Abstract
Background: Serological testing in the COVID-19 pandemic is mainly implemented to gain sero-epidemiological data, but can also retrospectively inform about suspected SARS-CoV-2 infection.
Method: We verified and applied a two-tiered testing strategy combining a SARS-CoV-2 receptor-binding domain (RBD)-specific lateral flow assay (LFA) with a nucleocapsid protein (NCP) IgG ELISA to assess seroconversion in n = 7241 individuals. The majority had experienced symptoms consistent with COVID-19, but had no access to RT-PCR testing. Longitudinal follow-up in n = 97 LFA + individuals was performed up to 20 weeks after initial infection using NCP and spike protein S1 domain (S1) IgG ELISAs and a surrogate virus neutralization test (sVNT).
Results: Individuals reporting symptoms from January 2020 onwards showed seroconversion, as did a considerable proportion of asymptomatic individuals. Seroconversion for symptomatic and asymptomatic individuals was higher in an area with a known infection cluster compared to a low incidence area. Overall, 94% of individuals with a positive IgG result by LFA were confirmed by NCP ELISA. The proportion of ELISA-confirmed LFA results declined over time, in line with contracting NCP IgG titres during longitudinal follow-up. Neutralizing antibody activity was considerably more stable than S1 and NCP IgG titres, and both reach a plateau after approximately 100 d. The sVNT proved to be not only highly specific, but also more sensitive than the specificity-focussed two-tiered serology approach.
Conclusions: Our results demonstrate the high specificity of two-tiered serology testing and highlight the sVNT used as a valuable tool to support modelling of SARS-CoV-2 transmission dynamics, complement molecular testing and provide relevant information to individuals.
Keywords: ELISA; SARS-CoV-2; lateral flow assay; longevity; neutralizing antibodies; serology.
【저자키워드】 SARS-CoV-2, Neutralizing antibodies, serology, ELISA, lateral flow assay, Longevity, 【초록키워드】 IgG, Neutralizing antibodies, serology, antibody, SARS-COV-2 infection, COVID-19 pandemic, Infection, complement, Symptom, ELISA, Spike protein, nucleocapsid protein, lateral flow, specificity, SARS-CoV-2 transmission, Seroconversion, Asymptomatic individuals, Serological testing, serology testing, virus neutralization test, neutralization test, Cluster, Neutralizing, Follow-up, incidence, molecular, IgG ELISA, Longevity, information, longitudinal, surrogate virus neutralization test, an area, Support, RT-PCR testing, titres, individual, sVNT, domain, titre, positive, plateau, S1 domain, approach, highlight, initial, proportion, applied, was performed, majority, individuals, had no, declined, reporting symptom, symptomatic and asymptomatic, with COVID-19, 【제목키워드】 neutralizing antibody, Spike protein, stability, nucleocapsid, domain, Netherland,