Covid-19 in the Phase 3 Trial of mRNA-1273 During the Delta-variant Surge
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Abstract
Background
Following emergency use authorization in December 2020, the Coronavirus Efficacy (COVE) trial was amended to an open-label phase, where participants were unblinded and those randomized to placebo were offered vaccination. Emergence of the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with increased incidences of coronavirus disease 2019 (Covid-19) among unvaccinated and vaccinated persons. This exploratory analysis evaluated the incidence and genetic sequences of Covid-19 cases in the ongoing COVE trial during the open-label phase, with a focus on July-August 2021, when delta-variants surged in the US.
Methods
Covid-19 cases were identified in participants initially randomized to mRNA-1273 (vaccinated from July-December 2020) and those initially randomized to the placebo (vaccinated December 2020-April 2021) who received at least one dose and were SARS-CoV-2-negative at baseline in the modified-intent-to-treat population were analyzed. Included were Covid-19 cases occurring after 26-Mar-2021 with positive RT-PCR results in nasopharyngeal samples (central lab test) and reported Covid-19 symptoms. Genetic sequencing of Covid-19 cases was also performed.
Results
There were 14,746 participants in the earlier mRNA-1273 (mRNA-1273e) group and 11,431 in the later placebo-mRNA1273 (mRNA-1273p) group. Covid-19 cases increased from the start of the open-label phase to July-August 2021. During July and August, 162 Covid-19 cases occurred in the mRNA-1273e group and 88 in the mRNA-1273p group. Of the cases sequenced, 144/149 [97%]) in the mRNA-1273 and 86/88 (99%) in the mRNA-1273p groups were attributed to delta. The incidence rate of Covid-19 was lower for the mRNA-1273p (49.0/1000 person-years) versus mRNA-1273e (77.1/1000 person-years) group [36.4% (95% CI 17.1%-51.5%) reduction]. There were fewer severe Covid-19 cases in the mRNA-1273p (6; 6.2/1000 person-years) than mRNA-1273e (13; 3.3/1000 person-years) [46.0% (95% CI −52.4%-83.2%) reduction]. Three Covid-19 related hospitalizations occurred with two resulting deaths in the mRNA-1273e group.
Conclusion
Incidence rates of Covid-19 and severe Covid-19 were lower during the months when delta was the dominant variant (July/August 2021) among COVE participants vaccinated more recently. Analysis of COVID-19 cases from the open-label phase of the COVE study is ongoing.
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SciScore for 10.1101/2021.09.17.21263624: (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 This is an exploratory analysis of the previously reported phase 3, randomized, observer-blind, placebo-controlled Coronavirus Efficacy (COVE) trial that enrolled medically stable adults 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 … SciScore for 10.1101/2021.09.17.21263624: (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 This is an exploratory analysis of the previously reported phase 3, randomized, observer-blind, placebo-controlled Coronavirus Efficacy (COVE) trial that enrolled medically stable adults 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 The analysis was performed in participants who were randomized and received mRNA-1273 (mRNA-1273 group; vaccinated from 27-July-2020 to 16-Dec-2020) in the blinded phase, and participants randomized to placebo in the blinded phase and receiving mRNA-1273 in the open-label phase (Placebo-mRNA-1273 group; vaccinated from 29-Dec-2020 to 30-Apr-2021) and were SARS-CoV-2 uninfected at the beginning of the open-label phase. Power Analysis not detected. Table 2: Resources
No key resources detected.
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).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.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 … 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.
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