Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

Antiviral Research, Journal Year: 2023, Volume and Issue: 214, P. 105609 - 105609

Published: April 20, 2023

Language: Английский

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HIV and COVID-19 Co-Infection: Epidemiology, Clinical Characteristics, and Treatment

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 577 - 577

Published: Feb. 20, 2023

The COVID-19 pandemic has been a global medical emergency with significant socio-economic impact. People HIV (PWH), due to the underlying immunosuppression and particularities of stigma, are considered vulnerable population at high risk. In this review, we report what is currently known in available literature regards clinical implications overlap two epidemics. PWH share same risk factors for severe as general (age, comorbidities), but virological immunological status also plays an important role. Clinical presentation does not differ significantly, there some opportunistic infections that can mimic or co-exist COVID-19. should be prime candidates preventative treatments when they available, setting resistant strains, might easy. When considering small-molecule medications, physicians need always remember address potential interactions ART, immunosuppressants, aware risks infections. shares similarities how public perceives patients—with fear unknown prejudice. There opportunities treatment hidden research leaps gained both monoclonal antibody vaccine development.

Language: Английский

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Molnupiravir When Used Alone Seems to Be Safe and Effective as Outpatient COVID-19 Therapy for Hemodialyzed Patients and Kidney Transplant Recipients

Viruses, Journal Year: 2022, Volume and Issue: 14(10), P. 2224 - 2224

Published: Oct. 9, 2022

Background: Molnupiravir demonstrated an in vitro antiviral activity against positive-sense RNA viruses, including SARS-CoV-2. The study aimed to present the results of outpatient molnupiravir use kidney transplant recipients and hemodialysis patients during first months 2022 Poland. Methods: retrospective observational cohort at one center included 36 diagnosed with COVID-19 automated nucleic acid amplification test on nasopharyngeal swab specimens. All received for home-based therapy a dose 800 mg every 12 h orally 5 days. Both (n = 16) 20) presented lot comorbidities Charlson comorbidity index 4.1 5.1, respectively. Results: Patients fever, cough, weakness followed by muscle joint pain. Five experienced acute injury rise serum creatinine level from 0.4 1.9 mg/dL. No serious side effects or interactions immunosuppressive medications were observed. Symptoms improved rapidly resolved within 24–48 starting treatment. Conclusion: suggests safety efficacy alone early after onset SARS-CoV-2 infection, but further investigations should be performed confirm our preliminary results. To best authors’ knowledge, it is published report end-stage disease (ESKD) third concerning recipients.

Language: Английский

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Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study

Infectious Diseases and Therapy, Journal Year: 2023, Volume and Issue: 12(4), P. 1189 - 1203

Published: April 1, 2023

In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% day 28 in high-risk, non-hospitalized patients. Here we report results assessment heterogeneity effect (HTE) outpatient remdesivir, focusing on time from symptom onset and number baseline factors (RFs).PINETREE was a double-blind, placebo-controlled trial patients with COVID-19 who were randomized within 7 days had ≥ 1 RF for progression (age 60 years, obesity [body mass index 30], certain coexisting medical conditions). Patients received intravenously (200 mg 100 2 3) placebo.In this subgroup analysis, HTE at initiation RFs not detected. Treatment COVID-19-related independent stratification to randomization. Of enrolled ≤ 5 onset, 1/201 (0.5%) receiving 9/194 (4.6%) hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). those > 1/78 (1.3%) 6/89 (6.7%) (HR 0.19; CI 0.02-1.61). Remdesivir also effective reducing when stratified severe disease. RFs, 0/159 (0.0%) 4/164 (2.4%) hospitalized; 3 2/120 (1.7%) 11/119 (9.2%) 0.16; 0.04-0.73).In setting, benefit initiated symptoms appeared be consistent across RFs. Therefore, it may reasonable broadly treat regardless comorbidities.ClinicalTrials.gov NCT04501952.

