Stringent thresholds for SARS-CoV-2 IgG assays result in under-detection of cases reporting loss of taste/smell

Eyre, David W; Lumley, Sheila F; Stoesser, Nicole E; Matthews, Philippa C; Howarth, Alison; Hatch, Stephanie B; Marsden, Brian D; Cox, Stuart; James, Tim; Cornall, Richard; Stuart, David I; Screaton, Gavin; Ebner, Daniel; Crook, Derrick W; Conlon, Christopher P; Jeffery, Katie; Walker, Timothy M; Peto, Tim EA

Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. Assay performance following mild/asymptomatic infection is unclear. We assessed IgG responses in asymptomatic healthcare workers with a high pre-test probability of Covid-19, e.g. 807/9292(8.9%) reported loss of smell/taste. The proportion reporting anosmia/ageusia increased at antibody titres below diagnostic thresholds for both an in-house ELISA and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA): 424/903(47%) reported anosmia/ageusia with a positive ELISA, 59/387(13.2%) with high-negative titres, and 324/7943(4.1%) with low-negative results. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays is lower than previously reported: Oxford ELISA 90.8% (95%CI 86.1-92.1%) and Abbott CMIA 80.9% (77.5-84.3%). However, the sensitivity may be lower if some anosmia/ageusia in those with low-negative titres is Covid-19-associated. Samples from individuals with mild/asymptomatic infection should be included in SARS-CoV-2 immunoassay evaluations. Reporting equivocal SARS-CoV-2 antibody results should be considered.