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Molnupiravir for COVID-19
46 studies from 873 scientists
151,398 patients in 11 countries
Statistically significant lower risk for mortality, progression, recovery, and viral clearance.
22 studies from 19 teams in 8 countries show significant improvements.
Potential risks include the creation of dangerous variants, carcinogenicity, and genotoxicity.
COVID-19 Molnupiravir studies. Nov 2024. c19early.org
0 0.5 1 1.5+ All studies 11% With exclusions 14% Mortality 15% Hospitalization 2% Recovery 12% Cases 24% Viral clearance 25% RCTs 23% RCT mortality -1% Prophylaxis 24% Early 12% Late 11% Favorsmolnupiravir Favorscontrol
Home   Post   Share   @CovidAnalysis   OutcomesOutcomes   Potential risks include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity Chamod, Gruber, Hadj Hassine, Huntsman, Marikawa, Shiraki, Shum, Standing, Swanstrom, Waters, Zhou, Zibat. Multiple analyses have identified variants potentially created by molnupiravir Focosi, Fountain-Jones, Kosakovsky Pond, Sanderson, twitter.com. There is substantial publication bias. Multiple trials have not reported results and did not respond to requests Lawrence. Recent:
Focosi
Tanbek
Quinlan
Boretti
Zabek
Kumar
Gentile.
Molnupiravir was adopted in 33 countries. Submit updates/corrections. Summary.
Nov 8
Wang et al., Journal of Global Health, doi:10.7189/jogh.14.05032 Low antiviral uptake of nirmatrelvir/ritonavir and molnupiravir in adult patients with COVID-19 in Taiwan in 2022
Retrospective 96,398 adult COVID-19 patients in Taiwan showing very low use of approved antivirals nirmatrelvir/ritonavir (5.1%) and molnupiravir (1.9%) in 2022, especially in moderate-to-high risk groups eligible for treatment per WHO gu..
Nov 8
Focosi et al., Intervirology, doi:10.1159/000540282 The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country
Analysis of GISAID SARS-CoV-2 sequences showing a strong correlation between molnupiravir prescriptions and putative molnupiravir-generated variants by country. Authors identify 1,094 sequences with a molnupiravir mutational signature, pr..
Oct 3
Quinlan et al., MMWR. Morbidity and Mortality Weekly Report, doi:10.15585/mmwr.mm7339a3 Differences in COVID-19 Outpatient Antiviral Treatment Among Adults Aged ≥65 Years by Age Group — National Patient-Centered Clinical Research Network, United States, April 2022–September 2023
Retrospective 393,390 COVID-19 patients aged ≥65 years showing underutilization of antiviral treatment, with lower use for older patients at higher risk for severe outcomes.
Sep 27
Zabek, M., Electronic Thesis and Dissertation Repository, 10427 The Transfer of Molnupiravir and Nirmatrelvir Across the Human Placenta and Prediction of Drug Safety in Pregnancy
Ex Vivo study showing placental transfer of molnupiravir (NHC) and nirmatrelvir in human placentas. Author used a placental perfusion model to assess drug transfer across the human placental barrier. Both compounds readily crossed the pla..
Sep 19
Kumar et al., Antiviral Research, doi:10.1016/j.antiviral.2024.106006 Identification of antibody-resistant SARS-CoV-2 mutants via N4-Hydroxycytidine mutagenesis
In Vitro selection study identifying SARS-CoV-2 spike mutations that confer resistance to therapeutic antibodies. Using a Wuhan-like strain and omicron B.1.1.529, the authors used sequential mutagenesis with the molnupiravir active compou..
Sep 9
Harris et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00431-6 Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC): a randomised controlled trial
27% higher mortality (p=0.5), 7% lower hospitalization (p=1), 1% improved recovery (p<0.0001), and 14% worse results (p=0.01). PRINCIPLE molnupiravir long-term followup showing improvements in time off work, healthcare use, severe symptoms, and quality of life over 6 months, however there was higher mortality (without statistical significance) and no difference i..
Sep 9
Gentile et al., medRxiv, doi:10.1101/2024.09.09.24313305 Efficacy of Molnupiravir in reducing the risk of severe outcome in patients with SARS-CoV-2 infection: a real-life full-matched case-control study (SAVALO Study).
4% lower mortality (p=0.79), 26% lower hospitalization (p=0.74), and 65% lower progression (p=0.01). PSM retrospective case-control study with 1,382 SARS-CoV-2 positive outpatients in Italy, showing lower risk for a composite outcome of hospitalization, ICU admission, or death with molnupiravir, but no significant difference for mortalit..
Aug 23
Chen et al., Biomedical Chromatography, doi:10.1002/bmc.5996 Mass spectrometry‐based metabolomics reveals metabolism of molnupiravir may lead to metabolic disorders and hepatotoxicity
Analysis of molnupiravir induced liver injury. Molnupiravir treatment may disrupt metabolic homeostasis and cause liver injury by increasing levels of certain metabolites and activating inflammatory pathways.
Aug 20
Yen et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09654-w Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan
18% lower mortality (p=0.43). Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing lower mortality with molnupiravir, without statistical significance. Authors report that all infected patients were hospitalized at the time..
Aug 14
Lai et al., Age and Ageing, doi:10.1093/ageing/afae180 Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study
10% lower mortality (p=0.007). Target trial emulation study of 13,642 (molnupiravir) and 9,553 (paxlovid) elderly hospitalized patients in Hong Kong showing lower mortality with treatment.
