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

Brown et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac527

Oct 2022

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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 indication.

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-10. Multiple analyses have identified variants potentially created by molnupiravir11-15.

This study is excluded in the after exclusion results of meta analysis: unadjusted results with no group details; significant unadjusted confounding possible.

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Study covers sotrovimab and molnupiravir.

risk of hospitalization, 100.9% higher, RR 2.01, p = 0.51, treatment 8 of 442 (1.8%), control 2 of 222 (0.9%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. Swanstrom et al., Lethal mutagenesis as an antiviral strategy, Science, doi:10.1126/science.abn0048.science.org, doi.org.

2. Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.mdpi.com, doi.org.

3. Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.wiley.com, doi.org.

4. Huntsman, M., An assessment of the reproductive toxicity of the anti-COVID-19 drug molnupiravir using stem cell-based embryo models, Master's Thesis, scholarspace.manoa.hawaii.edu/items/cd11342c-b4dc-44c0-8b44-ce6e3369c40b.hawaii.edu.

5. Zibat et al., N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody, iScience, doi:10.1016/j.isci.2023.107786.sciencedirect.com, doi.org.

6. Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.sciencedirect.com, doi.org.

7. Gruber et al., Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study, Journal of Medical Virology, doi:10.1002/jmv.29642.wiley.com, doi.org.

8. Marikawa et al., An active metabolite of the anti-COVID-19 drug molnupiravir impairs mouse preimplantation embryos at clinically relevant concentrations, Reproductive Toxicology, doi:10.1016/j.reprotox.2023.108475.sciencedirect.com, doi.org.

9. Zhou et al., β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247.oup.com, doi.org.

10. Chamod et al., Molnupiravir Metabolite--N4-hydroxycytidine Causes Cytotoxicity and DNA Damage in Mammalian Cells in vitro: N4-hydroxycytidine Induced Cytotoxicity DNA Damage, Asian Medical Journal and Alternative Medicine, 23:3, asianmedjam.com/index.php/amjam/article/view/1448.asianmedjam.com.

11. Focosi et al., The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country, Intervirology, doi:10.1159/000540282.karger.com, doi.org.

12. Sanderson et al., A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes, Nature, doi:10.1038/s41586-023-06649-6.nature.com, doi.org.

13. Fountain-Jones et al., Effect of molnupiravir on SARS-CoV-2 evolution in immunocompromised patients: a retrospective observational study, The Lancet Microbe, doi:10.1016/S2666-5247(23)00393-2.sciencedirect.com, doi.org.

14. Kosakovsky Pond et al., Anti-COVID drug accelerates viral evolution, Nature, doi:10.1038/d41586-023-03248-3.nature.com, doi.org.

15. twitter.com, twitter.com/LongDesertTrain/status/1597353291868155906.twitter.com/LongDesertTrain/status/1597353291868155906.

Brown et al., 6 Oct 2022, retrospective, United Kingdom, peer-reviewed, 17 authors. Contact: michael.marks@lshtm.ac.uk, anna.goodman@gstt.nhs.uk.

This Paper Molnupiravir All

M Brown, J Gahir, Simpson, K Elgizouli, 10 Marks, Michael Marks, Anna Goodman

doi:10.1093/ofid/ofac527/6750023

Title 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.

Funding No specific funding for this work. MM is supported by NIHR and the EDCTP. Conflict of Interest The authors have no conflicts of interest to declare

References

Bernal, Da Silva, Musungaie, Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med

Carr, Wu, Harvey, Omicron neutralising antibodies after COVID-19 vaccination in haemodialysis patients, The Lancet

Cheng, Mok, Leung, Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination, Nat Med

Gottlieb, Vaca, Paredes, Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients, N Engl J Med

Gupta, Gonzalez-Rojas, Juarez, Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab, N Engl J Med

Menni, Valdes, Polidori, Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study, The Lancet

Nyberg, Ferguson, Nash, Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study, The Lancet

Planas, Saunders, Maes, Considerable escape of SARS-CoV-2 Omicron to antibody neutralization, Nature

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We ' 'assessed demographics and triage outcomes of CMDU referral, uptake of antiviral therapy and ' 'the rate of subsequent hospitalisations within two weeks of CMDU referral.\n' ' \n' ' \n' ' Results\n' ' Over a three week period 4,788 patients were referred and 3,989 ' 'were ultimately assessed by a CMDU. Overall, 832 of the patients referred (17%) were judged ' 'eligible for treatment and 628 (13%) were ultimately prescribed an antiviral agent. The ' 'overall rate of admission within 14 days was 1%. Patients who were admitted were ' 'significantly older than those who did not require hospitalisation. Of patients prescribed ' 'molnupiravir and sotrovimab 1.8% and 3.2% were admitted respectively.\n' ' \n' ' \n' ' Conclusion\n' ' There were a high volume of referrals to CMDU service during the ' 'the initial surge of the Omicron wave in the UK. A minority of patients were judged to be ' 'eligible for therapy. In a highly vaccinated population, the overall hospitalisation rate was ' 'low.\n' ' ', 'DOI': '10.1093/ofid/ofac527', 'type': 'journal-article', 'created': {'date-parts': [[2022, 10, 6]], 'date-time': '2022-10-06T20:13:46Z', 'timestamp': 1665087226000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': '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.', 'prefix': '10.1093', 'author': [ { 'given': 'M', 'family': 'Brown', 'sequence': 'first', 'affiliation': [ { 'name': 'Division of Infection, University College London Hospitals NHS ' 'Foundation Trust , London , UK'}, { 'name': 'Clinical Research Dept, London School of Hygiene & Tropical ' 'Medicine , London , UK'}]}, { 'given': 'J', 'family': 'Saund', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Infection, University College London Hospitals NHS ' 'Foundation Trust , London , UK'}]}, { 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