Unità Operativa Complessa Cardiologia con UTIC ed Emodinamica-Dipartimento Emergenza Accettazione, Azienda Ospedaliera "Antonio Cardarelli", 80131 Napoli, Italy.
Dipartimento di Scienze Biomediche Avanzate, Università FEDERICO II, 80131 Napoli, Italy.
Int J Mol Sci. 2020 Nov 15;21(22):8612. doi: 10.3390/ijms21228612.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) determines the angiotensin converting enzyme 2 (ACE2) down-regulation and related decrease in angiotensin II degradation. Both these events trigger "cytokine storm" leading to acute lung and cardiovascular injury. A selective therapy for COVID-19 has not yet been identified. Clinical trials with remdesivir gave discordant results. Thus, healthcare systems have focused on "multi-targeted" therapeutic strategies aiming at relieving systemic inflammation and thrombotic complications. No randomized clinical trial has demonstrated the efficacy of renin angiotensin system antagonists in reducing inflammation related to COVID-19. Dexamethasone and tocilizumab showed encouraging data, but their use needs to be further validated. The still-controversial efficacy of these treatments highlighted the importance of organ injury prevention in COVID-19. Neprilysin (NEP) might be an interesting target for this purpose. NEP expression is increased by cytokines on lung fibroblasts surface. NEP activity is elevated in acute respiratory distress syndrome and it is conceivable that it is also high in COVID-19. NEP is implicated in the degradation of natriuretic peptides, bradykinin, substance P, adrenomedullin, and apelin that account for prevention of organ injury. Thus, NEP/angiotensin receptor type 1 (AT1R) inhibitor sacubitril/valsartan (SAC/VAL) may increase levels of these molecules and block AT1Rs required for ACE2 endocytosis in SARS-CoV-2 infection. Moreover, SAC/VAL has a positive impact on acute heart failure that is very frequently observed in deceased COVID-19 patients. The current review aims to summarize actual therapeutic strategies for COVID-19 and to examine the data supporting the potential benefits of SAC/VAL in COVID-19 treatment.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）疾病（COVID-19）确定血管紧张素转换酶 2（ACE2）下调和相关的血管紧张素 II 降解减少。这两个事件都引发了“细胞因子风暴”，导致急性肺和心血管损伤。目前尚未确定 COVID-19 的选择性治疗方法。瑞德西韦的临床试验结果不一致。因此，医疗保健系统专注于“多靶点”治疗策略，旨在缓解全身炎症和血栓并发症。没有随机临床试验证明肾素血管紧张素系统拮抗剂在减轻与 COVID-19 相关的炎症方面的疗效。地塞米松和托珠单抗显示出令人鼓舞的数据，但它们的使用需要进一步验证。这些治疗方法的疗效仍存在争议，这突出表明 COVID-19 中预防器官损伤的重要性。 Neprilysin（NEP）可能是为此目的的一个有趣目标。细胞因子可增加肺成纤维细胞表面的 NEP 表达。NEP 活性在急性呼吸窘迫综合征中升高，可以想象它在 COVID-19 中也很高。NEP 参与了利钠肽、缓激肽、P 物质、肾上腺髓质素和 Apelin 的降解，这些肽类可预防器官损伤。因此，NEP/血管紧张素受体 1（AT1R）抑制剂沙库巴曲缬沙坦（SAC/VAL）可能会增加这些分子的水平，并阻断 SARS-CoV-2 感染中 ACE2 内吞所需的 AT1R。此外，SAC/VAL 对急性心力衰竭有积极影响，而急性心力衰竭在 COVID-19 死亡患者中非常常见。本综述旨在总结 COVID-19 的当前治疗策略，并研究支持 SAC/VAL 在 COVID-19 治疗中潜在益处的数据。
