Frequency of serological non-responders and false-negative RT-PCR results in SARS-CoV-2 testing: a population-based study
Rita Christiane Baron, Lorenz Risch, Myriam Weber, Sarah Thiel, Kirsten Grossmann, Nadia Wohlwend, Thomas Lung, Dorothea Hillmann, Michael Ritzler, Susanna Bigler, Konrad Egli, Francesca Ferrara, Thomas Bodmer, Mauro Imperiali, Sonja Heer, Harald Renz, Lukas Flatz, Philipp Kohler, Pietro Vernazza, Christian R. Kahlert, Matthias Paprotny & Martin Risch
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abstract
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Objectives The sensitivity of molecular and serological methods for
COVID-19 testing in an epidemiological setting is not well
described. The aim of the study was to determine the frequency of
negative RT-PCR results at first clinical presentation as well as
negative serological results after a follow-up of at least
3 weeks. Methods Among all patients seen for suspected COVID-19
in Liechtenstein (n=1921), we included initially RT-PCR positive
index patients (n=85) as well as initially RT-PCR negative (n=66)
for follow-up with SARS-CoV-2 antibody testing. Antibodies were
detected with seven different commercially available immunoassays.
Frequencies of negative RT-PCR and serology results in individuals
with COVID-19 were determined and compared to those observed in a
validation cohort of Swiss patients (n=211). Results Among COVID-19
patients in Liechtenstein, false-negative RT-PCR at initial
presentation was seen in 18% (12/66), whereas negative serology in
COVID-19 patients was 4% (3/85). The validation cohort showed
similar frequencies: 2/66 (3%) for negative serology, and 16/155
(10%) for false negative RT-PCR. COVID-19 patients with negative
follow-up serology tended to have a longer disease duration (p=0.05)
and more clinical symptoms than other patients with COVID-19
(p<0.05). The antibody titer from quantitative immunoassays was
positively associated with the number of disease symptoms and
disease duration (p<0.001). Conclusions RT-PCR at initial
presentation in patients with suspected COVID-19 can miss infected
patients. Antibody titers of SARS-CoV-2 assays are linked to the
number of disease symptoms and the duration of disease. One in 25
patients with RT-PCR-positive COVID-19 does not develop antibodies
detectable with frequently employed and commercially available
immunoassays.
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citation
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Baron R C, Risch L, Weber M, Thiel S, Grossmann K, Wohlwend N, Lung
T, Hillmann D, Ritzler M, Bigler S, Egli K, Ferrara F, Bodmer T,
Imperiali M, Heer S, Renz H, Flatz L, Kohler P, Vernazza P, Kahlert
C R, Paprotny M, Risch M. Frequency of serological non-responders
and false-negative RT-PCR results in SARS-CoV-2 testing: a
population-based study. Clin Chem Lab Med 2020;.
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type
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journal paper/review (English)
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date of publishing
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31-08-2020
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journal title
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Clin Chem Lab Med
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ISSN electronic
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1437-4331
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PubMed
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32866113
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DOI
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10.1515/cclm-2020-0978
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