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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

abstract 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.
   
citation 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;.
   
type journal paper/review (English)
date of publishing 31-08-2020
journal title Clin Chem Lab Med
ISSN electronic 1437-4331
PubMed 32866113
DOI 10.1515/cclm-2020-0978