Migo William, Boskovic Marko, Likic Robert
University of Zagreb School of Medicine, Croatia.
Clinical Hospital Centre Zagreb, Department of Internal Medicine, Division of Clinical Pharmacology and Therapeutics, Croatia.
Curr Res Pharmacol Drug Discov. 2021;2:100064. doi: 10.1016/j.crphar.2021.100064. Epub 2021 Oct 9.
Development of novel antibodies to combat the novel SARS-CoV-2 virus is ongoing. Importantly, particular subgroups are more prone to severe disease, namely patients with poor immune responses. This includes cancer patients with solid and haematological disease, solid organ transplant (SOT) patients and those with congenital or acquired immunodeficiency. Outcomes for patients with poor immune responses receiving antibody therapy for underlying disease and SARS-CoV-2 severe infection are undergoing investigation. The objective of this study was to perform a search on patients with poor immune responses with severe SARS-CoV-2 infection, to assess if antibody therapy is beneficial in such populations. We performed searches using PubMED and medrXiv up to May 2021 of patients with solid and hematologic malignancy, SOT patients and acquired or congenital immunodeficiency. The primary outcome was to assess if antibody therapy was included during SARS-CoV-2 infection and the clinical outcomes of such treatment in this population. Here we find that there is a repurposing of monoclonal antibodies to target cytokine release syndrome, along with the use of convalescent plasma (CP). Despite CP demonstrating promising results, we reiterate evidence that CP forces mutational escape and subsequent variant development. Repurposing of antibody therapies (such as Tocilizumab) proved effective, especially in SOT patients. This also potentially opens an avenue for the use of anti-SARS-CoV-2 spike protein neutralizing monoclonal antibodies; however, studies have yet to focus on patients with poor immune responses as a subpopulation.
针对新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒的新型抗体研发工作正在进行中。重要的是，特定亚组更容易发展为重症疾病，即免疫反应较差的患者。这包括患有实体瘤和血液系统疾病的癌症患者、实体器官移植（SOT）患者以及先天性或获得性免疫缺陷患者。针对免疫反应较差的患者接受针对基础疾病和SARS-CoV-2严重感染的抗体治疗的结果正在进行研究。本研究的目的是对免疫反应较差的SARS-CoV-2严重感染患者进行检索，以评估抗体治疗在此类人群中是否有益。我们使用PubMed和medrXiv对截至2021年5月的实体和血液系统恶性肿瘤患者、SOT患者以及获得性或先天性免疫缺陷患者进行了检索。主要结果是评估在SARS-CoV-2感染期间是否采用了抗体治疗以及该治疗在此类人群中的临床结果。在此我们发现，正在重新利用单克隆抗体来靶向细胞因子释放综合征，同时也在使用康复期血浆（CP）。尽管CP显示出了有前景的结果，但我们重申有证据表明CP会促使病毒发生突变逃逸并随后产生变异。抗体疗法（如托珠单抗）的重新利用被证明是有效的，尤其是在SOT患者中。这也可能为抗SARS-CoV-2刺突蛋白中和单克隆抗体的使用开辟一条途径；然而，研究尚未将免疫反应较差的患者作为一个亚组进行重点关注。
