J Clin Invest . Convalescent plasma anti-SARS-CoV-2 spike protein ectodomain and receptor binding domain IgG correlate with virus neutralization

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J Clin Invest


. 2020 Sep 10;141206.
doi: 10.1172/JCI141206. Online ahead of print.
Convalescent plasma anti-SARS-CoV-2 spike protein ectodomain and receptor binding domain IgG correlate with virus neutralization


Eric Salazar ¹ , Suresh V Kuchipudi ² , Paul A Christensen ¹ , Todd Eagar ¹ , Xin Yi ¹ , Picheng Zhao ¹ , Zhicheng Jin ¹ , S Wesley Long ¹ , Randall J Olsen ¹ , Jian Chen ¹ , Brian Castillo ¹ , Christopher Leveque ¹ , Dalton Towers ³ , Jason J Lavinder ³ , Jimmy Gollihar ⁴ , Jose A Cardona ⁴ , Gregory C Ippolito ³ , Ruth H Nissly ⁵ , Ian Bird ⁵ , Denver Greenawalt ⁵ , Randall M Rossi ⁶ , Abhinay Gontu ⁵ , Sreenidhi Srinivasan ⁶ , Indira Poojary ⁶ , Isabella M Cattadori ⁷ , Peter Hudson ⁷ , Nicole M Josleyn ⁸ , Laura Prugar ⁸ , Kathleen E Huie ⁸ , Andrew S Herbert ⁸ , David W Bernard ¹ , John M Dye ⁸ , Vivek Kapur ⁷ , James M Musser ¹



Affiliations

• PMID: 32910806
• DOI: 10.1172/JCI141206

Free article

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 between anti-spike ectodomain (ECD), anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two in vitro assays using convalescent plasma samples from 68 COVID-19 patients. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titer. The probability of a VN titer ≥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 ≥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 2,814 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 ≥1:160, all of which had anti-RBD titer ≥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.

Keywords: Adaptive immunity; Cellular immune response; Immunology; Infectious disease; Molecular pathology.