Evaluation of the Treatment Efficacy and Safety of Remdesivir for COVID-19: a Meta-analysis

Tao, Jun; Aristotelidis, Rebecca; Zanowick-Marr, Alexandra; Chambers, Laura C; McDonald, James; Mylonakis, Eleftherios; Chan, Philip A.

doi:10.1007/s42399-021-01014-y

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…Additionally, a genotyping assay may have utility to distinguish between persistent infection with the same viral strain vs. reinfection due to a new strain in an individual with recurrent positive molecular test results for SARS-CoV-2. Finally, a genotyping assay could be designed to detect select variants in the spike (S), RdRp polymerase, or the nsp5 protease coding regions associated with reduced efficacy to therapeutics including spike-targeting monoclonal antibodies ( Kreuzberger et al., 2021 ), polymerase inhibitors such as remdesivir ( Tao et al., 2021a ) and molnupiravir ( Pourkarim et al., 2022 ), and protease inhibitors such as nirmatrelvir ( Vangeel et al., 2022 ). An RT-PCR genotyping assay may be performed in a high-throughput manner and at a lower cost than WGS.…”

Section: Discussionmentioning

confidence: 99%

Rapid and Accurate Identification of SARS-CoV-2 Variants Using Real Time PCR Assays

Borillo

Kagan

Marlowe

2022

Front. Cell. Infect. Microbiol.

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BackgroundGenomic surveillance efforts for SARS-CoV-2 are needed to understand the epidemiology of the COVID-19 pandemic. Viral variants may impact routine diagnostic testing, increase viral transmissibility, cause differences in disease severity, have decreased susceptibility to therapeutics, and/or confer the ability to evade host immunity. While viral whole-genome sequencing (WGS) has played a leading role in surveillance programs, many laboratories lack the expertise and resources for performing WGS. This study describes the performance of multiplexed real-time reverse transcription-PCR (RT-PCR) assays for identification of SARS-CoV-2 variants.MethodsSARS-CoV-2 specimens were tested for spike-gene variants using a combination of allele-specific primer and allele-specific detection technology (PlexPrime® and PlexZyme®). Targeted detection of spike gene mutations by RT-PCR was compared to variant detection in positive specimens by WGS, including the recently emerged SARS-CoV-2 Omicron variant.ResultsA total of 398 SAR-CoV-2 RT-PCR positive and 39 negative specimens previously tested by WGS were re-tested by RT-PCR genotyping. PCR detection of spike gene mutations N501Y, E484K, and S982A correlated 100% with WGS for the 29 lineages represented, including Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Incorporating the P681R spike gene mutation also allowed screening for the SARS-CoV-2 Delta variant (B.1.617.2 and AY sublineages). Further sampling of 664 specimens that were screened by WGS between June and August 2021 and then re-tested by RT-PCR showed strong agreement for Delta variant positivity: 34.5% for WGS vs 32.9% for RT-PCR in June; 100% vs 97.8% in August. In a blinded panel of 16 Omicron and 16 Delta specimens, results of RT-PCR were 100% concordant with WGS results.ConclusionsThese data demonstrate that multiplexed real-time RT-PCR genotyping has strong agreement with WGS and may provide additional SARS-CoV-2 variant screening capabilities when WGS is unavailable or cost-prohibitive. RT-PCR genotyping assays may also supplement existing sequencing efforts while providing rapid results at or near the time of diagnosis to help guide patient management.

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Section: Discussionmentioning

confidence: 99%

Rapid and Accurate Identification of SARS-CoV-2 Variants Using Real Time PCR Assays

Borillo

Kagan

Marlowe

2022

Front. Cell. Infect. Microbiol.

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“… 19 According to a meta-analysis, a substantial number of patients (20–30%) has been reported to exhibit serious adverse events or Grade 3 or 4 adverse events during the course of the treatment with remdesivir. 22 Another systematic review and meta-analysis indicated that remdesivir showed neither benefit against all-cause mortality nor significant treatment efficacy in COVID-19 patients in comparison to placebo/ no treatment groups. Rather patients treated with remdesivir revealed increased risk of nausea than no treatment/placebo groups.…”

Section: Discussionmentioning

confidence: 99%

Candida Pneumonia with Lung Abscess as a Complication of Severe COVID-19 Pneumonia