Aug 3
Shen, Y., Doctoral dissertation, University of Cincinnati Hydrolytic Activation and Drug-Drug Interactions of COVID-19 Therapeutics Remdesivir and Molnupiravir: The Role of CES2 Covalent Inhibition and the Impact of Genetic Polymorphism
In Vitro and Ex Vivo study showing significant potential drug-drug interactions between remdesivir and molnupiravir. Author found that remdesivir irreversibly inhibits CES2, an enzyme crucial for activating molnupiravir in the body, which..
Jul 30
Shum, C., The University of Hong Kong, PhD Thesis An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses
In Vitro and hamster study of drug associated SARS-CoV-2 mutations with several drugs including molnupiravir and favipiravir. Next-generation sequencing was used to identify de novo mutational spectra and single base substitution mutation..
Jul 26
Shiraki et al., Heliyon, doi:10.1016/j.heliyon.2024.e35331 Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans
Reproductive toxicity analysis of antiviral drugs in C. elegans, showing increased incidence of arrested embryos with molnupiravir, favipiravir, ribavirin, acyclovir, ganciclovir, zidovudine, and thalidomide compared to controls. Authors ..
Jul 4
Razia et al., Frontiers in Transplantation, doi:10.3389/frtra.2024.1408289 Remdesivir and molnupiravir had comparable efficacy in lung transplant recipients with mild-to-moderate COVID-19: a single center experience
272% higher mortality (p=0.28) and 28% lower hospitalization (p=0.58). Retrospective 113 lung transplant recipients with mild-to-moderate COVID-19 showing higher mortality with remdesivir and molnupiravir in unadjusted analysis, with statistical significance for remdesivir. mAb PrEP and treatment and the dom..
Jun 24
Lv et al., Journal of Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, doi:10.1631/jzus.B2300538 Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave: a single-center cohort study
53% higher mortality (p=0.22). Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January ..
Jun 3
Verma et al., bioRxiv, doi:10.1101/2024.06.02.596989 Persistent Neurological Deficits in Mouse PASC Reveal Antiviral Drug Limitations
Mouse study showing persistent neurological deficits after SARS-CoV-2 infection, and failure of nirmatrelvir and molnupiravir to prevent neurological damage. Authors found decreased tyrosine hydroxylase expression in the olfactory bulb an..
May 24
Horby et al., medRxiv, doi:10.1101/2024.05.23.24307731 Molnupiravir or nirmatrelvir-ritonavir versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
11% higher mortality (p=0.55), 43% higher ventilation (p=0.59), 9% lower hospital discharge (p=0.46), and 12% improved viral clearance (p<0.0001). RECOVERY RCT showing no significant differences in mortality, ventilation, or discharge with either molnupiravir (923 patients) or paxlovid (137 patients). Viral load was improved with treatment but did not translate into clinical benefit..
Sep 17
Lieber et al., Journal of Virology, doi:10.1128/jvi.00905-24 (date from preprint) Efficacy of late-onset antiviral treatment in immunocompromised hosts with persistent SARS-CoV-2 infection
Mouse study showing that late-onset treatment with paxlovid, molnupiravir, or 4'-FlU significantly reduced persistent SARS-CoV-2 infection in immunocompromised mice, with 4'-FlU being most effective. Authors used a CD4+ and CD8+ T cell-de..
May 13
Pakotiprapha et al., ASPET 2024 Annual Meeting Abstract - Toxicology, doi:10.1124/jpet.212.937140 Molnupiravir Active Metabolite–N4 hydroxycytidine causes Cytotoxicity to Mammalian Cells In Vitro
In Vitro study showing cytotoxicity of N4-hydroxycytidine (NHC), the active metabolite of molnupiravir, at concentrations relevant to therapeutic doses of molnupiravir in COR-L23 and HepG2 cancer cell lines, and compared with cytotoxicity..
May 6
Gruber et al., Journal of Medical Virology, doi:10.1002/jmv.29642 Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study
Analysis of 38 COVID-19 outpatients treated with molnupiravir showing significantly increased SARS-CoV-2 genetic diversity and complexity compared to 17 patients treated with tixagevimab/cilgavimab. Molnupiravir increased the mutation rat..
Apr 25
Bessi et al., ACS Central Science, doi:10.1021/acscentsci.4c00146 The Tautomeric State of N4-Hydroxycytidine within Base-Paired RNA
In Vitro study showing that NHC, the active form of molnupiravir, can base pair with both G and A in two different tautomeric forms. This ambiguous base pairing enables NHC to induce mutations in the viral RNA. However, it raises the poss..
Apr 23
Amani et al., Immunity, Inflammation and Disease, doi:10.1002/iid3.1262 Comparison of effectiveness and safety of molnupiravir versus sotrovimab for COVID‐19: A systematic review and meta‐analysis
Meta analysis of 13 studies involving 16,166 patients showing higher mortality and higher incidence of adverse events with molnupiravir compared with sotrovimab.
Mar 31
Choe et al., Pharmacoepidemiology and Risk Management, doi:10.56142/perm.24.0006 Safety Monitoring of Oral Antiviral COVID-19 Treatment Using Korea Adverse Event Reporting System (KAERS) Database
Safety analysis of paxlovid and molnupiravir. Disproportionality analysis found significant signals for paxlovid with sensory abnormalities, interactions, fecal abnormalities, and signals not on the label including olfactory nerve disorde..
