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大流行对全球卫生和医疗系统构成了前所未有的威胁。死亡人数最多的原因是老年人受到与年龄相关疾病的影响，这些疾病发展为高炎症综合征。在这方面，我们假设COVID-19的严重程度可能与发炎有关。在这里，我们检查了30名来自临床试验NCT04315480的患者的血清样品，评估了单剂量静脉输注抗IL-6受体药物Tocilizumab（TCZ）在多灶性间质性肺炎的COVID-19患者中的临床反应。

在这些血清样本以及29位年龄和性别匹配的健康对照受试者中，我们评估了一组调节发炎的microRNA，即miR-146a-5p，miR-21-5p和miR-126-3p，通过RT-PCR和Droplet Digital PCR进行定量。

我们显示，对TCZ无反应的COVID-19患者在治疗后血清miR-146a-5p水平较低（p = 0.007）。在无反应者中，miR-146a-5p血清水平最低的反应者遭受的不良后果最大（p = 0.008）。我们的数据表明，基于血液的生物标志物，例如miR-146a-5p，可以提供有关炎症和COVID-19临床过程之间的分子联系的线索，从而可以更好地了解针对这种全球性健康威胁的生物药物库的使用。