{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:52:53Z","timestamp":1772553173414,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormal liver function tests are frequently reported in patients with COVID-19. This study aimed to identify potential treatment-associated hepatocellular injury in COVID-19 patients by dynamically assessing circulating miR-122, a biomarker with high hepatic specificity and sensitivity. An exploratory approach was additionally used, given the limited evidence regarding factors influencing miR-122 expression in this setting. We performed a prospective cohort study including 96 adult participants enrolled at a tertiary hospital in Bucharest, Romania, between March 2022 and July 2023: 78 COVID-19 patients (57 with baseline and follow-up miR-122 assessment after 5 days of treatment and 21 with a single measurement) and 18 non-COVID-19 participants included for comparison. Plasma miR-122 levels were measured using quantitative polymerase chain reaction, normalized to U6 small nuclear RNA, and expressed as log10(2\u2212\u0394Ct). No associations were observed between miR-122 expression and remdesivir administered for standard treatment durations (3\u20135 days) or other COVID-19\u2013specific therapies. However, a duration-dependent relationship with remdesivir cannot be excluded. Moreover, therapeutic paracetamol use prior to presentation was positively associated with miR-122 expression at follow-up and remained significant after adjustment. Additionally, bivariate analyses revealed inverse correlations between baseline miR-122 and inflammatory biomarkers, with multivariable analysis showing an independent positive association with lymphocyte count.<\/jats:p>","DOI":"10.3390\/ijms27052288","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:24:34Z","timestamp":1772447074000},"page":"2288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Liver-Enriched miR-122 in COVID-19 Patients: A Longitudinal Real-Life Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3953-0767","authenticated-orcid":false,"given":"Nicoleta","family":"Mihai","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"\u201cProf. Dr. Matei Bal\u0219\u201d National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u0103t\u0103lin","family":"Tili\u0219can","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"\u201cProf. Dr. Matei Bal\u0219\u201d National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2703-6586","authenticated-orcid":false,"given":"Iulia Virginia","family":"Iancu","sequence":"additional","affiliation":[{"name":"\u201c\u015etefan S. Nicolau\u201d Institute of Virology, 285 Mihai Bravu Road, 030304 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oana-Alexandra","family":"Ganea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"\u201cProf. Dr. Matei Bal\u0219\u201d National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8520-0375","authenticated-orcid":false,"given":"Aida-Isabela","family":"Adamescu","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"\u201cProf. Dr. Matei Bal\u0219\u201d National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0019-934X","authenticated-orcid":false,"given":"\u0218tefan Sorin","family":"Aram\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"\u201cProf. Dr. Matei Bal\u0219\u201d National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9478-6176","authenticated-orcid":false,"given":"Andreea Leti\u021bia","family":"Arsene","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2492-6073","authenticated-orcid":false,"given":"Simona-Maria","family":"Ru\u021b\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"\u201c\u015etefan S. Nicolau\u201d Institute of Virology, 285 Mihai Bravu Road, 030304 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Aram\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania"},{"name":"\u201cProf. Dr. Matei Bal\u0219\u201d National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","first-page":"162","article-title":"MicroRNAs in Drug-induced Liver Injury","volume":"2","author":"Li","year":"2014","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhep.2014.10.004","article-title":"miR-122\u2014A key factor and therapeutic target in liver disease","volume":"62","author":"Bandiera","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rahmel, T., Sch\u00e4fer, S.T., Frey, U.H., Adamzik, M., and Peters, J. (2018). Increased circulating microRNA-122 is a biomarker for discrimination and risk stratification in patients defined by sepsis-3 criteria. