Validation of an Internationally Derived Patient Severity Phenotype to Support COVID-19 Analytics from Electronic Health Record Data

J Am Med Inform Assoc. 2021 Feb 10;ocab018. doi: 10.1093/jamia/ocab018. Online ahead of print.


Introduction: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing COVID-19 with federated analyses of electronic health record (EHR) data.

Objective: We sought to develop and validate a computable phenotype for COVID-19 severity.

Methods: Twelve 4CE sites participated. First we developed an EHR-based severity phenotype consisting of six code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of ICU admission and/or death. We also piloted an alternative machine-learning approach and compared selected predictors of severity to the 4CE phenotype at one site.

Results: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability - up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean AUC 0.903 (95% CI: 0.886, 0.921), compared to AUC 0.956 (95% CI: 0.952, 0.959) for the machine-learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared to chart review.

Discussion: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine-learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly due to heterogeneous pandemic conditions.

Conclusion: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites.

Keywords: computable phenotype; data interoperability; data networking; disease severity; medical informatics; novel coronavirus.