Recent Advances in the Evaluation of Serological Assays for the Diagnosis of SARS-CoV-2 Infection and COVID-19

Front Public Health. 2021 Feb 18:8:620222. doi: 10.3389/fpubh.2020.620222. eCollection 2020.


Introduction: Few data on the diagnostic performance of serological tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are currently available. We evaluated sensitivity and specificity of five different widely used commercial serological assays for the detection of SARS-CoV-2-specific IgG, IgM, and IgA antibodies using reverse transcriptase-PCR assay in nasopharyngeal swab as reference standard test. Methods: A total of 337 plasma samples collected in the period April-June 2020 from SARS-CoV-2 RT-PCR positive (n = 207) and negative (n = 130) subjects were investigated by one point-of-care lateral flow immunochromatographic assay (LFIA IgG and IgM, Technogenetics) and four fully automated assays: two chemiluminescence immunoassays (CLIA-iFlash IgG and IgM, Shenzhen YHLO Biotech and CLIA-LIAISON® XL IgG, DiaSorin), one electrochemiluminescence immunoassay (ECLIA-Elecsys® total predominant IgG, Roche), and one enzyme-linked immunosorbent assay (ELISA IgA, Euroimmune). Results: The overall sensitivity of all IgG serological assays was >80% and the specificity was >97%. The sensitivity of IgG assays was lower within 2 weeks from the onset of symptoms ranging from 70.8 to 80%. The LFIA and CLIA-iFlash IgM showed an overall low sensitivity of 47.6 and 54.6%, while the specificity was 98.5 and 96.2%, respectively. The ELISA IgA yielded a sensitivity of 84.3% and specificity of 81.7%. However, the ELISA IgA result was indeterminate in 11.7% of cases. Conclusions: IgG serological assays seem to be a reliable tool for the retrospective diagnosis of SARS-CoV-2 infection. IgM assays seem to have a low sensitivity and IgA assay is limited by a substantial rate of indeterminate results.

Keywords: CLIA; COVID-19; ECLIA and ELISA; LFIA; SARS-CoV-2 RT-PCR; SARS-CoV-2 infection; SARS-CoV-2-specific antibodies; sensitivity and specificity.

MeSH terms

  • Antibodies, Viral / blood*
  • COVID-19 / blood
  • COVID-19 / diagnosis*
  • COVID-19 / immunology
  • COVID-19 Serological Testing*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • ROC Curve
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • Sensitivity and Specificity


  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M