Evaluation of Serological Tests for SARS-CoV-2: Implications for Serology Testing in a Low-Prevalence Setting

J Infect Dis. 2020 Sep 14;222(8):1280-1288. doi: 10.1093/infdis/jiaa467.

Abstract

Background: Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little premarket validation.

Methods: Performance characteristics for 5 PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralization test (sVNT).

Results: Sensitivities for PoCT ranged from 51.8% (95% confidence interval [CI], 43.1%-60.4%) to 67.9% (95% CI, 59.4%-75.6%), and specificities from 95.6% (95% CI, 89.2%-98.8%) to 100.0% (95% CI, 96.1%-100.0%). ELISA sensitivity for IgA or IgG detection was 67.9% (95% CI, 59.4%-75.6%), increasing to 93.8% (95% CI, 85.0%-98.3%) for samples >14 days post symptom onset. sVNT sensitivity was 60.9% (95% CI, 53.2%-68.4%), rising to 91.2% (95% CI, 81.8%-96.7%) for samples >14 days post symptom onset, with specificity 94.4% (95% CI, 89.2%-97.5%).

Conclusions: Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.

Keywords: COVID-19; ELISA; lateral flow; neutralization; serology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antibodies, Viral / blood
  • Australia / epidemiology
  • Betacoronavirus / isolation & purification
  • COVID-19
  • COVID-19 Testing
  • Clinical Laboratory Techniques
  • Coronavirus Infections / blood*
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / epidemiology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Neutralization Tests / methods
  • Pandemics
  • Pneumonia, Viral / blood*
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / epidemiology
  • Prevalence
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • SARS-CoV-2
  • Serologic Tests / methods
  • Serologic Tests / standards

Substances

  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G