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

Rolando Pajón ,Lindsey R Baden,Weiping Deng,Kathleen M Mullane,Florian Schödel,Hana M El Sahly,Joanne E Tomassini,Yamuna Devi Paila ,Brandon Essink,Katherine Kacena,Edward Kerwin,Honghong Zhou,Groves Dixon,Brett Leav,Douglas Denhan,Ian Frank,Xiaoping Zhao,Baoyu Ding,Bethany Girard

doi:10.1038/s41591-022-01679-5

Abstract

The mRNA-1273 vaccine for coronavirus disease 2019 (COVID-19) demonstrated 93.2% efficacy in reduction of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the blinded portion of the Phase 3 Coronavirus Efficacy (COVE) trial. While mRNA-1273 demonstrated high efficacy in prevention of COVID-19, including severe disease, its effect on the viral dynamics of SARS-CoV-2 infections is not understood. Here, in exploratory analyses, we assessed the impact of mRNA-1273 vaccination in the ongoing COVE trial (number NCT04470427) on SARS-CoV-2 copy number and shedding, burden of disease and infection, and viral variants. Viral variants were sequenced in all COVID-19 and adjudicated COVID-19 cases (n = 832), from July 2020 in the blinded part A of the study to May 2021 of the open-label part B of the study, in which participants in the placebo arm started to receive the mRNA-1273 vaccine after US Food and Drug Administration emergency use authorization of mRNA-1273 in December 2020. mRNA-1273 vaccination significantly reduced SARS-CoV-2 viral copy number (95% confidence interval) by 100-fold on the day of diagnosis compared with placebo (4.1 (3.4–4.8) versus 6.2 (6.0–6.4) log10 copies per ml). Median times to undetectable viral copies were 4 days for mRNA-1273 and 7 days for placebo. Vaccination also substantially reduced the burden of disease and infection scores. Vaccine efficacies (95% confidence interval) against SARS-CoV-2 variants circulating in the United States during the trial assessed in this post hoc analysis were 82.4% (40.4–94.8%) for variants Epsilon and Gamma and 81.2% (36.1–94.5%) for Epsilon. The detection of other, non-SARS-CoV-2, respiratory viruses during the trial was similar between groups. While additional study is needed, these data show that in SARS-CoV-2-infected individuals, vaccination reduced both the viral copy number and duration of detectable viral RNA, which may be markers for the risk of virus transmission.

Highlights

The mRNA-1273 vaccine for coronavirus disease 2019 (COVID-19) demonstrated 93.2% efficacy in reduction of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the blinded portion of the Phase 3 Coronavirus Efficacy (COVE) trial
The aim of this study was to assess the effect of mRNA-1273 vaccination on viral copy number and viral shedding, the burden of disease and infection and on viral variants detected in participants with COVID-19 by study group in the blinded part A of the COVE ongoing trial
SARS-CoV-2 genomic copy number was assessed in post hoc analyses of the cohort of participants with adjudicated COVID-19 cases that occurred at an illness visit (onset of participant COVID19 symptoms and a positive virologic test by reverse transcription polymerase chain reaction (RT–PCR) testing for SARS-CoV-2 by nasopharyngeal swab or, alternatively, if a clinic or home visit was not possible, by saliva samples, in the per-protocol (PP) population during the blinded and placebo-controlled phase of the COVE study[1,2]