Real-world clinical outcomes of treatment with molnupiravir for patients with mild- to-moderate coronavirus disease 2019 during the Omicron variant pandemic
Yasuhito Suzuki, Yoko Shibata, Hiroyuki Minemura, Takefumi Nikaido, Yoshinori Tanino, Atsuro Fukuhara, Ryuzo Kanno, Hiroyuki Saito, Shuzo Suzuki, Yayoi Inokoshi, Eiichiro Sando, Hirofumi Sakuma, Tatsuho Kobayashi, Hiroaki Kume, Masahiro Kamimoto, Hideko Aoki, Akira Takama, Taku Iizuka, Takamichi Kamiyama, Masaru Nakayama, Kiyoshi Saito, Koichi Tanigawa, Masahiko Sato, Yuichi Waragai, Toshiyuki Kambe, Norio Kanzaki, Teruhisa Azuma, Hiromasa Okamoto, Keiji Sakamoto, Yuichi Nakamura, Hiroshi Ohtani, Mitsuru Waragai, Shinsaku Maeda, Tokiya Ishida, Keishi Sugino, Wataru Abe, Yasuhiko Tsukada, Tomoyoshi Lee, Ryuki Yamada, Riko Sato, Takumi Onuma, Hikaru Tomita, Mikako Saito, Natsumi Watanabe, Mami Rikimaru, Takaya Kawamata, Julia Morimoto, Ryuichi Togawa, Yuki Sato, Junpei Saito, Kenya Kanazawa, Sugihiro Hamaguchi, Ken Iseki
Background It is unclear whether molnupiravir has a bene cial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the e cacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan.
Methods We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 281) and non-users (n = 1,636).
Results The molnupiravir users were older (P < 0.0001), and had greater rates of history of chronic respiratory disease (P = 0.039), hypertension (P < 0.0001), dyslipidemia (P < 0.0001), diabetes mellitus (P < 0.0001), and cardiac disease (P = 0.003) than the non-users. The clinical deterioration rate was signi cantly lower in the molnupiravir users compared to the non-users (3.92% vs 7.46%; P = 0.021). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.426; 95% con dence interval 0.208-0.871; P = 0.019), independent of receiving the SARS-CoV-2 vaccine. Furthermore, in 259 patients who were selected from each group after matching on the propensity score, the rate of deterioration was signi cantly lower among those receiving molnupiravir compared to those not receiving molnupiravir (3.86% vs 9.65%; p = 0.008).
Conclusion This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase.
Author contribution Conception and design: Yasuhito Suzuki and Yoko Shibata. Analysis and drafting the manuscript: Yasuhito Suzuki and Yoko Shibata. Data curation: all authors. Final approval of the manuscript: all authors.
Ethic This study was performed in line with the principles of the Declaration of Helsinki. The protocol was approved by the local ethical committee.
Consent to publication The authors seen the nal version of the manuscript and approved submission for publication.
Aggarwal, Beaty, Bennett, Real World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients, J Infect Dis, doi:10.1093/infdis/jiac206
Austin, Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies, Pharm Stat, doi:10.1002/pst.433
Bernal, Da Silva, Musungaie, Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med, doi:10.1056/NEJMoa2116044
Bojkova, Widera, Ciesek, Wass, Michaelis et al., Reduced interferon antagonism but similar drug sensitivity in Omicron variant compared to Delta variant of SARS-CoV-2 isolates, Cell Res, doi:10.1038/s41422-022-00619-9
Carlos, Wong, Lau, Lau, Cowling et al., Realworld 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, doi:10.1016/S1473-3099(22)00507-2
Gupta, Gonzalez-Rojas, Juarez, Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial, Jama, doi:10.1001/jama.2022.2832
Hammond, Leister-Tebbe, Gardner, Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2118542
Hirotsu, Maejima, Shibusawa, SARS-CoV-2 Omicron sublineage BA.2 replaces BA.1.1: Genomic surveillance in Japan from September 2021 to March 2022, J Infect, doi:10.1016/j.jinf.2022.04.040
Hoffmann, Krüger, Schulz, The Omicron variant is highly resistant against antibodymediated neutralization: Implications for control of the COVID-19 pandemic, Cell, doi:10.1016/j.cell.2021.12.032
Korber, Fischer, Gnanakaran, Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus, Cell, doi:10.1016/j.cell.2020.06.043
Liu, Rocklöv, The effective reproductive number of the Omicron variant of SARS-CoV-2 is several times relative to Delta, J Travel Med, doi:10.1093/jtm/taac037
Ohashi, Hishiki, Akazawa, Different e cacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2 Antiviral Res, doi:10.1016/j.antiviral.2022.105372
Ong, Ren, Lee, Real-World Use of Sotrovimab for Pre-Emptive Treatment in High-Risk Hospitalized COVID-19 Patients: An Observational Cross-Sectional Study, Antibiotics, doi:10.3390/antibiotics11030345
Ren, Nishimura, Tjan, Large-scale serosurveillance of COVID-19 in Japan: Acquisition of neutralizing antibodies for Delta but not for Omicron and requirement of booster vaccination to overcome the Omicron's outbreak, PLoS One, doi:10.1371/journal.pone.0266270
Rosenke, Okumura, Lewis, MK-4482) is e cacious against Omicron and other SARS-CoV-2 variants in the Syrian hamster COVID-19 model, doi:10.1101/2022.02.22.481491v1
Shibata, Minemura, Suzuki, Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19, doi:10.1101/2021.12.13.21267698v1
Takashita, Kinoshita, Yamayoshi, E cacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2, N Engl J Med, doi:10.1056/NEJMc2201933
Vanblargan, Errico, Halfmann, An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies, Nat Med, doi:10.1038/s41591-021-01678-y
Weinreich, Sivapalasingam, Norton, REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2035002
Yamamoto, Wada, Ichikawa, Evaluation of Biomarkers of Severity in Patients with COVID-19 Infection, J Clin Med, doi:10.3390/jcm10173775