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. 2020 Aug 31;58(12):2131-2140.
doi: 10.1515/cclm-2020-0978.

Frequency of serological non-responders and false-negative RT-PCR results in SARS-CoV-2 testing: a population-based study

Rita Christiane Baron  1 , Lorenz Risch  2   3   4 , Myriam Weber  5 , Sarah Thiel  5 , Kirsten Grossmann  3 , Nadia Wohlwend  2 , Thomas Lung  2 , Dorothea Hillmann  2 , Michael Ritzler  2 , Susanna Bigler  6 , Konrad Egli  6 , Francesca Ferrara  2 , Thomas Bodmer  6 , Mauro Imperiali  7 , Sonja Heer  8 , Harald Renz  9   10 , Lukas Flatz  11 , Philipp Kohler  12 , Pietro Vernazza  12 , Christian R Kahlert  12   13 , Matthias Paprotny  5 , Martin Risch  14
Affiliations
Free article

Frequency of serological non-responders and false-negative RT-PCR results in SARS-CoV-2 testing: a population-based study

Rita Christiane Baron et al. Clin Chem Lab Med. .
Free article

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.

Keywords: COVID-19; RT-PCR; SARS-CoV-2; antibodies; prevalence; sensitivity; serum; specificity.

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