The majority of infections with SARS-CoV-2 are asymptomatic or mild without the necessity of hospitalization. It is of importance to reveal if these patients develop an antibody response against SARS-CoV-2 and to define which antibodies confer virus neutralization. We conducted a comprehensive serological survey of 49 patients with a mild course of disease and quantified neutralizing antibody responses against a clinical SARS-CoV-2 isolate employing human cells as targets. Four patients (8%), even though symptomatic, did not develop antibodies against SARS-CoV-2, and two other patients (4%) were positive in only one of the six serological assays employed. For the remaining 88%, antibody response against the S protein correlated with serum neutralization whereas antibodies against the nucleocapsid were poor predictors of virus neutralization. None of the sera enhanced infection of human cells with SARS-CoV-2 at any dilution, arguing against antibody-dependent enhancement of infection in our system. Regarding neutralization, only six patients (12%) could be classified as high neutralizers. Furthermore, sera from several individuals with fairly high antibody levels had only poor neutralizing activity. In addition, employing a novel serological Western blot system to characterize antibody responses against seasonal coronaviruses, we found that antibodies against the seasonal coronavirus 229E might contribute to SARS-CoV-2 neutralization. Altogether, we show that there is a wide breadth of antibody responses against SARS-CoV-2 in patients that differentially correlate with virus neutralization. This highlights the difficulty to define reliable surrogate markers for immunity against SARS-CoV-2.

中文翻译：

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非住院 COVID-19 患者对 SARS-CoV-2 和季节性冠状病毒的抗体反应

大多数 SARS-CoV-2 感染是无症状或轻微的，无需住院。重要的是要揭示这些患者是否对 SARS-CoV-2 产生抗体反应，并确定哪些抗体可以中和病毒。我们对 49 名病程较轻的患者进行了全面的血清学调查，并量化了针对以人类细胞为靶点的临床 SARS-CoV-2 分离株的中和抗体反应。四名患者 (8%) 尽管有症状，但并未产生针对 SARS-CoV-2 的抗体，另外两名患者 (4%) 在所采用的六项血清学检测中仅一项呈阳性。对于剩余的 88%，针对 S 蛋白的抗体反应与血清中和相关，而针对核衣壳的抗体则是病毒中和的不良预测因子。任何稀释的血清都没有增强 SARS-CoV-2 对人类细胞的感染，这与我们系统中抗体依赖的感染增强相矛盾。关于中和，只有六名患者 (12%) 可以归类为高中和。此外，来自具有相当高抗体水平的几个个体的血清仅具有较差的中和活性。此外，采用新型血清学蛋白质印迹系统来表征针对季节性冠状病毒的抗体反应，我们发现针对季节性冠状病毒 229E 的抗体可能有助于中和 SARS-CoV-2。总而言之，我们表明，在与病毒中和存在差异的患者中，存在广泛的针对 SARS-CoV-2 的抗体反应。