Comparison of two assays to detect IgG antibodies to the receptor binding domain of SARS‑CoV‑2 as a surrogate marker for assessing neutralizing antibodies in COVID-19 patients

Background: Neutralizing antibodies (NAbs) are important for protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. In this study, two assays that are correlated with NAbs were compared: the haemagglutination test (HAT) and the surrogate virus neutralization test (sVNT).

Methods: The specificity of the HAT was compared with the sVNT, and the sensitivity and persistence of antibodies in patients with varying severity of illness was assessed in a cohort of 71 patients at 4-6 weeks and 13-16 weeks. The kinetics were assessed in the first, second, and third weeks in patients with varying severity of acute illness.

Results: The specificity of the HAT was >99%, and sensitivity was similar to the sVNT. The levels of HAT were significantly and positively correlated with those of the sVNT (Spearman's r = 0.78, P < 0.0001). Patients with moderate and severe illness had higher HAT titres when compared to those with mild illness. Six of seven patients with severe illness had a titre of >1:640 during the second week of illness, whereas only five of 31 patients with a mild illness had a titre of >1:160 in the second week of illness.

Conclusions: Since the HAT is a simple and very cheap assay to perform, it would be ideal to use as an indicator of NAbs in resource-poor settings.