Kantonsspital St.Gallen

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 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.
citation 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.
type journal paper/review (English)
date of publishing 16-11-2020
journal title Biomed Res Int (2020)
ISSN electronic 2314-6141
pages 9878453
PubMed 33224987
DOI 10.1155/2020/9878453