Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study

  1. Jason Rosado
  2. Stéphane Pelleau
  3. Charlotte Cockram
  4. Sarah Hélène Merkling
  5. Narimane Nekkab
  6. Caroline Demeret
  7. Annalisa Meola
  8. Solen Kerneis
  9. Benjamin Terrier
  10. Samira Fafi-Kremer
  11. Jerome de Seze
  12. Timothée Bruel
  13. François Dejardin
  14. Stéphane Petres
  15. Rhea Longley
  16. Arnaud Fontanet
  17. Marija Backovic
  18. Ivo Mueller
  19. Michael T White

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Abstract

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  1. Version published to 10.1016/s2666-5247(20)30197-x
  2. ScreenIT

    SciScore for 10.1101/2020.05.07.20093963: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Abstract Methods A multiplex serological assay was developed to measure IgG and IgM antibody responses to four SARS-CoV-2 Spike ( S ) antigens: spike trimeric ectodomain ( Stri) , its receptor-binding domain ( RBD) , spike subunit 1 ( S1) , and spike subunit 2 ( S2) .
    antigens: spike trimeric ectodomain ( Stri) , its receptor-binding domain ( RBD) , spike subunit 1
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>spike subunit 2</b></div>
        <div>suggested: (Thermo Fisher Scientific Cat# MA5-29983, <a href="https://scicrunch.org/resources/Any/search?q=AB_2785782">AB_2785782</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Serum samples positive for anti-malaria IgG antibodies were tested before and after the inactivation protocol .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>anti-malaria IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">R-PE ) conjugated Donkey Anti-Human IgM ( Fc5μ ) F(ab’)2 ( cat#709-116-073; JacksonImmunoResearch , UK ) antibody was used as detector antibody at 1/120 dilution .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Anti-Human IgM</b></div>
        <div>suggested: (Jackson ImmunoResearch Labs Cat# 709-116-073, <a href="https://scicrunch.org/resources/Any/search?q=AB_2340518">AB_2340518</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">For IgM measurements , samples were diluted at 1/200 , and R-Phycoerythrin - ( R-PE ) Donkey Anti-Human IgG ( Fcγ ) F(ab’)2 ( cat#709-116-098; JacksonImmunoResearch , UK ) antibody was used as detector antibody at 1/400 dilution .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>R-Phycoerythrin</b></div>
        <div>suggested: (Jackson ImmunoResearch Labs Cat# 709-116-098, <a href="https://scicrunch.org/resources/Any/search?q=AB_2340519">AB_2340519</a>)</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>Anti-Human IgG</b></div>
        <div>suggested: (Jackson ImmunoResearch Labs Cat# 709-116-098, <a href="https://scicrunch.org/resources/Any/search?q=AB_2340519">AB_2340519</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Mathematical model of antibody kinetics SARS-CoV-2 antibody kinetics are described using a previously published mathematical model of the immunological processes underlying the generation and waning of antibody responses following infection or infection [ 10] .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>SARS-CoV-2</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">= − ,   =  −   ,   = ( 1 − ) −   ,   =  +  −   where M denotes memory B cells , δ is the rate of differentiation of memory B cells into antibody secreting plasma cells ( ASC) , Bs denotes short-lived ASCs , Bl denotes long-lived ASCs , ρ is the proportion of ASCs that are short-lived , g is the rate of generation of antibodies ( IgG or IgM ) from ASCs , and r is the rate of decay of antibody molecules .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>− ,   =  −   ,   = ( 1 − ) −   ,</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Results Single biomarker classification IgG and IgM antibody responses to Stri , RBD , S1 and S2 were measured as median fluorescence intensity ( MFI ) and converted to antibody dilutions ( Figure 1) .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>IgM</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">The poorer classification performance of IgM antibodies is a consequence of the smaller relative difference in measurements between positive and negative sample , compared to IgG antibodies .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">IgG antibody dilution compared with ( A ) anti-RBD IgG antibody dilution; ( B ) antiS1 IgG antibody dilution; ( C ) anti-S2 IgG antibody dilution; and ( D ) anti-Stri IgM antibody dilution .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>anti-Stri IgM</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">( A ) Measured anti-Stri and anti-RBD IgG antibody responses .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>anti-Stri</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>anti-RBD IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Discussion Infection with SARS-CoV-2 induces antibodies of multiple isotypes ( IgG , IgM , IgA ) targeting multiple epitopes on spike proteins exposed on the virus surface , and nucleoprotein .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>IgM , IgA</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr></table>

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  3. Version published to 10.1101/2020.05.07.20093963 on medRxiv