Antibody testing for COVID-19: A report from the National COVID Scientific Advisory Panel
Adams E., Ainsworth M., Anand R., Andersson M., Auckland K., Baillie K., Barnes E., Beer S., Bell J., Berry T., Bibi S., Carroll M., Chinnakannan S., Clutterbuck E., Cornall R., Crook D., de Silva T., Dejnirattisai W., Dingle K., Dold C., Espinosa A., Eyre D., Farmer H., Mendoza MF., Georgiou D., Hoosdally S., Hunter A., Jeffery K., Klenerman P., Knight J., Knowles C., Kwok A., Leuschner U., Levin R., Liu C., López-Camacho C., Martinez J., Matthews P., McGivern H., Mentzer A., Milton J., Mongkolsapaya J., Moore S., Oliveira M., Pereira F., Perez E., Peto T., Ploeg R., Pollard A., Prince T., Roberts D., Rudkin J., Sanchez V., Screaton G., Semple M., Skelly D., Slon-Campos J., Smith EN., Sobrinodiaz A., Staves J., Stuart D., Supasa P., Surik T., Thraves H., Tsang P., Turtle L., Walker S., Wang B., Washington C., Watkins N., Whitehouse J.
ABSTRACT Objectives 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. Design We tested plasma for COVID (SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. Setting We performed laboratory work at the University of Oxford. Participants 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). Main outcome measures We recorded optical density results from ELISA experiments and positive/negative/invalid results from LFIA devices. 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. 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.