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197637"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0960-9822(02)00809-6","article-title":"Identification of tissue-specific microRNAs from mouse","volume":"12","author":"Rauhut","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4161\/rna.1.2.1066","article-title":"miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1","volume":"1","author":"Chang","year":"2004","journal-title":"RNA Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/cvr\/cvab338","article-title":"Association of cardiometabolic microRNAs with COVID-19 severity and mortality","volume":"118","author":"Gutmann","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Franco, S., Mateu, L., Pluvinet, R., Sanchez-Herrero, J.F., Toledo, R., Sumoy, L., Massanella, M., and Martinez, M.A. (2024). Altered Plasma microRNA Signature in Hospitalized COVID-19 Patients Requiring Oxygen Support. Microorganisms, 12.","DOI":"10.20944\/preprints202312.1840.v2"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.jhep.2020.04.006","article-title":"COVID-19: Abnormal liver function tests","volume":"73","author":"Cai","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mihai, N., Tiliscan, C., Visan, C.A., Stratan, L., Ganea, O., Arama, S.S., Lazar, M., and Arama, V. (2022). Evaluation of Drug-Induced Liver Injury in Hospitalized Patients with SARS-CoV-2 Infection. Microorganisms, 10.","DOI":"10.3390\/microorganisms10102045"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3748\/wjg.v29.i2.241","article-title":"Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments","volume":"29","author":"Zhao","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mihai, N., Olariu, M.C., Ganea, O.-A., Adamescu, A.-I., Molagic, V., Aram\u0103, \u0218.S., Tili\u0219can, C., and Aram\u0103, V. (2024). Risk of Hepatitis B Virus Reactivation in COVID-19 Patients Receiving Immunosuppressive Treatment: A Prospective Study. J. Clin. Med., 13.","DOI":"10.20944\/preprints202409.1173.v1"},{"key":"ref_12","unstructured":"Food and Drug Administration (FDA), and Center for Drug Evaluation and Research (CDER) (2026, February 13). Summary Review: Remdesivir, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/214787Orig1s000Sumr.pdf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20900","DOI":"10.1038\/s41598-025-05541-9","article-title":"The impact of remdesivir on renal and liver functions in severe COVID-19 patients with presence of viral load","volume":"15","author":"Waldauf","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","article-title":"Remdesivir for the treatment of COVID-19\u2014Final report","volume":"383","author":"Beigel","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Almutairi, A.O., El-Readi, M.Z., Althubiti, M., Alhindi, Y.Z., Ayoub, N., Alzahrani, A.R., Al-Ghamdi, S.S., and Eid, S.Y. (2023). Liver injury in favipiravir-treated COVID-19 patients: Retrospective single-center cohort study. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8020129"},{"key":"ref_16","unstructured":"Food and Drug Administration (FDA) (2026, February 13). Center for Drug Evaluation and Research (CDER). Medical Review: Tocilizumab, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2010\/125276s000MedR.pdf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1002\/jmv.26429","article-title":"Late onset infectious complications and safety of tocilizumab in the management of COVID-19","volume":"93","author":"Pettit","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_18","unstructured":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (2026, February 13). Low-Molecular-Weight Heparins, LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548009\/."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"EVIDoa2100043","DOI":"10.1056\/EVIDoa2100043","article-title":"Phase 2\/3 trial of molnupiravir for treatment of COVID-19 in nonhospitalized adults","volume":"1","author":"Caraco","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1053\/j.gastro.2022.09.008","article-title":"Minimal risk of drug-induced liver injury with molnupiravir and ritonavir-boosted nirmatrelvir","volume":"164","author":"Wong","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_21","unstructured":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (2026, February 13). Corticosteroids, LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548400\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.taap.2012.01.009","article-title":"Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans","volume":"259","author":"Jetten","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.jare.2024.12.020","article-title":"Advances in statin adverse reactions and the potential mechanisms: A systematic review","volume":"76","author":"Zeng","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1530\/EJE-14-0867","article-title":"Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults","volume":"172","author":"Wang","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1002\/hep.24538","article-title":"Circulating microRNAs as potential markers of human drug-induced liver injury","volume":"54","author":"Dear","year":"2011","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Manea, M., Apostol, D., and Constantinescu, I. (2023). The Connection between MiR-122 and Lymphocytes in Patients Receiving Treatment for Chronic Hepatitis B Virus Infection. Microorganisms, 11.","DOI":"10.3390\/microorganisms11112731"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shi, L., Zheng, X., Fan, Y., Yang, X., Li, A., and Qian, J. (2019). The contribution of miR-122 to the innate immunity by regulating toll-like receptor 4 in hepatoma cells. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-1048-3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1507\/endocrj.EJ24-0317","article-title":"MicroRNA-122 protects against interferon-\u03b1-induced hepatic inflammatory response via the Janus kinase-signal transducer and activator of transcription pathway","volume":"72","author":"Liu","year":"2025","journal-title":"Endocr. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s42003-024-06288-1","article-title":"Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response","volume":"7","author":"Ehle","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.imlet.2020.06.015","article-title":"Upregulation of RelB in the miR-122 knockout mice contributes to increased levels of proinflammatory chemokines\/cytokines in the liver and macrophages","volume":"226","author":"Hsu","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zeinali, F., Aghaei Zarch, S.M., Jahan-Mihan, A., Kalantar, S.M., Mehrjardi, M.Y.V., Fallahzadeh, H., Hosseinzadeh, M., Rahmanian, M., and Mozaffari-Khosravi, H. (2021). Circulating microRNA-122, microRNA-126-3p and microRNA-146a are associated with inflammation in patients with pre-diabetes and type 2 diabetes mellitus: A case control study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251697"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Osman, E.A., Eltaweel, N.H., Madbouly, M., Mosbah, O., Gaber, M.G., and Khanany, F.M. (2025). Evaluation of serum miR-122-5p, miR-486-5p, miR-21-5p, and their interplay with inflammatory markers in diabetic nephropathy: A case control study. BMC Nephrol., 26.","DOI":"10.1186\/s12882-025-04619-w"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Farr, R.J., Rootes, C.L., Rowntree, L.C., Nguyen, T.H.O., Hensen, L., Kedzierski, L., Cheng, A.C., Kedzierska, K., Au, G.G., and Marsh, G.A. (2021). Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection. PLoS Pathog., 17.","DOI":"10.21203\/rs.3.rs-253459\/v1"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Fleta, P., Vera-Tom\u00e9, P., Jim\u00e9nez-Fern\u00e1ndez, M., Requena, S., Roy-Vallejo, E., Sanz-Garc\u00eda, A., Lozano-Prieto, M., L\u00f3pez-Sanz, C., Vara, A., and Lancho-S\u00e1nchez, \u00c1. (2022). A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.815651"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Alam, T., and Lipovich, L. (2021). miRCOVID-19: Potential Targets of Human miRNAs in SARS-CoV-2 for RNA-Based Drug Discovery. Noncoding RNA, 7.","DOI":"10.3390\/ncrna7010018"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2021.2010959","article-title":"Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene","volume":"19","author":"Akula","year":"2022","journal-title":"RNA Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100287","DOI":"10.1016\/j.xcrm.2021.100287","article-title":"Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions","volume":"2","author":"Filbin","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.7150\/thno.19851","article-title":"Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest","volume":"7","author":"Devaux","year":"2017","journal-title":"Theranostics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4161\/rna.18827","article-title":"Liver-specific microRNA-122: Biogenesis and function","volume":"9","author":"Jopling","year":"2012","journal-title":"RNA Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mohany, K.M., Al Rugaie, O., Al-Wutayd, O., and Al-Nafeesah, A. (2021). Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with\/without type 2 diabetes: A case control study. BMC Endocr. Disord., 21.","DOI":"10.1186\/s12902-021-00829-z"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Garmaa, G., Bunduc, S., K\u00f3i, T., Hegyi, P., Csupor, D., Ganbat, D., Dembrovszky, F., Meznerics, F.A., Nasirzadeh, A., and Barbagallo, C. (2024). A Systematic Review and Meta-Analysis of microRNA Profiling Studies in Chronic Kidney Diseases. Non-Coding RNA, 10, Correction in Non-Coding RNA 2025, 11, 57. https:\/\/doi.org\/10.3390\/ncrna11040057.","DOI":"10.3390\/ncrna11040057"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1093\/ndt\/gfr485","article-title":"Circulating microRNA expression is reduced in chronic kidney disease","volume":"26","author":"Neal","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/bcp.13136","article-title":"The effect of renal dysfunction and haemodialysis on circulating liver specific miR-122","volume":"83","author":"Rivoli","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_44","first-page":"1281","article-title":"miR-122 inhibits viral replication and cell proliferation in hepatitis B virus-related hepatocellular carcinoma and targets NDRG3","volume":"26","author":"Fan","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Feng, Y., Kang, Y., He, Y., Liu, J., Liang, B., Yang, P., and Yu, Z. (2014). microRNA-99a acts as a tumor suppressor and is down-regulated in bladder cancer. BMC Urol., 14.","DOI":"10.1186\/1471-2490-14-50"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:51:31Z","timestamp":1772542291000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052288"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052288","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,28]]}}}