Kanal Singh, Kevin Rubenstein, Viviane Callier, K. Shaw-Saliba, Adam W. Rupert, Robin L. Dewar, S. Laverdure, Helene Highbarger, P. Lallemand, Meei-Li W Huang, Keith R Jerome, R. Sampoleo, Margaret G. Mills, Alexander L. Greninger, K. Juneja, D. Porter, Constance A Benson, Walla Dempsey, Hana M. El Sahly, Chris Focht, N. Jilg, Catharine I. Paules, Rekha R Rapaka, T. Uyeki, H. C. Lane, J. Beigel, Lori E Dodd, Aneesh K Mehta, Nadine G Rouphael, Jessica J. Traenkner, V. Cantos, Ghina Alaaeddine, Barry S. Zingman, R. Grossberg, Paul F. Riska, Elizabeth Hohmann, Mariam Torres-Soto, N. Jilg, Helen Y Chu, Anna Wald, Margaret Green, Anne Luetkemeyer, Pierre-Cedric B. Crouch, Hannah Jang, Susan Kline, Joanne Billings, B. Noren, Diego López de Castilla, Jason W. Van Winkle, Francis X. Riedo, Robert W. Finberg, Jennifer P. Wang, Mireya Wessolossky, Kerry Dierberg, Benjamin Eckhardt, Henry J. Neumann, Victor F. Tapson, Jonathan Grein, F. Sutterwala, L. Hsieh, Alpesh N Amin, Thomas F. Patterson, H. Javeri, Trung Vu, R
{"title":"SARS-CoV-2 RNA 和核壳抗原是与严重疾病后果相关的血液生物标志物,对雷米替韦的反应有所改善。","authors":"Kanal Singh, Kevin Rubenstein, Viviane Callier, K. Shaw-Saliba, Adam W. Rupert, Robin L. Dewar, S. Laverdure, Helene Highbarger, P. Lallemand, Meei-Li W Huang, Keith R Jerome, R. Sampoleo, Margaret G. Mills, Alexander L. Greninger, K. Juneja, D. Porter, Constance A Benson, Walla Dempsey, Hana M. El Sahly, Chris Focht, N. Jilg, Catharine I. Paules, Rekha R Rapaka, T. Uyeki, H. C. Lane, J. Beigel, Lori E Dodd, Aneesh K Mehta, Nadine G Rouphael, Jessica J. Traenkner, V. Cantos, Ghina Alaaeddine, Barry S. Zingman, R. Grossberg, Paul F. Riska, Elizabeth Hohmann, Mariam Torres-Soto, N. Jilg, Helen Y Chu, Anna Wald, Margaret Green, Anne Luetkemeyer, Pierre-Cedric B. Crouch, Hannah Jang, Susan Kline, Joanne Billings, B. Noren, Diego López de Castilla, Jason W. Van Winkle, Francis X. Riedo, Robert W. Finberg, Jennifer P. Wang, Mireya Wessolossky, Kerry Dierberg, Benjamin Eckhardt, Henry J. Neumann, Victor F. Tapson, Jonathan Grein, F. Sutterwala, L. Hsieh, Alpesh N Amin, Thomas F. Patterson, H. Javeri, Trung Vu, R","doi":"10.1093/infdis/jiae198","DOIUrl":null,"url":null,"abstract":"BACKGROUND\nAlthough antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter ACTT-1 clinical trial that randomized patients to remdesivir or placebo.\n\n\nMETHODS\nLongitudinal specimens collected during hospitalization from a substudy of 642 COVID-19 patients were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed.\n\n\nRESULTS\nHigher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95%CI 1.40-2.71) for levels >245 pg/ml vs 1.04 (95%CI 0.76-1.42) for levels < 245 pg/ml. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive.\n\n\nCONCLUSIONS\nReductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir.\",\"authors\":\"Kanal Singh, Kevin Rubenstein, Viviane Callier, K. Shaw-Saliba, Adam W. Rupert, Robin L. Dewar, S. Laverdure, Helene Highbarger, P. Lallemand, Meei-Li W Huang, Keith R Jerome, R. Sampoleo, Margaret G. Mills, Alexander L. Greninger, K. Juneja, D. Porter, Constance A Benson, Walla Dempsey, Hana M. El Sahly, Chris Focht, N. Jilg, Catharine I. Paules, Rekha R Rapaka, T. Uyeki, H. C. Lane, J. Beigel, Lori E Dodd, Aneesh K Mehta, Nadine G Rouphael, Jessica J. Traenkner, V. Cantos, Ghina Alaaeddine, Barry S. Zingman, R. Grossberg, Paul F. Riska, Elizabeth Hohmann, Mariam Torres-Soto, N. Jilg, Helen Y Chu, Anna Wald, Margaret Green, Anne Luetkemeyer, Pierre-Cedric B. Crouch, Hannah Jang, Susan Kline, Joanne Billings, B. Noren, Diego López de Castilla, Jason W. Van Winkle, Francis X. Riedo, Robert W. Finberg, Jennifer P. Wang, Mireya Wessolossky, Kerry Dierberg, Benjamin Eckhardt, Henry J. Neumann, Victor F. Tapson, Jonathan Grein, F. Sutterwala, L. Hsieh, Alpesh N Amin, Thomas F. Patterson, H. Javeri, Trung Vu, R\",\"doi\":\"10.1093/infdis/jiae198\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"BACKGROUND\\nAlthough antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter ACTT-1 clinical trial that randomized patients to remdesivir or placebo.\\n\\n\\nMETHODS\\nLongitudinal specimens collected during hospitalization from a substudy of 642 COVID-19 patients were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed.\\n\\n\\nRESULTS\\nHigher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95%CI 1.40-2.71) for levels >245 pg/ml vs 1.04 (95%CI 0.76-1.42) for levels < 245 pg/ml. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive.\\n\\n\\nCONCLUSIONS\\nReductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.\",\"PeriodicalId\":501010,\"journal\":{\"name\":\"The Journal of Infectious Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Infectious Diseases\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/infdis/jiae198\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Infectious Diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/infdis/jiae198","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir.
BACKGROUND
Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter ACTT-1 clinical trial that randomized patients to remdesivir or placebo.
METHODS
Longitudinal specimens collected during hospitalization from a substudy of 642 COVID-19 patients were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed.
RESULTS
Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95%CI 1.40-2.71) for levels >245 pg/ml vs 1.04 (95%CI 0.76-1.42) for levels < 245 pg/ml. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive.
CONCLUSIONS
Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.