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新冠病毒感染后肺纤维化:治疗前景

Lung Fibrosis after COVID-19: Treatment Prospects.

作者信息

Bazdyrev Evgeny, Rusina Polina, Panova Maria, Novikov Fedor, Grishagin Ivan, Nebolsin Vladimir

机构信息

Research Institute for Complex Issues of Cardiovascular Diseases, 6, Sosnoviy Blvd., 650002 Kemerovo, Russia.

PHARMENTERPRISES LLC, Skolkovo Innovation Center, Bolshoi Blvd., 42(1), 143026 Moscow, Russia.

出版信息

Pharmaceuticals (Basel). 2021 Aug 17;14(8):807. doi: 10.3390/ph14080807.

Abstract

At the end of 2019, a highly contagious infection began its ominous conquest of the world. It was soon discovered that the disease was caused by a novel coronavirus designated as SARS-CoV-2, and the disease was thus abbreviated to COVID-19 (COVID). The global medical community has directed its efforts not only to find effective therapies against the deadly pathogen but also to combat the concomitant complications. Two of the most common respiratory manifestations of COVID are a significant reduction in the diffusing capacity of the lungs (DLCO) and the associated pulmonary interstitial damage. One year after moderate COVID, the incidence rate of impaired DLCO and persistent lung damage still exceeds 30%, and one-third of the patients have severe DLCO impairment and fibrotic lung damage. The persistent respiratory complications may cause substantial population morbidity, long-term disability, and even death due to the lung fibrosis progression. The incidence of COVID-induced pulmonary fibrosis caused by COVID can be estimated based on a 15-year observational study of lung pathology after SARS. Most SARS patients with fibrotic lung damage recovered within the first year and then remained healthy; however, in 20% of the cases, significant fibrosis progression was found in 5-10 years. Based on these data, the incidence rate of post-COVID lung fibrosis can be estimated at 2-6% after moderate illness. What is worse, there are reasons to believe that fibrosis may become one of the major long-term complications of COVID, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. In this review, we analyze the latest data from ongoing clinical trials aimed at treating post-COVID lung fibrosis and analyze the rationale for the current drug candidates. We discuss the use of antifibrotic therapy for idiopathic pulmonary fibrosis, the IN01 vaccine, glucocorticosteroids as well as the stromal vascular fraction for the treatment and rehabilitation of patients with COVID-associated pulmonary damage.

摘要

2019年末,一种极具传染性的感染开始了对世界的不祥征服。很快人们发现,该疾病是由一种名为严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的新型冠状病毒引起的,因此该疾病被简称为2019冠状病毒病(COVID-19,简称“新冠”)。全球医学界不仅致力于寻找针对这种致命病原体的有效疗法,还努力应对随之而来的并发症。新冠最常见的两种呼吸道表现是肺弥散能力(DLCO)显著降低以及相关的肺间质损伤。中度新冠感染一年后,DLCO受损和持续性肺损伤的发生率仍超过30%,三分之一的患者存在严重的DLCO损害和肺纤维化损伤。由于肺纤维化进展,持续性呼吸道并发症可能导致大量人群发病、长期残疾甚至死亡。基于对SARS后肺部病理的15年观察性研究,可以估算新冠引起的肺纤维化发病率。大多数有肺纤维化损伤的SARS患者在第一年内康复,之后保持健康;然而,在20%的病例中,在5至10年内发现了明显的纤维化进展。基于这些数据,中度疾病后新冠后肺纤维化的发病率估计为2%至6%。更糟糕的是,有理由相信纤维化可能成为新冠的主要长期并发症之一,即使在无症状个体中也是如此。目前,尽管全球医学界已尽最大努力,但仍没有针对新冠引起的肺纤维化的治疗方法。在这篇综述中,我们分析了旨在治疗新冠后肺纤维化的正在进行的临床试验的最新数据,并分析了当前候选药物的理论依据。我们讨论了抗纤维化疗法用于特发性肺纤维化、IN01疫苗、糖皮质激素以及用于治疗和康复新冠相关肺损伤患者的基质血管成分的应用。

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