Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study DOI Creative Commons
Meiping Chen,

Dixuan Jiang,

Jiaxi Rang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 9, 2024

Abstract This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, molnupiravir in adult patients with mild-to-moderate COVID-19. retrospective cohort included COVID-19 (asymptomatic, mild, common types) at First Hospital Changsha (Hunan Province, China) between March November 2022. Eligible were classified into or groups according antiviral agents they received. The outcomes times nucleic acid negative conversion (NANC). 157 treated azvudine (n = 66), nirmatrelvir/ritonavir 25). There no statistically significant differences time from diagnosis NANC among molnupiravir, [median, 9 (95% CI 9–11) vs. 11 10–12) 8–12) days, P 0.15], administration 8–10) 10 9.48–11) 8.708 7.51–11) 0.50], hospital stay 11–13) 13 12–14) 12 10–14) 0.14], even after adjustment for sex, age, type, comorbidities, Ct level, treatment, number symptoms. cumulative rates 15.2%/12.3%/16.0% day 5 ( 0.858), 34.8%/21.5%/32.0% 7 0.226), 66.7%/52.3%/60.0% days 0.246), 86.4%/86.2%/80.0% 14 0.721). No serious adverse events reported. Azvudine may be comparable regarding NANC, stay, AEs.

Language: Английский

Therapeutic strategies for COVID-19: progress and lessons learned DOI Open Access
Guangdi Li, Rolf Hilgenfeld, Richard J. Whitley

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 449 - 475

Published: April 19, 2023

Language: Английский

Citations

420
Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system DOI Creative Commons
Yuyong Zhou, Karen Anbro Gammeltoft, Line A. Ryberg

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(51)

Published: Dec. 21, 2022

The oral protease inhibitor nirmatrelvir is of key importance for prevention severe coronavirus disease 2019 (COVID-19). To facilitate resistance monitoring, we studied acute respiratory syndrome 2 (SARS-CoV-2) escape from in cell culture. Resistant variants harbored combinations substitutions the SARS-CoV-2 main (Mpro). Reverse genetics revealed that E166V and L50F + conferred high infectious culture, replicon, Mpro systems. While L50F, E166V, decreased replication activity, had fitness system. Naturally occurring compensated cost promoted viral escape. Molecular dynamics simulations weakened nirmatrelvir-Mpro binding. Polymerase remdesivir monoclonal antibody bebtelovimab retained activity against nirmatrelvir-resistant variants, combination with enhanced treatment efficacy compared to individual compounds. These findings have implications monitoring ensuring treatments emerging sarbecoviruses.

Language: Английский

Citations

175
Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir DOI
Yinkai Duan, Hao Zhou, Xiang Liu

et al.

Nature, Journal Year: 2023, Volume and Issue: 622(7982), P. 376 - 382

Published: Sept. 11, 2023

Language: Английский

Citations

105
Efficacy and safety of Paxlovid for COVID-19:a meta-analysis DOI
Qian Zheng,

Pengfei Ma,

Mingwei Wang

et al.

Journal of Infection, Journal Year: 2022, Volume and Issue: 86(1), P. 66 - 117

Published: Sept. 30, 2022

Language: Английский

Citations

78
Therapeutics for COVID-19 DOI Creative Commons

Sima S. Toussi,

Jennifer Hammond, Brian S. Gerstenberger

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(5), P. 771 - 786

Published: May 4, 2023

Vaccines and monoclonal antibody treatments to prevent severe coronavirus disease 2019 (COVID-19) illness were available within a year of the pandemic being declared but there remained an urgent need for therapeutics treat patients who not vaccinated, immunocompromised or whose vaccine immunity had waned. Initial results investigational therapies mixed. AT-527, repurposed nucleoside inhibitor hepatitis C virus, enabled viral load reduction in hospitalized cohort did reduce outpatients. The molnupiravir prevented death failed hospitalization. Nirmatrelvir, main protease (Mpro), co-dosed with pharmacokinetic booster ritonavir, reduced hospitalization death. Nirmatrelvir–ritonavir received Emergency Use Authorization United States at end 2021. Immunomodulatory drugs such as baricitinib, tocilizumab corticosteroid, which target host-driven COVID-19 symptoms, are also use. We highlight development challenges that remain anticoronavirals. Therapeutics their during reviewed, including future prospects

Language: Английский

Citations

73
Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection DOI

Rinki Deo,

Manish C. Choudhary, Carlee Moser

et al.

