CAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Wuhan Institute of Virology, 430071 Wuhan, China.
University of Chinese Academy of Sciences, 100049 Beijing, China.
Viruses. 2021 Dec 11;13(12):2483. doi: 10.3390/v13122483.
Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.
COVID-19 患者通常在感染后会产生针对 SARS-CoV-2 的抗体，且抗体水平与疾病严重程度呈正相关。病毒抗体是否通过抗体依赖性增强（ADE）使 COVID-19 恶化尚不完全清楚。在这里，我们进行了体外评估，以确定恢复期血清是否增强了 SARS-CoV-2 感染或在免疫细胞中诱导了过度的免疫反应。我们的数据显示，表达可变水平 FcγR 的原代 B 细胞、巨噬细胞和单核细胞的 SARS-CoV-2 感染可被 COVID-19 患者的恢复期血清增强。我们还确定了与 ADE 相关的因素，并发现其表现出时间依赖性而非病毒剂量依赖性。此外，在测试来自不同患者的血清样本时，ADE 效应与中和滴度或 RBD 抗体水平无关。然而，在表现出 ADE 效应的给定样本中，中稀释度比低稀释度或高稀释度更高，这与登革热相似。最后，我们证明在 ADE 条件下，病毒基因或失调的宿主免疫基因表达更多。总的来说，我们的研究为理解 COVID-19 重症患者高病毒抗体滴度和严重肺部病理之间的关联提供了新的认识。
