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

Nat Biomed Eng. 2020 Dec;4(12):1180-1187. doi: 10.1038/s41551-020-00611-x. Epub 2020 Sep 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies / immunology
  • COVID-19 / immunology*
  • Humans
  • Immunoassay / methods*
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Pandemics / prevention & control
  • SARS-CoV-2 / immunology
  • Sensitivity and Specificity
  • Seroconversion / physiology*

Substances

  • Antibodies
  • Immunoglobulin G