Remdesivir: Critical Clinical Appraisal for COVID 19 Treatment.
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ABSTRACT:
SUBMITTER: Chatterjee S
PROVIDER: S-EPMC8043717 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background & aimsRemdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19.MethodsWe systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as "Remdesivir" or 'GS-5734″ AND "COVID-19" or "SARS-CoV-2" and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19.ResultsInitial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality.ConclusionsRemdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.
| S-EPMC7214279 | biostudies-literature
Project description:A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome. The objective of this review is to summarize the clinical, biological, and neuroimaging features of published cases describing COVID-19-related parkinsonism and to discuss the possible pathophysiological mechanisms. A comprehensive literature search was performed using NCBI's PubMed database and standardized search terms. Thirteen cases of COVID-19-related parkinsonism were included (7 males; mean age: 51 years ± 14.51, range 31-73). Patients were classified based on the possible mechanisms of post-COVID-19 parkinsonism: extensive inflammation or hypoxic brain injury within the context of encephalopathy (n = 5); unmasking of underlying still non-symptomatic Parkinson's Disease (PD) (n = 5), and structural and functional basal ganglia damage (n = 3). The various clinical scenarios show different outcomes and responses to dopaminergic treatment. Different mechanisms may play a role, including vascular damage, neuroinflammation, SARS-CoV-2 neuroinvasive potential, and the impact of SARS-CoV-2 on α-synuclein. Our results confirm that the appearance of parkinsonism during or immediately after COVID-19 infection represents a very rare event. Future long-term observational studies are needed to evaluate the possible role of SARS-CoV-2 infection as a trigger for the development of PD in the long term.
| S-EPMC9313170 | biostudies-literature
Project description:ObjectivesThis study investigated remdesivir's clinical use to provide direct evidence of effectiveness for a low-middle income Asian setting.DesignA one-to-one propensity score matching retrospective cohort study.SettingA tertiary hospital with COVID-19 treatment facilities in Vietnam.ParticipantsA total of 310 patients in standard of care (SoC) group were matched with 310 patients in SoC+remdesivir (SoC+R) group.Primary and secondary outcome measuresThe primary outcome was time to critical progression, defined as all-cause mortality or critical illness. The secondary outcomes were length of oxygen therapy/ventilation and need for invasive mechanical ventilation. Outcome reports were presented as HR, OR or effect difference with 95% CI.ResultsPatients receiving remdesivir had a lower risk for mortality or critical illness (HR=0.68, 95% CI 0.47 to 0.96, p=0.030). Remdesivir was not associated with a shorter length of oxygen therapy/ventilation (effect difference -0.17 days, 95% CI -1.29 to 0.96, p=0.774). The need for invasive mechanical ventilation was lower in SoC+R group (OR=0.57, 95% CI 0.38 to 0.86, p=0.007).ConclusionsThis study's results showing remdesivir's benefits in non-critical patients with COVID-19 may be extrapolated to other similar low-middle income countries, allowing more regimens for limited resource areas and reducing poor outcomes and equity gap worldwide.
| S-EPMC10276957 | biostudies-literature
Project description: Not available
| S-EPMC8406992 | biostudies-literature
Project description: Not available
| S-EPMC7837362 | biostudies-literature
Project description:Compared with other deadly diseases, the coronavirus disease 2019 (COVID-19) is highly infectious with a relatively low mortality rate. Although critical cases account for only 5% of cases, the mortality rate for the same is nearly 50%. Therefore, the key to the COVID-19 treatment is to effectively treat severe patients and reduce the transition from severe to critical cases. A retrospective study was carried out to evaluate outcomes of treatment in patients with severe and critical COVID-19 admitted to a COVID-19 special hospital in Wuhan, China. A total of 75 severe and critical COVID-19 patients were admitted and treated with immunomodulation as the main strategy combined with anti-inflammatory therapy and appropriate anticoagulation. Leukocyte levels in patients with 7-14 days of onset to diagnosis were significantly lower than in those with >14 days. Higher levels of globulin and D-dimer and lower lymphocyte levels were found in the older age group (>65 years) than in the middle-aged group (50-64 years). Patients with comorbidity had higher levels of inflammatory indicators. After treatment, 65 (86.67%) patients were cured, 7 (9.33%) had improved, and 3 (4.00%) had died. Median hospitalization duration was 23 days. Fatal cases showed continuously increased levels of globulin, dehydrogenase (LDH), hypersensitive C-reactive protein (hs-CRP), D-dimer, and cytokines during treatment. Time from onset to diagnosis, age, and comorbidity are important influencing factors on treatment effects. The occurrence of immunosuppression, "cytokine storm," and thrombosis may be an important cause of death in severely infected cases. In conclusion, high cure rate and low mortality suggested that immunomodulation combined with anti-inflammatory therapy and appropriate anticoagulant therapy is a good strategy for treatment of patients with severe and critical COVID-19.
| S-EPMC8483935 | biostudies-literature
Project description: Not available
| S-BSST416 | biostudies-other
Project description:The emergence of the novel beta coronavirus SARS-CoV-2 and the ensuing COVID-19 pandemic has generated a rapidly evolving research landscape in the search for new therapeutic agents. The intravenous antiviral drug remdesivir has in vitro activity against SARS-CoV-2 and now studies have reported its clinical efficacy, demonstrating shorter time to recovery in hospitalised patients with severe COVID-19. Adverse event rates were low and remdesivir has now received conditional marketing authorisation from the European Medicines Agency. An interim clinical commissioning policy is in place in the UK. These studies make remdesivir the first antiviral drug able to alter the natural history of severe COVID-19, and a benchmark for the comparison of new therapies in the future. Ongoing studies are investigating its use in early mild/moderate COVID-19, alternative formulations, and the combination of remdesivir with immunomodulatory agents.
| S-EPMC7687338 | biostudies-literature
Project description:BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.ResultsA total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).ConclusionsOur data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
| S-EPMC7262788 | biostudies-literature
Project description:Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.
| S-EPMC7431338 | biostudies-literature