Marsiglia Matteo Domenico, Bianchi Silvia, Bai Francesca, Tincati Camilla, Ottaviano Emerenziana, Ancona Silvia, Marchetti Giulia, Borghi Elisa
Department of Health Sciences, Università degli Studi di Milano, Milano, Italy.
Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, Italy.
PLoS One. 2025 Apr 25;20(4):e0321356. doi: 10.1371/journal.pone.0321356. eCollection 2025.
Anti-SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) have been shown to have clinical benefits in treating high-risk patients with mild-moderate COVID-19. SARS-CoV-2 RNA in serum (RNAemia), is usually associated with severe disease and deaths. This study evaluates real-life data on the effectiveness of mAbs therapies against SARS-CoV-2 infections by different viral variants, particularly in the presence of RNAemia, focusing on clinical outcomes.
From March 2021 to May 2022, high-risk patients with PCR-confirmed mild-moderate COVID-19 were enrolled at the Clinic of Infectious Diseases, San Paolo Hospital in Milan. Patients received Bamlanivimab/Bamlanivimab + Etesevimab/Casirivimab + Imdevimab/Sotrovimab based on Agenzia Italiana del Farmaco (AIFA) guidelines and prevalent SARS-CoV-2 variants. Nasopharyngeal swabs (NPS) and plasma samples were collected at infusion (t0) and after 7 days (t1). NPS viral loads and RNAemia were quantified using RT-qPCR, and variant typing was conducted. Clinical outcomes were evaluated, including time to symptom resolution and adverse effects.
Among 176 enrolled patients, treatment efficacy was observed in 96.6% with a median time to symptom resolution of 12 days (IQR 10-19). Viral load significantly decreased in both NPS and plasma by day 7 post-treatment (p<0.001). At t0, RNAemia was present in 61.9% of patients and NPS viral loads were higher in patients with RNAemia (p=0.002). However, after treatment, no significant differences in viral loads and times to symptom resolution were noted between patients with and without RNAemia. Omicron-infected patients exhibited higher plasma viral loads compared to Alpha and Delta variants (p<0.001) and the presence of RNAemia was significantly associated with Omicron (p<0.001). Vaccinated patients achieved faster recovery regardless of variant type (p=0.001).
Early administration of anti-SARS-CoV-2 mAbs in high-risk patients significantly reduced viral loads in NPS and plasma and improved clinical outcomes. Despite the presence of RNAemia, these tailored mAb therapies led to favorable recovery times and minimal adverse effects.
抗SARS-CoV-2中和单克隆抗体（mAbs）已被证明在治疗轻度至中度COVID-19的高危患者中具有临床益处。血清中的SARS-CoV-2 RNA（病毒血症）通常与严重疾病和死亡相关。本研究评估了mAbs疗法针对不同病毒变体的SARS-CoV-2感染有效性的真实数据，特别是在存在病毒血症的情况下，重点关注临床结果。
2021年3月至2022年5月，在米兰圣保罗医院传染病诊所招募了经PCR确诊为轻度至中度COVID-19的高危患者。患者根据意大利药品管理局（AIFA）指南和流行的SARS-CoV-2变体接受巴瑞替尼单抗/巴瑞替尼单抗+依替西单抗/卡西瑞单抗+英地西单抗/索托维单抗治疗。在输注时（t0）和7天后（t1）采集鼻咽拭子（NPS）和血浆样本。使用RT-qPCR对NPS病毒载量和病毒血症进行定量，并进行变体分型。评估临床结果，包括症状缓解时间和不良反应。
在176名入组患者中，96.6%观察到治疗效果，症状缓解的中位时间为12天（IQR 10-19）。治疗后第7天，NPS和血浆中的病毒载量均显著下降（p<0.001）。在t0时，61.9%的患者存在病毒血症，病毒血症患者的NPS病毒载量更高（p=0.002）。然而，治疗后，有病毒血症和无病毒血症的患者在病毒载量和症状缓解时间上没有显著差异。与阿尔法和德尔塔变体相比，奥密克戎感染患者的血浆病毒载量更高（p<0.001），且病毒血症的存在与奥密克戎显著相关（p<0.001）。无论变体类型如何，接种疫苗的患者恢复得更快（p=0.001）。
在高危患者中早期给予抗SARS-CoV-2 mAbs可显著降低NPS和血浆中的病毒载量，并改善临床结果。尽管存在病毒血症，但这些量身定制的mAb疗法导致了良好的恢复时间和最小的不良反应。
