Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019

Martinot, M.; Jary, Aude; Fafi‐Kremer, Samira; Leducq, Valentin; Delagrèverie, Héloïse; Garnier, Marc; Pacanowski, Jérôme; Mékinian, A.; Tiberghien, Pierre; Cálvez, Vincent; Humbrecht, Catherine; Marcelin, Anne‐Geneviève; Lacombe, Karine

doi:10.1093/cid/ciaa1474

Cited by 107 publications

(100 citation statements)

References 9 publications

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“…Patient sequences all belonged to clade 20B, corresponding to lineage B.1.1. According to literature data, [18][19][20][21][22][23][24][25] no mutations related to possible resistance to remdesivir were observed, also as minority variant when considering a cut off of 1%.…”

Section: Case Historymentioning

confidence: 97%

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Sepulcri

Dentone

Mikulska

et al. 2021

Preprint

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BackgroundImmunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a lymphoma patient.MethodsNasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients’ adaptive and innate immunity to characterize T and NK cell subsets.FindingsSARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive with cycle threshold mean values of 22 ± 1·3 for over 8 months. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course.InterpretationIn our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia.FundingNone.

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Section: Case Historymentioning

confidence: 97%

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Sepulcri

Dentone

Mikulska

et al. 2021

Preprint

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“…However, with the increased mutation rate of SARS-CoV-2, the susceptibility of the virus to remdesivir drugs has been challenged. In addition, there are certain cases across 30 different countries associated with the failure of this antiviral agent (Martinot et al 2020). Therefore, until the availability of specific treatment against COVID-19, prevention is the only measure.…”

Section: Resultsmentioning

confidence: 99%

Probiotics in the prophylaxis of COVID-19: something is better than nothing

et al. 2020

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The new viral pandemic of COVID-19 is caused by a novel coronavirus (SARS-CoV-2) that has brought the world at another unprecedented crisis in terms of health and economy. The lack of specific therapeutics necessitates other strategies to prevent the spread of infection caused by this previously unknown viral etiological agent. Recent pieces of evidence have shown an association between COVID-19 disease and intestinal dysbiosis. Probiotics comprise living microbes that upon oral administration benefit human health by reshaping the composition of gut microbiota. The close kinship of the gastrointestinal and respiratory tract suggests why the dysfunction of one may incite illness in others. The emerging studies suggest the capability of probiotics to regulate immune responses in the respiratory system. The efficacy of probiotics has been studied previously on several respiratory tract viral infections. Therefore, the purpose of this review is to comprehend existing information on the gut mediated-pulmonary immunity conferred by probiotic bacteria, in the course of respiratory virus infections and administration as a prophylactic measure in COVID-19 pandemic in managing intestinal dysbiosis as well.

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“…Previous studies have shown that naturally emerging mutations in RdRp may lead to drug resistance or reduce treatment efficacy due to weakened drug-RdRp binding, particularly near the mutation sites [35] , [107] , [108] , [109] . In a recently published case report, a point mutation in RdRp (D484Y) was associated with the failure of remdesivir treatment in a 76-year-old female COVID-19 patient with post-rituximab B-cell immunodeficiency [110] . It is suspected that resistant mutations emerge under remdesivir treatment pressure which leads to treatment failure [110] .…”

Section: The Impact Of Mutations On Drug Safety and Efficacymentioning

confidence: 97%

“…In a recently published case report, a point mutation in RdRp (D484Y) was associated with the failure of remdesivir treatment in a 76-year-old female COVID-19 patient with post-rituximab B-cell immunodeficiency [110] . It is suspected that resistant mutations emerge under remdesivir treatment pressure which leads to treatment failure [110] . Therefore, it is crucial to identify resistant mutations and evaluate their impact on the conformation and activity of RdRp and its susceptibility to antiviral treatment.…”

Section: The Impact Of Mutations On Drug Safety and Efficacymentioning

confidence: 97%

Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics

Zeng

Tong

et al. 2021

Biochemical Pharmacology

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Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019

Cited by 107 publications

References 9 publications

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Probiotics in the prophylaxis of COVID-19: something is better than nothing

Biochemical features and mutations of key proteins in SARS-CoV-2 and their impacts on RNA therapeutics

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