Abstract
We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has spread rapidly around the world since first identified in Wuhan, China, in December 2019 (1)
We characterize the kinetics and antibody isotype profile to the receptor binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a longitudinal cohort of North American patients infected with SARS-CoV-2, most of whom were hospitalized for COVID-19, and in pre-pandemic controls
Study cohorts Using an in-house enzyme linked immunosorbent assay (ELISA), we measured anti-RBD antibody responses in two cohorts: 1) symptomatic patients who tested positive for SARS-CoV-2 by PCR (n = 343) and 2) healthy (n = 1,515) and febrile controls (n = 33) collected prior to the SARS-CoV-2 pandemic
Summary
CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has spread rapidly around the world since first identified in Wuhan, China, in December 2019 (1). Our understanding of antibody responses following infection with SARS-CoV-2 is limited (3–5). We lack detailed descriptions and precise estimates concerning the magnitude and duration of responses, crossreactivity with other coronaviruses and viral respiratory pathogens, and correlates of protective immunity following infection. A detailed characterization of antibody responses is needed to determine whether antibody-based tests can augment viral detection-based assays in the diagnosis of active. We characterize the kinetics and antibody isotype profile to the receptor binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a longitudinal cohort of North American patients infected with SARS-CoV-2, most of whom were hospitalized for COVID-19, and in pre-pandemic controls. We evaluated the cross-reactivity of these responses with other coronavirus RBDs and characterize assay performance using dried blood spots as an alternative to serum or plasma
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