Reactions Weekly, Год журнала: 2023, Номер 1963(1), С. 454 - 454
Опубликована: Июнь 30, 2023
Язык: Английский
International Journal of COPD, Год журнала: 2024, Номер Volume 19, С. 77 - 86
Опубликована: Янв. 1, 2024
Introduction: Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 hospitalized patients, especially among adult patients who are unvaccinated had chronic respiratory diseases. Methods: A territory-wide retrospective study conducted Hong Kong to compare the efficacy of NMV-r MOL against with asthma, obstructive pulmonary disease, bronchiectasis interstitial lung diseases presenting moderate from 16th February 2022 15th March 2023. Results: total 1354 included, 738 received 616 MOL. more effective reducing 90-day mortality adjusted hazard ratios (aHR) 0.508 (95% confidence interval [CI] = 0.314– 0.822, p 0.006). Patients also significantly shorter length stay (LOS) than those receiving MOL, median LOS 4 (Interquartile range [IQR] 2– 7) 6 (IQR 3– 10) (p-value < 0.001). no statistically significant difference development failure severe two groups. Discussion: adults without hypoxaemia admission. Keywords: COPD, bronchiectasis, molnupiravir, nirmatrelvir-ritonavir,
Язык: Английский
Процитировано
5
The Lancet Regional Health - Europe, Год журнала: 2023, Номер 31, С. 100684 - 100684
Опубликована: Июль 14, 2023
Comparative data on mortality in COVID-19 patients treated with molnupiravir or nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause community-dwelling these drugs during the Omicron era.
Язык: Английский
Процитировано
11
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Март 28, 2025
Patients with acute SARS-CoV-2 and pre-existing oncohematological conditions challenge clinicians due to a heightened risk for severe COVID-19 forced deferral of cancer treatment. Different treatment approaches aim either prevent the progression mild disease ("early therapy") or treat more COVID-19. Currently, there is limited evidence supporting effectiveness tailored approach patients. We present real-world experience from two university hospitals. In this retrospective study we recruited patients hospitalized pneumonia between March 2020 June 2023 hospitals in Latium, Italy. received antiviral monoclonal antibodies (MoAb) alone, dual therapy (antiviral MoAb) triple (two different antivirals MoAb). The aimed evaluate practical management focused on impact related specific therapies, early treatment, tixagevimab-cilgavimab prophylaxis in-hospital mortality viral clearance time. Overall, 101 were recruited, 76 (75.24%) developed pneumonia, 16 (15.84%) died any cause. While most (75,25%) did not receive "early therapy", those who had higher chance survival (p=0.04). Furthermore, subgroup treated demonstrated rate as well (p=0.02). Out resulted lower (all survive group). This group also showed significant reduction time first day evaluated (6 days [IQR 4;9]), compared only remdesivir (17 8;37]) (p=0.03). Our findings demonstrate that significantly reduces mortality, while accelerates These results, line recent studies, underscore critical importance prompt multitargeted pharmacological optimizing outcomes SARS-CoV-2. Future research, involving larger cohorts, should delve deeper into strategies vulnerable population, particular emphasis elderly, continue high rates.
