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Volume 28, Number 3—March 2022
Research

Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications

Mars Stone1Comments to Author , Eduard Grebe1, Hasan Sulaeman, Clara Di Germanio, Honey Dave, Kathleen Kelly, Brad J. Biggerstaff, Bridgit O. Crews, Nam Tran, Keith R. Jerome, Thomas N. Denny, Boris Hogema, Mark Destree, Jefferson M. Jones, Natalie Thornburg, Graham Simmons, Mel Krajden, Steve Kleinman, Larry J. Dumont, and Michael P. Busch
Author affiliations: Vitalant Research Institute, San Francisco, California, USA (M. Stone, E. Grebe, H. Sulaeman, C. Di Germanio, H. Dave, K. Kelly, G. Simmons, L.J. Dumont, M.P. Busch); University of California–San Francisco, San Francisco (M. Stone, E. Grebe, G. Simmons, M.P. Busch); South African Centre for Epidemiological Modelling and Analysis, Stellenbosch University, Stellenbosch, South Africa (E. Grebe); Centers for Disease Control and Prevention, Fort Collins, Colorado, USA (B.J. Biggerstaff); University of California Irvine Medical Center, Orange, California, USA (B.O. Crews); University of California–Davis, Davis, California, USA (N. Tran); Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA (K.R. Jerome); Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA (T.N. Denny); Sanquin Research, Amsterdam, the Netherlands (B. Hogema); BloodWorks NorthWest, Seattle (M. Destree); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (J.M. Jones, N. Thornburg); British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada (M. Krajden); University of British Columbia, Vancouver (S. Kleinman); University of Colorado School of Medicine, Denver, Colorado, USA (L.J. Dumont)

Main Article

Figure 5

Intraclass correlation coefficients based on blinded replicate sample testing, reflecting the proportion of total variance that is between-sample rather than within-sample variability of severe acute respiratory syndrome coronavirus 2 antibody detection in study of commercially available high-throughput assays for serosurveillance. Results falling outside the primary measurement range were excluded. On-board dilutions were used to estimate reactivity in specimens where initial results fell outside the primary measurement range. Horizontal dotted lines show conventional (although arbitrary) thresholds for moderate (0.5), good (0.75), and excellent (0.9) repeatability (17). Assays are described in Table 1. Ab, antibody; Ag, antigen; N, nucleocapsid; PRNT, plaque reduction neutralization test; RBD, receptor binding domain; S, spike protein.

Figure 5. Intraclass correlation coefficients based on blinded replicate sample testing, reflecting the proportion of total variance that is between-sample rather than within-sample variability of severe acute respiratory syndrome coronavirus 2 antibody detection in study of commercially available high-throughput assays for serosurveillance. Results falling outside the primary measurement range were excluded. On-board dilutions were used to estimate reactivity in specimens where initial results fell outside the primary measurement range. Horizontal dotted lines show conventional (although arbitrary) thresholds for moderate (0.5), good (0.75), and excellent (0.9) repeatability (17). Assays are described in Table 1. Ab, antibody; Ag, antigen; N, nucleocapsid; PRNT, plaque reduction neutralization test; RBD, receptor binding domain; S, spike protein.

