Antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus have a theoretical potential to amplify the infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in the pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we review observations relevant to the risks of ADE of disease, and their potential implications for SARS-CoV-2 infection. At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe viral infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same and designing animal models depends on understanding how antiviral host responses may become harmful in humans. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, because ADE of disease cannot be reliably predicted after either vaccination or treatment with antibodies—regardless of what virus is the causative agent—it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 move forward. The antibody-dependent enhancement of disease is reviewed, with an emphasis on implications for the prevention and treatment of SARS-CoV-2 infection.

中文翻译：

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SARS-CoV-2潜在抗体依赖性增强的观点

疾病的抗体依赖性增强 (ADE) 是疫苗和抗体疗法开发的普遍关注点，因为作为针对任何病毒的抗体保护基础的机制具有放大感染或引发有害免疫病理学的理论潜力。这种可能性需要在由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的 2019 年冠状病毒病 (COVID-19) 大流行的关键时刻仔细考虑。在这里，我们回顾了与疾病 ADE 风险相关的观察结果，以及它们对 SARS-CoV-2 感染的潜在影响。目前，无论是通过测量抗体、T 细胞还是内在宿主反应，都没有已知的临床发现、免疫分析或生物标志物可以区分任何严重的病毒感染和免疫增强疾病。体外系统和动物模型不能预测疾病 ADE 的风险，部分原因是保护性和潜在有害的抗体介导机制是相同的，设计动物模型取决于了解抗病毒宿主反应如何对人类有害。我们缺乏知识的影响是双重的。首先，迫切需要综合研究来定义针对 SARS-CoV-2 的保护性免疫的临床相关性。其次，由于在接种疫苗或用抗体治疗后都无法可靠地预测疾病的 ADE——无论病原体是什么病毒——随着 COVID-19 免疫干预措施的推进，必须依赖对人类安全性的仔细分析。回顾了疾病的抗体依赖性增强，