Association of miR-144 levels in the peripheral blood with COVID-19 severity and mortality

Alisia Madè; Simona Greco; Melanie Vausort; Marios Miliotis; Eric Schordan; Shounak Baksi; Lu Zhang; Ekaterina Baryshnikova; Marco Ranucci; Rosanna Cardani; Guy Fagherazzi; Markus Ollert; Spyros Tastsoglou; Giannis Vatsellas; Artemis Hatzigeorgiou; Hüseyin Firat; Yvan Devaux; Fabio Martelli

doi:10.1038/s41598-022-23922-2

Association of miR-144 levels in the peripheral blood with COVID-19 severity and mortality

Alisia Madè
, Simona Greco
, Melanie Vausort
, Marios Miliotis
, Eric Schordan
, Shounak Baksi
, Lu Zhang
, Ekaterina Baryshnikova
, Marco Ranucci
, Rosanna Cardani
, Guy Fagherazzi
, Markus Ollert
, Spyros Tastsoglou
, Giannis Vatsellas
, Artemis Hatzigeorgiou
, Hüseyin Firat
, Yvan Devaux
, Fabio Martelli^*

^*Kontaktforfatter

Policlinico San Donato Research Hospital
Luxembourg Institute of Health
National Influenza Reference Laboratory of Southern Greece Hellenic Pasteur Institute
University of Thessaly
Firalis SAS
Biomedical Research Foundation of the Academy of Athens

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

Coronavirus disease-2019 (COVID-19) can be asymptomatic or lead to a wide symptom spectrum, including multi-organ damage and death. Here, we explored the potential of microRNAs in delineating patient condition and predicting clinical outcome. Plasma microRNA profiling of hospitalized COVID-19 patients showed that miR-144-3p was dynamically regulated in response to COVID-19. Thus, we further investigated the biomarker potential of miR-144-3p measured at admission in 179 COVID-19 patients and 29 healthy controls recruited in three centers. In hospitalized patients, circulating miR-144-3p levels discriminated between non-critical and critical illness (AUC_miR-144-3p = 0.71; p = 0.0006), acting also as mortality predictor (AUC_miR-144-3p = 0.67; p = 0.004). In non-hospitalized patients, plasma miR-144-3p levels discriminated mild from moderate disease (AUC_miR-144-3p = 0.67; p = 0.03). Uncontrolled release of pro-inflammatory cytokines can lead to clinical deterioration. Thus, we explored the added value of a miR-144/cytokine combined analysis in the assessment of hospitalized COVID-19 patients. A miR-144-3p/Epidermal Growth Factor (EGF) combined score discriminated between non-critical and critical hospitalized patients (AUC_{miR-144-3p/EGF} = 0.81; p < 0.0001); moreover, a miR-144-3p/Interleukin-10 (IL-10) score discriminated survivors from nonsurvivors (AUC_{miR-144-3p/IL-10} = 0.83; p < 0.0001). In conclusion, circulating miR-144-3p, possibly in combination with IL-10 or EGF, emerges as a noninvasive tool for early risk-based stratification and mortality prediction in COVID-19.

Originalsprog	Engelsk
Artikelnummer	20048
Tidsskrift	Scientific Reports
Vol/bind	12
ISSN	2045-2322
DOI	https://doi.org/10.1038/s41598-022-23922-2
Status	Udgivet - dec. 2022