Язык: Английский
Процитировано
0
Global Health, Год журнала: 2025, Номер 2025(1)
Опубликована: Янв. 1, 2025
Background: SARS-CoV-2 is a positive-sense single-stranded RNA virus that has propensity for infecting epithelial cells and the respiratory system. The two important proteins, structural nonstructural make architecture of this virus. Aim: This research aimed at studying significant mutations in spike protein variants concern (VoCs) finding shared among omicron other four (alpha, beta, gamma, delta). purpose study was to draw comparisons between wild type mutant followed by identifying potent inhibitors (ligand) could be used against its latest VoC. Methodology: In research, we had studied 16 major as well (6) present region SARS-CoV-2. Subsequently, determined structure wild-type from Protein Data Bank (PDB) with ID 7R4I. Furthermore, variant modeled SWISS-MODEL. ligand dataset also collected literature different databases. Both proteins were docked database Molecular Operating Environment (MOE). docking analysis performed, best molecules, AZ_2 AZ_13, finalized based on their energy values, interactions, scores our proteins. Results: demonstrated score -6.1753 MOE, values -4.3889 -6.1753. It formed key hydrogen bond interactions. AZ_13 showed -5.9, -9.3 forming donor acceptor interactions Asp950 (3.06 Å), Ile312 (3.13 Glu309 (3.27 Å). These suggest strong binding affinity potential efficacy. Thus, work emphasized identification target-based drug variant. Outcomes: Based computational it suggested proposed compound can remedy
Язык: Английский
Процитировано
0
Microorganisms, Год журнала: 2025, Номер 13(5), С. 1076 - 1076
Опубликована: Май 6, 2025
Immunocompromised (IC) patients continue to be at risk of severe COVID-19 despite vaccination and anti-SARS-CoV-2 therapies. The comparative effectiveness antiviral agents (AVAs) monoclonal antibodies (MoAbs) as early treatment SARS-CoV-2 in IC is described this work. This retrospective multicenter cohort study included outpatients diagnosed with between March 2021 2022 the National Institute for Infectious Diseases "Lazzaro Spallanzani" Santa Maria Goretti University Hospital, Italy. Patients received either AVAs or MoAbs based on national guidelines. primary outcome was time negative nasopharyngeal swab (NPS). secondary outcomes were COVID-19-related hospitalization death by day 30. Among 1472 (with a median age 58 years, 45% male), 688 (46%) treated MoAbs, 783 (54%) AVAs. had higher duration NPS (17 vs. 11 days, p < 0.05) sustained positivity 7 (OR: 3.0, 95% CI: 1.72-5.23, 0.01) 30 6.0, 3.7-10.5, than those There no differences mortality. associated more rapid viral clearance suggesting potential advantage reducing infectious patients. Additional studies are necessary further optimize high-risk population.
Язык: Английский
Процитировано
0
Viruses, Год журнала: 2023, Номер 15(11), С. 2180 - 2180
Опубликована: Окт. 30, 2023
Clinical trials demonstrated the role of vaccines and antiviral treatments against SARS-CoV-2 in reducing likelihood disease progression death. However, there are limited data available regarding time to negativity people who received these treatments. Further, several comorbidities risk factors might affect impact To this end, we aimed evaluate disentangle anti-SARS-CoV-2 that underlying clinical associated with a shortened length infection. Hence, recorded timeframe positive nasopharyngeal swab infected while being hospitalized for reasons other than All patients died or were discharged excluded from study. A total 175 included conditions encompass malignancies, immunological disorders, cardiovascular, metabolic, neurodegenerative, chronic kidney disease. Most participants (91.4%) vaccinated before admission hospital, 65.1% treatment within three days after symptom's onset. Unvaccinated had longer median at least two doses vaccine (18 vs. 10 days). Concerning all patients, multivariate analysis highlighted lower probability 14-day conversion antigenic test positivity hematological malignancy, including those exposed therapies. In conclusion, our showed prompt administration accelerates clearance SARS-CoV-2. elderly under study, previous vaccination synergize reduce negativity. This translates into shorter hospitalization transmission through connected healthcare workers hospital ward setting, considerable improvement cost-effective care management.
Язык: Английский
Процитировано
7
Опубликована: Янв. 3, 2024
Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection, however no clinical trial data are available and combined use direct acting antivirals (DAA) monoclonal antibodies (mAb) has been reported only anecdotally. To assess cooperative effects dual drug combinations vitro, we used a VERO E6 cell based vitro system with ancestral B.1 or highly divergent BQ.1.1 virus to test pairwise licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) active metabolite molnupiravir (EIDD-1931) as well combination RDV four mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested susceptible virus). According SynergyFinder 3.0 summary weighted scores, all had an additive effect. Within DAA/DAA combinations, paired scores variants were comparable. In post-hoc analysis weighting synergy by concentrations, several cases synergistic detected at specific both for RDV/mAb combinations. This was supported confirmation experiments showing more than linear shift effective concentration (IC50) increasing concentrations companion drug, although effect prominent but minimal null These results support which should further investigated animal models before introduction into clinic.
