Journal Article

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

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

2022

Overview

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) log 10 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. The COVID-19 vaccine mRNA-1273 reduced SARS-CoV-2 copy number and duration of virus shedding, in addition to disease burden and infections, in exploratory analyses of breakthrough infections in the COVE trial.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 2019-nCoV Vaccine mRNA-1273 / 692/308/153 / 692/700/459/1748 / Biomedical and Life Sciences / Biomedicine / Cancer Research / Confidence intervals / Copy number / Coronaviruses / COVID-19 / COVID-19 - epidemiology / COVID-19 - prevention & control / COVID-19 vaccines / Disease transmission / Humans / Immunization / Infections / Infectious Diseases / Metabolic Diseases / Molecular Medicine / mRNA / Neurosciences / Placebos / Respiratory diseases / SARS-CoV-2 - genetics / Severe acute respiratory syndrome coronavirus 2 / United States / Vaccination / Vaccine efficacy / Vaccines / Viral diseases / Viruses