Early trajectories of virologic and immunologic biomarkers and clinical outcomes in patients hospitalized for COVID-19: an international, prospective, cohort study

作者：T. Jensen, Thomas A. Murray, Greg A. Grandits, Mamta K. Jain, B. Grund, Kathryn Shaw-Saliba, M. A. Matthay, M. Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L. Dewar, Anna L. Goodman, T. Hatlen, H. Highbarger, M. Holodniy, P. Lallemand, S. Laverdure, Bradley G Leshnower, David Looney, C. Moschopoulos, H. Mugerwa, Daniel D. Murray, E. Mylonakis, S. Nagy-Agren, M. T. Rehman, Adam W. Rupert, Randy A Stevens, S. Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R. Ko, D. Sahner, John Tierney, Susan E. Vogel, B. Herpin, M. Smolskis, L. A. McKay, Kelly Cahill, Page Crew, Ratna Sardana, Sharon Segal Raim, Lisa Hensely, J. Lorenzo, R. Mock, J. Zuckerman, Negin Atri, Mark Miller, D. Vallée, Lucy Chung, Nayon Kang, K. Barrett, S. J. Adam, Sarah Read, R. Draghia‐Akli, Judy Currier, E. Hughes, Rachel H. Harrigan, Laura Amos, Amy Carlsen, Anita Carter, G. Collins, Bionca Davis, E. Denning, Alain DuChêne, Kate Eckroth, N. Engen, Alex Frase, Greg Gandits, M. Harrison, Nancy L. Hurlbut, Payton Kaiser, Joseph S Koopmeiners, G. Larson, Sue Meger, Shweta Mistry, Thomas A. Murray, Rachel Nelson, K. Quan, S. Quan, Cavan Reilly, L. Siegel, G. Thompson, David M Vock, Jamie Walski, A. Gelijns, Alan J. Moskowitz, E. Bagiella, E. Moquete, K. O’Sullivan, M. Marks, Evan Accardi, Emily Kinzel, Sara W. Burris, Gabriela Bedoya, L. Gupta, J. Overbey, Milerva Santos, M. Gillinov, Marissa A. Miller, W. Taddei-Peters, Kathleen Fenton, U. Sandkovsky, Robert L Gottlieb, Michael Mack, M. Berhe, Clinton Haley, Emma Dishner, Christopher J Bettacchi, Kevin Golden, Erin Duhaime, Madison Ryan, Catherine Tallmadge, Lorie Estrada, Felecia Jones, S. Villa, S. Wang, Raven Robert, T. Coleman, Laura Clariday, R. Baker, Marian Hurutado-Rodriguez, Nazia Iram, Michelle Fresnedo, Allyson Davis, Kiara Leonard, Noelia Ramierez, Jon Thammavong, Krizia Duque, Emma Turner, Tammy Fisher, Dianna Robinson, Desirae Ransom, Nicholas Maldonado, Erica Lusk, A. Killian, Adriana Palacious, Edilia Solis, Janet Jerrow, Matthew Watts, Heath W. Whitacre, Elizabeth Cothran, Peter K. Smith, Christina E. Barkauskas, A. Vekstein, Emily R. Ko, Grace R. Dreyer, N. Stafford, M. Brooks, Tatyana Der, Marie-Louise Witte, R. Gamarallage, John Franzone, Noel Ivey, Rebecca Lumsden, N. Mosaly, A. Mourad, T.L. Holland, Mary Motta, K. Lane, Lauren M. McGowan, J. Stout, Heather Aloor, Kennesha M. Bragg, Barvina Toledo, Beth McLendon-Arvik, Barbara Bussadori, Beth A. Hollister, M. Griffin, D. Giangiacomo, V. Rodríguez, Gordon Bokhart, Sharon M. Eichman, P. E. Parrino, Steven A. Spindel, Aditya Bansal, Katherine Baumgarten, Johnathan Hand, D. Vonderhaar, Bobby Nossaman, Sylvia Laudun, D. Ames, S. Broussard, N. Hernandez, G. Isaac, Huan Dinh, Yiling Zheng, Sonny Tran, Hunter McDaniel, Nicolle