Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial

Article activity feed

1. Version published to 10.1038/s41591-022-01679-5

   Feb 10, 2022
2. 

   ScreenIT

   Oct 1, 2021

   SciScore for 10.1101/2021.09.28.21264252: (What is this?)

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

   Table 1: Rigor

   Ethics	IRB: The central Institutional Review Board/Ethics Committee, Advarra, Inc., 6100 Merriweather Drive, Columbia, MD 21044 approved the protocol and consent forms. Consent: All participants provided written informed consent.
   Sex as a biological variable	not detected.
   Randomization	Trial Design: This is an analysis of the previously reported COVE study, a phase 3 randomized, observer-blinded, placebo-controlled trial that enrolled adults in medically-stable condition at 99 US sites (clintrials.gov NCT04470427).1,2 Eligible participants included adults 18 years or older with no known history of SARS-CoV-2 infection, whose circumstances put them at appreciable risk for SARS-CoV-2 infection and/or …

   SciScore for 10.1101/2021.09.28.21264252: (What is this?)

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

   Table 1: Rigor

   Ethics	IRB: The central Institutional Review Board/Ethics Committee, Advarra, Inc., 6100 Merriweather Drive, Columbia, MD 21044 approved the protocol and consent forms. Consent: All participants provided written informed consent.
   Sex as a biological variable	not detected.
   Randomization	Trial Design: This is an analysis of the previously reported COVE study, a phase 3 randomized, observer-blinded, placebo-controlled trial that enrolled adults in medically-stable condition at 99 US sites (clintrials.gov NCT04470427).1,2 Eligible participants included adults 18 years or older with no known history of SARS-CoV-2 infection, whose circumstances put them at appreciable risk for SARS-CoV-2 infection and/or high risk of severe Covid-19.
   Blinding	Part A was the observer blinded to-treatment phase which concluded when participants unblinded and consideration given those on placebo to receive mRNA-1273.
   Power Analysis	not detected.

   Table 2: Resources

   Software and Algorithms
   Sentences	Resources
   The Agilent 2200 or 4200 TapeStation in conjunction with D5000 ScreenTapes, D5000 reagents and the TapeStation Analysis software was used to assess purified libraries for presence, average fragment size, and concentration of the fragment distributions generated.	TapeStation Analysis suggested: None
   SARS-CoV-2 S gene NGS runs using MiSeq v2 chemistry reagents running paired-end 2 × 151 reads must exhibit the following criteria: Cluster densities approximating 600 - 1,200K/mm2; >80% of bases called exhibit Q-scores ≥30.	MiSeq suggested: (A5-miseq, RRID:SCR_012148)
   The resulting amplicon is purified and normalized before undergoing NGS library preparation (Kapa).	NGS suggested: (PM4NGS, RRID:SCR_019164)
   Whole Genome Sequencing Assay (WGS) from Eurofins Viracor (Kansas City, MO): Viral RNA from nasal swabs is extracted using the Kingfisher Flex platform and GSD NovaPrime® RNA extraction kit.	WGS suggested: None
   The fragment size distribution of the final pooled library was confirmed using the Agilent TapeStation 4200 or ThermoFisher BioAnalyzer 2100 DNA fragment analyzer prior to preparation for sequencing.	ThermoFisher BioAnalyzer suggested: None

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   Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   There are several limitations to consider. First, it should be noted that the analyses presented here are based upon an initial evaluation of data that will continue to accrue over time and will be subject to future updates. Although the BOD and BOI results were statistically significant over the entire PP set, the results were driven by the overall high vaccine efficacy and a numerically dominant prevalence of mild-to-moderate disease, including asymptomatic infections for BOI. With increased follow-up times and inevitably acquired disease in participants, the proportions of BOD and BOI may change. A prespecified, proportional means model was used for the analysis, to allow direct comparison across different periods of follow-up, minimizing these effects. The sequence data also come with known caveats, some demonstrated through this work. For example, the fact that the vaccine has a marked effect on lowering SARS-CoV-2 viral loads hampered our efforts to generate an unbiased sequence data set. Even though sequencing efforts were performed in a blinded manner and the team was unaware of participant treatment assignments, the success rates in obtaining good quality sequences from samples of vaccine breakthrough cases was 50% or less, while it was over 80% for placebo-originated samples. Although this is a clear, unavoidable bias in the available sequence data, it does not affect the overall assessment of the biological effect of vaccination on viral load. While a highly-aggres...

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   Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
   

   Identifier	Status	Title
   NCT04470427	Active, not recruiting	A Study to Evaluate Efficacy, Safety, and Immunogenicity of …

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

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

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   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.

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

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   Read the original source
3. 

   Version published to 10.1101/2021.09.28.21264252v1 on medRxiv

   Sep 29, 2021