Correlation of Automated Chemiluminescent Method with Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titers in Convalescent COVID-19 Plasma Samples: Development of Rapid, Cost-Effective Semi-Quantitative Diagnostic Methods

Rachelle Mendoza,¹ Michael Silver,^2,3 Alejandro R Zuretti,^1,4 Manan Christian,⁴ Ballabh Das,⁵ Allen J Norin,⁵ Patrick Borgen,⁶ Jenny Libien,^1,4 Martin H Bluth<sup>4

1</sup>Department of Pathology, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; ²School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; ³Department of Medicine, Maimonides Medical Center, Brooklyn, NY, USA; ⁴Department of Pathology, Maimonides Medical Center, Brooklyn, NY, USA; ⁵Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, USA; ⁶Department of Surgery, Maimonides Medical Center, Brooklyn, NY, USA

Correspondence: Martin H Bluth
Blood Transfusion and Donor Services, Clinical Laboratories, Translational Research (Pathology), Maimonides Medical Center, 4802 10 th Avenue, Brooklyn, NY, 11219, USA
Email [email protected]

Background: We investigated the utility of an automated chemiluminescent SARS-CoV-2 IgG antibody assay platform in quantifying the amount of binding antibodies present in donated convalescent plasma.
Methods: A total of 179 convalescent plasma units were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Beckman-Coulter chemiluminescent immunoassay (CLIA) platform. The equipment-derived numerical values (S/Co ratio) were recorded. Aliquots from the same units were subjected to enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 S1 protein. The relationship between ELISA titers and CLIA S/Co values was analyzed using linear regression and receiver operating characteristics (ROC) curve.
Results: Twenty-one samples (11.7%) had S/Co values of less than 1.0 and were deemed negative for antibodies and convalescent plasma had S/Co values between > 1.0 and 5.0 (70/179, 39.1%). Fifteen units (8.4%) had negative ELISA titer. The majority of the units (95/179. 53.1%) had titers ≥ 1:1024. The sensitivities of ELISA to CLIA were comparable (90.5% vs 88.3%, respectively; p=0.18). There was positive linear correlation between CLIA S/Co values and ELISA IgG titer (Rho = 0.75; Spearman’s rank = 0.82, p-value = < 0.0001). The agreement between the two methods was fair, with a κ index of 0.2741. Using the ROC analysis, we identified a CLIA S/Co cutoff value of 8.2, which gives a sensitivity of 90% and a specificity of 82% in predicting a titer dilution of ≥ 1:1024.
Conclusion: The utility of automated antibody detection systems can be extended from simply a screening method to a semi-quantitative and quantitative functional antibody analysis. CLIA S/Co values can be used to reliably estimate the ELISA antibody titer. Incorporation of chemiluminescent-based methods can provide rapid, cost-effective means of identifying anti-SARS-CoV-2 antibody titers in donated plasma for use in the treatment of COVID-19 infection.

Keywords: COVID-19, ELISA, chemiluminescence, antibody, titers