Studying temporal titre evolution of commercial SARS-CoV-2 assays reveals significant shortcomings of using BAU standardization for comparison

Author:

Kroidl Inge,Winter Simon,Rubio-Acero Raquel,Bakuli Abhishek,Geldmacher Christof,Eser Tabea M.,Déak Flora,Horn Sacha,Zielke Anna,Ahmed Mohamed I. M.,Diepers Paulina,Guggenbühl Jessica,Frese Jonathan,Bruger Jan,Puchinger Kerstin,Reich Jakob,Falk Philine,Markgraf Alisa,Fensterseifer Heike,Paunovic Ivana,Thomschke Angelika,Pritsch Michael,Riess Friedrich,Saathoff Elmar,Hoelscher Michael,Olbrich Laura,Castelletti Noemi,Wieser Andreas,Alamoudi Emad,Anderson Jared,Baldassarre Valeria,Baumann Maximilian,Becker Marc,Bednarski Franziska,Behlen Marieke,Bemirayev Olimbek,Beyerl Jessica,Bitzer Patrick,Böhnlein Rebecca,Brand Isabel,Brauer Anna,Britz Vera,Bünz Franziska,Caroli Friedrich,Coleman Josephine,Contento Lorenzo,Czwienzek Alina,Deák Flora,Diefenbach Maximilian N,Diekmannshemke Jana,Do Anna,Dobler Gerhard,Durner Jürgen,Eser Tabea,Eberle Ute,Eckstein Judith,Feyereisen Manuela,Fingerle Volker,Fischer Stefanie,Forster Felix,Fröschl Günter,Fuchs Christiane,Geisenberger Otto,Garí Mercè,Gasser Marius,Gauder Sonja,Geier Raffaela,Gillig Kristina,Gezgin Keisha,Gilberg Leonard,Gillig Kristina,Girl Philipp,Golschan Elias,Grauvogl Vitus,Noller Jessica Michelle Guggenbuehl,Guglielmini Elena Maria,Gutierrez Pablo,Haderer Anslem,Halfmann Celina,Hannes Marlene,Hartinger Lena,Haselwarter Timm,Hasenauer Jan,Hernandez Alejandra,Heller Luca,Heiber Arlett,Herrmann Matthias,Hillari Leah,Hillmann Stefan,Hinske Christian,Hoefflin Janna,Hofberger Tim,Höfinger Michael,Hofmann Larissa,Huber Kristina,Janke Christian,Karger Lilian,Kappl Ursula,Keßler Antonia,Khan Zohaib,Kiani Charlotte,Klugherz Isabel,Kreider Norah,Kresin Johanna,Kroidl Arne,Kunder Pratik,Lang Magdalena,Lang Clemens,Lange Silvan,Lapteva Ekaterina,Laxy Michael,Le Gleut Ronan,Leidl Reiner,Liedl Leopold,Lindner Felix,Lucaj Xhovana,Lucke Elisabeth,Luppa Fabian,Nafziger Alexandra Sophie,Maczka Alexander,Mang Petra,Matcau Paula,Mayrhofer Rebecca,Mekota Anna-Maria,Metaxa Dafni,Mohr Emily,Müller Hannah,Müller Katharina,Nascimento Nathalia,Niermeyer Kasimir,Nikolaides Sophia,Noreña Ivan,Pattard Leonie,Plank Michael,Pleimelding Claire,Pletschette Michel,Poll Viona,Prückner Stephan,Pusl Konstantin,Pütz Peter,Radon Katja,Raimúndez Elba,Raschka Julius,Reinkemeyer Christina,Rothe Camilla,Ruci Viktoria,Schäfer Nicole,Schälte Yannik,Schandelmaier Paul,Schluse Benedikt,Schneider Annika,Schneider Lara,Schultz Sophie,Schunk Mirjam,Schwettmann Lars,Sedlmeier Josefin,Sintu-Sempta Linda,Soler Alba,Sothmann Peter,Strobl Katharina,Strüber Aida,Strüber Laura,Tang Jeni,Theis Fabian,Thiel Verena,Thumser Eva,Thur Niklas,Thiesbrummel Sophie,Ullrich Julian,Vollmayr Vincent,Von Lovenberg Emilia,Von Lovenberg Jonathan,Vos Carsten,Waibel Julia,Wallrauch Claudia,Weigl Nikolas,Wölfl Roman,Wolff Julia,Wullinger Pia,Würfel Tobias,Wustrow Patrick,Zange Sabine,Zeggini Eleftheria,Zimmer Thorbjörn,Zimmermann Thomas,Zuche Lea,

Abstract

Abstract Background Measuring specific anti-SARS-CoV-2 antibodies has become one of the main epidemiological tools to survey the ongoing SARS-CoV-2 pandemic, but also vaccination response. The WHO made available a set of well-characterized samples derived from recovered individuals to allow normalization between different quantitative anti-Spike assays to defined Binding Antibody Units (BAU). Methods To assess sero-responses longitudinally, a cohort of ninety-nine SARS-CoV-2 RT-PCR positive subjects was followed up together with forty-five vaccinees without previous infection but with two vaccinations. Sero-responses were evaluated using a total of six different assays: four measuring anti-Spike proteins (converted to BAU), one measuring anti-Nucleocapsid proteins and one SARS-CoV-2 surrogate virus neutralization. Both cohorts were evaluated using the Euroimmun Anti-SARS-CoV-2-ELISA anti-S1 IgG and the Roche Elecsys Anti-SARS-CoV-2 anti-S1 assay. Results In SARS-CoV-2-convalesce subjects, the BAU-sero-responses of Euroimmun Anti-SARS-CoV-2-ELISA anti-S1 IgG and Roche Elecsys Anti-SARS-CoV-2 anti-S1 peaked both at 47 (43–51) days, the first assay followed by a slow decay thereafter (> 208 days), while the second assay not presenting any decay within one year. Both assay values in BAUs are only equivalent a few months after infection, elsewhere correction factors up to 10 are necessary. In contrast, in infection-naive vaccinees the assays perform similarly. Conclusion The results of our study suggest that the establishment of a protective correlate or vaccination booster recommendation based on different assays, although BAU-standardised, is still challenging. At the moment the characteristics of the available assays used are not related, and the BAU-standardisation is unable to correct for that.

Funder

Bavarian State Ministry of Science and the Arts

University Hospital, LMU Munich

German Ministry for Education and Research

Euroimmun and Roche provided kits and machines for analyses at discounted rates for the study

European-wide Consortium ORCHESTRA

Universitätsklinik München

Publisher

Springer Science and Business Media LLC

Subject

Infectious Diseases,Virology

Reference47 articles.

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