SARS-CoV-2 specific antibody responses in COVID-19 patients

NISREEN M.A. OKBA; Marcel A Muller; Wentao Li; Chunyan Wang; Corine H. GeurtsvanKessel; Victor M. Corman; Mart M. Lamers; Reina S. Sikkema; Erwin de Bruin; Felicity D. Chandler; Yazdan Yazdanpanah; Quentin Le Hingrat; Diane Descamps; Nadhira Houhou-Fidouh; Chantal B. E. M. Reusken; Berend-Jan Bosch; Christian Drosten; Marion P.G. Koopmans; Bart L. Haagmans

Validated SARS-CoV-2 serological assays are currently lacking, yet urgently needed for contact tracing, epidemiological and vaccine evaluation studies. Since the N and the S proteins are the main immunogenic CoV proteins, we developed ELISA-based assays, which were able to detect antibodies to these two proteins along with the two spike domains, S1 A and RBD. Those correlated strongly with virus neutralizing antibodies detected by a PRNT50 assay. Since the majority of the human population has antibodies against the four endemic human coronaviruses, it was crucial to verify the specificity of these assays to avoid false positive results. Additionally, the two zoonotic coronaviruses, SARS-CoV and MERS-CoV, are also beta-coronaviruses, raising potential for cross-reactivity. Among the spike protein antigens tested, the S1 was more specific than S in detecting SARS-CoV-2 antibodies, as MERS-CoV-S cross-reactive antibodies were detected in the serum of one of the COVID-19 patients which was not seen when MERS-CoV S1 was used for testing. This could be explained by the high degree of conservation in the CoV S2 subunit relative to the S1 ( Table 2) . Therefore, consistent with our earlier findings for MERS-CoV serology (6), S1 is a specific antigen for SARS-CoV-2 diagnostics. All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.