Dynamics and significance of the antibody response to SARS-CoV-2 infection

Abstract

BACKGROUND Characterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODS We measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic. RESULTS Between 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63. CONCLUSIONS Among symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.

Kinetics of Nucleo- and Spike Protein-Specific Immunoglobulin G and of Virus-Neutralizing Antibodies after SARS-CoV-2 Infection

“…Very recently, differences in the kinetics of N- or S-specific IgG came into the focus of research [ 16 ]. While a decline in the IgG directed against the N protein was evident, the response to the S protein or its RBD was found to be more stable [ 16 , 17 ] and was associated with the presence of virus-neutralizing antibodies [ 17 ]. To the best of our knowledge, clinically validated assays for the specific detection of IgG directed against the SARS-CoV-2 surface proteins E and M are not yet available.…”

Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

“…In the past few months, several studies have focused on studying the humoral response against SARS-CoV-2 in COVID-19 patients, with antibodies against S1 and N antigens found to emerge as early as one week following disease onset and persist for at least three month after infection [18,[20][21][22][23][24]. Here, we studied the kinetics of SARS-CoV-2 specific antibodies to S1 and N viral proteins in blood samples collected between 4 to 70 days post-symptoms onset from a cohort of 87 COVID-19 patients with different disease presentations (i.e.…”

SARS-CoV-2 vaccines in development

“…Antibodies directed to S, including ones targeting the RBD and with targets outside of the RBD, have been shown to neutralize the virus [14][15][16][17][18] . In addition, while the magnitude of the antibody response to S is very heterogenous, it looks so far like a normal antibody response to a respiratory virus with an initial plasmablast-derived boost of antibodies, followed by some decline and then a potential stabilization at a baseline maintained by long lived plasma cells 17,19,20 . Mucosal antibody responses are also induced by natural infection in humans 19,21 .…”