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

• Published in: Mechanisms of ageing and development Vol. 193; p. 111413
• Main Authors: Sabbatinelli, Jacopo, Giuliani, Angelica, Matacchione, Giulia, Latini, Silvia, Laprovitera, Noemi, Pomponio, Giovanni, Ferrarini, Alessia, Svegliati Baroni, Silvia, Pavani, Marianna, Moretti, Marco, Gabrielli, Armando, Procopio, Antonio Domenico, Ferracin, Manuela, Bonafè, Massimiliano, Olivieri, Fabiola
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2021
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Biomarkers - blood; Circulating MicroRNA - blood; COVID-19; COVID-19 - blood; COVID-19 - drug therapy; COVID-19 - epidemiology; Female; Humans; Inflammaging; Inflammation - blood; Inflammation - drug therapy; Inflammation - epidemiology; interleukin-6; Male; microRNA; MicroRNAs - blood; Middle Aged; Pandemics; SARS-CoV-2; Tocilizumab; COVID-19; microRNA; Inflammaging; Tocilizumab; interleukin-6
• ISSN: 0047-6374; 1872-6216; 1872-6216
• DOI: 10.1016/j.mad.2020.111413

•Tocilizumab (TCZ) is currently being tested in COVID‐19‐induced cytokine storm.•COVID-19 patients responding to TCZ have higher post-treatment levels of circulating miR-146a.•Low levels of miR-146a are associated with death in COVID-19 patients not responding to TCZ.•MicroRNAs can represent biomarkers of response to anti-inflammatory interventions in COVID-19. 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.