An ordinal severity scale for COVID-19 retrospective studies using Electronic Health Record data

Lay Summary Electronic Health Record (EHR) data collected during routine clinical care offer real-world evidence to support decision-making and observational research. In the wake of the COVID-19 pandemic, one of the most powerful tools used in clinical trials is the World Health Organization Clinical Progression Scale, which provides a minimal set of common outcome measures for guiding research. We developed a generalizable disease severity framework to facilitate research studies utilizing EHR data. EHR data on 2 880 456 SARS-CoV-2-infected patients from 63 health centers across the United States were examined using the National COVID Cohort Collaborative. We identified and validated concept sets using standard medical terminologies necessary to assign a level of disease severity to each patient. Patterns of change in disease severity among patients during the 28-day period following a COVID-19 diagnosis were characterized and usefulness of the proposed scale was demonstrated. Our severity scale can be used in other COVID-19 observational studies and potentially future diseases requiring point-in-time monitoring of real-world data. Objectives Although the World Health Organization (WHO) Clinical Progression Scale for COVID-19 is useful in prospective clinical trials, it cannot be effectively used with retrospective Electronic Health Record (EHR) datasets. Modifying the existing WHO Clinical Progression Scale, we developed an ordinal severity scale (OS) and assessed its usefulness in the analyses of COVID-19 patient outcomes using retrospective EHR data. Materials and Methods An OS was developed to assign COVID-19 disease severity using the Observational Medical Outcomes Partnership common data model within the National COVID Cohort Collaborative (N3C) data enclave. We then evaluated usefulness of the developed OS using heterogenous EHR data from January 2020 to October 2021 submitted to N3C by 63 healthcare organizations across the United States. Principal component analysis (PCA) was employed to characterize changes in disease severity among patients during the 28-day period following COVID-19 diagnosis. Results The data set used in this analysis consists of 2 880 456 patients. PCA of the day-to-day variation in OS levels over the totality of the 28-day period revealed contrasting patterns of variation in disease severity within the first and second 14 days and illustrated the importance of evaluation over the full 28-day period. Discussion An OS with well-defined, robust features, based on discrete EHR data elements, is useful for assessments of COVID-19 patient outcomes, providing insights on the progression of COVID-19 disease severity over time. Conclusions The OS provides a framework that can facilitate better understanding of the course of acute COVID-19, informing clinical decision-making and resource allocation.