Convalescent plasma anti–SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization
Eric Salazar, … , Vivek Kapur, James M. Musser
Eric Salazar, … , Vivek Kapur, James M. Musser
Published September 10, 2020
Citation Information: J Clin Invest. 2020;130(12):6728-6738. https://doi.org/10.1172/JCI141206.
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Research Article Immunology Infectious disease

Convalescent plasma anti–SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization

Abstract

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), anti–receptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was ≥80% when anti-RBD or anti-ECD titers were ≥1:1350. Of all donors, 37% lacked VN titers of ≥160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of ≥1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of ≥1:160, and all of them had anti-RBD titers of ≥1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of ≥1:1350 may provide critical information about protection against COVID-19 disease.

Authors

Eric Salazar, Suresh V. Kuchipudi, Paul A. Christensen, Todd Eagar, Xin Yi, Picheng Zhao, Zhicheng Jin, S. Wesley Long, Randall J. Olsen, Jian Chen, Brian Castillo, Christopher Leveque, Dalton Towers, Jason Lavinder, Jimmy Gollihar, Jose Cardona, Gregory Ippolito, Ruth Nissly, Ian Bird, Denver Greenawalt, Randall M. Rossi, Abhinay Gontu, Sreenidhi Srinivasan, Indira Poojary, Isabella M. Cattadori, Peter J. Hudson, Nicole M. Josleyn, Laura Prugar, Kathleen Huie, Andrew Herbert, David W. Bernard, John M. Dye, Vivek Kapur, James M. Musser

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Figure 2

Prevalence of donors with VN >160 for VN2, ECD, and RBD.

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Prevalence of donors with VN >160 for VN2, ECD, and RBD. Probabilitie...
Probabilities of VN ≥160 were plotted for 6 range classes, with an interclass interval of 1.8 log2 IC50 values (class 1, <2; class 2, 2–12; class 3, 12–42; class 4, 42–147; class 5, 147–512; and class 6, >512) or observed classes for ECD (n = 6) and RBD (n = 8) reciprocal ELISA titers. A spline curve (dotted line, smoothness shape = 1) has been fitted to the probability values and standard errors (bars) are reported. The numbers of donor samples are shown above the bars.