Mar 25
Özdemir et al., Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, doi:10.34087/cbusbed.1423523 COVID-19 enfeksi̇yonunda molnupiravi̇r tedavi̇si̇ alan hastalarin değerlendi̇ri̇lmesi̇
50% higher mortality (p=1) and no change in ICU admission (p=1). Retrospective study of 78 hospitalized COVID-19 patients in Turkey showing no significant difference in mortality or discharge rates with molnupiravir treatment.
Mar 22
Fountain-Jones et al., The Lancet Microbe, doi:10.1016/S2666-5247(23)00393-2 Effect of molnupiravir on SARS-CoV-2 evolution in immunocompromised patients: a retrospective observational study
Analysis of immunocompromised COVID-19 showing rapid creation of new variants with molnupiravir. Some mutations became fixed in the viral population and the distinctive mutational pattern, dominated by G-to-A and C-to-T transitions, persi..
Mar 2
Schreiber et al., Antiviral Research, doi:10.1016/j.antiviral.2024.105840 The host-targeted antiviral drug Zapnometinib exhibits a high barrier to the development of SARS-CoV-2 resistance
In Vitro study showing that molnupiravir and paxlovid induced resistant variants in SARS-CoV-2 during serial passaging, while the host-directed antiviral zapnometinib did not. Authors found that molnupiravir did not lead to abrogated vira..
Feb 23
Standing et al., Nature Communications, doi:10.1038/s41467-024-45641-0 Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
103% worse viral clearance (p=0.33). PANORAMIC virology-sub-study showing increased viral persistence with molnupiravir treatment. Molnupiravir 800mg twice daily for 5 days led to faster initial viral decline but 86% still had detectable virus by day 5. By day 14, molnupirav..
Feb 9
Chen et al., Scientific Reports, doi:10.1038/s41598-024-53862-y Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study
Retrospective 157 hospitalized mild-to-moderate COVID-19 patients showing no significant differences between azvudine, molnupiravir, and paxlovid for time to viral clearance and length of hospitalization.
Feb 9
Cheng et al., Kidney International Reports, doi:10.1016/j.ekir.2024.02.009 Effectiveness of molnupiravir and nirmatrelvir–ritonavir in CKD patients with COVID-19
15% lower mortality (p=0.003), no change in oxygen therapy (p=1), and 12% lower ICU admission (p=0.52). Retrospective emulated target trial of hospitalized COVID-19 patients with chronic kidney disease in Hong Kong showing lower mortality with molnupiravir and paxlovid treatment. No significant reduction was found in ICU admission or ventil..
Feb 6
Yoshida et al., Cureus, doi:10.7759/cureus.61048 (date from preprint) Real-World Efficacy of Ensitrelvir in Hospitalized Patients With COVID-19 in Japan: A Retrospective Observational Study
Retrospective 154 hospitalized COVID-19 patients in Japan showing faster viral clearance and shorter hospitalization with ensitrelvir treatment compared to remdesivir or molnupiravir. There was no significant difference for fever resoluti..
Jan 26
Wilcock et al., JAMA Health Forum, doi:10.1001/jamahealthforum.2023.5044 Clinical Risk and Outpatient Therapy Utilization for COVID-19 in the Medicare Population
Analysis of Medicare beneficiaries in 2022 showing that outpatient COVID-19 treatments like antivirals and monoclonal antibodies were disproportionately used by patients at lower risk of severe infection and outcomes. Retrospective studie..
Jan 24
Guermazi et al., Research Square, doi:10.21203/rs.3.rs-3876022/v1 Oral antivirals for COVID-19 among patients with cancer
Retrospective 67 cancer outpatients treated with nirmatrelvir/ritonavir or molnupiravir, compared to 56 untreated concurrent controls, reporting lower mortality with treatment. However, Figure 3 shows the opposite results for invasive mec..
Jan 4
Illingworth et al., Virus Evolution, doi:10.1093/ve/veae001 Genetic consequences of effective and suboptimal dosing with mutagenic drugs in a hamster model of SARS-CoV-2 infection
Syrian hamster study showing that short-term treatment with the mutagenic antiviral drugs favipiravir and molnupiravir led to increased genetic variation in SARS-CoV-2 viral populations. Treatment with effective antiviral doses resulted i..
Dec 28
2023
Chamod et al., Asian Medical Journal and Alternative Medicine, 23:3 Molnupiravir Metabolite--N4-hydroxycytidine Causes Cytotoxicity and DNA Damage in Mammalian Cells in vitro: N4-hydroxycytidine Induced Cytotoxicity DNA Damage
In Vitro study showing concentration-dependent cytotoxicity and DNA damage in human skin and lung cell lines with NHC, the active metabolite of molnupiravir, at concentrations spanning the therapeutic range. The genotoxic effects raise co..
Dec 6
2023
Bacigalupo et al., Frontiers in Medicine, doi:10.3389/fmed.2023.1287542 Unveiling patenting strategies of therapeutics and vaccines: evergreening in the context of COVID-19 pandemic
Review of the patenting activity and evergreening approaches for three major COVID-19 antiviral medications – remdesivir, molnupiravir, and favipiravir. Authors found extensive primary and secondary patent filing, with 29 applications cov..
