Commercial Serology Assays Predict Neutralization Activity against SARS-CoV-2

Clin Chem. 2021 Jan 30;67(2):404-414. doi: 10.1093/clinchem/hvaa262.

Abstract

Background: It is unknown whether a positive serology result correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value of SARS-CoV-2 serology tests, especially when testing populations with low disease prevalence.

Methods: A neutralization assay was validated in a set of PCR-confirmed positive specimens and in a negative cohort. In addition, 9530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N = 164 individuals) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and neutralizing activity was determined. Neutralizing antibody titers (50% inhibitory dilution, ID50) were also longitudinally monitored in patients confirmed to have SARS-CoV-2 by PCR.

Results: The SARS-CoV-2 neutralization assay had a positive percentage agreement (PPA) of 96.6% with a SARS-CoV-2 PCR test and a negative percentage agreement (NPA) of 98.0% across 100 negative control individuals. ID50 neutralization titers positively correlated with all 3 clinical serology platforms. Longitudinal monitoring of hospitalized PCR-confirmed patients with COVID-19 demonstrated they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2 and 78.4%, respectively.

Conclusions: These 3 clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in patients with COVID-19. All patients confirmed SARS-CoV-2 positive by PCR develop neutralizing antibodies.

Keywords: COVID-19; SARS-CoV-2; immunity; neutralizing antibodies; serology.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / blood*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • COVID-19 / immunology
  • COVID-19 Serological Testing / methods*
  • COVID-19 Serological Testing / statistics & numerical data
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Regression Analysis
  • Retrospective Studies
  • SARS-CoV-2 / immunology*
  • Severe acute respiratory syndrome-related coronavirus / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral