Longitudinal detection of SARS-CoV-2-specific antibody responses with different serological methods

J Med Virol. 2021 Oct;93(10):5816-5824. doi: 10.1002/jmv.27113. Epub 2021 Jun 11.

Abstract

Serological testing for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with polymerase chain reaction-confirmed coronavirus disease 2019 (COVID-19) and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using enzyme-linked immunosorbent assays. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were the highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed the highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information on whether or not the individual has been infected with SARS-CoV-2. Enzyme-linked immunosorbent assays provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2.

Keywords: COVID-19; ELISA; SARS-CoV-2; antibodies; immunofluorescence; serology.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • COVID-19 / blood*
  • COVID-19 / diagnosis
  • COVID-19 Serological Testing*
  • Coronavirus Nucleocapsid Proteins / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunoglobulin Isotypes / blood
  • Kinetics
  • Male
  • Middle Aged
  • Phosphoproteins / immunology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • Sensitivity and Specificity
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Immunoglobulin Isotypes
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2