Evolution of viral variants in remdesivir‐treated and untreated SARS‐CoV‐2‐infected pediatrics patients

Boshier, Florencia A.T.; Pang, Juanita; Penner, Justin; Parker, Matthew; Alders, Nele; Bamford, Alasdair; Grandjean, Louis; Grünewald, Stéphanie; Hatcher, James; Best, Timothy; Dalton, Caroline; Bynoe, Patricia Dyal; Frauenfelder, Claire; Köeglmeier, Jutta; P, Myerson; Roy, Sunando; Williams, Rachel; Silva, Thushan I.; Goldstein, Richard A.; Breuer, Judith

doi:10.1002/jmv.27285

Cited by 15 publications

(9 citation statements)

References 55 publications

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“…Accordingly, remdesivir has been postulated to increase the rate of immune escape mutations ( Colson et al, 2021 ). Furthermore, remdesivir has poor penetration in lungs ( Wang and Chen, 2020 ), and could facilitate emergence of compartmentalized resistance ( Boshier et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: A GISAID exploratory analysis

Focosi¹,

Maggi

McConnell³

et al. 2022

Antiviral Research

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Massive usage of antiviral compounds during a pandemic creates an ideal ground for emergence of resistant strains. Remdesivir, a broad-spectrum inhibitor of the viral RNA-dependent RNA polymerase (RdRp), was extensively prescribed under emergency use authorization during the first 18 months of the COVID19 pandemic, before randomized controlled trials showed poor efficacy in hospitalized patients. RdRp mutations conferring resistance to remdesivir are well known from in vitro studies, and the huge SARS-CoV-2 sequencing effort during the ongoing COVID19 pandemic represents an unprecedented opportunity to assess emergence and fitness of antiviral resistance in vivo . We mined the GISAID database to extrapolate the frequency of remdesivir escape mutations. Our analysis reveals very low levels of remdesivir resistance worldwide despite massive usage.

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Section: Introductionmentioning

confidence: 99%

Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: A GISAID exploratory analysis

Focosi¹,

Maggi

McConnell³

et al. 2022

Antiviral Research

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show abstract

“…The ongoing coronavirus disease 2019 (COVID-19) [ 1 ] pandemic [ 2 ] is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a sarbecovirus of the pisoniviricete order Nidovirales [ 3 , 4 ]. Since the beginning of the pandemic in late 2019 [ 5 , 6 ], SARS-CoV-2 has evolved into numerous distinct lineages, including variants of concern with varying levels of transmission, immune evasion, and disease severity [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…When detecting the SARS-CoV-2 gN target, assays cannot distinguish an actively replicating virus from the input viral load; however, RT-qPCR detection of subgenomic E ( sgE ) differentiates an actively replicating virus from the viral RNA load [ 32 ]. Furthermore, fewer sgRNAs were found in COVID-19 patients and SARS-CoV-2-exposed animals after treatment with antivirals, suggesting that sgRNA concentration may help track the success of the therapeutic intervention [ 1 , 32 ]. On the contrary, some studies reported high correlation and similar trends between genomic and subgenomic RNA copy numbers longitudinally in post-exposure clinical samples, indicating a limited additional benefit of detecting sgRNA [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Duplex One-Step RT-qPCR Assays for Simultaneous Detection of Genomic and Subgenomic RNAs of SARS-CoV-2 Variants

Bhosle

Tran

Yú

et al. 2022

Viruses

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A hallmark of severe acute respiratory syndrome virus (SARS-CoV-2) replication is the discontinuous transcription of open reading frames (ORFs) encoding structural virus proteins. Real-time reverse transcription PCR (RT-qPCR) assays in previous publications used either single or multiplex assays for SARS-CoV-2 genomic RNA detection and a singleplex approach for subgenomic RNA detection. Although multiplex approaches often target multiple genomic RNA segments, an assay that concurrently detects genomic and subgenomic targets has been lacking. To bridge this gap, we developed two duplex one-step RT-qPCR assays that detect SARS-CoV-2 genomic ORF1a and either subgenomic spike or subgenomic ORF3a RNAs. All primers and probes for our assays were designed to bind to variants of SARS-CoV-2. In this study, our assays successfully detected SARS-CoV-2 Washington strain and delta variant isolates at various time points during the course of live virus infection in vitro. The ability to quantify subgenomic SARS-CoV-2 RNA is important, as it may indicate the presence of active replication, particularly in samples collected longitudinally. Furthermore, specific detection of genomic and subgenomic RNAs simultaneously in a single reaction increases assay efficiency, potentially leading to expedited lucidity about viral replication and pathogenesis of any variant of SARS-CoV-2.

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“…Moreover, Remdesivir efficacy in reducing both SARS-CoV-2 viral RNA and subgenomic RNA has been demonstrated both in vitro and in vivo [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Remdesivir over Two Waves of the SARS-CoV-2 Pandemic

et al. 2021

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The aim of this study is to describe the features, the outcomes, and the clinical issues related to Remdesivir administration of a cohort of 220 patients (pts) with COVID-19 hospitalized throughout the last two pandemic waves in Italy. One hundred and nine pts were enrolled from 1 September 2020, to 28 February 2021 (Group A) and 111 from 1 March to 30 September 2021 (Group B). Notably, no differences were reported between the two groups neither in the timing of hospitalization. nor in the timing of Remdesivir administration from symptoms onset. Remarkably, a higher proportion of pts with severe COVID-19 was observed in Group B (25% vs. 10%, p < 0.001). At univariate and multivariate analysis, rather than the timing of Remdesivir administration, age, presence of coexisting conditions, D-dimers, and O2 flow at admission correlated positively to progression to non-invasive ventilation, especially for patients in Group B. However, the rate of admission in the Intensive Care Unit and/or death was comparable in the two groups (7% vs. 4%). Negligible variations in serum GOT, GPT, GGT, and eGFR levels were detected. A mean reduction in heart rate was noticed within the first three days of antiviral treatment (p < 0.001). Low rate of ICU admission, high rate of clinical recovery, and good drug safety were observed in COVID-19 patients treated with Remdesivir during two diverse pandemic waves.

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Evolution of viral variants in remdesivir‐treated and untreated SARS‐CoV‐2‐infected pediatrics patients

Cited by 15 publications

References 55 publications

Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: A GISAID exploratory analysis

Very low levels of remdesivir resistance in SARS-COV-2 genomes after 18 months of massive usage during the COVID19 pandemic: A GISAID exploratory analysis

Duplex One-Step RT-qPCR Assays for Simultaneous Detection of Genomic and Subgenomic RNAs of SARS-CoV-2 Variants

Efficacy and Safety of Remdesivir over Two Waves of the SARS-CoV-2 Pandemic

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