Bibliografisk note

Funding Information:
FM is funded by the Italian Ministry of Health “Ricerca Corrente” that partially supported this study and is gratefully acknowledged. FM is also supported by Telethon Foundation (#4462 GGP19035A) and AFM-Telethon (# 23054). FM and YD are also supported by the EU Horizon 2020 project COVIRNA (Grant #101016072) and EU-CardioRNA COST action (CA17129). The Italian Cardiology Network IRCCS (RCR-2020-23670065 and RCR-2021-23671212) also supported the study. The Predi-COVID study is supported by the Luxembourg National Research Fund (FNR) (Predi-COVID grant number 14716273 and COVID-19/2020-1/14719577/miRCOVID), the André Losch Foundation, the Luxembourg Institute of Health and the European Regional Development Fund (FEDER, convention 2018-04-026-21).This work was also supported by ‘ELIXIR-GR: The Greek Research Infrastructure for Data Management and Analysis in Life Sciences’ [MIS-5002780], implemented under the Action ‘Reinforcement of the Research and Innovation Infrastructure’, funded by the Operational Programme ‘Competitiveness, Entrepreneurship and Innovation’ [NSRF 2014-2020] and co-financed by Greece and the European Union (European Regional Development Fund) and by the Flagship Action to address the SARS-CoV-2 crisis: “Epidemiological study in Greece through extensive testing for virus and antibody detection, viral genome sequencing and genetic analysis of patients”. FM, YD and HF have filed a patent (FRL22P01EP1, 2022-01-14) on microRNAs as biomarker in COVID-19. Other authors declare that they have no competing interests.

Funding Information:
We thank Federica Poli for patient recruitment, Laura Valentina Renna for samples collection and all the clinical and technical personnel of PSD that made this study possible. We are thankful to the Predi-COVID study participants, the Predi-COVID study group and the funders for their support of this initiative. We also thank Michel Vaillant and his team who performed the NIH classification for the LIH Predi-COVID study and Christelle Nicolas for expert technical support. The contribution of Dimitris Thanos, Efthimia Petinaki and Georgia Papadamou, University Hospital of Larissa, Greece, is also gratefully acknowledged. Figures were partly generated by using BioRender.com. This work is dedicated to dr. Armando Felsani, a brilliant scientist and a great mentor that passed away on April 21, 2022.

Finansiering

FM is funded by the Italian Ministry of Health “Ricerca Corrente” that partially supported this study and is gratefully acknowledged. FM is also supported by Telethon Foundation (#4462 GGP19035A) and AFM-Telethon (# 23054). FM and YD are also supported by the EU Horizon 2020 project COVIRNA (Grant #101016072) and EU-CardioRNA COST action (CA17129). The Italian Cardiology Network IRCCS (RCR-2020-23670065 and RCR-2021-23671212) also supported the study. The Predi-COVID study is supported by the Luxembourg National Research Fund (FNR) (Predi-COVID grant number 14716273 and COVID-19/2020-1/14719577/miRCOVID), the André Losch Foundation, the Luxembourg Institute of Health and the European Regional Development Fund (FEDER, convention 2018-04-026-21).This work was also supported by ‘ELIXIR-GR: The Greek Research Infrastructure for Data Management and Analysis in Life Sciences’ [MIS-5002780], implemented under the Action ‘Reinforcement of the Research and Innovation Infrastructure’, funded by the Operational Programme ‘Competitiveness, Entrepreneurship and Innovation’ [NSRF 2014-2020] and co-financed by Greece and the European Union (European Regional Development Fund) and by the Flagship Action to address the SARS-CoV-2 crisis: “Epidemiological study in Greece through extensive testing for virus and antibody detection, viral genome sequencing and genetic analysis of patients”. FM, YD and HF have filed a patent (FRL22P01EP1, 2022-01-14) on microRNAs as biomarker in COVID-19. Other authors declare that they have no competing interests. We thank Federica Poli for patient recruitment, Laura Valentina Renna for samples collection and all the clinical and technical personnel of PSD that made this study possible. We are thankful to the Predi-COVID study participants, the Predi-COVID study group and the funders for their support of this initiative. We also thank Michel Vaillant and his team who performed the NIH classification for the LIH Predi-COVID study and Christelle Nicolas for expert technical support. The contribution of Dimitris Thanos, Efthimia Petinaki and Georgia Papadamou, University Hospital of Larissa, Greece, is also gratefully acknowledged. Figures were partly generated by using BioRender.com. This work is dedicated to dr. Armando Felsani, a brilliant scientist and a great mentor that passed away on April 21, 2022.