Nov 30
2023
Xu et al., Clinical Interventions in Aging, doi:10.2147/cia.s431271 Factors Affecting Mortality in Elderly Hypertensive Hospitalized Patients with COVID-19: A Retrospective Study
232% higher mortality (p=0.006). Retrospective 748 elderly hospitalized COVID-19 patients in China showing increased risk of death with paxlovid/molnupiravir. Multivariate analysis showed that paxlovid/molnupiravir was independently associated with higher in-hospital mor..
Nov 30
2023
Uraki et al., iScience, doi:10.1016/j.isci.2023.108147 Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate
In Vitro and animal study showing that the SARS-CoV-2 omicron subvariant XBB.1.9.1 has similar antigenicity, antiviral susceptibility, and replicative ability compared to XBB.1.5. Casirivimab, imdevimab, tixagevimab, cilgavimab, sotrovima..
Nov 23
2023
Strizki et al., Infectious Diseases and Therapy, doi:10.1007/s40121-023-00891-1 Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial
Virological outcomes for the MOVe-OUT trial. Results are shown with the main paper [Jayk Bernal].
Nov 22
2023
Park et al., Infection & Chemotherapy, doi:10.3947/ic.2023.0087 Effectiveness of Molnupiravir Treatment in Patients with COVID-19 in Korea: A Propensity Score Matched Study
25% lower mortality (p<0.0001) and 29% lower progression (p<0.0001). PSM retrospective 190,692 COVID-19 patients treated with molnupiravir and 762,768 matched controls, showing lower mortality and combined severe/critical illness and mortality with treatment.
Nov 20
2023
Tare et al., BJGP Open, doi:10.3399/bjgpo.2023.0109 The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice
83% worse recovery (p=0.36). Very small early terminated RCT with 8 molnupiravir and 17 placebo patients showing worse recovery with molnupiravir, without statistical significance.
Nov 11
2023
Xu et al., Nucleic Acids Research, doi:10.1093/nar/gkad1002 Uridine–cytidine kinase 2 potentiates the mutagenic influence of the antiviral β-d-N4-hydroxycytidine
In Vitro study showing that molnupiravir increased mutation rates in mouse blood cancer cell lines. The mutagenic effects were enhanced by overexpression of the enzyme uridine-cytidine kinase 2 (Uck2), and lessened in Uck2 knockout cells...
Nov 4
2023
Tanbek et al., Archives of Pharmacology and Therapeutics, doi:10.33696/Pharmacol.4.044 Dose-dependent Oxidative Damage of Molnupiravir (Antiviral Drug for Treatment of COVID-19) in Lung, Liver, Heart, and Kidney Tissues in Rats
Rat study showing dose-dependent oxidative damage with molnupiravir in lung, liver, heart, and kidney tissues. Authors found that molnupiravir decreased SOD activity and increased MDA, TOS, and OSI levels in multiple tissues, indicating o..
Oct 31
2023
Winyupakorn et al., Research Square, doi:10.21203/rs.3.rs-3484296/v1 Liver injury in non-severe COVID-19 with various pandemic phases: a real-world study
Prospective study of 300 patients with mild to moderate COVID-19 in Thailand, showing the highest risk of liver injury with molnupiravir treatment, OR 3.4 (p = 0.06).
Oct 24
2023
Kosakovsky Pond et al., Nature, doi:10.1038/d41586-023-03248-3 Anti-COVID drug accelerates viral evolution
Discussion of the creation of new COVID-19 variants via treatment with molnupiravir. Sanderson et al. [Sanderson] showed that thousands of viruses with many mutations - sometimes more than 100 - survived molnupiravir treatment, and that m..
Oct 23
2023
Fung et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2023.5099 Nirmatrelvir and Molnupiravir and Post–COVID-19 Condition in Older Patients
4% lower PASC (p=0.001). Retrospective 8,089 molnupiravir patients in the USA showing a small reduction in long COVID with treatment. Confounding is likely significant as below, and may eliminate the benefit. Results specific to the COVID-19 code should be closer..
Sep 25
2023
Sanderson et al., Nature, doi:10.1038/s41586-023-06649-6 A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes
Identification of SARS-CoV-2 variants created by molnupiravir treatment, including cases of onwards transmission. Authors find a class of long phylogenetic branches almost exclusively matching the time period, location, and age groups of ..
Sep 23
2023
Marikawa et al., Reproductive Toxicology, doi:10.1016/j.reprotox.2023.108475 An active metabolite of the anti-COVID-19 drug molnupiravir impairs mouse preimplantation embryos at clinically relevant concentrations
Analysis of molnupiravir active metabolite N4-hydroxycytidine's effects on mouse preimplantation embryos in vitro, showing embryotoxicity at clinically relevant concentrations. The researchers found that N4-hydroxycytidine impaired blasto..
Sep 8
2023
Alpizar et al., Journal of Infection, doi:10.1016/j.jinf.2023.08.016 Molnupiravir for Intra-Household Prevention of COVID-19: the MOVe-AHEAD Randomized, Placebo-Controlled Trial
24% fewer symptomatic cases (p=0.06). PEP RCT 1,527 patients showing lower COVID-19 cases with molnupiravir, without statistical significance.
