Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy.
Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
Mech Ageing Dev. 2021 Jan;193:111413. doi: 10.1016/j.mad.2020.111413. Epub 2020 Dec 8.
Current COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. The most amount of the death toll is accounted by old people affected by age-related diseases that develop a hyper-inflammatory syndrome. In this regard, we hypothesized that COVID-19 severity may be linked to inflammaging. Here, we examined 30 serum samples from patients enrolled in the clinical trial NCT04315480 assessing the clinical response to a single-dose intravenous infusion of the anti-IL-6 receptor drug Tocilizumab (TCZ) in COVID-19 patients with multifocal interstitial pneumonia. In these serum samples, as well as in 29 age- and gender-matched healthy control subjects, we assessed a set of microRNAs that regulate inflammaging, i.e. miR-146a-5p, miR-21-5p, and miR-126-3p, which were quantified by RT-PCR and Droplet Digital PCR. We showed that COVID-19 patients who did not respond to TCZ have lower serum levels of miR-146a-5p after the treatment (p = 0.007). Among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p = 0.008). Our data show that a blood-based biomarker, such as miR-146a-5p, can provide clues about the molecular link between inflammaging and COVID-19 clinical course, thus allowing to better understand the use of biologic drug armory against this worldwide health threat.
当前的 COVID-19 大流行对全球健康和医疗保健系统构成了前所未有的威胁。死亡人数最多的是受与年龄相关的疾病影响的老年人，这些疾病会发展出一种过度炎症综合征。在这方面，我们假设 COVID-19 的严重程度可能与炎症衰老有关。在这里，我们检查了 30 份来自临床试验 NCT04315480 的血清样本，该试验评估了 COVID-19 伴有多灶性间质性肺炎的患者单次静脉输注抗白细胞介素 6 受体药物托珠单抗 (TCZ) 的临床反应。在这些血清样本以及 29 名年龄和性别匹配的健康对照者中，我们评估了一组调节炎症衰老的 microRNAs，即 miR-146a-5p、miR-21-5p 和 miR-126-3p，这些 microRNAs 通过 RT-PCR 和数字 PCR 进行定量。我们表明，对 TCZ 无反应的 COVID-19 患者在治疗后血清 miR-146a-5p 水平降低（p=0.007）。在无反应者中，血清 miR-146a-5p 水平最低的患者预后最差（p=0.008）。我们的数据表明，miR-146a-5p 等基于血液的生物标志物可以提供有关炎症衰老与 COVID-19 临床病程之间分子联系的线索，从而更好地了解针对这一全球健康威胁使用生物药物武器。