Язык: Английский
Процитировано
2
Viruses, Год журнала: 2024, Номер 16(2), С. 168 - 168
Опубликована: Янв. 23, 2024
Combination antiviral therapy may be helpful in the treatment of SARS-CoV-2 infection; however, no clinical trial data are available, and combined use direct-acting antivirals (DAA) monoclonal antibodies (mAb) has been reported only anecdotally. To assess cooperative effects dual drug combinations vitro, we used a VERO E6 cell-based vitro system with ancestral B.1 or highly divergent BQ.1.1 virus to test pairwise licensed DAA, including nirmatrelvir (NRM), remdesivir (RDV) active metabolite molnupiravir (EIDD-1931) as well combination RDV four mAbs (sotrovimab, bebtelovimab, cilgavimab, tixagevimab; tested susceptible virus). According SynergyFinder 3.0 summary weighted scores, all had an additive effect. Within DAA/DAA combinations, paired scores variants were comparable. In post hoc analysis weighting synergy by concentrations, several cases synergistic detected at specific both for RDV/mAb combinations. This was supported confirmation experiments showing more than linear shift drug-effective concentration (IC50) increasing concentrations companion drug, although effect prominent minimal null These results support which should further investigated animal models before introduction into clinic.
Язык: Английский
Процитировано
2
Diabetes Obesity and Metabolism, Год журнала: 2024, Номер 26(10), С. 4653 - 4664
Опубликована: Авг. 7, 2024
Abstract Aims To compare the effectiveness of molnupiravir and nirmatrelvir‐ritonavir for non‐hospitalized hospitalized COVID‐19 patients with type 2 diabetes (T2DM). Materials Methods Territory‐wide electronic health records in Hong Kong were used to perform target trial emulation using a sequential approach. Patients (1) aged ≥18 years, (2) T2DM, (3) infection, (4) who received or within 5 days infection between 16 March 2022 31 December non‐hospital hospital settings included. Molnupiravir initiators matched one‐to‐one propensity‐score matching followed 28 days. Risk outcomes was compared groups by Cox regression adjusted baseline characteristics. Subgroup analyses performed on age (<70 ≥70 years), sex, Charlson comorbidity index (<4, ≥4), number vaccine doses (<2 doses, ≥2 doses). Results Totals 17 974 (8987 each group) 3678 (1839 identified. Non‐hospitalized had lower risk all‐cause mortality (absolute reduction [ARR] at 0.80%, 95% confidence interval [CI] 0.56–1.04; hazard ratio [HR] 0.47, CI 0.30–0.73) hospitalization (ARR 4.01%, 3.19–4.83; HR 0.73, 0.66–0.82) as initiators. Hospitalized reduced 2.94%, 1.65–4.23; 0.56, 0.40–0.80) Consistent findings found across all subgroups. Conclusions The use may be preferred T2DM without contraindication either treatment.
Язык: Английский
Процитировано
2
Antimicrobial Agents and Chemotherapy, Год журнала: 2024, Номер unknown
Опубликована: Дек. 17, 2024
ABSTRACT Novel and repurposed antiviral drugs are available for the treatment of coronavirus disease 2019 (COVID-19). However, combinations may be more potent lead to faster viral clearance, but methods screening against respiratory viruses not well established labor-intensive. Here, we describe a time-efficient (72–96 h) simple in vitro drug-sensitivity assay severe acute syndrome 2 (SARS-CoV-2) using standard 96-well plates. We employ different synergy models (zero interaction potency, highest single agent, Loewe, Bliss) determine efficacy therapies synergistic ancestral emerging clinical SARS-CoV-2 strains. found that monotherapy remdesivir, nirmatrelvir, active metabolite molnupiravir (EIDD-1931) demonstrated baseline EC50s within clinically achievable levels 4.34 mg/L (CI: 3.74–4.94 mg/L), 1.25 1.10–1.45 0.25 0.20–0.30 respectively, strain. their varied newer Omicron variants BA.1.1.15 BA.2, particularly with protease inhibitor nirmatrelvir. also remdesivir nirmatrelvir have consistent, strong effect (Bliss score >10) at relevant drug concentrations (nirmatrelvir 0.25–1 1–4 mg/L) across all strains tested. This method offers practical tool streamlines identification effective combination detection resistance. Our findings support use targeting multiple components enhance COVID-19 efficacy, context
Язык: Английский
Процитировано
1