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Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients
Signal Transduction and Targeted Therapy  (IF38.104),  Pub Date : 2021-09-24, DOI: 10.1038/s41392-021-00759-1
Yuanling Yu, Meiyu Wang, Xiaoai Zhang, Shufen Li, Qingbin Lu, Haolong Zeng, Hongyan Hou, Hao Li, Mengyi Zhang, Fei Jiang, Jiajing Wu, Ruxia Ding, Zehua Zhou, Min Liu, Weixue Si, Tao Zhu, Hangwen Li, Jie Ma, Yuanyuan Gu, Guangbiao She, Xiaokun Li, Yulan Zhang, Ke Peng, Weijin Huang, Wei Liu, Youchun Wang

Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11–20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.