Characterization of Virologic Rebound Following Nirmatrelvir-Ritonavir Treatment for Coronavirus Disease 2019 (COVID-19)

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Abstract

We enrolled 7 individuals with recurrent symptoms or antigen test conversion following nirmatrelvir-ritonavir treatment. High viral loads (median 6.1 log10 copies/mL) were detected after rebound for a median of 17 days after initial diagnosis. Three had culturable virus for up to 16 days after initial diagnosis. No known resistance-associated mutations were identified.

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  1. SciScore for 10.1101/2022.05.24.22275326: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Individuals were identified through the Mass General Brigham health system or upon referral from treating providers and contacted by phone for informed consent at the time of symptom recurrence.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingAfter 15 minutes, result were interpreted as positive, negative, or discordant by a reader blinded to the viral load result.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Briefly, aliquoted viral transport media were filtered with 0.45-0.65um centrifugal filters and added to Vero-E6 cells plated in DMEM culture media supplemented with 2% fetal bovine serum, HEPES, antibiotic-antimycotic solution and 5ug/mL of polybrene.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Antigen testing using Abbott BinaxNow SARS-CoV-2 Rapid Antigen Assay: Frozen viral transport media aliquots were thawed on ice and 50uL was transferred to a test tube.
    Abbott BinaxNow
    suggested: None

    Results from OddPub: Thank you for sharing your data.


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study should be interpreted in the context of limitations. Most notably, this represents a small case series so precise estimates of culture positivity, duration of viral shedding, or incidence of drug resistance cannot be made. We also enrolled individuals after clinical rebound, so cannot determine the incidence of this syndrome among individuals taking nirmatrelvir-ritonavir treatment. Finally, we use viral culture as a proxy measure of contagiousness but cannot quantify the risk of transmission for this patient population. In summary, recurrent clinical disease after nirmatrelvir-ritonavir therapy for COVID-19 is associated with high viral load and, in some cases, culturable virus. Culturable virus was present for up to two weeks after completion of therapy. Consideration should be given to revising public health guidelines to specifically recommend repeat testing and isolation in these cases. Future work is needed to better understand the causes, clinical significance, and public health consequences of symptomatic relapse after nirmatrelvir-ritonavir.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.


    About SciScore

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