Maor Yasmin, Zimhony Oren
Infectious Disease Unit, E. Wolfson Medical Center, Halochamim 62, 58100, Holon, Israel.
Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Curr Top Microbiol Immunol. 2025;443:149-164. doi: 10.1007/82_2024_277.
The COVID-19 pandemic, resulting from the emergence of the novel coronavirus SARS-CoV-2, posed unprecedented challenges to global health systems as no proven therapy was available. Initially, COVID-19 convalescent plasma (CCP) from recovered COVID-19 patients showed promise as a therapeutic option. However, the efficacy of this approach was closely correlated with the neutralizing antibody titer in the administered plasma and thus effectiveness was not always guaranteed. In response, hyperimmune immunoglobulins (hIG) derived from CCP obtained by apheresis from recovered or vaccinated individuals emerged as a potential alternative. hIG were purified through stringent chromatographic processing from CCP units and displayed varying results in clinical trials, although it seems likely that they improved outcomes compared to placebo or CCP at day 28, particularly in unvaccinated patients. The variability in the effect of hIG likely stems from factors such as the timing of outcome assessment, the administered dose of hIG, the patients' immunological background, and the matching between the variant infecting patients and the neutralization ability of the immunoglobulin batch, which depended on the timing of the CCP collection. Despite logistical challenges and high production costs, hIG showcase advantages over CCP, offering versatility in administration routes and eliminating the need for blood matching, thus facilitating administration in the community, and allowing for variant-specific preparations. hIG appear to be of particular importance in the treatment of immunocompromised patients and patients with persistent COVID-19, although studies in these populations are lacking. Non-human alternatives, such as equine-derived hIG and recombinant hIG, may provide a solution to the logistical challenges of large-scale hIG preparation. Further study is needed to explore these avenues. Establishing the infrastructure for large-scale hIG production independent of plasma donations emerges as a strategic approach for future pandemics, justifying exploration and promotion by health authorities.
由新型冠状病毒SARS-CoV-2的出现导致的新冠疫情，给全球卫生系统带来了前所未有的挑战，因为当时没有经过验证的治疗方法。最初，来自康复的新冠患者的新冠康复期血浆（CCP）显示出作为一种治疗选择的潜力。然而，这种方法的疗效与所输注血浆中的中和抗体滴度密切相关，因此效果并不总是能得到保证。作为回应，通过单采从康复或接种疫苗的个体获得的源自CCP的高效价免疫球蛋白（hIG）成为一种潜在的替代方案。hIG通过严格的色谱处理从CCP单位中纯化出来，在临床试验中显示出不同的结果，尽管在第28天时，与安慰剂或CCP相比，它们似乎改善了治疗结果，特别是在未接种疫苗的患者中。hIG效果的变异性可能源于多种因素，如结果评估的时间、hIG的给药剂量、患者的免疫背景以及感染患者的病毒变体与免疫球蛋白批次中和能力之间的匹配情况，而这又取决于CCP采集的时间。尽管存在后勤挑战和高生产成本，但hIG相对于CCP具有优势，在给药途径上具有通用性，无需进行血型匹配，从而便于在社区中给药，并允许制备针对特定变体的制剂。hIG在免疫功能低下的患者和持续性新冠患者的治疗中似乎尤为重要，尽管缺乏针对这些人群的研究。非人类替代品，如马源hIG和重组hIG，可能为大规模hIG制备的后勤挑战提供解决方案。需要进一步研究来探索这些途径。建立独立于血浆捐赠的大规模hIG生产基础设施，成为应对未来大流行的一种战略方法，值得卫生当局进行探索和推广。
