Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients

Yip et al., Clinical Infectious Diseases, doi:10.1093/cid/ciac687 (date from preprint)

May 2022

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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 with molnupiravir, without statistical significance; and lower hospitalization and combined mortality/mechanical ventilation/ICU admission with paxlovid, statistically significant only for hospitalization.

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.

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Study covers paxlovid and molnupiravir.

combined death/ventilation/ICU, 12.0% higher, HR 1.12, p = 0.66, treatment 53 of 5,808 (0.9%), control 151 of 83,154 (0.2%), propensity score weighting, Cox proportional hazards, day 30.

risk of hospitalization, 17.0% higher, HR 1.17, p = 0.06, treatment 437 of 5,808 (7.5%), control 1,322 of 83,154 (1.6%), propensity score weighting, Cox proportional hazards, day 30.

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

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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.

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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.

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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.

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Yip et al., 24 May 2022, retrospective, placebo-controlled, China, peer-reviewed, 11 authors, study period 16 February, 2022 - 31 March, 2022. Contact: wonglaihung@cuhk.edu.hk.

This Paper Molnupiravir All

PhD Terry Cheuk-Fung Yip, MD Chung-Yan Lui, BSc Mandy Sze-Man Lai, MD Wai-Sun Wong, MPhil Yee-Kit Tse, Hon-Ming Bosco, MD Ma, MD Elsie Hui, MFM Maria Kw Leung, Henry Lik-Yuen, MD Chan, MD Shu-Cheong Hui, Lai-Hung Grace, MBChB Wong

Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 patients

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Patients hospitalized on the day of the first ' 'clinic appointment or used both oral antivirals were excluded. The primary endpoint was ' 'hospitalization. The secondary endpoint was a composite of intensive care unit admission, ' 'invasive mechanical ventilation use, and/or death.\n' ' \n' ' \n' ' Results\n' ' Of 93,883 patients, 83,154 (88.6%), 5,808 (6.2%), and 4,921 (5.2%) ' 'were oral antiviral non-users, molnupiravir users, and nirmatrelvir/ritonavir users ' 'respectively. Compared to non-users, oral antiviral users were older and had more ' 'comorbidities, lower complete vaccination rate, and more hospitalizations in the previous ' 'year. Molnupiravir users were older, and had more comorbidities, lower complete vaccination ' 'rate, and more hospitalizations in the previous year than nirmatrelvir/ritonavir users. At a ' 'median follow-up of 30 days, 1,931 (2.1%) patients were hospitalized and 225 (0.2%) patients ' 'developed the secondary endpoint. After propensity score weighting, nirmatrelvir/ritonavir ' 'use (weighted hazard ratio 0.79, 95%CI 0.65-0.95, P\u2009=\u20090.011) but not molnupiravir ' 'use (weighted hazard ratio 1.17, 95%CI 0.99-1.39, P\u2009=\u20090.062) was associated with a ' 'reduced risk of hospitalization than non-users. The use of molnupiravir or ' 'nirmatrelvir/ritonavir was not associated with a lower risk of the secondary endpoint as ' 'compared to non-users.\n' ' \n' ' \n' ' Conclusion\n' ' Use of nirmatrelvir/ritonavir but not molnupiravir was associated ' 'with a reduced risk of hospitalization in real-world non-hospitalized COVID-19 ' 'patients.\n' ' ', 'DOI': '10.1093/cid/ciac687', 'type': 'journal-article', 'created': {'date-parts': [[2022, 8, 29]], 'date-time': '2022-08-29T01:48:15Z', 'timestamp': 1661737695000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Impact of the use of oral antiviral agents on the risk of hospitalization in community COVID-19 ' 'patients', 'prefix': '10.1093', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-1819-2464', 'authenticated-orcid': False, 'given': 'Terry Cheuk Fung', 'family': 'Yip', 'sequence': 'first', 'affiliation': [ {'name': 'Department of Medicine and Therapeutics'}, {'name': 'Medical Data Analytics Centre (MDAC)'}, {'name': 'Institute of Digestive Disease'}]}, { 'given': 'Grace Chung Yan', 'family': 'Lui', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Medicine and Therapeutics'}, {'name': 'Medical Data Analytics Centre (MDAC)'}, { 'name': 'Stanley Ho Centre for Emerging Infectious Diseases, Jockey Club ' 'School of Public Health & Primary Care'}]}, { 'given': 'Mandy Sze Man', 'family': 'Lai', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Medicine and Therapeutics'}, {'name': 'Medical Data Analytics Centre (MDAC)'}]}, { 'given': 'Vincent Wai Sun', 'family': 'Wong', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Medicine and Therapeutics'}, {'name': 'Medical Data Analytics Centre (MDAC)'}, { 'name': 'Stanley Ho Centre for Emerging Infectious Diseases, Jockey Club ' 'School of Public Health & Primary Care'}]}, { 'given': 'Yee Kit', 'family': 'Tse', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Medicine and Therapeutics'}, {'name': 'Medical Data Analytics Centre (MDAC)'}, {'name': 'Institute of Digestive Disease'}]}, { 'given': 'Bosco Hon Ming', 'family': 'Ma', 'sequence': 'additional', 'affiliation': [{'name': 'Department of Medicine and Therapeutics'}]}, { 'given': 'Elsie', 'family': 'Hui', 'sequence': 'additional', 'affiliation': [{'name': 'Department of Medicine and Therapeutics'}]}, { 'given': 'Maria KW', 'family': 'Leung', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Family Medicine, Prince of Wales Hospital, ' 'Hospital Authority , Hong Kong'}]}, { 'given': 'Henry Lik Yuen', 'family': 'Chan', 'sequence': 'additional', 'affiliation': [ {'name': 'Medical Data Analytics Centre (MDAC)'}, { 'name': 'Faculty of Medicine, The Chinese University of Hong Kong ; Hong ' 'Kong'}, {'name': 'Department of Internal Medicine, Union Hospital , Hong Kong'}]}, { 'given': 'David Shu Cheong', 'family': 'Hui', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Medicine and Therapeutics'}, {'name': 'Medical Data Analytics Centre (MDAC)'}, { 'name': 'Stanley Ho Centre for Emerging Infectious Diseases, Jockey Club ' 'School of Public Health & Primary Care'}]}, { 'ORCID': 'http://orcid.org/0000-0002-2863-9389', 'authenticated-orcid': False, 'given': 'Grace Lai Hung', 'family': 'Wong', 'sequence': 'additional', 'affiliation': [ {'name': 'Department of Medicine and Therapeutics'}, {'name': 'Medical Data Analytics Centre (MDAC)'}, {'name': 'Institute of Digestive Disease'}]}], 'member': '286', 'published-online': {'date-parts': [[2022, 8, 29]]}, 'container-title': 'Clinical Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciac687/45601511/ciac687.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciac687/45601511/ciac687.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 8, 29]], 'date-time': '2022-08-29T01:48:16Z', 'timestamp': 1661737696000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac687/6678124'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 8, 29]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.1093/cid/ciac687', 'relation': {}, 'ISSN': ['1058-4838', '1537-6591'], 'subject': ['Infectious Diseases', 'Microbiology (medical)'], 'published': {'date-parts': [[2022, 8, 29]]}}

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