Sestili Piero, Fimognari Carmela
Department of Biomolecular Sciences (DISB), Università degli Studi di Urbino Carlo Bo, Urbino, Italy.
Dipartimento di Scienze per la Qualità della Vita, Università degli Studi di Bologna, Rimini, Italy.
Front Pharmacol. 2020 Oct 7;11:579944. doi: 10.3389/fphar.2020.579944. eCollection 2020.
COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of early symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention and seriousness. In analogy with other airways viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever, and control inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in common airways viral infections and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is still, discouraged while the alternative adoption of paracetamol is still preferred. On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may be the better choice.
治疗该疾病的抗病毒药物和针对宿主的药物亟待研发。人们已付出巨大努力为住院的重症患者寻找药物和治疗方法。然而，用于居家管理早期症状的药物，尽管其重要性不言而喻，但过去未得到、目前也未受到同等程度的关注和重视。与其他呼吸道病毒感染类似，新冠早期患者需要特效抗病毒药物（目前仍未找到）以及非特异性药物来减轻疼痛、降低体温并控制炎症。非甾体抗炎药（NSAIDs）和对乙酰氨基酚（PAC）在常见呼吸道病毒感染中被广泛用作非特异性药物，因此理论上二者都可用于新冠治疗。然而，一些研究报告和国家当局发出警告，由于NSAIDs可能会升高血管紧张素转换酶2（ACE2）水平（SARS-CoV2进入宿主呼吸道细胞所使用的受体）、增加细菌二重感染风险以及掩盖疾病症状，从而引发了对其安全性的担忧。因此，NSAIDs的使用过去不被鼓励，现在仍然不被提倡，而对乙酰氨基酚仍是首选替代药物。基于关于谷胱甘肽（GSH）水平不足在新冠病情加重中可能发挥的作用以及PAC具有消耗GSH活性的新数据和假说，本评论提出了一个问题：PAC是否可能是更好的选择。
