Persistent infection with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in a patient with untreated human immunodeficiency virus (HIV)

Zhabokritsky, Alice; Mubareka, Samira; Kozak, Robert; Maguire, Finlay; Yip, Lily; Yip, Paul; Powis, Jeff

doi:10.1017/ice.2022.140

Cited by 4 publications

(2 citation statements)

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“…We speculate that minimal intra‐host diversity and the emergence of low‐frequency variants arise stochastically due to genetic drift and not from RDV selective pressures. Other studies in persistently infected immunocompromised patients have also failed to identify resistance mutations to RDV, 30 although interestingly, mutations that reduce monoclonal antibody neutralization efficacy arise more easily.…”

Section: Discussionmentioning

confidence: 99%

Use of whole genome sequencing to identify low‐frequency mutations in SARS‐CoV‐2 patients treated with remdesivir

Nirmalarajah,

Yim,

Aftanas

et al. 2023

Influenza Resp Viruses

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BackgroundRemdesivir (RDV) has been shown to reduce hospitalization and mortality in COVID‐19 patients. Resistance mutations caused by RDV are rare and have been predominantly reported in patients who are on prolonged therapy and immunocompromised. We investigate the effects of RDV treatment on intra‐host SARS‐CoV‐2 diversity and low‐frequency mutations in moderately ill hospitalized COVID‐19 patients and compare them to patients without RDV treatment.MethodsFrom March 2020 to April 2022, sequential collections of nasopharyngeal and mid‐turbinate swabs were obtained from 14 patients with and 30 patients without RDV treatment. Demographic and clinical data on all patients were reviewed. A total of 109 samples were sequenced and mutation analyses were performed.ResultsPreviously reported drug resistant mutations in nsp12 were not identified during short courses of RDV therapy. In genes encoding and surrounding the replication complex (nsp6‐nsp14), low‐frequency minority variants were detected in 7/14 (50%) and 18/30 (60%) patients with and without RDV treatment, respectively. We did not detect significant differences in within‐host diversity and positive selection between the RDV‐treated and untreated groups.ConclusionsMinimal intra‐host variability and stochastic low‐frequency variants detected in moderately ill patients suggests little selective pressure in patients receiving short courses of RDV. The barrier to RDV resistance is high in patients with moderate disease. Patients undergoing short regimens of RDV therapy should continue to be monitored.

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Section: Discussionmentioning

confidence: 99%

Use of whole genome sequencing to identify low‐frequency mutations in SARS‐CoV‐2 patients treated with remdesivir

Nirmalarajah,

Yim,

Aftanas

et al. 2023

Influenza Resp Viruses

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“…We speculate that minimal intra-host diversity and the emergence of low-frequency variants as observed in both our RDV-treated and untreated groups arise stochastically due to genetic drift and not from RDV selective pressures. Other studies in persistently infected immunocompromised patients have also failed to identify resistance mutations to RDV [32], although interestingly, mutations that reduce monoclonal antibody neutralization efficacy arise more easily [33, 34].…”

Section: Discussionmentioning

confidence: 99%

Use of whole genome sequencing to identify low-frequency mutations in COVID-19 patients treated with remdesivir

Nirmalarajah

Maguire

Yim

et al. 2022

Preprint

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Background: We investigate the effects of remdesivir (RDV) treatment on intra-host SARS-CoV-2 diversity and low-frequency mutations in moderately ill hospitalized COVID-19 patients and compare them to patients without RDV treatment. Methods: Sequential collections of nasopharyngeal and mid-turbinate swabs were obtained from 16 patients with and 31 patients without RDV treatment. A total of 113 samples were sequenced and mutation analyses were performed. Results: We did not identify any drug resistant mutations during RDV therapy. In genes encoding and associated with the replication complex, low-frequency minority variants that do not reach fixation within the sampling period were detected in 6/16 (37.5%) and 14/31 (45%) patients with and without RDV treatment respectively. We did not detect significant differences in within-host diversity and positive selection between the RDV-treated and untreated groups. Conclusions: Minimal intra-host variability and stochastic low-frequency variants detected in moderately ill patients suggests little selective pressure in patients receiving short courses of RDV. Patients undergoing short regimens of RDV therapy should continue to be monitored.

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Elasomeran

2024

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Persistent infection with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in a patient with untreated human immunodeficiency virus (HIV)

Cited by 4 publications

References 10 publications

Use of whole genome sequencing to identify low‐frequency mutations in SARS‐CoV‐2 patients treated with remdesivir

Use of whole genome sequencing to identify low‐frequency mutations in SARS‐CoV‐2 patients treated with remdesivir

Use of whole genome sequencing to identify low-frequency mutations in COVID-19 patients treated with remdesivir

Elasomeran

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