TY - JOUR
T1 - Decreased serum levels of the inflammaging marker miR-146a are associated with non-clinical response to tocilizumab in COVID-19 patients
AU - Sabbatinelli, Jacopo
AU - Giuliani, Angelica
AU - Matacchione, Giulia
AU - Latini, Silvia
AU - Laprovitera, Noemi
AU - Pomponio, Giovanni
AU - Ferrarini, Alessia
AU - Svegliati Baroni, Silvia
AU - Pavani, Marianna
AU - Moretti, Marco
AU - Gabrielli, Armando
AU - Procopio, Antonio Domenico
AU - Ferracin, Manuela
AU - Bonafè, Massimiliano
AU - Olivieri, Fabiola
N1 - Funding Information:
This study was supported by grants from Università Politecnica delle Marche (RSA grant) and Italian Ministry of Health (“Ricerca corrente” ). MF lab is supported by Italian Association for Cancer Research (AIRC), Italy and Pallotti Fund, United States . MB is supported by Pallotti Fund.
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - COVID-19
KW - Inflammaging
KW - interleukin-6
KW - microRNA
KW - Tocilizumab
UR - http://www.scopus.com/inward/record.url?scp=85097476302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097476302&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2020.111413
DO - 10.1016/j.mad.2020.111413
M3 - Article
C2 - 33307107
AN - SCOPUS:85097476302
VL - 193
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
M1 - 111413
ER -