Aug 31
2023
Zibat et al., iScience, doi:10.1016/j.isci.2023.107786 N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody
In Vitro study showing that NHC, the active compound molnupiravir, can promote rapid selection of immune escape mutants. NHC treatment enabled selection of nanobody-resistant mutants much faster than without NHC. While an in vitro model w..
Aug 7
2023
Gbinigie et al., BMJ Open, doi:10.1136/bmjopen-2022-069176 Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease
PANORAMIC protocol paper, published over 9 months after publication of the molnupiravir arm [Butler].
Aug 7
2023
Shiau et al., Virology, doi:10.1016/j.virol.2023.109865 Molnupiravir, a ribonucleoside antiviral prodrug against SARS-CoV-2, alters the voltage-gated sodium current and causes adverse events
In vitro study showing that molnupiravir inhibited sodium channel currents by altering channel gating kinetics, which may explain some of the neurological and gastrointestinal side effects.
Jul 19
2023
Guan et al., Clinical Infectious Diseases, doi:10.1093/cid/ciad409 Impact of Molnupiravir Treatment on Patient-Reported Coronavirus Disease 2019 (COVID-19) Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial
Symptom recovery details for the MOVe-OUT trial. Results are shown with the main paper [Jayk Bernal].
Jun 1
2023
Butt et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiad195 Molnupiravir Use and 30-Day Hospitalizations or Death in Previously Uninfected Non-hospitalized High-risk Population with COVID-19
9% higher combined mortality/hospitalization (p=0.75). Retrospective 65,010 veterans in the USA, showing no significant difference in hospitalization/death with molnupiravir treatment. 1,729 patients received molnupiravir. Authors emulate a target trial closely matching the MOVe-OUT RCT and u..
May 16
2023
Tazare et al., medRxiv, doi:10.1101/2023.05.12.23289914 Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform
9% higher combined mortality/hospitalization (p=0.28). OpenSAFELY retrospective 75,048 outpatients in the UK, using the clone-censor-weight approach to address immortal time bias, showing no significant difference in combined mortality/hospitalization with molnupiravir treatment.
May 10
2023
Torti et al., Elsevier BV, doi:10.2139/ssrn.4444431 Real-Life Comparison of Mortality in Non-Hospitalised Patients with SARS-CoV-2 Infection at Risk for Clinical Progression Treated with Molnupiravir or Nirmatrevir Plus Ritonavir During the Omicron Era in Italy: A Nationwide, Observational Study
47% higher mortality (p=0.0001). Prospective study of 17,977 outpatients treated with molnupiravir and 11,576 treated with paxlovid, showing significant mortality with both treatments, and lower mortality with paxlovid.
Apr 30
2023
Wan et al., Annals of Internal Medicine, doi:10.7326/M22-3057 Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Hospitalized Patients With COVID-19
13% lower mortality (p<0.0001), 7% higher ventilation (p=0.49), and 2% higher ICU admission (p=0.9). Target trial emulation retrospective with 16,495 patients in Hong Kong, showing lower mortality with molnupiravir, but no significant difference for ventilation and ICU admission. See also [acpjournals.org], [acpjournals.org].
Mar 15
2023
Goodwin et al., PLOS ONE, doi:10.1371/journal.pone.0281915 Evaluation of outpatient treatment for non-hospitalised patients with COVID-19: The experience of a regional centre in the UK
110% higher mortality (p=0.47) and 58% lower hospitalization (p=0.7). Retrospective 604 outpatients in the UK, showing lower risk of hospitalization with molnupiravir treatment, without statistical significance due to the small number of hospitalizations.
Feb 24
2023
European Medicines Agency Refusal of the marketing authorisation for Lagevrio (molnupiravir)
The European Medicines Agency has recommended the refusal of the marketing authorisation of molnupiravir.
Feb 22
2023
Wan et al., Journal of Infection, doi:10.1016/j.jinf.2023.02.029 Molnupiravir and nirmatrelvir-ritonavir reduce mortality risk during post-acute COVID-19 phase
11% lower mortality (p=0.02), 1% lower hospitalization (p=0.76), and 4% higher progression (p=0.18). Retrospective 30,040 hospitalized patients in Hong Kong, showing lower mortality with molnupiravir treatment.
Feb 21
2023
Merck, Press Release Merck Provides Update on Phase 3 MOVe-AHEAD Trial Evaluating LAGEVRIO™ (molnupiravir) for Post-exposure Prophylaxis for Prevention of COVID-19
MOVe-AHEAD PEP RCT reporting no significant difference in cases. Limited information is available. There were 23.6% fewer cases with treatment, but the number of cases and confidence interval are not provided.
Feb 8
2023
Boretti, A., Clinical and Experimental Medicine, doi:10.1007/s10238-023-01010-7 On the choice of Molnupiravir and Paxlovid as the only antivirals permitted for COVID-19 infection in Australia
Letter to the editor discussing the choice of molnupiravir and paxlovid as the only approved COVID-19 antiviral therapies in Australia in 2022, despite other therapies showing higher efficacy and lower cost in clinical trials. The author ..
Feb 1
2023
Service, R., Science, doi:10.1126/science.adg9677 Could a popular COVID-19 antiviral supercharge the pandemic?
Coverage of [Fountain-Jones, Sanderson] which show evidence for molnupiravir creating new variants. The quote "Right now, it’s much ado about nothing" is from Emory University, where Molnupiravir was invented..
