Journal Article

Ultrasensitive high-resolution profiling of early seroconversion in patients with COVID-19

Chen, Bing, Mao, Chih-Ping, Caradonna, Timothy M., Busch, Evan L., Hauser, Blake M., Ryan, Edward T., Walt, David R., Ogata, Alana F., Schmidt, Aaron G., Charles, Richelle C., Feldman, Jared E., Norman, Maia, Gilboa, Tal, Alter, Galit, Cohen, Limor, Maley, Adam M., Lazarovits, Roey, Cai, Yongfei, Zhang, Jun

2020

Overview

Sensitive assays are essential for the accurate identification of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we report a multiplexed assay for the fluorescence-based detection of seroconversion in infected individuals from less than 1 µl of blood, and as early as the day of the first positive nucleic acid test after symptom onset. The assay uses dye-encoded antigen-coated beads to quantify the levels of immunoglobulin G (IgG), IgM and IgA antibodies against four SARS-CoV-2 antigens. A logistic regression model trained using samples collected during the pandemic and samples collected from healthy individuals and patients with respiratory infections before the first outbreak of coronavirus disease 2019 (COVID-19) was 99% accurate in the detection of seroconversion in a blinded validation cohort of samples collected before the pandemic and from patients with COVID-19 five or more days after a positive nasopharyngeal test by PCR with reverse transcription. The high-throughput serological profiling of patients with COVID-19 allows for the interrogation of interactions between antibody isotypes and viral proteins, and should help us to understand the heterogeneity of clinical presentations. A multiplexed fluorescence-based assay detects seroconversion in individuals infected with SARS-CoV-2 from less than 1 µl of blood as early as the day of the first positive nasopharyngeal nucleic acid test after symptom onset.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 101/28 / 13/109 / 692/53/2421 / 692/699/255/2514 / 82/16 / 82/80 / 82/83 / 96/10 / 96/34 / Aged / Aged, 80 and over / Antibodies - immunology / Antigens / Assaying / Beads / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Blood / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 - immunology / Fluorescence / Heterogeneity / Humans / IgG antibody / Immunoassay - methods / Immunoglobulin A / Immunoglobulin G / Immunoglobulin G - immunology / Immunoglobulin M / Interrogation / Isotypes / Male / Middle Aged / Multiplexing / Nucleic acids / Pandemics / Pandemics - prevention & control / Regression models / Respiratory diseases / Reverse transcription / SARS-CoV-2 - immunology / Sensitivity and Specificity / Seroconversion / Seroconversion - physiology / Severe acute respiratory syndrome coronavirus 2 / Viral diseases