Temporal changes in SARS-CoV-2 clearance kinetics and the optimal design of antiviral pharmacodynamic studies: an individual patient data meta-analysis of a randomised, controlled, adaptive platform study (PLATCOV)

The Lancet Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(9), P. 953 - 963

Published: April 24, 2024

Effective antiviral drugs prevent hospitalisation and death from COVID-19. Antiviral efficacy can be efficiently assessed in vivo by measuring rates of SARS-CoV-2 clearance estimated serial viral genome densities quantitated nasopharyngeal or oropharyngeal swab eluates. We conducted an individual patient data meta-analysis unblinded arms the PLATCOV platform trial to characterise changes kinetics infer optimal design interpretation pharmacometric evaluations.

Language: Английский

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Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV)

EClinicalMedicine, Journal Year: 2025, Volume and Issue: 80, P. 103036 - 103036

Published: Jan. 18, 2025

Language: Английский

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Evaluation of the effects of pre-exposure treatment with hydroxychloroquine on the risk of COVID-19 infection and on the efficacy of anti-COVID-19 vaccination during lupus or Gougerot-Sjögren’s disease: Prepcov multicentre trial

Lupus Science & Medicine, Journal Year: 2025, Volume and Issue: 12(1), P. e001435 - e001435

Published: March 1, 2025

Some patients with SLE or Gougerot-Sjögren's disease (GSD) receive long-term treatment hydroxychloroquine (HCQ), sometimes combined immunosuppressive therapy (IS). This study sought to assess whether HCQ that had been initiated long before the COVID-19 pandemic a protective adverse effect on risk, severity of infection immunity protection. prospective multicentre included 547 SLE, GSD, autoimmune hepatitis, primary biliary cholangitis cured viral hepatitis C divided into four groups according (+/-) and IS intake prior pandemic: HCQ+IS+ (n=112), HCQ+IS- (n=121), HCQ-IS+ (n=115) HCQ-IS- (n=199). When vaccination was possible, were vaccinated as recommended. Vaccination efficacy prospectively assessed basis postvaccination antibody titre. Compared patients, decreased risk (p<0.001). contracting Patients in group lower symptomatic severe than did (p=0.001 p<0.001, respectively). Only who two more exposures (to vaccine and/or infection) an increased likelihood after last dose not protect against infection. Moreover, non-exposure (combined IS) associated developing do influence response. doses result good NCT04481633.

Language: Английский

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Efficacy of combined folic acid, cyanocobalamin, and pyridoxine hydrochloride therapy in the comprehensive management of pneumonia associated with COVID-19

Bulletin physiology and pathology of respiration, Journal Year: 2025, Volume and Issue: 95, P. 40 - 57

Published: March 19, 2025

Aim. To evaluate the clinical efficacy and effect on serum homocysteine levels of combined folic acid, cyanocobalamin, pyridoxine hydrochloride therapy in comprehensive treatment pneumonia hospitalized patients with COVID-19. Materials methods. An open-label, prospective, comparative study included 75 moderate to severe associated COVID-19 confirmed by detection SARS-CoV-2 RNA respiratory tract. The main group consisted 28 who received micronutrient 30 mg/day acid plus cyanocobalamin addition standard treatment. comparison comprised 47 did not receive additional therapy. Charlson Comorbidity Index was 1.14 ± 0.93 0.47 0.69 (p ≤ 0.001). Disease severity before after assessed using NEWS, qSOFA, 4C Mortality, WHO Ordinal scales. Chest computed tomography (CT) performed. Laboratory parameters complete blood count, C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), homocysteine, triglycerides, low- high-density lipoprotein cholesterol (LDL, HDL). Results. In group, elimination period achieved 7.2 3.4 days versus 15.6 6.3 < After therapy, disease decreased according qSOFA Mortality showed a reduction total volume from 32.0 (19.8–73.0)% 26.5 (11.8–50.8)% = 0.035) parenchymal consolidation 9.0 (0.0–37.3)% 2.0 (0.0–17.0)% 0.027). there no decrease lung involvement, area increased. These CT findings were reductions CRP, LDL levels. Multiple linear regression models demonstrated that administration combination shortened tract (regression coefficient β –8.648 1.781; p 0.001) contributed (β –13.492 4.834; 0.011), also linked baseline LDH 0.0235 0.00857; 0.008) patient age 0.167 0.0608; 0.008). Conclusion. use management COVID-19-associated is shorter upper tract, more pronounced severity, extent consolidation. effects coincide lower

Language: Английский

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Influence of viral load on severity and mortality in COVID-19

Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 8

Published: April 7, 2025

The relationship between the initial viral load in respiratory specimens and severity of COVID-19 is not fully elucidated. Studies on impact patient age SARS-CoV-2 have yielded divergent results. We aimed to investigate COVID-19. mined a dataset 259,511 SARS-CoV-2-infected individuals 0-105 years old which virus RNA was quantified nasopharyngeal swabs (viral load) using PCR at first healthcare contact. Subjects were stratified by vaccination pandemic variant wave. Severity assessed hospital admission or death. Multivariable models analysed influence load, severity. Among non-vaccinated (n = 140,905), loads lowest children 1-9 highest infants (<1 year old) subjects 70-105 years, with similar results across waves vaccinated individuals. High (≥9log10viral copies/swab) associated elevated risk groups. In adults (20-69 old), mortality largely confined those high (odds ratio [OR] 5.3, 95%CI 3.6-7.3). ≥ 70 old, deaths occurred but more frequent (OR 2.2, 95% CI 1.9-2.6). hospitalisation also 118,606). This study identified sampling as predictor severe infection and/or death groups patients.