Jan 25
2023
Evans et al., Journal of Infection, doi:10.1016/j.jinf.2023.02.012 Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study
51% lower combined mortality/hospitalization (p=0.008). Retrospective high risk outpatients in the UK, showing lower hospitalization/death with molnupiravir treatment. Residual confounding is likely with adjustments having no detail on specific comorbidities.
Jan 22
2023
Zheng et al., medRxiv, doi:10.1101/2023.01.20.23284849 Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform
285% higher combined mortality/hospitalization (p=0.004). OpenSAFELY retrospective 5,638 outpatients in the UK, showing significantly higher hospitalization/death for molnupiravir compared with paxlovid.
Jan 15
2023
Inaba et al., Research Square, doi:10.21203/rs.3.rs-2451986/v1 Real-world data concerning the efficacy of molnupiravir in patients vaccinated against COVID-19 during the Omicron surge in Japan
127% higher combined mortality/hospitalization (p=0.22) and 127% higher hospitalization (p=0.22). Retrospective 294 consecutive patients in Japan, showing higher risk of hospitalization/death with molnupiravir, without statistical significance.
Dec 21
2022
Santi Laurini et al., Journal of Clinical Medicine, doi:10.3390/jcm12010034 Safety Profile of Molnupiravir in the Treatment of COVID-19: A Descriptive Study Based on FAERS Data
Safety analysis of molnupiravir reporting an unexpectedly high rate of serious adverse reactions.
Dec 6
2022
Bajema et al., medRxiv, doi:10.1101/2022.12.05.22283134 Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes
18% lower mortality (p=0.4), 1% lower ICU admission (p=1), and 30% higher hospitalization (p=0.04). Retrospective 112,380 high-risk patients in the USA, showing significantly higher acute or long-term care admission at 180 days with molnupiravir treatment, and no significant difference for other outcomes. The title and headers of Table ..
Nov 16
2022
Zheng et al., BMJ, doi:10.1136/bmj-2022-071932 Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform
100% higher combined mortality/hospitalization (p=0.005). Retrospective 3,331 sotrovimab and 2,689 molnupiravir patients in the UK, showing higher risk of combined hospitalization/death with molnupiravir.
Nov 14
2022
Sinha et al., Cureus, doi:10.7759/cureus.31508 Efficacy and Safety of Molnupiravir in Mild COVID-19 Patients in India
65% lower hospitalization (p=0.005), 53% greater improvement (p=0.01), and 48% improved viral clearance (p<0.0001). RCT 1,218 outpatients in India, showing lower hospitalization, better clinical improvement, and improved viral clearance with molnupiravir.
Oct 30
2022
Liu et al., Infectious Diseases and Therapy, doi:10.1007/s40121-022-00716-7 Disease Progression of Hospitalized Elderly Patients with Omicron BA.2 Treated with Molnupiravir
18% shorter hospitalization (p=0.14) and 21% faster viral clearance (p=0.1). Retrospective 42 elderly patients in China showing faster viral clearance with molnupiravir.
Oct 8
2022
Wong et al., The Lancet, doi:10.1016/S0140-6736(22)01586-0 Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study
24% lower mortality (p=0.01), 60% lower ventilation (p=0.02), 26% lower ICU admission (p=0.24), and 2% lower hospitalization (p=0.58). PSM retrospective 1,074,856 outpatients in Hong Kong, showing lower mortality with molnupiravir.
Oct 6
2022
Butler et al., The Lancet, doi:10.1016/S0140-6736(22)02597-1 (date from preprint) Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial
27% higher mortality (p=0.5), 6% higher combined mortality/hospitalization (p=0.69), 7% higher hospitalization (p=0.67), and 2% lower transmission (p=0.88). 26,411 patient RCT in the UK, showing faster recovery but no significant difference in hospitalization/death or transmission. Improved recovery may be in part due to the open label design with self-reported symptomatic data. Viral load in..
Oct 6
2022
Alteri et al., Research Square, doi:10.21203/rs.3.rs-2105569/v1 Genomic Evolution of Sars-Cov-2 in Molnupiravir-Treated Patients Compared to Paxlovid-Treated and Drug-Naïve Patients: A Proof-of-Concept Study
Mutation analysis showing over 5x greater within-host genetic diversity with molnupiravir compared to paxlovid or no treatment.
Oct 6
2022
Brown et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac527 Demographics and outcomes of initial phase of COVID-19 Medicines Delivery Units across 4 UK centres during peak B1.1.529 omicron epidemic: a service evaluation
101% higher hospitalization (p=0.51). Retrospective 442 patients in the UK treated with molnupiravir, and 222 eligible but declining treatment, showing no significant difference in hospitalization. No group details are provided and the results are subject to confounding by in..
Oct 5
2022
Suzuki et al., Clinical and Experimental Medicine, doi:10.1007/s10238-022-00949-3 (date from preprint) Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic
53% lower progression (p=0.04). Retrospective 1,921 patients in Japan, showing lower progression with molnupiravir use.
Oct 1
2022
Miranda et al., Environmental and Molecular Mutagenesis, doi:10.1002/em.22510 Evaluation of the mutagenic effects of Molnupiravir and N4-hydroxycytidine in bacterial and mammalian cells by HiFi sequencing
In Vitro genotoxocity study of molnupiravir showing dose dependent increased genome-wide mutation frequencies with mouse lymphoma L5178Y and human lymphoblastoid TK6 cells.
