(270) Validation of Real-World Case Definitions for COVID-19 Diagnosis and Severe COVID-19 Illness Among Patients Infected with SARS-CoV-2: Translation of Clinical Trial Definitions to Real-World Settings

Publication Number: 603

Background: As polymerase chain reaction (PCR) tests for coronavirus disease 2019 (COVID-19) diagnosis are becoming less frequently conducted and a standardized surveillance case definition of severe COVID-19 illness is lacking, it is important to establish the accuracy of codified COVID-19 case definitions for the analyses of real-world datasets.

Objectives: To assess the performance of the International Classification of Diseases 10th Revision, Clinical Modification (ICD-10-CM) code for COVID-19 diagnosis (U07.1) against PCR test results (Objective 1); to translate severe COVID-19 illness endpoints from clinical trials to real-world case definitions through validation of electronic medical record (EMR)-based codified algorithms against chart review (Objective 2).

Methods: This retrospective, longitudinal cohort study utilized EMR data from the Mass General Brigham COVID-19 Data Mart (3/1/2020–11/19/2020) for adult patients with ≥1 PCR test, antigen test, or ICD-10-CM code for COVID-19 (U07.1) (Objective 1) and adult patients with a positive PCR test hospitalized with COVID-19 (Objective 2). Severe COVID-19 illness endpoints were defined using algorithms derived from the Pfizer-BioNTech COVID-19 vaccine trial and according to the World Health Organization (WHO).

Results: Among 354,124 patients included in Objective 1, 96% had ≥1 PCR test, 6% of whom had ≥1 positive PCR test, and 11% had ≥1 ICD-10-CM code U07.1. The ICD-10-CM code U07.1 had low sensitivity (54%) and positive predictive value [PPV] (63%) but high specificity (97%) against the PCR test. Among 300 patients hospitalized for COVID-19 who were randomly sampled for chart review in Objective 2, the EMR-based case definitions for severe COVID-19 illness endpoints based on the Pfizer–BioNTech COVID-19 vaccine trial definition had high PPV (>95%), showing better performance than severe or critical COVID-19 endpoints defined by the WHO (PPV: 79%).

Conclusions: COVID-19 diagnosis based on ICD-10-CM code U07.1 did not have adequate sensitivity; therefore, PCR test results may be required to confirm true COVID-19 cases in real-world datasets. The EMR-based case definition showed high positive predictive performance and can be used to identify cases of severe COVID-19 illness in real-world datasets. These findings highlight the importance of validating outcomes when conducting research using real-world data, and help orient researchers to COVID-19 patient data, especially in light of testing fatigue or increased home-based testing where PCR test results are not readily available.