Publication

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

Journal Paper/Review - Aug 31, 2020

Units
PubMed
Doi

Citation
Baron R, Bodmer T, Imperiali M, Heer S, Renz H, Flatz L, Kohler P, Vernazza P, Kahlert C, Paprotny M, Ferrara F, Egli K, Risch L, Weber M, Thiel S, Grossmann K, Wohlwend N, Lung T, Hillmann D, Ritzler M, Bigler S, 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; 58:2131-2140.
Type
Journal Paper/Review (English)
Journal
Clin Chem Lab Med 2020; 58
Publication Date
Aug 31, 2020
Issn Electronic
1437-4331
Pages
2131-2140
Brief description/objective

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.