McAndrews, Kathleen M.Dowlatshahi, Dara P.Dai, JianliBecker, Lisa M.Hensel, JanineSnowden, Laura M.Leveille, Jennifer M.Brunner, Michael R.Holden, Kylie W.Hopkins, Nikolas S.Harris, Alexandria M.Kumpati, JerushaWhitt, Michael A.Lee, J. JackOstrosky-Zeichner, Luis L.Papanna, RameshaLeBleu, Valerie S.Allison, James P.Kalluri, Raghu2021-08-032021-08-032020McAndrews, Kathleen M., Dowlatshahi, Dara P., Dai, Jianli, et al.. "Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity." <i>JCI Insight,</i> 5, no. 18 (2020) American Society for Clinical Investigation: https://doi.org/10.1172/jci.insight.142386.https://hdl.handle.net/1911/111072Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR–confirmed, SARS-CoV-2–hospitalized patients, as well as 464 healthy and non–COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non–COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD–binding antibodies exhibited neutralizing capacity, but only 74% of N-protein–positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein–binding antibodies does not always correlate with presence of S-RBD–neutralizing antibodies and caution against the extensive use of N-protein–based serology testing for determination of potential COVID-19 immunity.engThis work is licensed under the Creative Commons Attribution 4.0 International License.Journal articlehttps://doi.org/10.1172/jci.insight.142386