Abstract: Pharmacological Reports https://doi.org/10.1007/s43440-022-00408-6 SPECIAL ISSUE: ARTICLE The Post-COVID Era - Advances and Challenges in Pharmacology Real‑world experience with molnupiravir during the period of SARS‑CoV‑2 Omicron variant dominance Robert Flisiak1 · Dorota Zarębska‑Michaluk2,3 · Magdalena Rogalska1 · Justyna Anna Kryńska1 · Justyna Kowalska4 · Ewa Dutkiewicz5,6 · Krystyna Dobrowolska2 · Jerzy Jaroszewicz7 · Anna Moniuszko‑Malinowska8 · Marta Rorat9 · Regina Podlasin10 · Olga Tronina11 · Piotr Rzymski12 Received: 28 June 2022 / Revised: 12 August 2022 / Accepted: 17 August 2022 © The Author(s) 2022 Abstract Background The real-world effectiveness of molnupiravir (MOL) during the dominance of Omicron SARS-CoV-2 lineage is urgently needed since the available data relate to the period of circulation of other viral variants. Therefore, this study assessed the efficacy of MOL in patients hospitalized for COVID-19 in a real-world clinical practice during the wave of Omicron infections. Methods Among 11,822 patients hospitalized after 1 March 2020 and included in the SARSTer national database, 590 were treated between 1 January and 31 April 2022, a period of dominance of the Omicron SARS-CoV-2 variant. MOL was administered to 203 patients, whereas 387 did not receive any antiviral regimen. Both groups were similar in terms of sex, BMI and age allowing for direct comparisons. Results Patients who did not receive antiviral therapy significantly more often required the use of Dexamethasone and Baricitinib. Treatment with MOL resulted in a statistically significant reduction in mortality during the 28-day follow-up (9.9 vs. 16.3%), which was particularly evident in the population of patients over 80 years of age treated in the first 5 days of the disease (14.6 vs. 35.2%). MOL therapy did not affect the frequency of the need for mechanical ventilation, but patients treated with MOL required oxygen supplementation less frequently than those without antivirals (31.7 vs. 49.2%). The time of hospitalization did not differ between groups. Conclusions The use of molnupiravir in patients hospitalized for COVID-19 during the dominance of Omicron variant reduced mortality. This effect is particularly evident in patients over 80 years of age. Keywords Molnupiravir · COVID-19 · SARS-CoV-2 · Omicron · Treatment · Real-world experience Robert Flisiak and Dorota Zarębska-Michaluk contributed equally. * Robert Flisiak robert.flisiak1@gmail.com 1 2 Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15‑540, ul. Żurawia 14, Białystok, Poland Department of Infectious Diseases, Jan Kochanowski University, Kielce, Poland 3 Provincial Hospital, Kielce, Poland 4 Department of Adults’ Infectious Diseases, Medical University of Warsaw, Warsaw, Poland 5 ZOZ, Busko Zdroj, Poland 6 Jan Kochanowski University, Collegium Medicum, Kielce, Poland 7 Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice, Poland 8 Department of Infectious Diseases and Neuroinfections, Medical University of Białystok, Białystok, Poland 9 Department of Forensic Medicine, Wrocław Medical University, Wrocław, Poland 10 IV‑th Department, Hospital for Infectious Diseases, Warsaw, Poland 11 Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland 12 Department of Environmental Medicine, Poznan University of Medical Sciences, Poznan,..