Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate
et al., iScience, doi:10.1016/j.isci.2023.108147, Nov 2023
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, sotrovimab, and bebtelovimab were not effective against XBB, XBB.1.5, and XBB.1.9.1. XBB.1.9.1 and XBB.1.5 remained susceptible to remdesivir, molnupiravir, nirmatrelvir, and ensitrelvir. In hamsters infected with a mixture of the two variants, XBB.1.9.1 and XBB.1.5 showed similar replicative fitness in nasal turbinates and lungs.
Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury, Leo, Briciu, Muntean, Petrov show increased risk of liver injury, and Negru, Cheng, Mohammed show increased risk of cardiac disorders with remdesivir.
Study covers casirivimab/imdevimab, tixagevimab/cilgavimab, sotrovimab, bebtelovimab, ensitrelvir, paxlovid, molnupiravir, and remdesivir.
1.
Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.
2.
Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.
3.
Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.
4.
Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.
5.
Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.
6.
Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.
7.
Leo et al., Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points, Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014.
8.
Briciu et al., Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting, Pathogens, doi:10.3390/pathogens12121453.
9.
Muntean et al., Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre, Pharmaceuticals, doi:10.3390/ph17010003.
10.
Petrov et al., The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study, Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458.
11.
Negru et al., Comparative Pharmacovigilance Analysis of Approved and Repurposed Antivirals for COVID-19: Insights from EudraVigilance Data, Biomedicines, doi:10.3390/biomedicines13061387.
Uraki et al., 30 Nov 2023, peer-reviewed, 20 authors.
Contact: yoshihiro.kawaoka@wisc.edu (corresponding author), yoshihiro.kawaoka@wisc.edu (corresponding author).
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate
iScience, doi:10.1016/j.isci.2023.108147
Highlights The antigenicity of XBB.1.9.1 is similar to that of XBB.1.5 XBB.1.9.1 remains susceptible to antiviral drugs The replicative ability of XBB.1.9.1 is comparable to that of XBB.1.5
SUPPLEMENTAL INFORMATION Supplemental information can be found online at https://doi.org/10.1016/j.isci.2023.108147 .
AUTHOR CONTRIBUTIONS R.U.: conceptualization, formal analysis, validation, visualization, and writing of the first draft. M. Ito, M. Kiso: data curation, formal analysis, and methodology. S. Yamayoshi: conceptualization, data curation, formal analysis, and methodology. K.I-H.: resources and validation. Y.S-T., M.
Data and code availability All data used in this paper are available in the main text, in the supplemental information, or the sources have been clearly stated. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
EXPERIMENTAL MODEL AND STUDY PARTICIPANT DETAILS Animal studies were carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Animal Experiment Committee of the Institute of Medical Science, the University of Tokyo (approval number PA19-75). Virus inoculations were performed under isoflurane, and all efforts were made to minimize animal suffering. To collect and use clinical specimens, the research protocol was approved by the Research Ethics Review Committee of the Institute of Medical Science of the University of Tokyo (approval numbers: 2019-71-0201 and 2020-740226). After informed consent was..
References
Chen, Li, Peng, Tian, Ji et al., Neutralization against XBB.1 and XBB.1.5 after omicron subvariants breakthrough infection or reinfection, Lancet Reg. Health. West. Pac, doi:10.1016/j.lanwpc.2023.100759
Imai, Halfmann, Yamayoshi, Iwatsuki-Horimoto, Chiba et al., Characterization of a new SARS-CoV-2 variant that emerged in Brazil, Proc. Natl. Acad. Sci, doi:10.1073/pnas.2106535118
Imai, Ito, Kiso, Yamayoshi, Uraki et al., Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB, N. Engl. J. Med, doi:10.1056/NEJMc2214302
Imai, None
Imai, were propagated in the presence of 1 mg/ml geneticin (G418; Invivogen) and 5 mg/ml plasmocin prophylactic (Invivogen) in DMEM containing 10% FCS. Vero E6-TMPRSS2-T2A-ACE2 and VeroE6/TMPRSS2 cells were maintained at 37 C with 5% CO 2 . Chinese hamster ovary (CHO) cells were maintained in DMEM containing 10% FCS and antibiotics at 37 C with 5% CO 2 . Expi293F cells
Matsuyama, Nao, Shirato, Kawase, Saito et al., Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells, Proc. Natl. Acad. Sci, doi:10.1073/pnas.2002589117
Matsuyama, None
Matsuyama, None
Matsuyama, None
Muramoto, Takahashi, Halfmann, Gotoh, Noda et al., Replicative capacity of SARS-CoV-2 omicron variants BA.5 and BQ.1.1 at elevated temperatures, Lancet. Microbe, doi:10.1016/S2666-5247(23)00100-3
Qu, Faraone, Evans, Zheng, Carlin et al., Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants, Cell Rep, doi:10.1016/j.celrep.2023.112443
Takashita, Kinoshita, Yamayoshi, Sakai-Tagawa, Fujisaki et al., Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant, N. Engl. J. Med, doi:10.1056/NEJMc2119407
Takashita, Morita, Ogawa, Nakamura, Fujisaki et al., Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil, Front. Microbiol, doi:10.3389/fmicb.2018.03026
Takashita, Yamayoshi, Simon, Van Bakel, Sordillo et al., Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, BA.5 Subvariants. N. Engl. J. Med, doi:10.1056/NEJMc2207519
Uraki, Ito, Kiso, Yamayoshi, Iwatsuki-Horimoto et al., Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate, Lancet Infect. Dis, doi:10.1016/S1473-3099(23)00070-1
Uraki, Ito, Kiso, Yamayoshi, Iwatsuki-Horimoto et al., Efficacy of antivirals and mRNA vaccination against an XBF clinical isolate, Lancet Reg. Health. West. Pac, doi:10.1016/j.lanwpc.2023.100777
Uriu, Ito, Zahradnik, Fujita, Kosugi et al., Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant, Lancet Infect. Dis, doi:10.1016/S1473-3099(23)00051-8
Vanderheiden, Edara, Floyd, Kauffman, Mantus et al., Development of a Rapid Focus Reduction Neutralization Test Assay for Measuring SARS-CoV-2 Neutralizing Antibodies, Curr. Protoc. Immunol, doi:10.1002/cpim.116
Yue, Song, Wang, Jian, Chen et al., ACE2 binding and antibody evasion in enhanced transmissibility of XBB.1.5, Lancet Infect. Dis, doi:10.1016/S1473-3099(23)00010-5
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