Real-world data concerning the efficacy of molnupiravir in patients vaccinated against COVID-19 during the Omicron surge in Japan

{ 'institution': [{'name': 'Research Square'}], 'indexed': {'date-parts': [[2023, 4, 5]], 'date-time': '2023-04-05T04:43:20Z', 'timestamp': 1680669800369}, 'posted': {'date-parts': [[2023, 1, 16]]}, 'group-title': 'In Review', 'reference-count': 31, 'publisher': 'Research Square Platform LLC', 'license': [ { 'start': { 'date-parts': [[2023, 1, 16]], 'date-time': '2023-01-16T00:00:00Z', 'timestamp': 1673827200000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2023, 1, 7]]}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:p>Molnupiravir is among the antiviral agents used to treat COVID-19; however, ' 'reported data on the efficacy of this drug are based on results from unvaccinated patients. ' 'As such, the efficacy of molnupiravir among vaccinated patients during the B1.1.529 (Omicron) ' 'variant outbreak remains unknown. To address this issue, this study retrospectively analyzed ' 'data from 294 vaccinated patients with COVID-19 who had at least one risk factor, between May ' 'and October 2022. Patients were divided into the molnupiravir group and the control group to ' 'investigate the correlations of molnupiravir and other factors with rates of hospitalization ' 'and death (hospitalization/death) within 28 days of admission. Potential risk factors were ' 'also examined. The study findings indicated that molnupiravir was not associated with the ' 'rate of hospitalization/death, while age\u2009≥\u200980 years, residence in a long-term care ' 'facility, and presence of chronic obstructive pulmonary disease were significantly associated ' 'with the rate of hospitalization/death. Although the current results suggest that the effect ' 'of vaccination in preventing severe illness against the Omicron variant is well maintained, ' 'additional studies on risk factors and outcomes are required to validate this study’s ' 'findings.</jats:p>', 'DOI': '10.21203/rs.3.rs-2451986/v1', 'type': 'posted-content', 'created': {'date-parts': [[2023, 1, 16]], 'date-time': '2023-01-16T14:36:12Z', 'timestamp': 1673879772000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Real-world data concerning the efficacy of molnupiravir in patients vaccinated against COVID-19 ' 'during the Omicron surge in Japan', 'prefix': '10.21203', 'author': [ { 'given': 'Satoshi', 'family': 'Inaba', 'sequence': 'first', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Naoya', 'family': 'Nishioka', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Hisatoshi', 'family': 'Okumura', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Koshi', 'family': 'Nakao', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Yu', 'family': 'Hattori', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Shun', 'family': 'Futamura', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Tomohito', 'family': 'Hattori', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Kengo', 'family': 'Okabe', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}, { 'given': 'Daichi', 'family': 'Nishiyama', 'sequence': 'additional', 'affiliation': [{'name': 'Fukuchiyama City Hospital'}]}], 'member': '8761', 'reference': [ { 'key': 'ref1', 'doi-asserted-by': 'crossref', 'first-page': '1303', 'DOI': '10.1016/S0140-6736(22)00462-7', 'article-title': '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', 'volume': '399', 'author': 'Nyberg T', 'year': '2022', 'unstructured': 'Nyberg, T. et al. 