Research ArticleCORONAVIRUS

A comparison of four serological assays for detecting anti–SARS-CoV-2 antibodies in human serum samples from different populations

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Science Translational Medicine  02 Sep 2020:
Vol. 12, Issue 559, eabc3103
DOI: 10.1126/scitranslmed.abc3103

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  • RE: 1.8-4.7% false positive rate of COVID-19 in antibody testing with a nucleocapsid protein: A potential issue in seroepidemiological surveys?
    • Qiang Zeng, MD, Dean, Health Management Institute, Chinese PLA General Hospital
    • Other Contributors:
      • Yong-zhe Li, MD, Director, Department of Laboratory Medicine, Peking Union Medical College Hospital
      • Yang Xu, MD, Director, Shanghai University of Medicine and Health Sciences
      • Bo Ding, MD, Chinese PLA Hangzhou Sanatorium
      • Biao-yang Lin, PhD, Zhejiang University

    To The Editor:

    Serological testing is a critical investigative tool in the coronavirus disease (COVID-19) epidemic and can identify an infected family or school cluster, especially children or patients with mild or asymptomatic illness. So far, the mortality rate associated with COVID-19 has been calculated based on the incidence of symptomatic patients diagnosed by polymerase chain reaction (PCR).

    Lancet first reported false positive rate of COVID-19 in antibody testing in Spain (1). Pollán and colleagues observed an important national survey that seroprevalence was 5.0% by the point-of-care test and 4.6% by immunoassay, respectively (1). In PCR confirmed COVID-19 cases, the positive rate of serological testing was 45.6-88.6% by the point-of-care test, which is designed to detect antibodies to the spike protein of SARS-CoV-2 and 65.8-90.1% by an Abbott Architect SARS-CoV-2 IgG CMIA test kit (2), which is designed to detect IgG antibodies to the nucleocapsid (N) protein of SARS-CoV-2, suggesting that it has the cross-reactivity of SARS-CoV-2 antibody testing.

    NEJM confirmed false positive rate of COVID-19 in antibody testing. In the study by Gudbjartsson and colleagues, a false positive rate of 1.8% in samples collected in 2017 in Iceland is performed in an assay using an N protein of SARS-CoV-2 as an antigen (3).

    Grzelak and colleagues (4) also found that the false positive rate of COVID-19 in antibody testing with a SARS-CoV-2 N protein is a...

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    Competing Interests: None declared.
  • RE: False positive results in seroprevalence survey and the second infection of SARS-CoV-2
    • Yang Xv, MD, Chinese Academy of Medical Sciences

    To The Editor:

    As clinicians puzzling to deal with patients with second infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we want to understand why patients would get the second infection of SARS-CoV-2.

    In that vitality, I discovered 4.7% false positive result in antibody testing among persons without SARS-CoV-2 infection in France in this issue of Science Translational Medicine of interest (1). In this study, 23 of 491 samples collected pre-pandemic and without SARS-CoV-2 infection had a positive result in the SARS-CoV-2 antibody testing using a SARS-CoV-2 nucleocapsid (N) protein as an antigen. It is important to understand why some people without SARS-CoV-2 infection produce positive results in the SARS-CoV-2 antibody test.

    Grifoni et al. (2) demonstrated that common cold coronaviruses can exhibit substantial cross-reactivity to the N protein of SARS-CoV-2. If the person shows the N protein cross-reaction and an N antigen is used in the assay, it may cause the false positive result. If a person without symptoms is tested as false positive for COVID-19 in seroprevalence survey but is later infected with SARS-CoV-2, the infection will be erroneously considered as a second SARS-CoV-2 infection.

    Seasonal “common cold” human coronaviruses are continuously circulating among 7-18% of adults with upper respiratory tract infections (3). Answers to these pointed questions might lead to better understand why some patients will...

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    Competing Interests: None declared.

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