Sep 29
2022
Arbel et al., New England Journal of Medicine, doi:10.1056/NEJMoa2204919 (date from preprint) Molnupiravir Use and Severe Covid-19 Outcomes During the Omicron Surge
74% lower mortality (p=0.008) and 45% lower hospitalization (p=0.01). Retrospective 19,868 patients eligible for molnupiravir treatment in Israel with 1,069 treated, showing lower mortality and hospitalization with treatment for the subgroup of patients ≥65, and higher mortality for patients 40-64. Authors ..
Sep 20
2022
Najjar-Debbiny et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac781 Effectiveness of Molnupiravir in High Risk Patients: a Propensity Score Matched Analysis
19% lower mortality (p=0.48), 17% lower progression (p=0.34), and 25% lower severe cases (p=0.15). PSM retrospective 2,661 molnupiravir patients in Israel, showing lower mortality and severe COVID-19, without statistical significance. Significant benefit was seen in some subgroups, and significant harm was seen in the <75 subgroup.
Sep 9
2022
Kneidinger et al., Infection, doi:10.1007/s15010-022-01914-8 Outcome of lung transplant recipients infected with SARS-CoV-2/Omicron/B.1.1.529: a Nationwide German study
15% higher severe cases (p=0.71). Retrospective 218 COVID+ lung transplant patients in Germany, showing no significant difference in severe cases with early molnupiravir use.
Aug 2
2022
Lawrence et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkac440 (date from preprint) Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13,694 patients with meta-analysis
Meta analysis of molnupiravir trials showing 12 registered RCTs in India with only one presented at a conference, and two issuing press releases suggesting failure. Authors find that ~90% of the global data on molnupiravir has not been pu..
Jul 29
2022
Lieber et al., Nature Communications, doi:10.1038/s41467-022-32045-1 SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model
Roborovski dwarf hamster and in vitro study finding molnupiravir efficacy varied significantly by SARS-CoV-2 variant in the hamster model, in contrast to no significant difference seen in cultured cells and human organoids. Efficacy for o..
Jul 24
2022
Khoo et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(22)00644-2 (date from preprint) Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial
89% lower hospitalization (p=0.12), 12% worse recovery (p=0.74), and 23% improved viral clearance (p=0.07). RCT 90 molnupiravir and 90 placebo patients, showing faster viral clearance with treatment, not reaching the pre-defined threshold for superiority and recommendation as a candidate for large scale evaluation.
Jul 6
2022
Flisiak et al., Pharmacological Reports, doi:10.1007/s43440-022-00408-6 (date from preprint) Real-world experience with molnupiravir during the period of SARS-CoV-2 Omicron variant dominance
39% lower mortality (p=0.03), 5% lower ventilation (p=1), and 1% longer hospitalization (p=0.97). Retrospective 590 patients in Poland, 203 treated with mulnupiravir, showing lower mortality with treatment.
Jun 15
2022
Zou et al., Frontiers in Pharmacology, doi:10.3389/fphar.2022.939573 Antiviral Efficacy and Safety of Molnupiravir Against Omicron Variant Infection: A Randomized Controlled Clinical Trial
29% faster recovery (p=0.5) and 10% faster viral clearance (p=0.009). RCT 116 mild/moderate COVID-19 patients in China, showing improved viral clearance with treatment.
May 24
2022
Yip et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac687 (date from preprint) Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients
12% higher combined mortality/ICU admission (p=0.66) and 17% higher hospitalization (p=0.06). Propensity score weighted retrospective of 93,883 outpatients in Hong Kong, 5,808 treated with molnupiravir and 4,921 treated with paxlovid, showing higher hospitalization and higher combined mortality/mechanical ventilation/ICU admission..
May 20
2022
Wong et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(22)00507-2 (date from preprint) Real-world effectiveness of early molnupiravir or nirmatrelvir–ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study
52% lower mortality (p<0.0001), 58% lower ventilation (p=0.06), 40% lower progression (p<0.0001), and 6% shorter hospitalization (p=0.03). PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with molnupiravir treatment.
May 17
2022
Rosenke et al., JCI Insight, doi:10.1172/jci.insight.160108 Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model
Syrian hamster study showing efficacy of molnupiravir for multiple variants including omicron.
Apr 18
2022
Hadj Hassine et al., Viruses, doi:10.3390/v14040841 Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity
Review of lethal mutagenesis for RNA viruses, as used by molnupiravir, favipiravir, and ribavirin. Authors note the potential for permanently modifying the genomes of patients while causing teratogenicity or embryotoxicity, and the potent..
Apr 8
2022
Lee, T. PANORAMIC recruitment analysis
Analysis of the PANORAMIC trial recuitment suggesting that if the trial shows efficacy, the NNT will be >200.
Mar 11
2022
Thorlund et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.21-1339 Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial
Discussion of concerns with the MOVe-OUT trial, including the reversal of the treatment effect post-interim analysis.
Feb 24
2022
Tippabhotla et al., SSRN Electronic Journal, doi:10.2139/ssrn.4042673 Efficacy and Safety of Molnupiravir for the Treatment of Non-Hospitalized Adults With Mild COVID-19: A Randomized, Open-Label, Parallel-Group Phase 3 Trial
46% lower hospitalization (p=0.26), 46% greater improvement (p<0.0001), and 59% improved viral clearance (p<0.0001). RCT 1,220 patients in India, showing lower risk of hospitalization and improved recovery with treatment. CTRI/2021/07/034588.
