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Stringent thresholds in SARS-CoV-2 IgG assays lead to under-detection of mild infections.
Eyre, David W; Lumley, Sheila F; O'Donnell, Denise; Stoesser, Nicole E; Matthews, Philippa C; Howarth, Alison; Hatch, Stephanie B; Marsden, Brian D; Cox, Stuart; James, Tim; Cornall, Richard J; Stuart, David I; Screaton, Gavin; Ebner, Daniel; Crook, Derrick W; Conlon, Christopher P; Jeffery, Katie; Walker, Timothy M; Peto, Timothy E A.
  • Eyre DW; Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK. david.eyre@bdi.ox.ac.uk.
  • Lumley SF; Oxford University Hospitals NHS Foundation Trust, Oxford, UK. david.eyre@bdi.ox.ac.uk.
  • O'Donnell D; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. david.eyre@bdi.ox.ac.uk.
  • Stoesser NE; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, Oxford, UK. david.eyre@bdi.ox.ac.uk.
  • Matthews PC; Microbiology Department, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK. david.eyre@bdi.ox.ac.uk.
  • Howarth A; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Hatch SB; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Marsden BD; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Cox S; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • James T; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Cornall RJ; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, Oxford, UK.
  • Stuart DI; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Screaton G; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Ebner D; NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Crook DW; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Conlon CP; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Jeffery K; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Walker TM; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Peto TEA; Kennedy Institute of Rheumatology Research, University of Oxford, Oxford, UK.
BMC Infect Dis ; 21(1): 187, 2021 Feb 18.
Article in English | MEDLINE | ID: covidwho-1090687
Semantic information from SemMedBD (by NLM)
1. Assay USES SARS-CoV-2 IgG
Subject
Assay
Predicate
USES
Object
SARS-CoV-2 IgG
2. Assay USES Antibodies
Subject
Assay
Predicate
USES
Object
Antibodies
3. High probability PROCESS_OF Persons
Subject
High probability
Predicate
PROCESS_OF
Object
Persons
4. Assay USES SARS-CoV-2 IgG
Subject
Assay
Predicate
USES
Object
SARS-CoV-2 IgG
5. Assay USES Antibodies
Subject
Assay
Predicate
USES
Object
Antibodies
6. High probability PROCESS_OF Persons
Subject
High probability
Predicate
PROCESS_OF
Object
Persons
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / COVID-19 Serological Testing / COVID-19 / Antibodies, Viral Type of study: Diagnostic study / Risk factors 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / COVID-19 Serological Testing / COVID-19 / Antibodies, Viral Type of study: Diagnostic study / Risk factors 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