Crovetto, E. Perin, Briana Costello, Prasad Manian, M. Sohail, Alexander Postalian, Punit Hinsu, Carolyn Watson, James Chen, Melyssa Fink, Lydia Sturgis, K. Walker, Kim Mahon, Jennifer Parenti, Casey Kappenman, A. Knight, J. Sturek, A. Barros, Kyle B. Enfield, A. Kadl, C. Green, R. Simon, Ashley D Fox, Kara J. Thornton, Amy Adams, Vinay Badhwar, S. Sharma, Brian P. Peppers, P. McCarthy, Troy Krupica, Arif Sarwari, Rebecca Reece, Lisa Fornaresico, C. Glaze, R. Evans, Fang Di, Shawn L. Carlson, Tanja Aucremanne, C. Tennant, L. Sutton, Sabrina Buterbaugh, Roger Williams, R. Bunner, Jay H. Traverse, Frank Rhame, Joshua S. Huelster, Rajesh Kethireddy, I. Davies, J. Salamanca, Christine Majeski, P. Skelton, Maria Zarambo, Andrea Sarafolean, M. Bowdish, Zea Borok, Noah Wald-Dickler, Douglass Hutcheon, A. Towfighi, Mary Lee, M. Lewis, Brad Spellberg, Linda Sher, Aniket Sharma, Anna Olds, C. Justino, Edward Loxano, C. Romero, Jane Leong, V. Rodina, C. Quesada, Luke Hamilton, J. Escobar, Bradley G Leshnower, William S. Bender, M. Sharifpour, Jeffrey Miller, Woodrow Farrington, Kim T. Baio, Mary K. McBride, Michele Fielding, Sonya Mathewson, Kristina Porte, Missy Maton, C. Ponder, Elizabeth Haley, C. Spainhour, S. Rogers, Derrick Tyler, R. Madathil, Joseph Rabin, Andrea Levine, K. Saharia, Ali Tabatabai, C. Lau, J. Gammie, Maya-Loren Peguero, Kimberly McKernan, Mathew Audette, Emily Fleischmann, K. Akbari, Myounghee Lee, Andrew Chi, H. Salehi, Alan Pariser, Phuong Tran Nyguyen, J. Moore, Adrienne Gee, S. Vincent, Richard A. Zuckerman, Alexander Iribarne, S. Metzler, Samantha L. Shipman, Haley Johnson, C. Newton, D. Parr, L. Miller, Beth Schelle, S. McLean, Howard R. Rothbaum, M. S. Alvarez, Shivam P. Kalan, Heather H. Germann, J. Hendershot, Karen Moroney, K. Herring, S. Cook, Pamella Paul, Rebecca Walker-Ignasiak, Crystal North, C. Oldmixon, N. Ringwood, A. Muzikansky, Richard Morse, Laura Fitzgerald, H.D. Morin, R. G. Brower, L. Reineck, Karen Bienstock, J. Steingrub, Peter Hou, J. Steingrub, Mark A Tidswell, Lori-Ann Kozikowski, Cynthia Kardos, L. DeSouza, Sarah Romain, Sherell Thornton-Thompson, Daniel Talmor, N. Shapiro, Konstantinos Andromidas, V. Banner-Goodspeed, Michael Bolstad, Katherine L. Boyle, Payton Cabrera, Arnaldo Devilla, Joshua C. Ellis, Ana Grafals, S. Hayes, Conor Higgins, Lisa Kurt, Nicholas Kurtzman, K. Redman, Elinita Rosseto, Douglas Scaffidi, M. Filbin, Kathryn A. Hibbert, B. Parry, J. Margolin, Brooklynn Hillis, R. Hamer, K. Brait, Caroline Beakes, Brenna N. Mckaig, Eleonore Kugener, Alan E. Jones, J. Galbraith, U. Nandi, Rebekah K. Peacock, Gregory W. Hendey, Kirsten N. Kangelaris, Kimia Ashktorab, Rachel Gropper, Anika Agrawal, K. Yee, A. Jauregui, H. Zhuo, E. Almasri, M. Fayed, K. Hubel, A. Hughes, Rebekah L. Garcia, George Lim, Steven Y. Chang, Michael Y. Lin, J. Vargas, Hena Sihota, Rebecca M. Beutler, Trisha Agarwal, Jennifer G. Wilson, R. Vojnik, Cynthia