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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.18.20038059 doi: medRxiv preprint When testing the specificity S1 or its RBD for detecting SARS-CoV-2 antibodies, none of the sera form the validation cohorts (A-E) showed any reactivity; except for SARS-CoV patients sera. This -not-unexpected -cross-reactivity resulted from the high degree of similarity between the S1 and RBD of the SARS-CoV and SARS-CoV-2 ( Table 2) . However, SARS-CoV has not circulated in the human population since 2003, i.e. 17 years ago, and an earlier study reported waning of SARS-CoV-specific antibodies which made them undetectable in serum samples of 91% (21/23) of samples tested 6 years following infection (11) . It is therefore unlikely that antibodies to this virus are present in the population and thus there could hardly be a chance that false positives result from SARS-CoV-antibodies reactivity. Meanwhile, we made use of the high degree of similarity between the SARS-CoV and SARS-CoV-2 proteins for the development of our inhouse N ELISA, where we used SARS-CoV N (90% similar to SARS-CoV-2) as an antigen. The N-ELISA could detect SARS-CoV-2-specific antibodies with high specificity and sensitivity. Using the three different validated ELISAs, we found that antibody levels were higher following the severe infection compared to the mild ones; similar findings has been reported earlier for MERS-CoV (12, 13) . However, this needs to be confirmed with a larger cohort of patients with varying degrees of severity, while it still highlights the potential need of a sensitive assay to avoid missing those with milder infections in epidemiological studies. Among the 3 inhouse ELISAs tested, the RBD and N ELISAs were more sensitive than S1 ELISA in detecting antibodies in mildly infected patients and showed stronger correlation with PRNT50 titers. Therefore, detecting antibodies against two different antigens might be needed to confirm the findings and avoid false negatives in surveillance studies. However, the sensitivities of the assays need to be further validated with a larger cohort.