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. Lancet 399, 1303–1312 ' '(2022).', 'journal-title': 'Lancet'}, { 'key': 'ref2', 'doi-asserted-by': 'crossref', 'first-page': '139', 'DOI': '10.15585/mmwr.mm7104e3', 'article-title': 'Effectiveness of a third dose of mRNA vaccines against ' 'COVID-19-associated emergency department and urgent care encounters and ' 'hospitalizations among adults during periods of Delta and omicron ' 'variant predominance - VISION network, 10 states, August 2021–January ' '2022', 'volume': '71', 'author': 'Thompson MG', 'year': '2022', 'unstructured': 'Thompson, M. G. et al. Effectiveness of a third dose of mRNA vaccines ' 'against COVID-19-associated emergency department and urgent care ' 'encounters and hospitalizations among adults during periods of Delta and ' 'omicron variant predominance - VISION network, 10 states, August ' '2021–January 2022. MMWR Morb. Mortal. Wkly Rep. 71, 139–145 (2022).', 'journal-title': 'MMWR Morb. Mortal. Wkly Rep.'}, { 'key': 'ref3', 'first-page': '62', 'article-title': 'Orally efficacious broad-spectrum ribonucleoside analog inhibitor of ' 'influenza and respiratory syncytial viruses', 'author': 'Yoon JJ', 'year': '2018', 'unstructured': 'Yoon, J. J. et al. Orally efficacious broad-spectrum ribonucleoside ' 'analog inhibitor of influenza and respiratory syncytial viruses. ' 'Antimicrob. Agents Chemother. 62 (2018).', 'journal-title': 'Antimicrob. Agents Chemother.'}, { 'key': 'ref4', 'doi-asserted-by': 'crossref', 'first-page': '11', 'DOI': '10.1038/s41564-020-00835-2', 'article-title': 'Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 ' 'blocks SARS-CoV-2 transmission in ferrets', 'volume': '6', 'author': 'Cox RM', 'year': '2021', 'unstructured': 'Cox, R. M., Wolf, J. D. & Plemper, R. K. Therapeutically administered ' 'ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission ' 'in ferrets. Nat. Microbiol. 6, 11–18 (2021).', 'journal-title': 'Nat. Microbiol.'}, { 'key': 'ref5', 'doi-asserted-by': 'crossref', 'DOI': '10.1126/scitranslmed.abb5883', 'article-title': 'An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in ' 'human airway epithelial cell cultures and multiple coronaviruses in ' 'mice', 'volume': '12', 'author': 'Sheahan TP', 'year': '2020', 'unstructured': 'Sheahan, T. P. et al. An orally bioavailable broad-spectrum antiviral ' 'inhibits SARS-CoV-2 in human airway epithelial cell cultures and ' 'multiple coronaviruses in mice. Sci. Transl. Med. 12 (2020).', 'journal-title': 'Sci. Transl. Med.'}, { 'key': 'ref6', 'doi-asserted-by': 'crossref', 'first-page': '451', 'DOI': '10.1038/s41586-021-03312-w', 'article-title': 'SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801', 'volume': '591', 'author': 'Wahl A', 'year': '2021', 'unstructured': 'Wahl, A. et al. SARS-CoV-2 infection is effectively treated and ' 'prevented by EIDD-2801. Nature 591, 451–457 (2021).', 'journal-title': 'Nature'}, { 'key': 'ref7', 'doi-asserted-by': 'crossref', 'first-page': '749', 'DOI': '10.1093/infdis/jiab361', 'article-title': 'Molnupiravir inhibits replication of the emerging SARS-CoV-2 variants ' 'of concern in a hamster infection model', 'volume': '224', 'author': 'Abdelnabi R', 'year': '2021', 'unstructured': 'Abdelnabi, R. et al. Molnupiravir inhibits replication of the emerging ' 'SARS-CoV-2 variants of concern in a hamster infection model. J. Infect. ' 'Dis. 224, 749–753 (2021).', 'journal-title': 'J. Infect. Dis.'}, { 'key': 'ref8', 'first-page': '93', 'article-title': 'Small-molecule antiviral β-d-N4-hydroxycytidine inhibits a ' 'proofreading-intact coronavirus with a high genetic barrier to ' 'resistance', 'author': 'Agostini ML', 'year': '2019', 'unstructured': 'Agostini, M. L. et al. Small-molecule antiviral β-d-N4-hydroxycytidine ' 'inhibits a proofreading-intact coronavirus with a high genetic barrier ' 'to resistance. J. Virol. 