Department of Paediatrics, Magna Graecia University of Catanzaro, Italy.
Department of Biomedical Sciences, University of Cagliari, Italy.
Med Hypotheses. 2020 Jul;140:109776. doi: 10.1016/j.mehy.2020.109776. Epub 2020 Apr 22.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPARγ agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）已成为一种全球性流行疾病（COVID-19），导致超过 3 万人死亡。尽管全球付出了巨大而持续的努力，但仍未发现有效的药物来对抗这种瘟疫，因此，因呼吸窘迫而住进重症监护病房（ICU）的患者主要通过基于维持氧气的支持性护理来治疗。有几位作者报告说，COVID-19 患者中高血压、糖尿病、心血管和脑血管疾病合并症的患病率确实很高，这表明这些疾病可能会使病情恶化并使预后复杂化。上述疾病的共同点是存在潜在的慢性炎症状态，这可能与代谢综合征和胰岛素抵抗的典型实验室参数改变有关。在严重 COVID-19 患者中，许多患者的炎症标志物如 C 反应蛋白、IL-6、D-二聚体、血清铁蛋白和乳酸脱氢酶等均升高；这些标志物在发病后的第 4-6 天进行评估，似乎可以预测不良预后。我们的假设是，噻唑烷二酮（TZD）类药物，如吡格列酮或罗格列酮，可用于治疗胰岛素抵抗及其伴随的炎症，可能改善患有糖尿病、高血压和心血管疾病合并症的 COVID-19 患者的预后。TZD 是过氧化物酶体增殖物激活受体 γ（PPARγ）激动剂，作用于核受体，从而触发某些转录因子。TZD 在本世纪初被广泛用于 2 型糖尿病，尽管人们对长期治疗可能产生的副作用表示担忧，但它们的抗炎特性在许多医学疾病中的应用最近得到了重新评估。