Language: Английский

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Ensitrelvir in Hospitalized Patients with SARS-CoV-2 During the Omicron Epidemic: A Single-Center Observational Study

Infectious Diseases and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Ensitrelvir, a novel oral 3C-like protease inhibitor targeting severe acute respiratory syndrome coronavirus 2, has been available in Japan since November 2022. This report presents patient characteristics and treatment outcomes of patients receiving ensitrelvir with comparison to remdesivir during the same period. A single-center chart review was conducted at Rinku General Medical Center, one four designated medical institutions for specific infectious diseases Japan. All hospitalized disease 2019 (COVID-19) between 2022 August 2024 who received either or accordance on-label dosage administration were included review. Information on background, severity COVID-19, mortality after initiation treatment, post-treatment virologic outcomes, clinical collected from electronic records. Day 28 mortality, time discharge, viral clearance calculated without adjustment using inverse probability weighting (IPTW) method. During study period, 156 337 as initial treatments, average ages 76.8 75.7 years, respectively. For baseline severity, 24.4% recipients 50.7% had moderate COVID-19. All-cause day 1.9% 5.9% hazard ratio 0.32 (95% CI 0.09-1.07). IPTW 3.8% 5.7%, respectively, 0.66 0.19-2.29). Time discharge shorter ensitrelvir, similar groups. Ensitrelvir demonstrated low even among advanced age, immunosuppressive conditions, These findings may suggest potential role registered UMIN Clinical Trials Registry (study ID UMIN000056047).

Language: Английский

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Temporal changes in SARS-CoV-2 clearance kinetics and the optimal design of antiviral pharmacodynamic studies: an individual patient data meta-analysis of a randomised, controlled, adaptive platform study (PLATCOV)

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 17, 2024

Abstract Background Effective antiviral drugs prevent hospitalisation and death in COVID-19. Antiviral efficacy can be assessed efficiently in-vivo by measuring rates of SARS-CoV-2 clearance estimated from serial viral genome densities quantitated nasopharyngeal or oropharyngeal swab eluates. We carried out an individual patient data meta-analysis unblinded arms the PLATCOV platform trial to characterise changes kinetics infer optimal design interpretation pharmacometric evaluations. is registered at ClinicalTrials.gov, NCT05041907 . Methods Serial density were analysed symptomatic, previously healthy, adult patients (within 4 days symptom onset) enrolled a large multicentre randomised adaptive pharmacodynamic (PLATCOV) comparing interventions for SARS-CoV-2. Viral over one week under hierarchical Bayesian linear model with B-splines used temporal enrolment rates. Bootstrap re-sampling was assess duration follow-up assessment, where defined as maximising expected z-score when effective antivirals no treatment. Results Between 29 September 2021 20 October 2023, 1262 randomised. Unblinded available 800 (16,818 qPCR measurements) whom 63% (504/800) female. 98% (783/800) had received least vaccine dose 88% (703/800) fully vaccinated. biphasic (bi-exponential). The first phase ( α ) accelerated interventions. For all studied, maximum discriminative power (maximum z-score) obtained evaluating 5 after enrolment. Over two-year period median half-lives 7 have shortened 16.6 hours (interquartile range [IQR]: 15.3 18.2) 9.2 (IQR: 8.0 10.6) 2023 receiving drugs, equivalent relative reduction 44% [95% credible interval (CrI): 19 64%]. A parallel trend observed treated patients. In 158 ritonavir-boosted nirmatrelvir (3,380 measurements), half-life declined 6.4 5.7 7.3) June 2022 4.8 4.2 5.5) 26% [95%CrI: –4 42%]. Conclusions symptomatic vaccinated individuals substantially past two years. COVID-19 now using qPCRs duplicate eluates taken daily drug administration. Funding Wellcome Trust Grant ref: 223195/Z/21/Z through Therapeutics Accelerator.

Language: Английский

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A systematic review of nirmatrelvir/ritonavir and molnupiravir for the treatment of COVID-19

Open Forum Infectious Diseases, Journal Year: 2024, Volume and Issue: 11(9)

Published: Aug. 30, 2024

To address the need for treatments patients with coronavirus disease 2019 (COVID-19), 3 therapies have been given either full approval or Emergency Use Authorization. These were based on randomized data showing a reduction in deaths/hospitalization, but since then, circulating viral strains and population immunity changed.

Language: Английский

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Evidence that remdesivir treatment reduces viral titers in patients with COVID-19

Antimicrobial Agents and Chemotherapy, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Language: Английский

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Molnupiravir clinical trial simulation suggests that polymerase chain reaction underestimates antiviral potency against SARS-CoV-2

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication. reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral levels three separate trials. We used mathematical models to simulate these trials closely recapitulated their virologic outcomes. Model simulations suggest lower potency against pre-omicron variants than omicron. estimate vitro assays underestimate vivo 7-8 fold omicron variants. Our model suggests because polymerase chain reaction detects molnupiravir mutated variants, the true reduction non-mutated underestimated ∼0.5 log 10 two conducted while dominated. Viral area under curve estimates differ significantly between RNA. results reinforce past work suggesting are unreliable for estimating drug endpoints respiratory virus clinical should be catered mechanism of action.

Language: Английский

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