Stringent thresholds in SARS-CoV-2 IgG assays lead to under-detection of mild infections

BMC Infectious Diseases

David W. Eyre¹  Stephanie B. Hatch²  Richard J. Cornall²  Denise O’Donnell²  David I. Stuart²  Alison Howarth²  Brian D. Marsden²  Gavin Screaton²  Daniel Ebner²  Philippa C. Matthews³  Derrick W. Crook³  Katie Jeffery³  Stuart Cox³  Timothy M. Walker³  Tim James³  Christopher P. Conlon³  Nicole E. Stoesser³  Timothy E. A. Peto³  Sheila F. Lumley³ 

[1] Big Data Institute, Nuffield Department of Population Health, University of Oxford;Nuffield Department of Medicine, University of Oxford;Oxford University Hospitals NHS Foundation Trust;

关键词: SARS-CoV-2;    COVID-19;    Serology;    Antibodies;    Anosmia;    Ageusia;   

DOI  :  10.1186/s12879-021-05878-2

来源: DOAJ

【 摘 要 】

Abstract Background Thresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. In this setting the sensitivity and specificity of the best performing assays can both exceed 98%. However, antibody assay performance following mild infection is less clear. Methods We assessed quantitative IgG responses in a cohort of healthcare workers in Oxford, UK, with a high pre-test probability of Covid-19, in particular the 991/11,475(8.6%) who reported loss of smell/taste. We use anosmia/ageusia and other risk factors as probes for Covid-19 infection potentially undiagnosed by immunoassays by investigating their relationship with antibody readings either side of assay thresholds. Results The proportion of healthcare workers reporting anosmia/ageusia increased at antibody readings below diagnostic thresholds using an in-house ELISA (n = 9324) and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA; n = 11,324): 426/906 (47%) reported anosmia/ageusia with a positive ELISA, 59/449 (13.1%) with high-negative and 326/7969 (4.1%) with low-negative readings. Similarly, by CMIA, 518/1093 (47.4%) with a positive result reported anosmia/ageusia, 106/686 (15.5%) with a high-negative and 358/9563 (3.7%) with a low-negative result. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays in mild infection is lower than previously reported: Oxford ELISA 89.8% (95%CI 86.6–92.8%) and Abbott CMIA 79.3% (75.9–82.7%). Conclusion Following mild SARS-CoV-2 infection 10–30% of individuals may have negative immunoassay results. While lowered diagnostic thresholds may result in unacceptable specificity, our findings have implications for epidemiological analyses and result interpretation in individuals with a high pre-test probability. Samples from mild PCR-confirmed infections should be included in SARS-CoV-2 immunoassay evaluations.

【 授权许可】

Unknown