Dokumenter og links

10.1038/s41598-022-23922-2Licens: CC BY

Open Access VersionForlagets udgivne version, 1,75 MBLicens: CC BY

SDU link

Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

Citationsformater

Madè, A., Greco, S., Vausort, M., Miliotis, M., Schordan, E., Baksi, S., Zhang, L., Baryshnikova, E., Ranucci, M., Cardani, R., Fagherazzi, G., Ollert, M., Tastsoglou, S., Vatsellas, G., Hatzigeorgiou, A., Firat, H., Devaux, Y., & Martelli, F. (2022). Association of miR-144 levels in the peripheral blood with COVID-19 severity and mortality. Scientific Reports, 12, Artikel 20048. https://doi.org/10.1038/s41598-022-23922-2

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abstract = "Coronavirus disease-2019 (COVID-19) can be asymptomatic or lead to a wide symptom spectrum, including multi-organ damage and death. Here, we explored the potential of microRNAs in delineating patient condition and predicting clinical outcome. Plasma microRNA profiling of hospitalized COVID-19 patients showed that miR-144-3p was dynamically regulated in response to COVID-19. Thus, we further investigated the biomarker potential of miR-144-3p measured at admission in 179 COVID-19 patients and 29 healthy controls recruited in three centers. In hospitalized patients, circulating miR-144-3p levels discriminated between non-critical and critical illness (AUCmiR-144-3p = 0.71; p = 0.0006), acting also as mortality predictor (AUCmiR-144-3p = 0.67; p = 0.004). In non-hospitalized patients, plasma miR-144-3p levels discriminated mild from moderate disease (AUCmiR-144-3p = 0.67; p = 0.03). Uncontrolled release of pro-inflammatory cytokines can lead to clinical deterioration. Thus, we explored the added value of a miR-144/cytokine combined analysis in the assessment of hospitalized COVID-19 patients. A miR-144-3p/Epidermal Growth Factor (EGF) combined score discriminated between non-critical and critical hospitalized patients (AUCmiR-144-3p/EGF = 0.81; p < 0.0001); moreover, a miR-144-3p/Interleukin-10 (IL-10) score discriminated survivors from nonsurvivors (AUCmiR-144-3p/IL-10 = 0.83; p < 0.0001). In conclusion, circulating miR-144-3p, possibly in combination with IL-10 or EGF, emerges as a noninvasive tool for early risk-based stratification and mortality prediction in COVID-19.",

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Madè, A, Greco, S, Vausort, M, Miliotis, M, Schordan, E, Baksi, S, Zhang, L, Baryshnikova, E, Ranucci, M, Cardani, R, Fagherazzi, G, Ollert, M, Tastsoglou, S, Vatsellas, G, Hatzigeorgiou, A, Firat, H, Devaux, Y & Martelli, F 2022, 'Association of miR-144 levels in the peripheral blood with COVID-19 severity and mortality', Scientific Reports, bind 12, 20048. https://doi.org/10.1038/s41598-022-23922-2

TY - JOUR

T1 - Association of miR-144 levels in the peripheral blood with COVID-19 severity and mortality

