Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial
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 eff...
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| Veröffentlicht in: | Nature medicine 2022-04, Vol.28 (4), p.823-830 |
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| creator | Pajon, Rolando Paila, Yamuna D. Girard, Bethany Dixon, Groves Kacena, Katherine Baden, Lindsey R. El Sahly, Hana M. Essink, Brandon Mullane, Kathleen M. Frank, Ian Denhan, Douglas Kerwin, Edward Zhao, Xiaoping Ding, Baoyu Deng, Weiping Tomassini, Joanne E. Zhou, Honghong Leav, Brett Schödel, Florian |
| description | 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. |
| doi_str_mv | 10.1038/s41591-022-01679-5 |
| format | Article |
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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.</description><identifier>ISSN: 1078-8956</identifier><identifier>ISSN: 1546-170X</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/s41591-022-01679-5</identifier><identifier>PMID: 35145311</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><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</subject><ispartof>Nature medicine, 2022-04, Vol.28 (4), p.823-830</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-bef5fea744c655d2446de559488286bdb250a413983585aba8f448b320db56403</citedby><cites>FETCH-LOGICAL-c540t-bef5fea744c655d2446de559488286bdb250a413983585aba8f448b320db56403</cites><orcidid>0000-0002-1697-9036 ; 0000-0002-5155-5079 ; 0000-0002-9399-2867</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41591-022-01679-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41591-022-01679-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35145311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pajon, Rolando</creatorcontrib><creatorcontrib>Paila, Yamuna D.</creatorcontrib><creatorcontrib>Girard, Bethany</creatorcontrib><creatorcontrib>Dixon, Groves</creatorcontrib><creatorcontrib>Kacena, Katherine</creatorcontrib><creatorcontrib>Baden, Lindsey R.</creatorcontrib><creatorcontrib>El Sahly, Hana M.</creatorcontrib><creatorcontrib>Essink, Brandon</creatorcontrib><creatorcontrib>Mullane, Kathleen M.</creatorcontrib><creatorcontrib>Frank, Ian</creatorcontrib><creatorcontrib>Denhan, Douglas</creatorcontrib><creatorcontrib>Kerwin, Edward</creatorcontrib><creatorcontrib>Zhao, Xiaoping</creatorcontrib><creatorcontrib>Ding, Baoyu</creatorcontrib><creatorcontrib>Deng, Weiping</creatorcontrib><creatorcontrib>Tomassini, Joanne E.</creatorcontrib><creatorcontrib>Zhou, Honghong</creatorcontrib><creatorcontrib>Leav, Brett</creatorcontrib><creatorcontrib>Schödel, Florian</creatorcontrib><creatorcontrib>COVE Trial Consortium</creatorcontrib><creatorcontrib>the COVE Trial Consortium</creatorcontrib><title>Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>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
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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.</description><subject>2019-nCoV Vaccine mRNA-1273</subject><subject>692/308/153</subject><subject>692/700/459/1748</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Confidence intervals</subject><subject>Copy number</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - epidemiology</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 vaccines</subject><subject>Disease transmission</subject><subject>Humans</subject><subject>Immunization</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Metabolic Diseases</subject><subject>Molecular 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Florian</au><aucorp>COVE Trial Consortium</aucorp><aucorp>the COVE Trial Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>28</volume><issue>4</issue><spage>823</spage><epage>830</epage><pages>823-830</pages><issn>1078-8956</issn><issn>1546-170X</issn><eissn>1546-170X</eissn><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
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.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>35145311</pmid><doi>10.1038/s41591-022-01679-5</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-1697-9036</orcidid><orcidid>https://orcid.org/0000-0002-5155-5079</orcidid><orcidid>https://orcid.org/0000-0002-9399-2867</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-8956 |
| ispartof | Nature medicine, 2022-04, Vol.28 (4), p.823-830 |
| issn | 1078-8956 1546-170X 1546-170X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9018421 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 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 |
| title | Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T05%3A27%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Initial%20analysis%20of%20viral%20dynamics%20and%20circulating%20viral%20variants%20during%20the%20mRNA-1273%20Phase%203%20COVE%20trial&rft.jtitle=Nature%20medicine&rft.au=Pajon,%20Rolando&rft.aucorp=COVE%20Trial%20Consortium&rft.date=2022-04-01&rft.volume=28&rft.issue=4&rft.spage=823&rft.epage=830&rft.pages=823-830&rft.issn=1078-8956&rft.eissn=1546-170X&rft_id=info:doi/10.1038/s41591-022-01679-5&rft_dat=%3Cproquest_pubme%3E2628301015%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2652412302&rft_id=info:pmid/35145311&rfr_iscdi=true |