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

Baron, Rita Christiane; Risch, Lorenz; Weber, Myriam; Thiel, Sarah; Grossmann, Kirsten; Wohlwend, Nadia; Lung, Thomas; Hillmann, Dorothea; Ritzler, Michael; Bigler, Susanna; Egli, Konrad; Ferrara, Francesca; Bodmer, Thomas; Imperiali, Mauro; Heer, Sonja; Renz, Harald; Flatz, Lukas; Kohler, Philipp; Vernazza, Pietro; Kahlert, Christian R; ... (2020). Frequency of serological non-responders and false-negative RT-PCR results in SARS-CoV-2 testing: a population-based study. Clinical chemistry and laboratory medicine, 58(12), pp. 2131-2140. Walter de Gruyter 10.1515/cclm-2020-0978

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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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Risch, Lorenz


600 Technology > 610 Medicine & health




Walter de Gruyter




Karin Balmer

Date Deposited:

23 Nov 2022 07:48

Last Modified:

05 Dec 2022 16:28

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

COVID-19 RT-PCR SARS-CoV-2 antibodies prevalence sensitivity serum specificity




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