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), antireceptor-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.

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

“…Notably, one study showed that 40% of convalescent patients did not have any neutralizing activity (Prevost et al, 2020), suggesting that neutralizing antibodies are not absolutely required for infection resolution. As expected, significant correlations between neutralizing activities and anti-S protein antibody titers were observed (Ni et al, 2020;Prevost et al, 2020;Salazar et al, 2020;Wu et al, 2020a). Neutralizing antibody titers were also strongly correlated with the numbers of virus-specific T cells (Ni et al, 2020), suggesting coordinated humoral and cellular immune responses.…”

Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2

“…In addition to disease severity, we report for the first time that specific COVID-19 symptoms, namely fever, low appetite, abdominal pain, and diarrhea, consistently correlate with higher antibody titers (Table 3). Other symptoms did not correlate consistently or at all including shortness of breath, which a previous study of 68 COVID-19 convalescent subjects who donated plasma at various times post-infection found was associated with higher antibody titers (20). Fever and low appetite are signs of a systemic inflammatory response, suggesting that such an inflammatory response may be key for developing a strong anti-SARS-CoV-2 antibody response.…”

“…Also, different methods are used to detect antibody titers, and neutralizing titers tend to be low more often than anti-SARS-CoV-2 antibody levels (20,21). Of course, small sample size is a well-known cause of variable data.…”

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19

“… 27 Although this assay does not differentiate binding IgG antibodies from virus-neutralizing IgG antibodies, a strong correlation has been shown between the amount of antispike protein IgG and in vitro virus neutralization. 28 , 29 This IgG chemiluminescent immunoassay is a qualitative assay that is based on the detection of IgG antibodies against a recombinant form of the SARS-CoV-2 spike subunit 1 protein. Numerical results of the assay correspond to the ratio of the sample signal to a calibrator-assigned cutoff signal (the signal-to-cutoff ratio).…”