AU - Madè, Alisia

AU - Greco, Simona

AU - Vausort, Melanie

AU - Miliotis, Marios

AU - Schordan, Eric

AU - Baksi, Shounak

AU - Zhang, Lu

AU - Baryshnikova, Ekaterina

AU - Ranucci, Marco

AU - Cardani, Rosanna

AU - Fagherazzi, Guy

AU - Ollert, Markus

AU - Tastsoglou, Spyros

AU - Vatsellas, Giannis

AU - Hatzigeorgiou, Artemis

AU - Firat, Hüseyin

AU - Devaux, Yvan

AU - Martelli, Fabio

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N2 - Coronavirus disease-2019 (COVID-19) can be asymptomatic or lead to a wide symptom spectrum, including multi-organ damage and death. Here, we explored the potential of microRNAs in delineating patient condition and predicting clinical outcome. Plasma microRNA profiling of hospitalized COVID-19 patients showed that miR-144-3p was dynamically regulated in response to COVID-19. Thus, we further investigated the biomarker potential of miR-144-3p measured at admission in 179 COVID-19 patients and 29 healthy controls recruited in three centers. In hospitalized patients, circulating miR-144-3p levels discriminated between non-critical and critical illness (AUCmiR-144-3p = 0.71; p = 0.0006), acting also as mortality predictor (AUCmiR-144-3p = 0.67; p = 0.004). In non-hospitalized patients, plasma miR-144-3p levels discriminated mild from moderate disease (AUCmiR-144-3p = 0.67; p = 0.03). Uncontrolled release of pro-inflammatory cytokines can lead to clinical deterioration. Thus, we explored the added value of a miR-144/cytokine combined analysis in the assessment of hospitalized COVID-19 patients. A miR-144-3p/Epidermal Growth Factor (EGF) combined score discriminated between non-critical and critical hospitalized patients (AUCmiR-144-3p/EGF = 0.81; p < 0.0001); moreover, a miR-144-3p/Interleukin-10 (IL-10) score discriminated survivors from nonsurvivors (AUCmiR-144-3p/IL-10 = 0.83; p < 0.0001). In conclusion, circulating miR-144-3p, possibly in combination with IL-10 or EGF, emerges as a noninvasive tool for early risk-based stratification and mortality prediction in COVID-19.

AB - Coronavirus disease-2019 (COVID-19) can be asymptomatic or lead to a wide symptom spectrum, including multi-organ damage and death. Here, we explored the potential of microRNAs in delineating patient condition and predicting clinical outcome. Plasma microRNA profiling of hospitalized COVID-19 patients showed that miR-144-3p was dynamically regulated in response to COVID-19. Thus, we further investigated the biomarker potential of miR-144-3p measured at admission in 179 COVID-19 patients and 29 healthy controls recruited in three centers. In hospitalized patients, circulating miR-144-3p levels discriminated between non-critical and critical illness (AUCmiR-144-3p = 0.71; p = 0.0006), acting also as mortality predictor (AUCmiR-144-3p = 0.67; p = 0.004). In non-hospitalized patients, plasma miR-144-3p levels discriminated mild from moderate disease (AUCmiR-144-3p = 0.67; p = 0.03). Uncontrolled release of pro-inflammatory cytokines can lead to clinical deterioration. Thus, we explored the added value of a miR-144/cytokine combined analysis in the assessment of hospitalized COVID-19 patients. A miR-144-3p/Epidermal Growth Factor (EGF) combined score discriminated between non-critical and critical hospitalized patients (AUCmiR-144-3p/EGF = 0.81; p < 0.0001); moreover, a miR-144-3p/Interleukin-10 (IL-10) score discriminated survivors from nonsurvivors (AUCmiR-144-3p/IL-10 = 0.83; p < 0.0001). In conclusion, circulating miR-144-3p, possibly in combination with IL-10 or EGF, emerges as a noninvasive tool for early risk-based stratification and mortality prediction in COVID-19.

KW - Biomarkers/blood

KW - COVID-19/diagnosis

KW - Epidermal Growth Factor

KW - Humans

KW - Interleukin-10

KW - MicroRNAs/blood

U2 - 10.1038/s41598-022-23922-2

DO - 10.1038/s41598-022-23922-2

M3 - Journal article

C2 - 36414650

AN - SCOPUS:85142227266

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

M1 - 20048

ER -

Association of miR-144 levels in the peripheral blood with COVID-19 severity and mortality

Abstract

Bibliografisk note

Finansiering

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SDU link

Fingeraftryk

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