Temporal Course of SARS-CoV-2 Antibody Positivity in Patients with COVID-19 following the First Clinical Presentation
Martin Risch, Myriam Weber, Sarah Thiel, Kirsten Grossmann, Nadia Wohlwend, Thomas Lung, Dorothea Hillmann, Michael Ritzler, Francesca Ferrara, Susanna Bigler, Konrad Egli, Thomas Bodmer, Mauro Imperiali, Yacir Salimi, Felix Fleisch, Alexia Cusini, Harald Renz, Philipp Kohler, Pietro Vernazza, Christian R. Kahlert, Matthias Paprotny & Lorenz Risch
abstract
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Knowledge of the sensitivities of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) antibody tests beyond 35 days after the
clinical onset of COVID-19 is insufficient. We aimed to describe
positivity rate of SARS-CoV-2 assays employing three different
measurement principles over a prolonged period. Two hundred
sixty-eight samples from 180 symptomatic patients with COVID-19 and
a reverse transcription polymerase chain reaction (RT-PCR) test
followed by serological investigation of SARS-CoV-2 antibodies were
included. We conducted three chemiluminescence (including
electrochemiluminescence assay (ECLIA)), four enzyme-linked
immunosorbent assay (ELISA), and one lateral flow immunoassay (LFIA)
test formats. Positivity rates, as well as positive (PPVs) and
negative predictive values (NPVs), were calculated for each week
after the first clinical presentation for COVID-19. Furthermore,
combinations of tests were assessed within an orthogonal testing
approach employing two independent assays and predictive values were
calculated. Heat maps were constructed to graphically illustrate
operational test characteristics. During a follow-up period of more
than 9 weeks, chemiluminescence assays and one ELISA IgG test showed
stable positivity rates after the third week. With the exception of
ECLIA, the PPVs of the other chemiluminescence assays were ≥95%
for COVID-19 only after the second week. ELISA and LFIA had somewhat
lower PPVs. IgM exhibited insufficient predictive characteristics.
An orthogonal testing approach provided PPVs ≥ 95% for patients
with a moderate pretest probability (e.g., symptomatic patients),
even for tests with a low single test performance. After the second
week, NPVs of all but IgM assays were ≥95% for patients with low
to moderate pretest probability. The confirmation of negative
results using an orthogonal algorithm with another assay provided
lower NPVs than the single assays. When interpreting results from
SARS-CoV-2 tests, the pretest probability, time of blood draw, and
assay characteristics must be carefully considered. An orthogonal
testing approach increases the accuracy of positive, but not
negative, predictions.
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citation
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Risch M, Weber M, Thiel S, Grossmann K, Wohlwend N, Lung T, Hillmann
D, Ritzler M, Ferrara F, Bigler S, Egli K, Bodmer T, Imperiali M,
Salimi Y, Fleisch F, Cusini A, Renz H, Kohler P, Vernazza P, Kahlert
C R, Paprotny M, Risch L. Temporal Course of SARS-CoV-2 Antibody
Positivity in Patients with COVID-19 following the First Clinical
Presentation. Biomed Res Int 2020; 2020:9878453.
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type
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journal paper/review (English)
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date of publishing
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16-11-2020
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journal title
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Biomed Res Int (2020)
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ISSN electronic
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2314-6141
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pages
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9878453
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PubMed
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33224987
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DOI
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10.1155/2020/9878453
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