93 (2019).', 'journal-title': 'J. Virol.'}, { 'key': 'ref9', 'doi-asserted-by': 'crossref', 'first-page': '509', 'DOI': '10.1056/NEJMoa2116044', 'article-title': 'Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients', 'volume': '386', 'author': 'Jayk Bernal A', 'year': '2022', 'unstructured': 'Jayk Bernal, A. et al. Molnupiravir for oral treatment of Covid-19 in ' 'nonhospitalized patients. N. Engl. J. Med. 386, 509–520 (2022).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref10', 'doi-asserted-by': 'crossref', 'first-page': '1813', 'DOI': '10.1056/NEJMoa2007764', 'article-title': 'Remdesivir for the treatment of Covid-19 - Final report', 'volume': '383', 'author': 'Beigel JH', 'year': '2020', 'unstructured': 'Beigel, J. H. et al. Remdesivir for the treatment of Covid-19 - Final ' 'report. N. Engl. J. Med. 383, 1813–1826 (2020).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref11', 'doi-asserted-by': 'crossref', 'first-page': '995', 'DOI': '10.1056/NEJMc2119407', 'article-title': 'Efficacy of antibodies and antiviral drugs against Covid-19 omicron ' 'variant', 'volume': '386', 'author': 'Takashita E', 'year': '2022', 'unstructured': 'Takashita, E. et al. Efficacy of antibodies and antiviral drugs against ' 'Covid-19 omicron variant. N. Engl. J. Med. 386, 995–998 (2022).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref12', 'doi-asserted-by': 'crossref', 'first-page': '1397', 'DOI': '10.1056/NEJMoa2118542', 'article-title': 'Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19', 'volume': '386', 'author': 'Hammond J', 'year': '2022', 'unstructured': 'Hammond, J. et al. Oral nirmatrelvir for high-risk, nonhospitalized ' 'adults with Covid-19. N. Engl. J. Med. 386, 1397–1408 (2022).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref13', 'doi-asserted-by': 'crossref', 'first-page': '452', 'DOI': '10.1038/bmt.2012.244', 'article-title': 'Investigation of the freely available easy-to-use software ‘EZR’ for ' 'medical statistics', 'volume': '48', 'author': 'Kanda Y', 'year': '2013', 'unstructured': 'Kanda, Y. Investigation of the freely available easy-to-use software ' '‘EZR’ for medical statistics. Bone Marrow Transplant. 48, 452–458 ' '(2013).', 'journal-title': 'Bone Marrow Transplant.'}, { 'key': 'ref14', 'first-page': '10', 'article-title': 'Molnupiravir-A novel oral anti-SARS-CoV-2 agent', 'author': 'Lee CC', 'year': '2021', 'unstructured': 'Lee, C. C., Hsieh, C. C. & Ko, W. C. Molnupiravir-A novel oral ' 'anti-SARS-CoV-2 agent. Antibiotics (Basel) 10 (2021).', 'journal-title': 'Antibiotics (Basel)'}, { 'key': 'ref15', 'doi-asserted-by': 'crossref', 'first-page': '516', 'DOI': '10.1080/07853890.2022.2034936', 'article-title': 'Efficacy and safety of three new oral antiviral treatment ' '(molnupiravir, fluvoxamine and Paxlovid) for COVID-19: a meta-analysis', 'volume': '54', 'author': 'Wen W', 'year': '2022', 'unstructured': 'Wen, W. et al. Efficacy and safety of three new oral antiviral treatment ' '(molnupiravir, fluvoxamine and Paxlovid) for COVID-19: a meta-analysis. ' 'Ann. Med. 54, 516–523 (2022).', 'journal-title': 'Ann. Med.'}, { 'key': 'ref16', 'doi-asserted-by': 'crossref', 'first-page': '508', 'DOI': '10.1016/j.jsps.2022.03.002', 'article-title': 'The pill of recovery; Molnupiravir for treatment of COVID-19 patients; ' 'a systematic review', 'volume': '30', 'author': 'Kamal L', 'year': '2022', 'unstructured': 'Kamal, L., Ramadan, A., Farraj, S., Bahig, L. & Ezzat, S. The pill of ' 'recovery; Molnupiravir for treatment of COVID-19 patients; a systematic ' 'review. Saudi Pharm. J. 30, 508–518 (2022).', 'journal-title': 'Saudi Pharm. J.'