Main Article

References
  1. Jespersen  S, Mikkelsen  S, Greve  T, et al. SARS-CoV-2 seroprevalence survey among 17,971 healthcare and administrative personnel at hospitals, pre-hospital services, and specialist practitioners in the Central Denmark Region. Clin Infect Dis. 2021;73:e285360. DOIPubMedGoogle Scholar
  2. Pollán  M, Pérez-Gómez  B, Pastor-Barriuso  R, Oteo  J, Hernán  MA, Pérez-Olmeda  M, et al.; ENE-COVID Study Group. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet. 2020;396:53544. DOIPubMedGoogle Scholar
  3. Shioda  K, Lau  MSY, Kraay  ANM, Nelson  KN, Siegler  AJ, Sullivan  PS, et al. Estimating the cumulative incidence of SARS-CoV-2 infection and the infection fatality ratio in light of waning antibodies. Epidemiology. 2021;32:51824. DOIPubMedGoogle Scholar
  4. Slot  E, Hogema  BM, Reusken  CBEM, Reimerink  JH, Molier  M, Karregat  JHM, et al. Low SARS-CoV-2 seroprevalence in blood donors in the early COVID-19 epidemic in the Netherlands. Nat Commun. 2020;11:5744. DOIPubMedGoogle Scholar
  5. Mulenga  LB, Hines  JZ, Fwoloshi  S, Chirwa  L, Siwingwa  M, Yingst  S, et al. Prevalence of SARS-CoV-2 in six districts in Zambia in July, 2020: a cross-sectional cluster sample survey. Lancet Glob Health. 2021;9:e77381. DOIPubMedGoogle Scholar
  6. Hasan  T, Pham  TN, Nguyen  TA, Le  HTT, Van Le  D, Dang  TT, et al. Sero-prevalence of SARS-CoV-2 antibodies in high-risk populations in Vietnam. Int J Environ Res Public Health. 2021;18:6353. DOIPubMedGoogle Scholar
  7. Anand  S, Montez-Rath  M, Han  J, Bozeman  J, Kerschmann  R, Beyer  P, et al. Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study. Lancet. 2020;396:133544. DOIPubMedGoogle Scholar
  8. Goodhue Meyer  E, Simmons  G, Grebe  E, Gannett  M, Franz  S, Darst  O, et al. Selecting COVID-19 convalescent plasma for neutralizing antibody potency using a high-capacity SARS-CoV-2 antibody assay. Transfusion. 2021;61:116070. DOIPubMedGoogle Scholar
  9. US Food and Drug Administration. Investigational COVID-19 convalescent plasma: guidance for industry [cited 2021 Aug 11]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-covid-19-convalescent-plasma
  10. Belda  F, Lopez-Martinez  M, Torres  N, Cherenzia  R, Crowley  M. Available COVID-19 serial seroconversion panel for validation of SARS-CoV-2 antibody assays. Diagn Microbiol Infect Dis. 2021;100:115340. DOIPubMedGoogle Scholar
  11. Di Germanio  C, Simmons  G, Kelly  K, Martinelli  R, Darst  O, Azimpouran  M, et al. SARS-CoV-2 antibody persistence in COVID-19 convalescent plasma donors: Dependency on assay format and applicability to serosurveillance. Transfusion. 2021;61:267787. DOIPubMedGoogle Scholar
  12. R Core Team. R: a language and environment for statistical computing [cited 2021 Sep 1]. https://www.gbif.org/tool/81287/r-a-language-and-environment-for-statistical-computing
  13. Dorai-Raj  S. binom: binomial confidence intervals for several parameterizations [cited 2021 Sep 1]. https://rdrr.io/rforge/binom
  14. Marschner  IC. glm2: fitting generalized linear models with convergence problems. R J. 2011;3:125. DOIGoogle Scholar
  15. Wickham  H. ggplot2: elegant graphics for data analysis: Springer-Verlag: New York; 2016.
  16. Liljequist  D, Elfving  B, Skavberg Roaldsen  K. Intraclass correlation - A discussion and demonstration of basic features. PLoS One. 2019;14:e0219854. DOIPubMedGoogle Scholar
  17. Petersen  LR, Sami  S, Vuong  N, et al. Lack of antibodies to SARS-CoV-2 in a large cohort of previously infected persons. Clin Infect Dis. 2021;73:e306673. DOIPubMedGoogle Scholar
  18. Ibarrondo  FJ, Fulcher  JA, Goodman-Meza  D, Elliott  J, Hofmann  C, Hausner  MA, et al. Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19. N Engl J Med. 2020;383:10857. DOIPubMedGoogle Scholar
  19. Peluso  MJ, Takahashi  S, Hakim  J, Kelly  JD, Torres  L, Iyer  NS, et al. SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay. Sci Adv. 2021;7:eabh3409. DOIPubMedGoogle Scholar
  20. Sabino  EC, Buss  LF, Carvalho  MPS, Prete  CA Jr, Crispim  MAE, Fraiji  NA, et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet. 2021;397:4525. DOIPubMedGoogle Scholar
  21. Gallais  F, Velay  A, Nazon  C, Wendling  MJ, Partisani  M, Sibilia  J, et al. Intrafamilial exposure to SARS-CoV-2 associated with cellular immune response without seroconversion, France. Emerg Infect Dis. 2021;27:11321. DOIPubMedGoogle Scholar
  22. Faria  NR, Mellan  TA, Whittaker  C, Claro  IM, Candido  DDS, Mishra  S, et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science. 2021;372:81521. DOIPubMedGoogle Scholar
  23. Liu  H, Wu  NC, Yuan  M, Bangaru  S, Torres  JL, Caniels  TG, et al. Cross-neutralization of a SARS-CoV-2 antibody to a functionally conserved site is mediated by avidity. Immunity. 2020;53:12721280.e5. DOIPubMedGoogle Scholar
  24. Benner  SE, Patel  EU, Laeyendecker  O, Pekosz  A, Littlefield  K, Eby  Y, et al. SARS-CoV-2 antibody avidity responses in COVID-19 patients and convalescent plasma donors. J Infect Dis. 2020;222:197484. DOIPubMedGoogle Scholar
  25. Lumley  SF, Wei  J, O’Donnell  D, Stoesser  NE, Matthews  PC, Howarth  A, et al.; Oxford University Hospitals Staff Testing Group. The Duration, dynamics, and determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses in individual healthcare workers. Clin Infect Dis. 2021;73:e699709. DOIPubMedGoogle Scholar
  26. Gudbjartsson  DF, Norddahl  GL, Melsted  P, Gunnarsdottir  K, Holm  H, Eythorsson  E, et al. Humoral immune response to SARS-CoV-2 in Iceland. N Engl J Med. 2020;383:172434. DOIPubMedGoogle Scholar
  27. Garcia-Beltran  WF, Lam  EC, St Denis  K, Nitido  AD, Garcia  ZH, Hauser  BM, et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell. 2021;184:23722383.e9. DOIPubMedGoogle Scholar
  28. Gundlapalli  AV, Salerno  RM, Brooks  JT, Averhoff  F, Petersen  LR, McDonald  LC, et al. SARS-CoV-2 serologic assay needs for the next phase of the US COVID-19 pandemic response. Open Forum Infect Dis 2021;8:ofaa555.
  29. Moore  JP, Offit  PA. SARS-CoV-2 vaccines and the growing threat of viral variants. JAMA. 2021;325:8212. DOIPubMedGoogle Scholar
  30. Babiker  A, Marvil  CE, Waggoner  JJ, Collins  MH, Piantadosi  A. The importance and challenges of identifying SARS-CoV-2 reinfections. J Clin Microbiol. 2021;59:e0276920. DOIPubMedGoogle Scholar

Main Article

1These first authors contributed equally to this article.

Page created: January 12, 2022
Page updated: February 21, 2022
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