TY - JOUR
T1 - Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients
T2 - Results from the IMPACC study
AU - the IMPACC study group members
AU - Ozonoff, Al
AU - Schaenman, Joanna
AU - Jayavelu, Naresh Doni
AU - Milliren, Carly E.
AU - Calfee, Carolyn S.
AU - Cairns, Charles B.
AU - Kraft, Monica
AU - Baden, Lindsey R.
AU - Shaw, Albert C.
AU - Krammer, Florian
AU - van Bakel, Harm
AU - Esserman, Denise A.
AU - Liu, Shanshan
AU - Sesma, Ana Fernandez
AU - Simon, Viviana
AU - Hafler, David A.
AU - Montgomery, Ruth R.
AU - Kleinstein, Steven H.
AU - Levy, Ofer
AU - Bime, Christian
AU - Haddad, Elias K.
AU - Erle, David J.
AU - Pulendran, Bali
AU - Nadeau, Kari C.
AU - Davis, Mark M.
AU - Hough, Catherine L.
AU - Messer, William B.
AU - Higuita, Nelson I.Agudelo
AU - Metcalf, Jordan P.
AU - Atkinson, Mark A.
AU - Brakenridge, Scott C.
AU - Corry, David
AU - Kheradmand, Farrah
AU - Ehrlich, Lauren I.R.
AU - Melamed, Esther
AU - McComsey, Grace A.
AU - Sekaly, Rafick
AU - Diray-Arce, Joann
AU - Peters, Bjoern
AU - Augustine, Alison D.
AU - Reed, Elaine F.
AU - Altman, Matthew C.
AU - Becker, Patrice M.
AU - Rouphael, Nadine
AU - Bime, Chris
AU - McEnaney, Kerry
AU - Barton, Brenda
AU - Lentucci, Claudia
AU - Mosier, Jarrod
AU - Kimura, Hiroki
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
KW - Antibody
KW - COVID-19
KW - SARS-CoV-2
KW - Viral load
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U2 - 10.1016/j.ebiom.2022.104208
DO - 10.1016/j.ebiom.2022.104208
M3 - Article
C2 - 35952496
SN - 2352-3964
VL - 83
JO - EBioMedicine
JF - EBioMedicine
M1 - 104208
ER -