}, { 'key': 'ref17', 'doi-asserted-by': 'crossref', 'first-page': '5582', 'DOI': '10.1002/jmv.28011', 'article-title': 'Safety and efficacy of molnupiravir in SARS-CoV-2-infected patients: A ' 'real-life experience', 'volume': '94', 'author': 'Vito A', 'year': '2022', 'unstructured': 'De Vito, A. et al. Safety and efficacy of molnupiravir in ' 'SARS-CoV-2-infected patients: A real-life experience. J. Med. Virol. 94, ' '5582–5588 (2022).', 'journal-title': 'J. Med. Virol.'}, { 'key': 'ref18', 'doi-asserted-by': 'crossref', 'DOI': '10.3390/pathogens11101121', 'article-title': 'Molnupiravir as an early treatment for COVID-19: A real life study', 'volume': '11', 'author': 'Pontolillo M', 'year': '2022', 'unstructured': 'Pontolillo, M. et al. Molnupiravir as an early treatment for COVID-19: A ' 'real life study. Pathogens 11 (2022).', 'journal-title': 'Pathogens'}, { 'key': 'ref19', 'doi-asserted-by': 'crossref', 'first-page': '141', 'DOI': '10.1038/s41392-022-00997-x', 'article-title': 'SARS-CoV-2 Omicron variant: Recent progress and future perspectives', 'volume': '7', 'author': 'Fan Y', 'year': '2022', 'unstructured': 'Fan, Y. et al. SARS-CoV-2 Omicron variant: Recent progress and future ' 'perspectives. Signal Transduct. Target. Ther. 7, 141 (2022).', 'journal-title': 'Signal Transduct. Target. Ther.'}, { 'key': 'ref20', 'doi-asserted-by': 'crossref', 'first-page': 'n3103', 'DOI': '10.1136/bmj.n3103', 'article-title': 'Covid-19: Runny nose, headache, and fatigue are commonest symptoms of ' 'omicron, early data show', 'volume': '375', 'author': 'Iacobucci G', 'year': '2021', 'unstructured': 'Iacobucci, G. Covid-19: Runny nose, headache, and fatigue are commonest ' 'symptoms of omicron, early data show. BMJ 375, n3103 (2021).', 'journal-title': 'BMJ'}, { 'key': 'ref21', 'first-page': '838', 'article-title': 'SARS-CoV-2 Omicron variant: Characteristics and prevention', 'volume': '2', 'author': 'He X', 'year': '2021', 'unstructured': 'He, X., Hong, W., Pan, X., Lu, G. & Wei, X. SARS-CoV-2 Omicron variant: ' 'Characteristics and prevention. Med. 2, 838–845 (2021).', 'journal-title': 'Med.'}, { 'key': 'ref22', 'doi-asserted-by': 'crossref', 'first-page': '412', 'DOI': '10.1016/S0140-6736(22)00056-3', 'article-title': 'Omicron severity: Milder but not mild', 'volume': '399', 'author': 'Nealon J', 'year': '2022', 'unstructured': 'Nealon, J. & Cowling, B. J. Omicron severity: Milder but not mild. ' 'Lancet 399, 412–413 (2022).', 'journal-title': 'Lancet'}, { 'key': 'ref23', 'doi-asserted-by': 'crossref', 'first-page': '1286', 'DOI': '10.1001/jama.2022.2274', 'article-title': 'Estimates of SARS-CoV-2 omicron variant severity in Ontario, Canada', 'volume': '327', 'author': 'Ulloa AC', 'year': '2022', 'unstructured': 'Ulloa, A. C., Buchan, S. A., Daneman, N. & Brown, K. A. Estimates of ' 'SARS-CoV-2 omicron variant severity in Ontario, Canada. JAMA 327, ' '1286–1288 (2022).', 'journal-title': 'JAMA'}, { 'key': 'ref24', 'doi-asserted-by': 'crossref', 'first-page': '2043', 'DOI': '10.1001/jama.2021.19499', 'article-title': 'Association between mRNA vaccination and COVID-19 hospitalization and ' 'disease severity', 'volume': '326', 'author': 'Tenforde MW', 'year': '2021', 'unstructured': 'Tenforde, M. W. et al. Association between mRNA vaccination and COVID-19 ' 'hospitalization and disease severity. JAMA 326, 2043–2054 (2021).', 'journal-title': 'JAMA'}, { 'key': 'ref25', 'doi-asserted-by': 'crossref', 'first-page': '1532', 'DOI': '10.1056/NEJMoa2119451', 'article-title': 'Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant', 'volume': '386', 'author': 'Andrews N', 'year': '2022', 'unstructured': 'Andrews, N. et al. Covid-19 vaccine effectiveness against the omicron ' '(B.1.1.529) variant. N. Engl. J. Med. 386, 1532–1546 (2022).