Classifying COVID-19 hospitalizations in epidemiology cohort studies: The C4R study
Authors: Oelsner Elizabeth C. , Krishnaswamy Akshaya , Rustamov Rafail , Balte Pallavi P. , Ali Tauqeer , Allen Norrina B. , Andrews Howard F. , Anugu Pramod , Arynchyn Alexander , Bateman Lori A. , Cai Jianwen , Chang Harry , Chen Lucas , Elkind Mitchell S. V. , Floyd James S. , Gabriel Kelley Pettee , Gharib Sina A. , Gutierrez Jose D. , Stukovsky Karen Hinckley , Howard Virginia J. , Isasi Carmen R. , Jager Lauren , Jin Ling , Judd Suzanne E. , Kanaya Alka M. , Kandula Namratha R. , Kelly Maureen R. , Khan Sadiya S. , Kucharska-Newton Anna , Lee Joyce S. , Levitan Emily B. , Lewis Cora E. , Make Barry J. , Malloy Kimberly , Manly Jennifer J. , Mauger David , Min Yuan-I , Murabito Joanne M. , Murphy Charles G. , Norwood Arnita F. , O’Connor George T. , Ortega Victor E. , Patel Ashmi A. , Pirzada Amber , Regan Elizabeth A. , Ring Kimberly B. , Rosamond Wayne D. , Schwartz David A. , Shikany James M. , Sotres-Alvarez Daniela , Tarlton Cheryl , Tse Janis , Meneses Elman M. Urbina , Vankineni Maya , Wenzel Sally E. , Woodruff Prescott G. , Xanthakis Vanessa , Yang Ji Hyun , Zakai Neil A. , Zhang Ying , Post Wendy S. 
Published: February 2025

Rationale
Robust COVID-19 outcomes classification is important for ongoing epidemiology research on acute and post-acute COVID-19 conditions. Protocolized medical record review is an established method to validate endpoints for clinical trials and cardiovascular epidemiology cohorts; however, a protocol to adjudicate hospitalizations for COVID-19 among epidemiology cohorts was lacking.

Objectives
We developed a protocol to ascertain and adjudicate hospitalized COVID-19 across a meta-cohort of 14 US prospective cohort studies. This report describes the first three years of protocol implementation (October 1, 2020—October 1, 2023) and evaluates its repeatability and performance compared to classification by administrative codes.

Methods
The protocol was adapted from cohort approaches to clinical cardiovascular events ascertainment and adjudication. Potential COVID-19 hospitalizations and deaths were identified by self-/proxy-report and, in some cases, active surveillance. Medical records were requested from hospitals and adjudicated for COVID-19 outcomes by clinically trained personnel according to a standardized rubric. Inter-rater agreement was assessed. The sensitivity and specificity of discharge diagnosis codes was compared to adjudicated diagnoses.

Measurements and main results
The study obtained medical records for 1,167 potential COVID-19 hospitalizations, which underwent protocolized adjudication. Adjudication confirmed COVID-19 infection was present for 1,030 (88%) events, of which COVID-19 was not the cause of hospitalization for 78 (8%). Of 952 hospitalizations determined by adjudicators to be caused by COVID-19, 319 (34%) participants were critically ill and 210 (22%) died. Pneumonia was confirmed in 822 (86%) and acute kidney injury in 350 (37%); other cardiovascular and thrombotic complications were rare (2–5%). Interrater reliability among adjudicators was high (kappa = 0.85–1.00) except for myocardial infarction (kappa = 0.60). Compared to adjudication, sensitivity of discharge diagnosis codes was higher for pneumonia (84%) and pulmonary embolism (81%) than for other complications (48–70%).

Conclusions
Protocolized adjudication confirmed four out of five COVID-19 hospitalizations in a US meta-cohort and confirmed cases of pneumonia, pulmonary embolism, and other conditions that were not indicated by discharge diagnosis codes. These results highlight the importance of validating health outcomes for use in research on COVID-19 and post-COVID-19 conditions, and some limitations of claims-based data.