Collaborative networks enable the rapid establishment of serological assays for SARS-CoV-2 during nationwide lockdown in New Zealand
spike protein, serology, covid-19, SARS-CoV-2, neutralising antibodies
Background Serological assays that detect antibodies to SARS-CoV-2 are critical for determining past infection and investigating immune responses in the COVID-19 pandemic. We established ELISA-based immunoassays using locally produced antigens when New Zealand went into a nationwide lockdown and the supply chain of diagnostic reagents was a widely held domestic concern. The relationship between serum antibody binding measured by ELISA and neutralising capacity was investigated using a surrogate viral neutralisation test (sVNT). Methods A pre-pandemic sera panel (n = 113), including respiratory infections with symptom overlap with COVID-19, was used to establish assay specificity. Sera from PCR‑confirmed SARS-CoV-2 patients (n = 21), and PCR-negative patients with respiratory symptoms suggestive of COVID-19 (n = 82) that presented to the two largest hospitals in Auckland during the lockdown period were included. A two-step IgG ELISA based on the receptor binding domain (RBD) and spike protein was adapted to determine seropositivity, and neutralising antibodies that block the RBD/hACE‑2 interaction were quantified by sVNT. Results The calculated cut-off (>0.2) in the two-step ELISA maximised specificity by classifying all pre-pandemic samples as negative. Sera from all PCR-confirmed COVID-19 patients were classified as seropositive by ELISA ≥7 days after symptom onset. There was 100% concordance between the two-step ELISA and the sVNT with all 7+ day sera from PCR‑confirmed COVID-19 patients also classified as positive with respect to neutralising antibodies. Of the symptomatic PCR-negative cohort, one individual with notable travel history was classified as positive by two-step ELISA and sVNT, demonstrating the value of serology in detecting prior infection. Conclusions These serological assays were established and assessed at a time when human activity was severely restricted in New Zealand. This was achieved by generous sharing of reagents and technical expertise by the international scientific community, and highly collaborative efforts of scientists and clinicians across the country. The assays have immediate utility in supporting clinical diagnostics, understanding transmission in high-risk cohorts and underpinning longer‑term ‘exit’ strategies based on effective vaccines and therapeutics.
Michael G. Baker, Reuben McGregor, Alana L. Whitcombe, Campbell R. Sheen, James M. Dickson, Catherine L. Day, Lauren H. Carlton, Prachi Sharma, J. Shaun Lott, Barbara Koch, Julie Bennett, Stephen R. Ritchie, Shivani Fox-Lewis, Susan C. Morpeth, Susan L. Taylor, Sally A. Roberts, Rachel H. Webb, Nicole J. Moreland