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, K_d, 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.

中文翻译：

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微流体亲和力分析揭示了 COVID-19 幸存者血浆中抗 SARS-CoV-2 抗体的广泛靶点亲和力

SARS-CoV-2 感染的临床结果可以从无症状到致死不等，这在很大程度上取决于抗病毒抗体的浓度及其与目标的亲和力。然而，血浆中多克隆抗体反应的亲和力很难测量。在这里，我们使用微流体抗体亲和力分析 (MAAP) 来确定 42 名血清阳性个体的血浆样本中抗 SARS-CoV-2 抗体的总亲和力和浓度，其中 19 名是健康供体，20 名表现出轻微症状，3 名重症患者患病的。我们发现解离常数K _d, 的抗受体结合域抗体跨越 2.5 个数量级，从亚纳摩尔到 43 nM。使用 MAAP，我们发现血清阳性个体的抗体诱导了预先形成的刺突-ACE2 受体复合物的解离，这表明 MAAP 可以用作补充受体竞争测定。通过与基于细胞病变效应的中和试验相比，我们表明 MAAP 可以可靠地预测血清的细胞中和能力，这可能是选择最有效的血浆置换治疗样本和跟踪疫苗接种成功时的一个重要考虑因素。