Abstract:
Appropriately selected neutralising monoclonal antibodies (nmAbs) are an effective treatment for patients with mild or moderate coronavirus disease 2019 (COVID-19) who are at high risk of progression to severe disease. In contrast, the efficacy of nmAbs in patients hospitalised with COVID-19 has been mixed, and clinical benefit has largely been restricted to seronegative patients [i.e. those lacking endogenous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies] in the trials with positive outcomes. This review summarises the major clinical trial data investigating nmAb treatment for hospitalised patients with COVID-19, and explores current definitions of seropositivity, what they mean in a late-pandemic context and discusses the current late-pandemic challenges associated with defining \'seroprotection\' in a clinically meaningful way. We conclude that following widespread vaccination, increasing numbers of prior infections and emerging viral variants, seropositivity now reflects a range of immune coverage rather than a binary tool with which to aid decision-making on a clinically actionable timescale. Treatment decisions with nmAbs in a late-pandemic context would therefore likely best rely on information regarding clinical status, time since symptom onset, underlying patient condition(s) and the dominant circulating variant, should they be approved for future use in hospitalised patients with COVID-19.
摘要:
适当选择的中和单克隆抗体(nmAb)是患有轻度或中度冠状病毒病2019(COVID-19)的患者的有效治疗方法,这些患者有很高的发展为严重疾病的风险。相比之下,新冠肺炎住院患者的nmAbs疗效参差不齐,临床获益主要限于血清阴性患者[即缺乏内源性严重急性呼吸综合征冠状病毒2(SARS-CoV-2)抗体的患者]。这篇综述总结了调查nmAb治疗COVID-19住院患者的主要临床试验数据,并探讨了当前血清阳性的定义,它们在大流行后期的背景下意味着什么,并讨论了当前与以临床有意义的方式定义“血清保护”相关的大流行后期挑战。我们得出结论,在广泛接种疫苗后,越来越多的先前感染和新出现的病毒变体,血清阳性现在反映了一系列的免疫覆盖率,而不是一种在临床可操作的时间尺度上帮助决策的二元工具。因此,在大流行后期使用nmAbs的治疗决策可能最好依赖于有关临床状态的信息。自症状发作以来的时间,潜在的患者状况和主要的循环变异,它们是否应该被批准用于COVID-19住院患者。