The COVID-19 pandemic is now approaching 2 years old, with more than 440 million people infected and nearly six million dead worldwide, making it the most significant pandemic since the 1918 influenza pandemic. The severity and significance of SARS-CoV-2 was recognized immediately upon discovery, leading to innumerable companies and institutes designing and generating vaccines and therapeutic antibodies literally as soon as recombinant SARS-CoV-2 spike protein sequence was available. Within months of the pandemic start, several antibodies had been generated, tested, and moved into clinical trials, including Eli Lilly's bamlanivimab and etesevimab, Regeneron's mixture of imdevimab and casirivimab, Vir's sotrovimab, Celltrion's regdanvimab, and Lilly's bebtelovimab. These antibodies all have now received at least Emergency Use Authorizations (EUAs) and some have received full approval in select countries. To date, more than three dozen antibodies or antibody combinations have been forwarded into clinical trials. These antibodies to SARS-CoV-2 all target the receptor-binding domain (RBD), with some blocking the ability of the RBD to bind human ACE2, while others bind core regions of the RBD to modulate spike stability or ability to fuse to host cell membranes. While these antibodies were being discovered and developed, new variants of SARS-CoV-2 have cropped up in real time, altering the antibody landscape on a moving basis. Over the past year, the search has widened to find antibodies capable of neutralizing the wide array of variants that have arisen, including Alpha, Beta, Gamma, Delta, and Omicron. The recent rise and dominance of the Omicron family of variants, including the rather disparate BA.1 and BA.2 variants, demonstrate the need to continue to find new approaches to neutralize the rapidly evolving SARS-CoV-2 virus. This review highlights both convalescent plasma- and polyclonal antibody-based approaches as well as the top approximately 50 antibodies to SARS-CoV-2, their epitopes, their ability to bind to SARS-CoV-2 variants, and how they are delivered. New approaches to antibody constructs, including single domain antibodies, bispecific antibodies, IgA- and IgM-based antibodies, and modified ACE2-Fc fusion proteins, are also described. Finally, antibodies being developed for palliative care of COVID-19 disease, including the ramifications of cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS), are described.

中文翻译：

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针对 SARS-CoV-2 的被动免疫疗法：从血浆疗法到单一强效抗体，在变异病毒的竞争中保持领先地位。

COVID-19 大流行现已接近 2 年，全球有超过 4.4 亿人感染，近 600 万人死亡，使其成为自 1918 年流感大流行以来最严重的大流行。SARS-CoV-2 的严重性和重要性一经发现就立即得到认识，导致无数公司和机构在重组 SARS-CoV-2 刺突蛋白序列一获得后就开始设计和生产疫苗和治疗抗体。在大流行开始的几个月内，多种抗体被生产、测试​​并进入临床试验，包括礼来公司的 bamlanivimab 和 etesevimab、Regeneron 的 imdevimab 和 casirivimab 混合物、Vir 的 sotrovimab、Celltrion 的 regdanvimab 和礼来公司的 bebtelovimab。这些抗体现已至少获得紧急使用授权 (EUA)，其中一些抗体已在选定国家获得完全批准。迄今为止，已有三打以上的抗体或抗体组合进入临床试验。这些针对 SARS-CoV-2 的抗体均以受体结合域 (RBD) 为目标，其中一些抗体阻断 RBD 结合人类 ACE2 的能力，而其他抗体则结合 RBD 的核心区域以调节刺突稳定性或与宿主融合的能力细胞膜。在发现和开发这些抗体的同时，SARS-CoV-2 的新变种也实时出现，不断改变抗体格局。在过去的一年里，研究范围不断扩大，以寻找能够中和已出现的各种变体的抗体，包括 Alpha、Beta、Gamma、Delta 和 Omicron。Omicron 变体家族（包括相当不同的 BA.1 和 BA.2 变体）最近的兴起和主导地位表明需要继续寻找新方法来中和快速进化的 SARS-CoV-2 病毒。本综述重点介绍了基于恢复期血浆和多克隆抗体的方法，以及排名前 50 种的 SARS-CoV-2 抗体、它们的表位、它们与 SARS-CoV-2 变体结合的能力以及它们的传递方式。还描述了抗体构建体的新方法，包括单域抗体、双特异性抗体、基于 IgA 和 IgM 的抗体以及修饰的 ACE2-Fc 融合蛋白。最后，描述了正在开发的用于 COVID-19 疾病姑息治疗的抗体，包括细胞因子释放综合征 (CRS) 和急性呼吸窘迫综合征 (ARDS) 的后果。