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

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 greater than or equal to 160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was greater than or equal to 80 percent when anti-RBD or anti-ECD titers were greater than or equal to 1:1350. Of all donors, 37 percent lacked VN titers of greater than or equal to 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 greater than or equal to 1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of greater than or equal to 1:160, and all of them had anti-RBD titers of greater than or equal to 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 greater than or equal to 1:1350 may provide critical information about protection against COVID-19 disease.