Analytical and clinical evaluation of four anti-SARS-CoV-2 serologic (IgM, IgG, and total) immunoassays

Abstract

Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is diagnosed by molecular-based detection of SARS-CoV-2 RNA. Serologic testing detects antibodies specific to SARS-CoV-2 and IgM specifically may serve as an adjunct test to PCR early in disease. We evaluated the Abbott anti-SARS-CoV-2 IgM and IgG assays along with DiaSorin anti-SARS-CoV-2 IgG and Roche anti-SARS-CoV-2 Total. Methods: Specimens from 175 PCR-positive patients and 107 control specimens were analyzed using Abbott IgM and IgG, DiaSorin IgG, and Roche Total (IgA, IgG, IgM) assays. Sensitivity, specificity, cross-reactivity, concordance between assays, trends over time, positive predictive value (PPV), and negative predictive value (NPV) were determined. Results: Abbott IgM sensitivity was 63.6% at 0 days post-PCR positivity, 76.5% at 1-5d, 76.3% at 6-14d, 85.2% at 15-30d, and 63.6% at >30d. All assays exhibited highest sensitivity 15-30d post-PCR positivity (83.3-85.2%). Combining Abbott IgM and IgG improved sensitivity by 22.7% compared to IgG alone when tested 0d post-PCR positivity. All assays had a specificity of 100% and only Abbott IgG exhibited cross-reactivity (anti-dsDNA). Cohen's kappa varied between 0.86-0.93. Time to seroconversion from PCR positivity was lowest for Abbott IgM and highest for Abbott IgG. NPV was highest for Abbott IgM <14 days post-PCR positivity and Abbott IgG ≥14 days. Conclusion: The Abbott IgM assay exhibited the earliest response and greatest signal in most patients evaluated for serial sampling and had the highest NPV <14 days post-PCR positivity, suggesting its potential utility as an adjunct test to PCR early in disease course.

Quantitative Measurement of Anti-SARS-CoV-2 Antibodies: Analytical and Clinical Evaluation

“…CIs slightly overlapped (Figure1). Sensitivity was higher ≥14 days post-PCR positivity (82.5% [95% CI: 73.6-91.4%]) compared to <14 days post-PCR positivity (67.1% [95% CI: 57.8%-76.5%]), although the CIs slightly overlapped.We previously determined the sensitivity of qualitative anti-SARS-CoV-2 serology assays, including the qualitative Roche anti-SARS-CoV-2 assay, using the same patient samples(10). No samples positive by the qualitative Roche anti-SARS-CoV-2 assay, were negative by the quantitative Roche anti-SARS-CoV 2 S assay.…”

Pengukuran Antibodi Kuantitatif Antibodi Anti-Sars-Cov-2

“…Higgins dkk. sebelumnya menentukan sensitivitas kualitatif serologi anti-SARS-CoV-2, termasuk milik Roche, menggunakan sampel pasien yang sama (Higgins et al, 2020). Tidak ada sampel yang secara kualitatif yang oleh Roche anti-SARS-CoV-2 menunjukkan hasil positif, menjadi negatif secara kuantitatif.…”

“…Higgins dkk. juga melaporkan heterogenitas pada respon antibodi yang diobservasi dengan 4 pemeriksaan serologis kualitatif (yaitu Abbott SARS-CoV-2 IgG dan SARS-CoV-2 IgM, DiaSorin SARS-CoV-2 S1/S2 IgG, dan Roche Elecsys anti SARS-CoV-2) yang menunjukkan level antibodi relatif dengan nilai ambang batas dari pabrik pembuatnya (Higgins et al, 2020). Beberapa penelitian lain juga melaporkan perbedaan respon antibodi SARS-CoV-2 antar individu (Deeks et al, 2020;Zhao et al, 2020), akan tetapi penelitian Higgins dkk.…”