Feb 3
2022
Swanstrom et al., Science, doi:10.1126/science.abn0048 Lethal mutagenesis as an antiviral strategy
Review of the unknown long-term cancer, reproductive, and escape variant creation risks of molnupiravir. For more discussion see [twitter.com, twitter.com, twitter.com].
Jan 28
2022
Waters et al., Environmental and Molecular Mutagenesis, doi:10.1002/em.22471 Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir
Review of antiviral nucleoside analog drugs that induce lethal mutagenesis, including molnupiravir and favipiravir, and the potential mutagenic risks to human DNA and human mitochondrial DNA. Author recommends monitoring for mutagenicity,..
Dec 16
2021
Arribas et al., NEJM Evidence, doi:10.1056/EVIDoa2100044 Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19
282% higher mortality (p=0.31), 1% improved recovery (p=0.96), and 12% improved viral clearance (p=0.57). RCT 304 hospitalized patients, 218 treated with molnupiravir, showing no significant differences. MOVe-IN MK-4482-001. NCT04575584.
Dec 16
2021
Jayk Bernal et al., New England Journal of Medicine, doi:10.1056/NEJMoa2116044 Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
89% lower mortality (p=0.01), 30% lower combined mortality/hospitalization (p=0.05), 15% faster recovery (p=0.02), and 4% improved viral clearance (p=0.2). Systematic review and meta analysis of outpatient RCTs, showing hospitalization RR 0.75 [0.57-0.97]. For discussion see [web.archive.org].
Dec 3
2021
Anonymous, Authorea, doi:10.22541/au.163854323.34557301/v1 Treating a Pandemic Respiratory Disease with a Mutagen is a Doomsday Scenario
Review of molnupiravir's mutagenic mechanism of action, and analysis of the increased probability of creating dangerous variants.
Nov 6
2021
Goldstein, L., TrialSite News Molnupiravir: mutagenic, carcinogenic, authorized in the UK
Discussion of concerns with molnupiravir and the MOVe-OUT trial. Author notes that results showing bone marrow toxicity in dogs were mentioned in this preprint [medrxiv.org], but removed from the journal version [journals.asm.org]. Some a..
Oct 9
2021
Reuters Two Indian drugmakers to end trials of generic Merck pill for moderate COVID-19
no change in recovery (p=1). Trial CTRI/2021/08/035424 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].
Oct 9
2021
Reuters Two Indian drugmakers to end trials of generic Merck pill for moderate COVID-19
no change in recovery (p=1). Trial CTRI/2021/05/033864 for moderate condition patients has been reported as terminated for futility. Results are not available yet [trialsearch.who.int].
Sep 13
2021
Malone et al., Nature Structural & Molecular Biology, doi:10.1038/s41594-021-00657-8 Molnupiravir: coding for catastrophe
Review of recent studies on molnupiravir's mechanism of lethal mutagenesis. Authors note that potential off-target effects require further investigation, because molnupiravir may be mutagenic to host DNA during host DNA replication.
Aug 27
2021
Khoo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkab318 Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study
33% worse recovery (p=0.63). Dose and safety study of molnupiravir with 18 participants, finding no serious adverse events in short-term followup. There was no significant difference in clinical outcomes. NCT04746183.
Jul 21
2021
Optimus, Press Release Optimus announces Interim Clinical Results from Phase III Clinical Trials of Molnupiravir conducted in India
58% improved viral clearance (p<0.0001). Interim report on CTRI/2021/06/033992, showing faster viral clearance. Event counts are approximate, the press release only provides percentages.
Jul 9
2021
Hetero, Press Release Hetero Announces Interim Clinical Results from Phase III Clinical Trials of Molnupiravir conducted in India
70% lower hospitalization (p=0.003) and 33% faster recovery (p=0.0001). Interim results for CTRI/2021/05/033739, showing lower mortality and faster recovery.
Jul 9
2021
Abdelnabi et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiab361 Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model
Hamster study showing molnupiravir effective against the original, B.1.1.7, and B.1.351 variants.
Jun 18
2021
Fischer et al., medRxiv, doi:10.1101/2021.06.17.21258639 Molnupiravir, an Oral Antiviral Treatment for COVID-19
77% lower mortality (p=0.31) and 49% improved viral clearance (p=0.12). RCT 202 outpatients in the USA showing significantly faster viral clearance, but no significant differences in symptom duration or severity. NCT04405570.
May 7
2021
Zhou et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247 β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells
In Vitro study showing that NHC (initial metabolite of molnupiravir) has high antiviral activity against SARS-CoV-2, but also shows host mutational activity in an animal cell culture assay. Authors note the concern that mutations in host ..
Apr 15
2021
Merck, News Release Merck and Ridgeback Biotherapeutics Provide Update on Progress of Clinical Development Program for Molnupiravir, an Investigational Oral Therapeutic for the Treatment of Mild-to-Moderate COVID-19
News release reporting that the trial of molnupiravir with hospitalized patients (NCT04575584) has been discontinued because data indicates it is unlikely to demonstrate a clinical benefit in hospitalized patients. Results are not availab..
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