Abstract
Evaluation 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.
Highlights
COVID-19, a respiratory illness caused by infection with the novel coronavirus severe acute respiratory syndrome (SARS)-CoV-2, is a rampant health crisis that has severely affected the financial security and access to care of many, in particular our most vulnerable communities [1, 2]
Our study demonstrates ELISA-based detection of antibodies for spike protein receptor binding domain (S-RBD) and N-protein in the serum of patients infected with SARS-CoV-2
Our findings, obtained from the analysis of 138 serial serum samples from 30 SARS-CoV-2 reverse transcription PCR (RT-PCR)–positive patients with severe disease, and 464 control serum samples collected between June 2017 and June 2020, support other studies published recently, to a certain extent [10, 18, 21, 26]
Summary
COVID-19, a respiratory illness caused by infection with the novel coronavirus SARS-CoV-2, is a rampant health crisis that has severely affected the financial security and access to care of many, in particular our most vulnerable communities [1, 2]. The activation of the immune system in response to SARSCoV-2 infection and the clinical sequela is complex, and further studies are required to measure precise immune responses and development of immunity. Emerging data indicate that these unaccounted cases could underestimate the reported percentage of the population that has been exposed to, and possibly developed immunity to, SARS-CoV-2 [6,7,8,9]
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