Combined elevated C-reactive protein and detectable plasma RNA has predictive value for hospitalization during an outpatient COVID-19 convalescent plasma clinical trial
Year: 2026
Type: article
Abstract: Background: Laboratory biomarkers that predict progression from mild COVID-19 to hospitalization are not well defined. Objective: To evaluate the performance of C-reactive protein (CRP) and plasma SARS-CoV-2 RNA for predicting hospitalization among mild COVID-19 outpatients enrolled in a randomized controlled trial of COVID-19 convalescent plasma (CCP). Methods: CRP and plasma SARS-CoV-2 RNA were measured in 487 outpatient trial participants screened before March 2021. Weighted analyses accounting for sampling probabilities were used to estimate positive predictive values (PPVs) and sensitivities for progression to hospitalization, with performance compared across trial arms. Results: Elevated CRP (>1 mg/dL) was present in 27% (131/487) of participants, and plasma SARS-CoV-2 RNA was detectable in 15% (74/487). In weighted analyses, PPVs for hospitalization were 15% (95% CI, 10-21) for elevated CRP alone, 25% (95% CI, 16-35) for detectable plasma RNA alone, and 37% (95% CI, 23-52) when both biomarkers were present. Among participants with elevated CRP and plasma RNA >500 copies/mL, PPV increased to 72% (95% CI, 37-100). Elevated CRP demonstrated 100% sensitivity for hospitalization in CCP-transfused participants and 54% in control plasma-transfused participants, while detectable plasma RNA demonstrated sensitivities of 60% and 50%, respectively. Among individuals meeting severe COVID-19 risk criteria based on sex, age, obesity, or comorbidities, the combination of normal CRP and undetectable plasma RNA have a high negative predictive value for hospital progression risk. Conclusions: The combination of elevated CRP and detectable plasma SARS-CoV-2 RNA improves laboratory-based risk stratification for progression to hospitalization among outpatients with mild COVID-19.
Authors: Yuriko Fukuta, Atika Singh, Jiangda Ou, Leilani Montalvo, Clara Di Germanio, Moises A. Huaman, Aarthi G. Shenoy, Giselle S. Mosnaim, Bela Patel, Sonya L. Heath, Adam C. Levine, Barry R. Meisenberg, Shweta Anjan, Janis E. Blair, Judith S. Currier, James H. Paxton, Jonathan Gerber, Laura L. Hammitt, Catherine G. Sutcliffe, William Rausch, Patrick B. Broderick, Marie-Elena Cordisco, Benjamin Greenblatt, Valerie C. Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Donald N. Forthal, Martin S. Zand, Seble G. Kassaye, Edward R. Cachay, Jay S. Raval, Thomas J. Gniadek, Emily Spivak, Kelly A. Gebo, Shmuel Shoham, Arturo Casadevall, Nichol A. McBee, David M. Shade, Stephan Ehrardt, Oliver Layendecker, Sabra L. Klein, Evan M. Bloch, Aaron A.R. Tobian, Daniel Ford, Karen Lane, Daniel F. Hanley, Andrew Pekosz, Bryan Lau, Philip J. Norris, David J. Sullivan
Institutions: Baylor College of Medicine, Johns Hopkins University, Johns Hopkins Medicine, Vitalant Research Institute, University of Cincinnati, MedStar Washington Hospital Center, Endeavor Health, The University of Texas Health Science Center at Houston, University of Alabama at Birmingham, Brown University, University of Miami, Mayo Clinic Hospital, University of California, Los Angeles, Wayne State University, University of Massachusetts Chan Medical School, Nuvance Health, Danbury Hospital, Norwalk Hospital, Vassar Brothers Medical Center, University of California, Irvine, University of Rochester Medicine, University of Rochester, Georgetown University Medical Center, University of California San Diego, University of New Mexico, University of Utah, National Institute of Allergy and Infectious Diseases
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,320
Funders: U.S. Department of Homeland Security, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bloomberg Family Foundation, NorthShore University HealthSystem, Bloomberg Philanthropies, Shear Family Foundation, Octapharma, State of Maryland, Octapharma, National Institutes of Health, Defense Health Agency, Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences, NHLBI Division of Intramural Research
OpenAlex ID: W7212022020