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Abstract

Background

The ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making.

Aim

Our objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies.

Methods

We developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls.

Results

IgG and IgM RBD ELISA, MN and PRNT were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test.

Conclusion

Using IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT, is a valid approach for large-scale sero-epidemiology studies.

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/content/10.2807/1560-7917.ES.2020.25.16.2000421
2020-04-23
2020-07-08
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2020.25.16.2000421
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References

  1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.  https://doi.org/10.1056/NEJMoa2001017  PMID: 31978945 
  2. Word Health Organization (WHO). Coronavirus disease 2019 (COVID-19): Situation report 92. Geneva: WHO. [Accessed: 22 Apr 2020]. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200421-sitrep-92-covid-19.pdf?sfvrsn=38e6b06d_4
  3. Battegay M, Kuehl R, Tschudin-Sutter S, Hirsch HH, Widmer AF, Neher RA. 2019-novel Coronavirus (2019-nCoV): estimating the case fatality rate - a word of caution. Swiss Med Wkly. 2020;150:w20203.  https://doi.org/10.4414/smw.2020.20203  PMID: 32031234 
  4. Wu JT, Ma ES, Lee CK, Chu DK, Ho PL, Shen AL, et al. The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong. Clin Infect Dis. 2010;51(10):1184-91.  https://doi.org/10.1086/656740  PMID: 20964521 
  5. Wong JY, Kelly H, Ip DK, Wu JT, Leung GM, Cowling BJ. Case fatality risk of influenza A (H1N1pdm09): a systematic review. Epidemiology. 2013;24(6):830-41.  https://doi.org/10.1097/EDE.0b013e3182a67448  PMID: 24045719 
  6. Monto AS, Malosh RE, Petrie JG, Thompson MG, Ohmit SE. Frequency of acute respiratory illnesses and circulation of respiratory viruses in households with children over 3 surveillance seasons. J Infect Dis. 2014;210(11):1792-9.  https://doi.org/10.1093/infdis/jiu327  PMID: 24907381 
  7. Ekiert DC, Friesen RH, Bhabha G, Kwaks T, Jongeneelen M, Yu W, et al. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science. 2011;333(6044):843-50.  https://doi.org/10.1126/science.1204839  PMID: 21737702 
  8. Yuan M, Wu NC, Zhu X, Lee CD, So RTY, Lv H, et al. A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV. Science. 2020;eabb7269.  https://doi.org/10.1126/science.abb7269  PMID: 32245784 
  9. Moritz CP, Tholance Y, Lassablière F, Camdessanché JP, Antoine JC. Reducing the risk of misdiagnosis of indirect ELISA by normalizing serum-specific background noise: The example of detecting anti-FGFR3 autoantibodies. J Immunol Methods. 2019;466:52-6.  https://doi.org/10.1016/j.jim.2019.01.004  PMID: 30654043 
  10. Reed LJ, Muench H. A simple method of estimating fifty percent end points. Am J Hyg. 1938;27:493-7.
  11. Choe PG, Perera RAPM, Park WB, Song KH, Bang JH, Kim ES, et al. MERS-CoV antibody responses 1 year after symptom onset, South Korea, 2015. Emerg Infect Dis. 2017;23(7):1079-84.  https://doi.org/10.3201/eid2307.170310  PMID: 28585916 
  12. Chan CM, Tse H, Wong SS, Woo PC, Lau SK, Chen L, et al. Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA and neutralization assay against viral spike pseudotyped virus. J Clin Virol. 2009;45(1):54-60.  https://doi.org/10.1016/j.jcv.2009.02.011  PMID: 19342289 
  13. Gorse GJ, Patel GB, Vitale JN, O’Connor TZ. Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum. Clin Vaccine Immunol. 2010;17(12):1875-80.  https://doi.org/10.1128/CVI.00278-10  PMID: 20943876 
  14. Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease 2019 patients. Emerg Infect Dis. 2020;26(7): Epub ahead of print.  https://doi.org/10.3201/eid2607.200841  PMID: 32267220 
  15. Zhang B, Zhou X, Zhu C, Feng F, Qiu Y, Feng J, et al. Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19. medRxiv 2020.  https://doi.org/10.1101/2020.03.12.20035048 
  16. Wu JT, Leung K, Perera RA, Chu DK, Lee CK, Hung IF, et al. Inferring influenza infection attack rate from seroprevalence data. PLoS Pathog. 2014;10(4):e1004054.  https://doi.org/10.1371/journal.ppat.1004054  PMID: 24699693 
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