Abdelhadi¹,

Kassem²

2021

IMCRJ

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A South Asian male patient in his mid-forties presented with symptoms of severe 2019-nCoV (COVID-19) and recent brain infarction. Subsequently, he was found to have evidence of sepsis, underlying undetected diabetes mellitus (DM) and oral candida mucositis, possibly leading to the rare occurrence of direct spread to the lung, manifesting as a necrotizing candida lung abscess. We describe the diagnosis, clinical course, and management of the unique complication in this case that occurred during his admission, hospitalization, and eventual successful discharge from the hospital. This case highlights the importance of early identification and treatment of suspected COVID-19 infection based on clinical and radiological assessments before the confirmation of COVID-19 by real-time polymerase chain reaction (rtPCR) test result, especially in patients with hyperglycemia. It also indicates the complications that can occur due to COVID-19 such as arteriovenous manifestations and the rare occurrence of pulmonary candida lung abscess. Early detection and prompt management by interdisciplinary teams in the emergency room, followed by close monitoring of complications in the intensive care unit (ICU), can lead to successful outcomes in severe/critical COVID-19 infection.

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“…It is actually a phosphoramidate prodrug having broad-spectrum activity against various viruses, for example, Paramyxoviridae, Filoviridae, Pneumoviridae, and Orthocoronavirinae, that is, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), as described elsewhere (Sheahan et al, 2017;Martinez, 2020;Gavriatopoulou et al, 2021). Although the FDA has recommended emergency use of RDV in severe COVID-19 patients, however, the safety and efficacy of RDV in COVID-19 patients as evidenced in multiple recent meta-analyses are controversial and inconsistent (Angamo et al, 2021;Elsawah et al, 2021;Tao et al, 2021).…”

Section: Repurposing Drugs For Covid-19: Concept and Mechanism Of Actionmentioning

confidence: 99%

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

et al. 2022

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Many drugs are being administered to tackle coronavirus disease 2019 (COVID-19) pandemic situations without establishing clinical effectiveness or tailoring safety. A repurposing strategy might be more effective and successful if pharmacogenetic interventions are being considered in future clinical studies/trials. Although it is very unlikely that there are almost no pharmacogenetic data for COVID-19 drugs, however, from inferring the pharmacokinetic (PK)/pharmacodynamic(PD) properties and some pharmacogenetic evidence in other diseases/clinical conditions, it is highly likely that pharmacogenetic associations are also feasible in at least some COVID-19 drugs. We strongly mandate to undertake a pharmacogenetic assessment for at least these drug–gene pairs (atazanavir–UGT1A1, ABCB1, SLCO1B1, APOA5; efavirenz–CYP2B6; nevirapine–HLA, CYP2B6, ABCB1; lopinavir–SLCO1B3, ABCC2; ribavirin–SLC28A2; tocilizumab–FCGR3A; ivermectin–ABCB1; oseltamivir–CES1, ABCB1; clopidogrel–CYP2C19, ABCB1, warfarin–CYP2C9, VKORC1; non-steroidal anti-inflammatory drugs (NSAIDs)–CYP2C9) in COVID-19 patients for advancing precision medicine. Molecular docking and computational studies are promising to achieve new therapeutics against SARS-CoV-2 infection. The current situation in the discovery of anti-SARS-CoV-2 agents at four important targets from in silico studies has been described and summarized in this review. Although natural occurring compounds from different herbs against SARS-CoV-2 infection are favorable, however, accurate experimental investigation of these compounds is warranted to provide insightful information. Moreover, clinical considerations of drug–drug interactions (DDIs) and drug–herb interactions (DHIs) of the existing repurposed drugs along with pharmacogenetic (e.g., efavirenz and CYP2B6) and herbogenetic (e.g., andrographolide and CYP2C9) interventions, collectively called multifactorial drug–gene interactions (DGIs), may further accelerate the development of precision COVID-19 therapies in the real-world clinical settings.

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Evaluation of the Treatment Efficacy and Safety of Remdesivir for COVID-19: a Meta-analysis

Cited by 7 publications

References 31 publications

Rapid and Accurate Identification of SARS-CoV-2 Variants Using Real Time PCR Assays

Rapid and Accurate Identification of SARS-CoV-2 Variants Using Real Time PCR Assays

Candida Pneumonia with Lung Abscess as a Complication of Severe COVID-19 Pneumonia

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

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