TY - JOUR T1 - Microfluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101270 VL - 5 IS - 2 SP - e202101270 AU - Matthias M Schneider AU - Marc Emmenegger AU - Catherine K Xu AU - Itzel Condado Morales AU - Georg Meisl AU - Priscilla Turelli AU - Chryssa Zografou AU - Manuela R Zimmermann AU - Beat M Frey AU - Sebastian Fiedler AU - Viola Denninger AU - Raphaël PB Jacquat AU - Lidia Madrigal AU - Alison Ilsley AU - Vasilis Kosmoliaptsis AU - Heike Fiegler AU - Didier Trono AU - Tuomas PJ Knowles AU - Adriano Aguzzi Y1 - 2022/02/01 UR - https://www.life-science-alliance.org/content/5/2/e202101270.abstract N2 - The clinical outcome of SARS-CoV-2 infections, which can range from asymptomatic to lethal, is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets. However, the affinity of polyclonal antibody responses in plasma is difficult to measure. Here we used microfluidic antibody affinity profiling (MAAP) to determine the aggregate affinities and concentrations of anti–SARS-CoV-2 antibodies in plasma samples of 42 seropositive individuals, 19 of which were healthy donors, 20 displayed mild symptoms, and 3 were critically ill. We found that dissociation constants, Kd, of anti–receptor-binding domain antibodies spanned 2.5 orders of magnitude from sub-nanomolar to 43 nM. Using MAAP we found that antibodies of seropositive individuals induced the dissociation of pre-formed spike-ACE2 receptor complexes, which indicates that MAAP can be adapted as a complementary receptor competition assay. By comparison with cytopathic effect–based neutralisation assays, we show that MAAP can reliably predict the cellular neutralisation ability of sera, which may be an important consideration when selecting the most effective samples for therapeutic plasmapheresis and tracking the success of vaccinations. ER -