Journal
BMC INFECTIOUS DISEASES
Volume 21, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12879-021-05878-2
Keywords
SARS-CoV-2; COVID-19; Serology; Antibodies; Anosmia; Ageusia
Categories
Funding
- UK Government's Department of Health and Social Care
- National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University
- Public Health England (PHE) [HPRU-2012-10041]
- NIHR Biomedical Research Centre, Oxford
- Medical Research Council [MR/N00065X/1]
- Wellcome Intermediate Fellowship [110110/Z/15/Z]
- SGC, a registered charity [1097737]
- AbbVie
- Bayer Pharma AG
- Boehringer Ingelheim
- Canada Foundation for Innovation
- Eshelman Institute for Innovation
- Genome Canada through Ontario Genomics Institute [OGI-055]
- Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant] [115766]
- Janssen
- Merck KGaA, Darmstadt, Germany
- MSD
- Novartis Pharma AG
- Pfizer
- Sao Paulo Research Foundation-FAPESP
- Takeda
- Wellcome
- Kennedy Trust for Rheumatology Research
- Schmidt Foundation
- Wellcome Trust [214560/Z/18/Z]
- MRC [MR/N00065X/1, MC_UU_00008/6] Funding Source: UKRI
- Wellcome Trust [214560/Z/18/Z] Funding Source: Wellcome Trust
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This study evaluated quantitative IgG responses in a cohort of healthcare workers in Oxford, UK, finding that following mild SARS-CoV-2 infection, a certain percentage of individuals may have negative immunoassay results. This has implications for epidemiological analyses and result interpretation in individuals with a high pre-test probability.
BackgroundThresholds 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.MethodsWe 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.ResultsThe 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%).ConclusionFollowing 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.
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