Language: Английский

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Real world effectiveness of tixagevimab/cilgavimab (Evusheld) in the Omicron era

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(4), P. e0275356 - e0275356

Published: April 27, 2023

Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence Omicron variant. The effectiveness T/C has not been well described in era. We examined incidence symptomatic illness and hospitalizations among recipients when accounted virtually all local cases.Through retrospective electronic medical record chart review, we identified patients who between January 1 -July 31, 2022 within our quaternary referral health system. determined infections due or presumed be caused by early variants before after receiving (pre-T/C post-T/C). Chi square Mann-Whitney Wilcoxon two-sample tests were used examine differences characteristics those got prophylaxis, rate ratios (RR) 95% confidence intervals (CI) calculated assess hospitalization rates two groups.Of 1295 recipients, 105 (8.1%) developed infection T/C, 102 (7.9%) disease it. Of pre-T/C, 26 (24.8%) hospitalized, compared six (5.9%) diagnosed post-T/C (RR = 0.24; CI 0.10-0.55; p 0.0002). Seven (6.7%) infected but none required ICU care. No COVID-related deaths occurred either group. majority cases pre-T/C treatment during BA.1 surge, while BA.5 was predominant. In both groups, having at least one dose vaccine strongly protected against group RR 0.31, 0.17-0.57, 0.02; 0.15; 0.03-0.94; 0.04).We prophylaxis. Among institution, occurring one-fourth as likely require T/C. However, presence changing coverage, multiple therapies, variants, era remains difficult assess.

Language: Английский

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Impact of differences between interim and post-interim analysis populations on outcomes of a group sequential trial: Example of the MOVe-OUT study

Clinical Trials, Journal Year: 2025, Volume and Issue: unknown

Published: March 2, 2025

Pre-specified interim analyses allow for more timely evaluation of efficacy or futility, potentially accelerating decision-making on an investigational intervention. In such analysis, the randomized, double-blind MOVe-OUT trial demonstrated superiority molnupiravir over placebo outpatient treatment COVID-19 in high-risk patients. full analysis population, point estimate difference primary endpoint was notably lower than at analysis. We conducted a comprehensive assessment to investigate this unexpected effect size, with goal informing future clinical research evaluating treatments rapidly evolving infectious diseases. The modified intention-to-treat population divided into cohort (i.e. all participants included analysis; prospectively defined) and post-interim remaining participants; retrospectively defined). Baseline characteristics (including many well-established prognostic factors disease progression), outcomes, virologic outcomes were evaluated. impact changes baseline time explored using logistic regression modeling simulations. well-balanced between arms overall. However, between- within-arm differences known (e.g. comorbidities, SARS-CoV-2 viral load, anti-SARS-CoV-2 antibody status) observed cohorts. For individual factors, these generally minor otherwise not notable; as progressed, however, shifts combination increasingly favored arm across most evaluated cohort. Model-based simulations confirmed that reduction size could be accounted by longitudinal trends toward lower-risk study among participants. Infectivity load data molnupiravir's antiviral activity consistent both cohorts, which heavily dominated different clades (reflecting rapid evolution). cumulative randomly occurring within time, rather reduced against variants, likely impacted outcomes. Our results have broader implications group sequential trials seeking evaluate emerging pathogens. During dynamic epidemic pandemic conditions, adaptive should designed interpreted especially carefully, considering they will enroll large overrun even small multiple variables can disproportionately prespecified timepoints. Shifts may introduce additional variability difficult disentangle from temporal epidemiology evolutionary causative pathogen) management.(ClinicalTrials.gov: NCT04575597.).

