Stringent thresholds in SARS-CoV-2 IgG assays lead to under-detection of mild infections.
BMC Infect Dis
; 21(1): 187, 2021 Feb 18.
Article
in English
| MEDLINE | ID: covidwho-1090687
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Immunoglobulin G
/
COVID-19 Serological Testing
/
COVID-19
/
Antibodies, Viral
Type of study:
Cohort study
/
Diagnostic study
/
Experimental Studies
/
Observational study
/
Prognostic study
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
English
Journal:
BMC Infect Dis
Journal subject:
Communicable Diseases
Year:
2021
Document Type:
Article
Affiliation country:
S12879-021-05878-2
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