Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients

Mech Ageing Dev. 2021 Jan:193:111413. doi: 10.1016/j.mad.2020.111413. Epub 2020 Dec 8.

Abstract

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.

Keywords: COVID-19; Inflammaging; Tocilizumab; interleukin-6; microRNA.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Biomarkers / blood
  • COVID-19 Drug Treatment*
  • COVID-19* / blood
  • COVID-19* / epidemiology
  • Circulating MicroRNA / blood*
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / drug therapy
  • Inflammation / epidemiology
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Pandemics*
  • SARS-CoV-2*

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Circulating MicroRNA
  • MIRN146 microRNA, human
  • MicroRNAs
  • tocilizumab

Associated data

  • ClinicalTrials.gov/NCT04315480