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

Jacopo Sabbatinelli, Angelica Giuliani, Giulia Matacchione, Silvia Latini, Noemi Laprovitera, Giovanni Pomponio, Alessia Ferrarini, Silvia Svegliati Baroni, Marianna Pavani, Marco Moretti, Armando Gabrielli, Antonio Domenico Procopio, Manuela Ferracin, Massimiliano Bonafè, Fabiola Olivieri

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number111413
JournalMechanisms of Ageing and Development
Volume193
DOIs
Publication statusPublished - Jan 2021

Keywords

  • COVID-19
  • Inflammaging
  • interleukin-6
  • microRNA
  • Tocilizumab

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology

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