Comparison of diagnostic accuracy for eight SARS-CoV-2 serological assays.

Andrea Tešija Kuna,Marijana Jovanović,Marko Žarak,Valentina Vidranski,Milena Hanžek,Ivana Ćelap,Mario Štefanović,Ines Vukasović,Marijana Miler,Josipa Periša,Brankica Šimac,Nora Nikolac Gabaj,Ivan Šamija,Nevenka Stančin,Marcela Živković,Sanja Tadinac,Marta Kmet,Sandra Šupraha Goreta

doi:10.11613/bm.2021.010708

Abstract

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests have been suggested as an additional diagnostic tool in highly suspected cases with a negative molecular test and determination of seroprevalence in population. We compared the diagnostic performance of eight commercial serological assays for IgA, IgM, and IgG antibodies to the SARS-CoV-2 virus.Materials and methodsThe comparison study was performed on a total of 76 serum samples: 30 SARS-CoV-2 polymerase chain reaction (PCR)-negative and 46 SARS-CoV-2 PCR-positive patients with asymptomatic to severe disease and symptoms duration from 3-30 days. The study included: three rapid lateral flow immunochromatographic assays (LFIC), two enzyme-linked immunosorbent assays (ELISA), and three chemiluminescence immunoassays (CLIA).ResultsAgreement between IgM assays were minimal to moderate (kappa 0.26 to 0.63) and for IgG moderate to excellent (kappa 0.72 to 0.92). Sensitivities improved with > 10 days of symptoms and were: 30% to 89% for IgM; 89% to 100% for IgG; 96% for IgA; 100% for IgA/IgM combination; 96% for total antibodies. Overall specificities were: 90% to 100% for IgM; 85% to 100% for IgG; 90% for IgA; 70% for IgA/IgM combination; 100% for total antibodies. Diagnostic accuracy for IgG ELISA and CIA assays were excellent (AUC ≥ 0.90), without significant difference. IgA showed significantly better diagnostic accuracy than IgM (P < 0.001).ConclusionThere is high variability between IgM assays independently of the assay format, while IgG assays showed moderate to perfect agreement. The appropriate time for testing is crucial for the proper immunity investigation.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests have been suggested as an additional diagnostic tool in highly suspected cases with a negative molecular test and determination of seroprevalence in population
SARS-CoV-2 polymerase chain reaction (PCR)-negative patients (N = 30) included the patients referred for reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 testing before hospitalization in Sestre Milosrdnice University Hospital Centre due to different indications and did not have symptoms associated with COVID-19 nor evidence of the previous SARSCoV-2 infection
Three fully automated assays were: the chemiluminescence immunoassays (CLIA) MAGLUMI 2019-nCoV IgG/IgM on Snibe Maglumi 800 analyser, chemiluminescent microparticle immunoassay (CMIA) Abbott SARS-CoV-2 IgG on Abbott Architect i2000SR analyser and electrochemiluminescence immunoassay (ECLIA) Roche Elecsys Anti-SARS-CoV-2 total antibody assay on Cobas e601 analyser

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests have been suggested as an additional diagnostic tool in highly suspected cases with a negative molecular test and determination of seroprevalence in population. Spike glycoprotein is a transmembrane protein responsible for the crown-like appearance (corona) of the virus particle and contains two functional subunits: S1 and S2. Clinical presentation varies from asymptomatic through mild and moderate symptoms which include cough, fever, shortness of breath, asthenia, arthralgia, myalgia, anosmia, and ageusia to the very severe and critical cases of severe pneumonia, septic shock, and acute respiratory distress syndrome (ARDS) [1,5]

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