Annals of Internal Medicine, Journal Year: 2023, Volume and Issue: 176(3), P. 348 - 354

Published: Feb. 20, 2023

Although symptom and viral rebound have been reported after nirmatrelvir-ritonavir treatment, the trajectories of symptoms load during natural course COVID-19 not well described.To characterize in untreated outpatients with mild to moderate COVID-19.Retrospective analysis participants a randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04518410).Multicenter trial.563 receiving placebo ACTIV-2/A5401 (Adaptive Platform Treatment Trial for Outpatients With COVID-19) platform trial.Participants recorded severity 13 daily between days 0 28. Nasal swabs were collected SARS-CoV-2 RNA testing on 14, 21, Symptom was defined as 4-point increase total score improvement any time study entry. Viral an at least 0.5 log10 copies/mL from immediately preceding point 3.0 or higher. High-level 5.0 higher.Symptom identified 26% median 11 initial onset. detected 31% high-level 13% participants. Most events transient, because 89% 95% occurred only single before improving. The combination observed 3% participants.A largely unvaccinated population infected pre-Omicron variants evaluated.Symptom relapse absence antiviral treatment is common, but rare.National Institute Allergy Infectious Diseases.

Language: Английский

Citations

58
SARS-CoV-2 Virologic Rebound With Nirmatrelvir–Ritonavir Therapy DOI

Gregory E. Edelstein,

Julie Boucau, Rockib Uddin

et al.

Annals of Internal Medicine, Journal Year: 2023, Volume and Issue: 176(12), P. 1577 - 1585

Published: Nov. 13, 2023

Background: Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir−ritonavir (N-R) and virologic rebound (VR). Objective: To compare the frequency VR in patients without N-R for COVID-19. Design: Observational cohort study. Setting: Multicenter health care system Boston, Massachusetts. Participants: Ambulatory adults use N-R. Intervention: Receipt 5 days versus no therapy. Measurements: The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after prior negative or 2 consecutive loads above 4.0 log10 copies/mL that were also at least 1.0 higher than load below copies/mL. Results: Compared untreated persons (n = 55), those taking 72) older, received more vaccinations, commonly had immunosuppression. Fifteen participants (20.8%) 1 (1.8%) who (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 points]; P 0.001). All result. In multivariable models, only associated (adjusted odds ratio, 10.02 [CI, 1.13 88.74]; 0.038). Virologic common among started therapy within symptom onset (26.3%) (0%) (P 0.030). Among receiving N-R, prolonged shedding replication-competent virus compared did not have (median, 14 vs. 3 days). Eight 16 (50% 25% 75%]) reported rebound; completely asymptomatic. No post-VR resistance mutations detected. Limitations: study design differences treated groups; used surrogate marker risk ongoing transmission. Conclusion: occurred approximately people often rebound, virus. Primary Funding Source: National Institutes Health.

Language: Английский

Citations

48
Viral burden rebound in hospitalised patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study DOI Open Access
Carlos King Ho Wong, Kristy T. K. Lau, Ivan Chi Ho Au

et al.

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(6), P. 683 - 695

Published: Feb. 13, 2023

Language: Английский

Citations

45
Outcomes with and without outpatient SARS-CoV-2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: a retrospective cohort study DOI Creative Commons
Grace Qian, Xiaosong Wang, Naomi J. Patel

et al.

The Lancet Rheumatology, Journal Year: 2023, Volume and Issue: 5(3), P. e139 - e150

Published: Jan. 23, 2023

Language: Английский

Citations

44
Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance DOI Creative Commons
Tin Phan, Ruy M. Ribeiro,

Gregory E. Edelstein

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir-ritonavir, virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used mathematical model to describe longitudinal viral load dynamics 51 20 whom rebounded. Target cell preservation, either by robust innate immune response or initiation N-R near time symptom onset, coupled incomplete clearance, appears be main factor leading rebound. Moreover, occurrence is likely influenced treatment relative progression infection, earlier treatments higher chance A comparison an untreated cohort suggests that early nirmatrelvir-ritonavir may associated delay in onset adaptive response. Nevertheless, our demonstrates extending course 10-day regimen greatly diminish people mild-to-moderate COVID-19 and who at high risk severe disease. Altogether, results suggest some individuals, standard 5-day starting around completely eliminate virus. Thus, after ends, can if effective has fully developed. These findings on role target preservation clearance also offer possible explanation for other SARS-CoV-2. IMPORTANCE Nirmatrelvir-ritonavir initial reduction followed once stopped. show timing influence stops growth preserves cells but lead full adequately developed, remaining Our provide insights into help develop better strategies minimize possibility.

Language: Английский

Citations

2