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3 Clinical implications of the differential antibody response in mild-moderate SARS-CoV-2: a prospective multi-centre cross-sectional study
  1. Scott Pallett1,
  2. Rachael Jones2,
  3. Michael Rayment2,
  4. Mitchell A Pallett3,
  5. Nabeela Mughal2,
  6. Carolina Rosadas de Oliveira4,
  7. Paul Randell5,
  8. Gary W Davies2,
  9. Richard Tedder4,
  10. Myra O McClure4,
  11. Matthew K O’Shea1,6 and
  12. Luke SP Moore7
  1. 1Centre of Defence Pathology, Royal Centre for Defence Medicine, Birmingham, UK
  2. 2Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
  3. 3Department of Infectious Disease, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, UK
  4. 4North West London Pathology, Fulham Palace Road, London, UK
  5. 5Department of Infectious Disease, Faculty of Medicine, Imperial College London, St Mary’s Campus, UK
  6. 6Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
  7. 7NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, London, UK


Introduction Serological testing can augment delayed case identification programmes for Severe Acute Respiratory Syndrome coronoravirus-2 (SARS-CoV-2). Immunoassays employ anti-nucleocapsid (anti-NP; the majority) or potentially neutralising anti-spike (including anti-receptor binding domain; anti-RBD) antibody targets, yet correlation between assays and variability arising from disease symptomatology remains unclear. We explore these possibly differential immune responses across the disease spectrum.

Methods A multicentre prospective study was undertaken via a SARS-CoV-2 delayed case identification programme (08 May-11 July 2020). Matched samples were tested for anti-NP and anti-RBD (utilising an ‘inhouse’ double-antigen bridged assay), reactivity expressed as test/cut-off binding ratios (BR) and results compared. A multivariate linear regression model analysed age, sex, symptomatology, PCR positivity, anti-NP, and anti-RBD BRs. Participants were followed up for possible reinfection.

Results 902 individuals underwent matched testing; 109 were SARS-CoV-2 PCR swab positive. Anti-NP, anti-RBD immunoassay agreement was 87.5% (95% CI 85.3–89.6), with BRs strongly correlated (R=0.75). PCR confirmed cases were more frequently identified by anti-RBD (sensitivity 108/109, 99.1%, 95% CI 95.0–100.0) than anti-NP (102/109, 93.6%, 95% CI 87.2–97.4). Anti-RBD identified an additional 83/325 (25.5%) cases in those seronegative for anti-NP. Presence of anti-NP (p<0.0001), fever (p=0.005), or anosmia (p=0.002) were all significantly associated with an increased anti-RBD BR. Age was associated with reduced anti-RBD BR (p=0.052). Three cases with evidence of seroconversion (anti-RBD seropositive) presented with subsequent reactive PCR results, two of which coincided with first time onset of Public Heath England SARS-CoV-2 symptoms.

Conclusions SARS-CoV-2 anti-RBD shows significant correlation with anti-NP for absolute seroconversion, and BRs. Higher BRs are seen in symptomatic individuals with significantly higher levels seen in those with fever and anosmia. The degree of discordant results (12.5%) limits the use of anti-NP as a stand-alone for delayed case finding programmes. Similarly, this discordance limits the utility of non-neutralising anti-NP assays in place of potentially neutralising anti-RBD to infer possible immunity.

** this abstract presentation was awarded an Honourable Mention

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