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

  1. Jacopo Sabbatinelli
  2. Angelica Giuliani
  3. Giulia Matacchione
  4. Silvia Latini
  5. Noemi Laprovitera
  6. Giovanni Pomponio
  7. Alessia Ferrarini
  8. Silvia Svegliati Baroni
  9. Marianna Pavani
  10. Marco Moretti
  11. Armando Gabrielli
  12. Antonio Domenico Procopio
  13. Manuela Ferracin
  14. Massimiliano Bonafè
  15. Fabiola Olivieri
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Abstract

Background

Current COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. At least in western countries, the most amount of the death toll is accounted by old people affected by age-related diseases. In this regard, we proposed that COVID-19 severity may be tightly related to inflammaging, i.e. the age-related onset of inflammation, which is responsible for age-related diseases. It has been reported that systemic hyper-inflammation may turn to be detrimental in COVID-19 patients.

Objective

Here, we exploited a recently closed clinical trial (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04315480">NCT04315480</ext-link>) on the anti-IL-6 drug tocilizumab to assess whether microRNAs regulating inflammaging can be assessed as biomarkers of drug response and outcome.

Methods

Serum levels of miR-146a-5p, −21-5p, and −126-3p were quantified by RT-PCR and Droplet Digital PCR by two independent laboratories on 30 patients with virologically confirmed COVID-19, characterized by multifocal interstitial pneumonia confirmed by CT-scan and requiring oxygen therapy, and 29 age- and gender-matched healthy control subjects. COVID-19 patients were treated with a single-dose intravenous infusion of 8 mg/kg tocilizumab and categorized into responders and non-responders.

Results

We showed that COVID-19 patients who did not respond to tocilizumab have lower serum levels of miR-146a-5p after the treatment (p=0.007). Moreover, among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p=0.008).

Conclusion

Our data show that blood-based biomarkers, such as miR-146a-5p, can provide a molecular link between inflammaging and COVID-19 clinical course, thus allowing to enlarge the drug armory against this worldwide health threat.

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