Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study
Al Ozonoff, Joanna Schaenman, Naresh Doni Jayavelu, Carly E. Milliren, Carolyn S. Calfee, Charles B. Cairns, Monica Kraft, Lindsey R. Baden, Albert C. Shaw, Florian Krammer, Harm van Bakel, Denise Esserman, Shanshan Liu, Ana Fernandez Sesma, Viviana Simon, David A. Hafler, Ruth R. Montgomery, Steven H. Kleinstein, Ofer Levy, Christian Bime, Elias K. Haddad, David J. Erle, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Catherine L. Hough, William B. Messer, Nelson Iván Agudelo Higuita, Jordan P. Metcalf, Mark A. Atkinson, Scott C. Brakenridge, David B. Corry, Farrah Kheradmand, Lauren I. R. Ehrlich, Esther Melamed, Grace A. McComsey, Rafick‐Pierre Sékaly, Joann Diray‐Arce, Bjoern Peters, Alison D. Augustine, Elaine F. Reed, Matthew C. Altman, Patrice M. Becker, Nadine Rouphael, Al Ozonoff, Joanna Schaenman, Naresh Doni Jayavelu, Carly E. Milliren, Carolyn S. Calfee, Charles B. Cairns, Monica Kraft, Lindsey R. Baden, Albert C. Shaw, Florian Krammer, Harm van Bakel, Denise Esserman, Shanshan Liu, Ana Fernandez Sesma, Viviana Simon, David A. Hafler, Ruth R. Montgomery, Steven H. Kleinstein, Ofer Levy, Chris Bime, Elias K. Haddad, David J. Erle, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Catherine L. Hough, William B. Messer, Nelson Iván Agudelo Higuita, Jordan P. Metcalf, Mark A. Atkinson, Scott C. Brakenridge, David B. Corry, Farrah Kheradmand, Lauren I. R. Ehrlich, Esther Melamed, Grace A. McComsey, Rafick‐Pierre Sékaly, Joann Diray‐Arce, Bjoern Peters, Alison D. Augustine, Elaine F. Reed, Kerry McEnaney, Brenda Barton, Claudia Lentucci, Mehmet Saluvan, Ana C. Chang, Annmarie Hoch, Albert Marisa, Tanzia Shaheen, Alvin T. Kho, Sanya Thomas, Jing Chen, Maimouna D. Murphy, Mitchell Cooney, Scott Presnell, Gabriela K. Fragiadakis
Abstract
BACKGROUND: Better 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. METHODS: Immunophenotyping 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. FINDINGS: The 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. INTERPRETATION: Integration 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. FUNDING: NIH.