presentation, which can be taken as an argument for the early y-axis deviation from zero in the serology curve and a confirmation of date of symptom onset as an imperfect marker. We caution that the presented serology data are specific to our ELISA, and we cannot extrapolate to anti- SARS-CoV-2 antibody responses in general. Nonetheless, other publications indicate that the time courses are comparable (14, 17, 22). Our serological studies measured antibodies to the RBD of SARS-CoV-2. We chose this viral antigen because of its specificity to SARS-CoV-2, and because anti-RBD antibodies are typically ...
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.
-
