ABSTRACT
BackgroundDetailed understanding of the immune response to SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), has been hampered by a lack of quantitative antibody assays. ObjectiveTo develop a quantitative assay for IgG to SARS-CoV-2 proteins that could readily be implemented in clinical and research laboratories. MethodsThe biotin-streptavidin technique was used to conjugate SARS-CoV-2 spike receptor-binding-domain (RBD) or nucleocapsid protein to the solid-phase of the ImmunoCAP resin. Plasma and serum samples from patients with COVID-19 (n=51) and samples from donors banked prior to the emergence of COVID-19 (n=109) were used in the assay. SARS-CoV-2 IgG levels were followed longitudinally in a subset of samples and were related to total IgG and IgG to reference antigens using an ImmunoCAP 250 platform. ResultsPerformance characteristics demonstrated 100% sensitivity and 99% specificity at a cut-off level of 2.5 {micro}g/mL for both SARS-CoV-2 proteins. Among 36 patients evaluated in a post-hospital follow-up clinic, median levels of IgG to spike-RBD and nucleocapsid were 34.7 {micro}g/mL (IQR 18-52) and 24.5 {micro}g/mL (IQR 9-59), respectively. Among 17 patients with longitudinal samples there was a wide variation in the magnitude of IgG responses, but generally the response to spike-RBD and to nucleocapsid occurred in parallel, with peak levels approaching 100 {micro}g/mL, or 1% of total IgG. ConclusionsWe have described a quantitative assay to measure IgG to SARS-CoV-2 that could be used in clinical and research laboratories and implemented at scale. The assay can easily be adapted to measure IgG to novel antigens, has good performance characteristics and a read-out in standardized units.
ABSTRACT
BackgroundThe novel severe acute respiratory coronavirus 2 (SARS-CoV-2) that causes COVID-19 originated in December 2019 and has now infected over 3 million people in the United States. In Spring of 2020, private laboratories and some hospitals began antibody testing despite lacking evidence-based guidance. ObjectiveTo describe clinician-described indications for SARS-CoV-2 antibody testing, including cost implications, immediately following testing availability. DesignRetrospective chart review of patients who received antibody testing from May 14, 2020 to June 15, 2020. SettingA large academic medical center, one of the first in the US to provide antibody testing capability to individual clinicians. Patients447 consecutive patients who received SARS-CoV-2 antibody testing. MeasurementsClinician-described indications for SARS-CoV-2 antibody testing, cost implications, and comparison with current expert-based guidance from the IDSA and CDC. ResultsOf 444 individual antibody test results meeting inclusion criteria, the two most commonly described indications for ordering the antibody test, apart from public health epidemiology studies (n=223), were for patients with a now resolved COVID-19 compatible illness (n=105) with no previous molecular testing and in asymptomatic patients believed to have had a past exposure or contact with a person with COVID-19 compatible illness (n=60). The rate of positive SARS-CoV-2 antibody testing among those indications consistent with current IDSA and CDC guidance was 17% compared with 5% (p<0.0001) among those indications inconsistent with current IDSA and CDC guidance. Total cost estimates ranged from $57,720 to $97,680, of which 42% was for testing inconsistent with current expert-based guidance. LimitationsThe duration of antibody response following infection is unclear and asymptomatic individuals may not develop a positive antibody response. ConclusionsOur findings demonstrate a dissociation between clinician described indications for testing and expert-based guidance and a significantly different rate of positive testing between these two groups. Clinical curiosity and patient preference appear to have played a significant role in testing decisions and substantially contributed to testing costs.
