학술논문
Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study
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article
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Ozonoff, Al; Schaenman, Joanna; Jayavelu, Naresh Doni; Milliren, Carly E; Calfee, Carolyn S; Cairns, Charles B; Kraft, Monica; Baden, Lindsey R; Shaw, Albert C; Krammer, Florian; van Bakel, Harm; Esserman, Denise A; Liu, Shanshan; Sesma, Ana Fernandez; Simon, Viviana; Hafler, David A; Montgomery, Ruth R; Kleinstein, Steven H; Levy, Ofer; Bime, Christian; Haddad, Elias K; Erle, David J; Pulendran, Bali; Nadeau, Kari C; Davis, Mark M; Hough, Catherine L; Messer, William B; Higuita, Nelson I Agudelo; Metcalf, Jordan P; Atkinson, Mark A; Brakenridge, Scott C; Corry, David; Kheradmand, Farrah; Ehrlich, Lauren IR; Melamed, Esther; McComsey, Grace A; Sekaly, Rafick; Diray-Arce, Joann; Peters, Bjoern; Augustine, Alison D; Reed, Elaine F; Altman, Matthew C; Becker, Patrice M; Rouphael, Nadine; Bime, Chris; McEnaney, Kerry; Barton, Brenda; Lentucci, Claudia; Saluvan, Mehmet; Chang, Ana C; Hoch, Annmarie; Albert, Marisa; Shaheen, Tanzia; Kho, Alvin T; Thomas, Sanya; Chen, Jing; Murphy, Maimouna D; Cooney, Mitchell; Presnell, Scott; Fragiadakis, Gabriela K
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Abstract
BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.FundingNIH.