Rosa Luigi, Tripepi Giovanni, Naldi Enrico, Aimati Marina, Santangeli Stefano, Venditto Francesco, Caldarelli Marcello, Valenti Piera
Department of Public Health and Infectious Diseases, University of Rome "La Sapienza", 00185 Rome, Italy.
National Research Council (CNR), Institute of Clinical Physiology (IFC), Clinical Epidemiology of Renal Diseases and Hypertension, Ospedali Riuniti, 89124 Reggio Calabria, Italy.
J Clin Med. 2021 Sep 21;10(18):4276. doi: 10.3390/jcm10184276.
SARS-CoV-2, an enveloped, single-stranded RNA virus causing COVID-19, exerts morbidity and mortality especially in elderly, obese individuals and those suffering from chronic conditions. In addition to the availability of vaccines and the limited efficacy of the first dose of vaccine against SARS-CoV-2 variants, there is an urgent requirement for the discovery and development of supplementary antiviral agents. Lactoferrin (Lf), a pleiotropic cationic glycoprotein of innate immunity, has been proposed as a safe treatment combined with other therapies in COVID-19 patients. Here, we present a small retrospective study on asymptomatic, paucisymptomatic, and moderate symptomatic COVID-19 Lf-treated versus Lf-untreated patients. The time required to achieve SARS-CoV-2 RNA negativization in Lf-treated patients ( = 82) was significantly lower ( < 0.001) compared to that observed in Lf-untreated ones ( = 39) (15 versus 24 days). A link among reduction in symptoms, age, and Lf treatment was found. The Lf antiviral activity could be explained through the interaction with SARS-CoV-2 spike, the binding with heparan sulfate proteoglycans of cells, and the anti-inflammatory activity associated with the restoration of iron homeostasis disorders, which favor viral infection/replication. Lf could be an important supplementary treatment in counteracting SARS-CoV-2 infection, as it is also safe and well-tolerated by all treated patients.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种包膜单链RNA病毒，可导致冠状病毒病2019（COVID-19），尤其在老年人、肥胖个体以及患有慢性病的人群中会引发发病和死亡。除了疫苗的可及性以及首剂疫苗对SARS-CoV-2变体的疗效有限外，迫切需要发现和开发补充性抗病毒药物。乳铁蛋白（Lf）是一种具有多效性的先天性免疫阳离子糖蛋白，已被提议作为COVID-19患者与其他疗法联合使用的安全治疗方法。在此，我们针对无症状、症状轻微和中度症状的COVID-19患者进行了一项小型回顾性研究，比较了接受Lf治疗和未接受Lf治疗的患者。与未接受Lf治疗的患者（n = 39）相比，接受Lf治疗的患者（n = 82）实现SARS-CoV-2 RNA转阴所需的时间显著更短（P < 0.001）（分别为15天和24天）。研究发现症状减轻、年龄与Lf治疗之间存在关联。Lf的抗病毒活性可以通过与SARS-CoV-2刺突蛋白的相互作用、与细胞硫酸乙酰肝素蛋白聚糖的结合以及与铁稳态紊乱恢复相关的抗炎活性来解释，铁稳态紊乱有利于病毒感染/复制。Lf可能是对抗SARS-CoV-2感染的一种重要补充治疗方法，因为它对所有接受治疗的患者来说也是安全且耐受性良好的。
