tetano
Editor, Senior Moderator
Nat Med
. 2022 Feb 10.
doi: 10.1038/s41591-022-01679-5. Online ahead of print.
Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial
Rolando Pajon[SUP] 1 [/SUP], Yamuna D Paila[SUP] 2 [/SUP], Bethany Girard[SUP] 2 [/SUP], Groves Dixon[SUP] 2 [/SUP], Katherine Kacena[SUP] 2 [/SUP], Lindsey R Baden[SUP] 3 [/SUP], Hana M El Sahly[SUP] 4 [/SUP], Brandon Essink[SUP] 5 [/SUP], Kathleen M Mullane[SUP] 6 [/SUP], Ian Frank[SUP] 7 [/SUP], Douglas Denhan[SUP] 8 [/SUP], Edward Kerwin[SUP] 9 [/SUP], Xiaoping Zhao[SUP] 2 [/SUP], Baoyu Ding[SUP] 2 [/SUP], Weiping Deng[SUP] 2 [/SUP], Joanne E Tomassini[SUP] 2 [/SUP], Honghong Zhou[SUP] 2 [/SUP], Brett Leav[SUP] 2 [/SUP], Florian Schödel[SUP] 2 [/SUP], COVE Trial Consortium
Affiliations
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) log[SUB]10[/SUB] 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.
. 2022 Feb 10.
doi: 10.1038/s41591-022-01679-5. Online ahead of print.
Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial
Rolando Pajon[SUP] 1 [/SUP], Yamuna D Paila[SUP] 2 [/SUP], Bethany Girard[SUP] 2 [/SUP], Groves Dixon[SUP] 2 [/SUP], Katherine Kacena[SUP] 2 [/SUP], Lindsey R Baden[SUP] 3 [/SUP], Hana M El Sahly[SUP] 4 [/SUP], Brandon Essink[SUP] 5 [/SUP], Kathleen M Mullane[SUP] 6 [/SUP], Ian Frank[SUP] 7 [/SUP], Douglas Denhan[SUP] 8 [/SUP], Edward Kerwin[SUP] 9 [/SUP], Xiaoping Zhao[SUP] 2 [/SUP], Baoyu Ding[SUP] 2 [/SUP], Weiping Deng[SUP] 2 [/SUP], Joanne E Tomassini[SUP] 2 [/SUP], Honghong Zhou[SUP] 2 [/SUP], Brett Leav[SUP] 2 [/SUP], Florian Schödel[SUP] 2 [/SUP], COVE Trial Consortium
Affiliations
- PMID: 35145311
- 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) log[SUB]10[/SUB] 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.