Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel

Adams, Emily R.; Ainsworth, Mark; Anand, Rekha; Andersson, Monique I.; Auckland, Kathryn; Baillie, J. Kenneth; Barnes, Eleanor; Beer, Sally; Bell, John I.; Berry, Tamsin; Bibi, Sagida; Carroll, Miles; Chinnakannan, Senthil K.; Clutterbuck, Elizabeth; Cornall, Richard J.; Crook, Derrick W.; de Silva, Thushan; Dejnirattisai, Wanwisa; Dingle, Kate E.; Dold, Christina; Espinosa, Alexis; Eyre, David W.; Farmer, Helen; Fernandez Mendoza, Maria; Georgiou, Dominique; Hoosdally, Sarah J.; Hunter, Alastair; Jefferey, Katie; Kelly, Dominic F.; Klenerman, Paul; Knight, Julian; Knowles, Clarice; Kwok, Andrew J.; Leuschner, Ullrich; Levin, Robert; Liu, Chang; López-Camacho, César; Martinez, Jose; Matthews, Philippa C.; McGivern, Hannah; Mentzer, Alexander J.; Milton, Jonathan; Mongkolsapaya, Juthathip; Moore, Shona C.; Oliveira, Marta S.; Pereira, Fiona; Perez, Elena; Peto, Timothy; Ploeg, Rutger J.; Pollard, Andrew; Prince, Tessa; Roberts, David J.; Rudkin, Justine K.; Sanchez, Veronica; Screaton, Gavin R.; Semple, Malcolm G.; Slon-Campos, Jose; Skelly, Donal T.; Smith, Elliot Nathan; Sobrinodiaz, Alberto; Staves, Julie; Stuart, David I.; Supasa, Piyada; Surik, Tomas; Thraves, Hannah; Tsang, Pat; Turtle, Lance; Walker, A. Sarah; Wang, Beibei; Washington, Charlotte; Watkins, Nicholas; Whitehouse, James

Background: The COVID-19 pandemic caused >1 million infections during January-March 2020. There is an urgent need for reliable antibody detection approaches to support diagnosis, vaccine development, safe release of individuals from quarantine, and population lock-down exit strategies. We set out to evaluate the performance of ELISA and lateral flow immunoassay (LFIA) devices. Methods: We tested plasma for COVID (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. We used a panel of plasma samples from individuals who have had confirmed COVID infection based on a PCR result (n=40), and pre-pandemic negative control samples banked in the UK prior to December-2019 (n=142). Results: ELISA detected IgM or IgG in 34/40 individuals with a confirmed history of COVID infection (sensitivity 85%, 95%CI 70-94%), vs. 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 COVID-positive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%). IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions: Currently available commercial LFIA devices do not perform sufficiently well for individual patient applications. However, ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following first symptoms.