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Abstract

Introduction

Immunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear.

Aims

We aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology.

Methods

A multicentre prospective cross-sectional study was undertaken (April–July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR.

Results

We included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2–89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p < 0.001), fever (≥ 38°C; +1.81; p < 0.001) or anosmia (+1.91; p < 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p < 0.001).

Conclusion

SARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.

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/content/10.2807/1560-7917.ES.2022.27.4.2002076
2022-01-27
2024-11-23
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2022.27.4.2002076
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References

  1. World Health Organisation (WHO). WHO announces COVID-19 outbreak a pandemic. Geneva: WHO; 2020. Available from: https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic
  2. Gao Z, Xu Y, Sun C, Wang X, Guo Y, Qiu S, et al. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect. 2020;54(1):12-6.  https://doi.org/10.1016/j.jmii.2020.05.001  PMID: 32425996 
  3. Pallett SJC, Rayment M, Patel A, Fitzgerald-Smith SAM, Denny SJ, Charani E, et al. Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study. Lancet Respir Med. 2020;8(9):885-94.  https://doi.org/10.1016/S2213-2600(20)30315-5  PMID: 32717210 
  4. Ward H, Atchinson CJ, Whitaker M, Ainslie KEC, Elliott J, Okell LC, et al. Antibody prevalence for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults. medRxiv. 2020.08.12.20173690. preprint.  https://doi.org/10.1101/2020.08.12.20173690 . https://doi.org/10.1101/2020.08.12.20173690 
  5. Tré-Hardy M, Blairon L, Wilmet A, Beukinga I, Malonne H, Dogné JM, et al. The role of serology for COVID-19 control: Population, kinetics and test performance do matter. J Infect. 2020;81(2):e91-2.  https://doi.org/10.1016/j.jinf.2020.05.019  PMID: 32417311 
  6. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.  https://doi.org/10.1038/s41577-020-0311-8  PMID: 32346093 
  7. Lumley SF, O’Donnell D, Stoesser NE, Matthews PC, Howarth A, Hatch SB, et al. . Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med. 2021;384(6):533-40.  https://doi.org/10.1056/NEJMoa2034545  PMID: 33369366 
  8. Pallett SJC, Jones R, Pallett MA, Rayment M, Mughal N, Davies GW, et al. Characterising differential antibody response is integral to future SARS-CoV-2 serostudies. J Infect. 2020;81(6):e28-30.  https://doi.org/10.1016/j.jinf.2020.07.029  PMID: 32739486 
  9. Quinlan BD, Mou H, Zhang L, Guo Y, He W, Ojha A, et al. The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement. bioRxiv. 2020. Preprint.
  10. Huang AT, Garcia-Carreras B, Hitchings MDT, Yang B, Katzelnick LC, Rattigan SM, et al. A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat Commun. 2020;11(1):4704.  https://doi.org/10.1038/s41467-020-18450-4  PMID: 32943637 
  11. Rosadas C, Randell P, Khan M, McClure MO, Tedder RS. Testing for responses to the wrong SARS-CoV-2 antigen? Lancet. 2020;396(10252):e23.  https://doi.org/10.1016/S0140-6736(20)31830-4  PMID: 32866429 
  12. Interim Clinical Commissioning Policy. Casirivimab and imdevimab for patients hospitalised due to COVID-19. London: Department of Health and Social Care; 2021. Available from: https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2021/09/C1529-interim-clinical-comm-policy-neutralising-monoclonal-antibodies-and-intravenous-antivirals.pdf
  13. Public Health England (PHE). Government to offer antibody tests to health and social care staff and patients in England. London: PHE; 2020. Available from: https://www.gov.uk/government/news/government-to-offer-antibody-tests-to-health-and-social-care-staff-and-patients-in-england
  14. Abbott Laboratories. SARS-CoV-2 IgG. Abbott Park: Abbott Laboratories; 2020. https://www.fda.gov/media/137383/download
  15. Public Health England (PHE). Evaluation of the Abbott SARS-CoV-2 IgG for the detection of anti-SARS-CoV-2 antibodies. London: PHE; 2020. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/890566/Evaluation_of_Abbott_SARS_CoV_2_IgG_PHE.pdf
  16. Tedder RS, Parker E, Sureda-Vives M, Fernandez N, Randell P, Marchesin F, et al. Detection and quantification of antibody to SARS CoV 2 receptor binding domain provides enhanced sensitivity, specificity and utility. Rochester: Social Science Research Network ( SSRN); 2021. Preprint.
  17. Vergnaud A-C. The Airwave health monitoring study. London: Imperial College. [Accessed: 22 Jun 2021]. https://mrc.ukri.org/research/facilities-and-resources-for-researchers/cohort-directory/the-airwave-health-monitoring-study
  18. Templeton G. A two-step approach for transforming continuous variables to normal: implications and recommendations for IS research. Comm Assoc Inform Syst. 2011;28:41-58.  https://doi.org/10.17705/1CAIS.02804 
  19. Public Health England (PHE). SIREN (Sarscov2 Immunity & REinfection EvaluatioN). Impact of detectable anti-SARS-COV2 on the subsequent incidence of COVID-19 in healthcare workers. Protocol. London: PHE. [Accessed: 13 Jan 2022]. Available from: https://snapsurvey.phe.org.uk/sirenmasterfile/master_file/01.%20PROTOCOL/1a.%20Protocol/Superseded%20%20Protocols/SIREN%20Protocol%20v3.1_08062020-clean%20-%20Copy.pdf
  20. Pallett SJC, Denny SJ, Patel A, Charani E, Mughal N, Stebbing J, et al. Point-of-care serological assays for SARS-CoV-2 in a UK hospital population: potential for enhanced case finding. Sci Rep. 2021;11(1):5860.  https://doi.org/10.1038/s41598-021-85247-w  PMID: 33712679 
  21. Özçürümez MK, Ambrosch A, Frey O, Haselmann V, Holdenrieder S, Kiehntopf M, et al. SARS-CoV-2 antibody testing-questions to be asked. J Allergy Clin Immunol. 2020;146(1):35-43.  https://doi.org/10.1016/j.jaci.2020.05.020  PMID: 32479758 
  22. Ng KW, Faulkner N, Cornish GH, Rosa A, Harvey R, Hussain S, et al. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. 2020;370(6522):1339-43.  https://doi.org/10.1126/science.abe1107  PMID: 33159009 
  23. Bajaj V, Gadi N, Spihlman AP, Wu SC, Choi CH, Moulton VR. Aging, immunity, and COVID-19: how age influences the host immune response to coronavirus infections? Front Physiol. 2021;11:571416.  https://doi.org/10.3389/fphys.2020.571416  PMID: 33510644 
  24. Clarke CL, Prendecki M, Dhutia A, Gan J, Edwards C, Prout V, et al. Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection. Kidney Int. 2021;99(6):1470-7.  https://doi.org/10.1016/j.kint.2021.03.009  PMID: 33774082 
  25. Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020;26(8):1200-4.  https://doi.org/10.1038/s41591-020-0965-6  PMID: 32555424 
  26. Breathnach AS, Duncan CJA, Bouzidi KE, Hanrath AT, Payne BAI, Randell PA, et al. Prior COVID-19 protects against reinfection, even in the absence of detectable antibodies. J Infect. 2021;83(2):237-79.  https://doi.org/10.1016/j.jinf.2021.05.024  PMID: 34052242 
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