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref26', 'article-title': 'Clinical severity and mRNA vaccine effectiveness for omicron, delta, ' 'and alpha SARS-CoV-2 variants in the United States: A prospective ' 'observational study', 'author': 'Lauring AS', 'year': '2022', 'unstructured': 'Lauring, A. S. et al. Clinical severity and mRNA vaccine effectiveness ' 'for omicron, delta, and alpha SARS-CoV-2 variants in the United States: ' 'A prospective observational study. medRxiv (2022).', 'journal-title': 'medRxiv'}, { 'key': 'ref27', 'article-title': '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', 'author': 'Butler CC', 'year': '2022', 'unstructured': 'Butler, C. C. et al. 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. Lancet (2022).', 'journal-title': 'Lancet'}, { 'key': 'ref28', 'doi-asserted-by': 'crossref', 'first-page': '1681', 'DOI': '10.1016/S1473-3099(22)00507-2', 'article-title': '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', 'volume': '22', 'author': 'Wong CKH', 'year': '2022', 'unstructured': 'Wong, C. K. H. et al. 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. Lancet Infect. Dis. 22, ' '1681–1693 (2022).', 'journal-title': 'Lancet Infect. Dis.'}, { 'key': 'ref29', 'doi-asserted-by': 'crossref', 'first-page': '1915', 'DOI': '10.1002/jmv.25889', 'article-title': 'The impact of COPD and smoking history on the severity of COVID-19: A ' 'systemic review and meta-analysis', 'volume': '92', 'author': 'Zhao Q', 'year': '2020', 'unstructured': 'Zhao, Q. et al. The impact of COPD and smoking history on the severity ' 'of COVID-19: A systemic review and meta-analysis. J. Med. Virol. 92, ' '1915–1921 (2020).', 'journal-title': 'J. Med. Virol.'}, { 'key': 'ref30', 'doi-asserted-by': 'crossref', 'first-page': '100789', 'DOI': '10.1016/j.eclinm.2021.100789', 'article-title': 'COPD and the risk of poor outcomes in COVID-19: A systematic review and ' 'meta-analysis', 'volume': '33', 'author': 'Gerayeli FV', 'year': '2021', 'unstructured': 'Gerayeli, F. V. et al. COPD and the risk of poor outcomes in COVID-19: A ' 'systematic review and meta-analysis. EClinicalmedicine 33, 100789 ' '(2021).', 'journal-title': 'EClinicalmedicine'}, { 'key': 'ref31', 'doi-asserted-by': 'crossref', 'first-page': '712', 'DOI': '10.1164/rccm.202108-1901OC', 'article-title': 'Increased SARS-CoV-2 infection, protease, and inflammatory responses in ' 'chronic obstructive pulmonary disease primary bronchial epithelial ' 'cells defined with single-cell RNA sequencing', 'volume': '206', 'author': 'Johansen MD', 'year': '2022', 'unstructured': 'Johansen, M. D. et al. Increased SARS-CoV-2 infection, protease, and ' 'inflammatory responses in chronic obstructive pulmonary disease primary ' 'bronchial epithelial cells defined with single-cell RNA sequencing. Am. ' 'J. Respir. Crit. Care Med. 206, 712–729 (2022).', 'journal-title': 'Am. J. Respir. Crit. Care Med.'}], 'container-title': [], 'original-title': [], 'link': [ { 'URL': 'https://www.researchsquare.com/article/rs-2451986/v1', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.researchsquare.com/article/rs-2451986/v1.html', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 4, 4]], 'date-time': '2023-04-04T12:16:10Z', 'timestamp': 1680610570000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.researchsquare.com/article/rs-2451986/v1'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 1, 16]]}, 'references-count': 31, 'URL': 'http://dx.doi.org/10.21203/rs.3.rs-2451986/v1', 'relation': {}, 'published': {'date-parts': [[2023, 1, 16]]}, 'subtype': 'preprint'}