Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland.
Int J Mol Sci. 2021 Apr 17;22(8):4177. doi: 10.3390/ijms22084177.
The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-β and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.
导致当前 COVID-19 大流行的病毒是严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）：一种高传染性和中等致死率的新型病毒。COVID-19 的主要临床表现为间质性肺炎，可能进展为急性呼吸窘迫综合征（ARDS）。然而，该疾病引起强烈的全身炎症反应，即细胞因子风暴或巨噬细胞活化综合征（MAS），与血栓并发症有关。该疾病的复杂性需要适当的强化治疗。一种有前途的治疗方法是他汀类药物治疗，这些药物是 3-羟基-3-甲基戊二酰基辅酶 A 还原酶抑制剂，具有多种抗炎作用。最近的研究表明，他汀类药物治疗与 COVID-19 死亡率降低有关，这可能是由直接和间接机制引起的。根据文献数据，他汀类药物可以通过抑制主要蛋白酶（Mpro）和 RNA 依赖性 RNA 聚合酶（RdRp）来限制 SARS-CoV-2 细胞进入和复制。通过降低血清 IL-6 水平可以改善细胞因子风暴；这可以通过抑制 Toll 样受体 4（TLR4）和调节巨噬细胞活性来实现。他汀类药物还可以通过降低血清 PAI-1 水平、减轻肺组织中的 TGF-β和 VEGF 以及改善内皮功能来降低 COVID-19 的并发症，如血栓形成和肺纤维化。尽管有这些益处，但他汀类药物治疗可能有副作用，应予以考虑，例如肌酸激酶（CK）、肝酶和血清葡萄糖水平升高，这些在严重 COVID-19 感染中已经升高。本研究分析了他汀类药物治疗 COVID-19 患者的益处和局限性的最新发现。