Perez, Jordan H. McDowell, J. Roque, Henry Wang, Ryan Huebinger, Bela Patel, Elizabeth Vidales, Timothy Albertson, Erin Hardy, Richart Harper, M. Moss, Amiran Baduashvili, Lakshmi Chauhan, D. Douin, Flora Martinez, Lani L. Finck, Jill J. Bastman, Michelle P Howell, C. Higgins, J. Mckeehan, Jay Finigan, Peter Stubenrauch, William J. Janssen, C. Griesmer, Olivia VerBurg, R. Hyzy, Pauline K. Park, Kristine Nelson, Jake I. McSparron, Ivan N. Co, Bonnie R. Wang, J. Jiménez, Norman Olbrich, K. McDonough, Shijing Jia, Sinan Hanna, M. Gong, Lynne D. Richardson, Rahul R. Nair, Brenda Lopez, Omowunmi Amosu, Obiageli Offor, Hiwet Tzehaie, W. Nkemdirim, Sabah Boujid, J. Mosier, C. Hypes, Elizabeth Salvagio Campbell, Billie A Bixby, Boris Gilson, Anitza Lopez, C. Bime, Sairam Parthasarathy, A. M. Cano, R. D. Hite, Thomas E. Terndrup, Herbert P. Wiedemann, Kristin M. Hudock, Hammad Tanzeem, Harshada More, Jamie Martinkovic, S. Sellers, J. Houston, Mary Burns, Simra Kiran, Tammy Roads, Sarah Kennedy, A. Duggal, N. Thiruchelvam, Kiran Ashok, Alexander H. King, Omar Mehkri, S. Dugar, D. Sahoo, D. Yealy, D.C. Angus, A. J. Weissman, Tina Vita, Emily Berryman, Catherine L. Hough, Akram Khan, O. F. Krol, E. Mills, M. Kinjal, Genesis Briceño, Raju Reddy, K. Hubel, M. Jouzestani, M. McDougal, Rupal K. Deshmukh, N. Johnston, Bryce R. H. Robinson, Staphanie J. Gundel, S. Katsandres, Sam S. Torbati, T. Parimon, A. Caudill, Brittany Mattison, Susan E. Jackman, Po-En Chen, Emad Bayoumi, Cristabelle Ojukwu, Devin Fine, Gwendolyn Weissberg, Katherine Isip, Yunhee Choi-Kuaea, Shaunt Mehdikhani, T. Dar, Nsole Biteghe Fleury Augustin, Dana Tran · 发表于：The Lancet Microbe · 年份：2024 · DOI：10.1016/s2666-5247(24)00015-6 · 被引用次数：4 · 研究领域：Medicine

SUMMARY Background Serial measurement of virologic and immunologic biomarkers in patients hospitalized with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune-dysregulation. We aimed to characterize biomarker trajectories, and their associations with clinical outcomes. Methods Patients hospitalized with COVID-19 and enrolled in the TICO (Therapeutics for Inpatients with COVID-19) platform trial between August 5, 2020, and September 30, 2021, were included in a prospective cohort study. This included analysis of 2,149 participants with plasma nucleocapsid antigen (plasma N-Ag), antinucleocapsid antibody (anti-N-Ab), C-reactive protein (CRP), Interleukin-6 (IL-6), and D-dimer measured at baseline and days 1, 3 and 5 of enrollment. Day 90 follow-up status was available for 1,790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery. Findings Participants were included from 108 international sites. Median age was 57 years (IQR 46–68), 58% (1,246/2,149) were male. A pattern of less favorable trajectories of low anti-N-Ab, high plasma N-Ag, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease (CKD) demonstrated plasma N-Ag 424% higher (95% CI 319, 559...