Circulating Liver-Enriched miR-122 in COVID-19 Patients: A Longitudinal Real-Life Study

Mihai et al., International Journal of Molecular Sciences, doi:10.3390/ijms27052288, Feb 2026
2nd treatment shown to increase risk in November 2020, now with p = 0.00000029 from 27 studies, but still recommended in 103 countries.
6,500+ studies for 210+ treatments. c19early.org
Prospective cohort study of 78 COVID-19 patients and 18 non-COVID-19 participants in Romania, reporting that prior therapeutic paracetamol use before hospital presentation was independently associated with higher miR-122 (a liver-specific biomarker of hepatocellular injury) expression at follow-up, suggesting cumulative hepatic stress in the context of COVID-19.
The most clinically relevant findings concern drug-associated effects on follow-up miR-122 levels. In bivariate analyses, both remdesivir administered for ≥5 days (p = 0.012) and prior therapeutic paracetamol use (p = 0.001) were associated with higher miR-122 at follow-up. However, in a multivariable model, only paracetamol retained independent significance (p = 0.011), leading the authors to conclude that therapeutic paracetamol may contribute to hepatocellular stress in COVID-19 patients.
Several features of the data structure warrant caution when interpreting this distinction. Remdesivir was administered to 96.5% of the longitudinal subgroup while 84.2% reported prior paracetamol use, meaning near-complete overlap between the two exposures. With only 2 patients not receiving remdesivir, the dataset provides almost no contrast for separating a remdesivir effect from a paracetamol effect. The potentially more informative remdesivir comparison - treatment for ≥5 days versus shorter courses (32 vs 25 patients) - did yield a significant bivariate result, but the paper does not report how this variable was parameterized in the multivariable model, nor does it provide the adjusted coefficient or p-value for remdesivir. Without the full regression output, it is unclear whether remdesivir was borderline significant after adjustment (suggesting a real but underpowered signal partially absorbed by the paracetamol variable) or clearly non-significant (suggesting confounding drove the bivariate finding). A cross-tabulation of paracetamol use by remdesivir duration group would also clarify the degree of collinearity between these two predictors on the parameterization that provides the most statistical leverage.
Paracetamol is also known as acetaminophen, Tylenol, Panadol, Calpol, Tempra, Calprofen, Doliprane, Efferalgan, Grippostad C, Dolo, Acamol, Fevadol, Crocin, and Perfalgan.
Study covers acetaminophen and remdesivir.
Mihai et al., 28 Feb 2026, prospective, Romania, peer-reviewed, 9 authors, study period March 2022 - July 2023. Contact: catalin.tiliscan@umfcd.ro (corresponding author), nicoleta.mihai1@drd.umfcd.ro, oana-alexandra.ganea@drd.umfcd.ro, simona.ruta@umfcd.ro, victoria.arama@umfcd.ro, sorin.arama@umfcd.ro, andreea.arsene@umfcd.ro, iulia_iancu2005@yahoo.com, aida-isabela.adamescu@drd.umfcd.ro.
Abstract: Article Circulating Liver-Enriched miR-122 in COVID-19 Patients: ALongitudinal Real-Life Study Nicoleta Mihai 1,4 , C ă t ă lin Tilis , can 2,4, *, Iulia Virginia Iancu 5 , Oana-Alexandra Ganea 1,4 , Aida-Isabela Adamescu 2,4, * , S , tefan Sorin Aram ă 2,4 , Andreea Letit ,ia Arsene 3 , Simona-Maria Rut , ă 1,5 and Victoria Aram ă 1,4 - 1 Faculty of Medicine, 'Carol Davila' University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; nicoleta.mihai1@drd.umfcd.ro (N.M.); oana-alexandra.ganea@drd.umfcd.ro (O.-A.G.); simona.ruta@umfcd.ro (S.-M.R.); victoria.arama@umfcd.ro (V.A.) - 2 Faculty of Dental Medicine, 'Carol Davila' University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; sorin.arama@umfcd.ro - 3 Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; andreea.arsene@umfcd.ro - 4 'Prof. Dr. Matei Bals , ' National Institute for Infectious Diseases, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania - 5 '¸ Stefan S. Nicolau' Institute of Virology, 285 Mihai Bravu Road, 030304 Bucharest, Romania; iulia\_iancu2005@yahoo.com * Correspondence: catalin.tiliscan@umfcd.ro (C.T.); aida-isabela.adamescu@drd.umfcd.ro (A.-I.A.) Abstract 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 -∆ Ct ). No associations were observed between miR-122 expression and remdesivir administered for standard treatment durations (3-5 days) or other COVID-19-specific 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. Keywords: miR-122; COVID-19; remdesivir; paracetamol; drug-induced liver injury; systemic inflammation
DOI record: { "DOI": "10.3390/ijms27052288", "ISSN": [ "1422-0067" ], "URL": "http://dx.doi.org/10.3390/ijms27052288", "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−ΔCt). No associations were observed between miR-122 expression and remdesivir administered for standard treatment durations (3–5 days) or other COVID-19–specific 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. 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