Language: Английский

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The preclinical discovery and development of molnupiravir for the treatment of SARS-CoV-2 (COVID-19)

Expert Opinion on Drug Discovery, Journal Year: 2022, Volume and Issue: 17(12), P. 1299 - 1311

Published: Dec. 2, 2022

Introduction Molnupiravir (MOV) is a broad-spectrum oral antiviral agent approved for the treatment of COVID-19. The results from in vitro and vivo studies suggested MOV activity against many RNA viruses such as influenza virus some alphaviruses agents epidemic encephalitis. prodrug metabolized into ribonucleoside analog β-D-N4-hydroxycytidine. It incorporated viral chain causing mutations impairing coding virus, thereby inhibiting replication.Areas covered This review analyzes that have highlighted efficacy main pre-authorization randomized controlled trials evaluating its safety, tolerability, pharmacokinetics, well SARS-COV-2 infection.Expert opinion an with excellent tolerability profile few drug–drug interactions. Treatment mild-to-moderate COVID-19 can benefit administration precocious phases disease, prior to trigger aberrant immune response responsible parenchymal damage pulmonary extrapulmonary tissues. However, suspected mutagenic effect be factor limiting use at least selected populations on teratogen effects should planned before it authorized pediatric population or pregnant women.

Language: Английский

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An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: 6(9), P. 1248 - 1265

Published: Aug. 16, 2023

The appearance of several coronavirus pandemics/epidemics during the last two decades (SARS-CoV-1 in 2002, MERS-CoV 2012, and SARS-CoV-2 2019) indicates that humanity will face increasing challenges from coronaviruses future. emergence new strains with similar transmission characteristics as mortality rates to SARS-CoV-1 (∼10% mortality) or (∼35% future is a terrifying possibility. Therefore, getting enough preparations such risks an inevitable necessity. present study aims review drug achievements fight against combined perspective derived pharmacology, pharmacotherapy, medicinal chemistry insights. Appreciating all efforts made past few years, there strong evidence desired results have not yet been achieved research this area should still be pursued seriously. By expressing some pessimistic possibilities concluding discovery pharmacotherapy COVID-19 successful so far, short essay tries draw attention responsible authorities more prepared epidemics/pandemics.

Language: Английский

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Use of Monoclonal Antibodies in Immunocompromised Patients Hospitalized with Severe COVID-19: A Retrospective Multicenter Cohort

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(3), P. 864 - 864

Published: Jan. 21, 2023

We aim to describe the safety and efficacy of sotrovimab in severe cases COVID-19 immunocompromised hosts.We used a retrospective multicenter cohort including hospitalized patients with treated between October 2021 December 2021.We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) hematological malignancy (37.5%). Seven (21.9%) had respiratory progression: 12.5% died 9.4% required mechanical ventilation. Patients within first 14 days their symptoms lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed sotrovimab.Sotrovimab safe may be effective its use for COVID-19. More studies are needed confirm these preliminary data.

Language: Английский

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Outcomes of SARS‐CoV‐2 infection among lung transplant recipients: A single center retrospective study

Transplant Infectious Disease, Journal Year: 2023, Volume and Issue: 25(1)

Published: Jan. 5, 2023

Lung transplant recipients (LTRs) are at increased risk for coronavirus disease 2019 (COVID-19)-associated complications.We aimed to describe the outcomes of polymerase chain reaction-documented severe acute respiratory syndrome 2 (SARS-CoV-2) infection in LTRs followed our institution from March 2020 July 2022. The primary outcome investigated was hospitalization or death COVID-19-related symptoms within 28 days diagnosis.Overall, 60 cases were included, which 18 (30%) reached outcome. Only one patient (2%) died. Anti-spike monoclonal antibodies (mAbs) administered as early treatment 36 patients (casirivimab/imdevimab = 2, sotrovimab 31, and tixagevimab/cilgavimab 3). Multivariate analysis revealed that age >60 years (p .003; odds ratio [OR] 9.41; confidence interval [CI] 2.52-41.05) associated with a higher outcome, while administration mAbs .030; OR 0.23; CI 0.06-0.87) lower risk. No effect vaccination SARS-CoV-2 variant observed. Forced expiratory volume 1 s forced vital capacity values did not decrease among 37 who had spirometry performed month after COVID-19.We observed relatively low morbidity mortality COVID-19 LTR. mAb better

Language: Английский

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