Faculty Collaboration Database

Clinical Characterization and Prediction of Clinical Severity of SARS-CoV-2 Infection Among US Adults Using Data From the US National COVID Cohort Collaborative. JAMA Netw Open 2021 Jul 01;4(7):e2116901

Date

07/14/2021

Pubmed ID

34255046

Pubmed Central ID

PMC8278272

DOI

10.1001/jamanetworkopen.2021.16901

Scopus ID

2-s2.0-85109851689 (requires institutional sign-in at Scopus site)   149 Citations

Abstract

IMPORTANCE: The National COVID Cohort Collaborative (N3C) is a centralized, harmonized, high-granularity electronic health record repository that is the largest, most representative COVID-19 cohort to date. This multicenter data set can support robust evidence-based development of predictive and diagnostic tools and inform clinical care and policy.

OBJECTIVES: To evaluate COVID-19 severity and risk factors over time and assess the use of machine learning to predict clinical severity.

DESIGN, SETTING, AND PARTICIPANTS: In a retrospective cohort study of 1 926 526 US adults with SARS-CoV-2 infection (polymerase chain reaction >99% or antigen <1%) and adult patients without SARS-CoV-2 infection who served as controls from 34 medical centers nationwide between January 1, 2020, and December 7, 2020, patients were stratified using a World Health Organization COVID-19 severity scale and demographic characteristics. Differences between groups over time were evaluated using multivariable logistic regression. Random forest and XGBoost models were used to predict severe clinical course (death, discharge to hospice, invasive ventilatory support, or extracorporeal membrane oxygenation).

MAIN OUTCOMES AND MEASURES: Patient demographic characteristics and COVID-19 severity using the World Health Organization COVID-19 severity scale and differences between groups over time using multivariable logistic regression.

RESULTS: The cohort included 174 568 adults who tested positive for SARS-CoV-2 (mean [SD] age, 44.4 [18.6] years; 53.2% female) and 1 133 848 adult controls who tested negative for SARS-CoV-2 (mean [SD] age, 49.5 [19.2] years; 57.1% female). Of the 174 568 adults with SARS-CoV-2, 32 472 (18.6%) were hospitalized, and 6565 (20.2%) of those had a severe clinical course (invasive ventilatory support, extracorporeal membrane oxygenation, death, or discharge to hospice). Of the hospitalized patients, mortality was 11.6% overall and decreased from 16.4% in March to April 2020 to 8.6% in September to October 2020 (P = .002 for monthly trend). Using 64 inputs available on the first hospital day, this study predicted a severe clinical course using random forest and XGBoost models (area under the receiver operating curve = 0.87 for both) that were stable over time. The factor most strongly associated with clinical severity was pH; this result was consistent across machine learning methods. In a separate multivariable logistic regression model built for inference, age (odds ratio [OR], 1.03 per year; 95% CI, 1.03-1.04), male sex (OR, 1.60; 95% CI, 1.51-1.69), liver disease (OR, 1.20; 95% CI, 1.08-1.34), dementia (OR, 1.26; 95% CI, 1.13-1.41), African American (OR, 1.12; 95% CI, 1.05-1.20) and Asian (OR, 1.33; 95% CI, 1.12-1.57) race, and obesity (OR, 1.36; 95% CI, 1.27-1.46) were independently associated with higher clinical severity.

CONCLUSIONS AND RELEVANCE: This cohort study found that COVID-19 mortality decreased over time during 2020 and that patient demographic characteristics and comorbidities were associated with higher clinical severity. The machine learning models accurately predicted ultimate clinical severity using commonly collected clinical data from the first 24 hours of a hospital admission.

Author List

Bennett TD, Moffitt RA, Hajagos JG, Amor B, Anand A, Bissell MM, Bradwell KR, Bremer C, Byrd JB, Denham A, DeWitt PE, Gabriel D, Garibaldi BT, Girvin AT, Guinney J, Hill EL, Hong SS, Jimenez H, Kavuluru R, Kostka K, Lehmann HP, Levitt E, Mallipattu SK, Manna A, McMurry JA, Morris M, Muschelli J, Neumann AJ, Palchuk MB, Pfaff ER, Qian Z, Qureshi N, Russell S, Spratt H, Walden A, Williams AE, Wooldridge JT, Yoo YJ, Zhang XT, Zhu RL, Austin CP, Saltz JH, Gersing KR, Haendel MA, Chute CG, National COVID Cohort Collaborative (N3C) Consortium

Author

Carlos E. Figueroa Castro MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Comorbidity
Databases, Factual
Extracorporeal Membrane Oxygenation
Female
Forecasting
Hospitalization
Humans
Hydrogen-Ion Concentration
Male
Middle Aged
Models, Biological
Pandemics
Respiration, Artificial
Retrospective Studies
Risk Factors
Severity of Illness Index
United States
Young Adult