Defining the Subtypes of Long COVID and Risk Factors for Prolonged Disease (Preprint)

BACKGROUND Importance: There have been over 759 million confirmed cases of COVID-19 worldwide. A significant portion of these infections will lead to long COVID and its attendant morbidities and costs. OBJECTIVE Objective: To empirically derive a long COVID case definition consisting of significantly increased signs, symptoms, and diagnoses to support clinical, public health, research, and policy initiatives related to the pandemic. METHODS Design: Case-Crossover Population-based study. Setting: Veterans Affairs (VA) medical centers across the United States between January 1, 2020 and August 18, 2022. Participants: 367,148 individuals with positive COVID-19 tests and preexisting ICD-10-CM codes recorded in the VA electronic health record were enrolled. Trigger: SARS-CoV-2 infection documented by positive laboratory test. Case Window: One to seven months following positive COVID testing. Main Outcomes and Measures: We defined signs, symptoms, and diagnoses as being associated with long COVID if they had a novel case frequency of >= 1:1000 and they were significantly increased in our entire cohort after a positive COVID test when compared to case frequencies before COVID testing. We present odds ratios with confidence intervals for long COVID signs, symptoms, and diagnoses, organized by ICD-10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based upon a patient’s demographics, Elixhauser score, vaccination status, and COVID disease severity. RESULTS Results: We developed a long COVID definition consisting of 323 ICD-10-CM diagnosis codes grouped into 143 ICD-10-CM functional groups that were significantly increased in our 367,148 patient post-COVID population. We define seventeen medical-specialty long COVID subtypes such as cardiology long COVID. COVID-19 positive patients developed signs, symptoms, or diagnoses included in our long COVID definition at a proportion of at least 59.7% (based on all COVID positive patients). Patients with more severe cases of COVID-19 and multiple comorbidities were more likely to develop long COVID. CONCLUSIONS Conclusions and Relevance: An actionable, empirical definition for long COVID can help clinicians screen for and diagnose long COVID, allowing identified patients to be admitted into appropriate monitoring and treatment programs. An actionable long COVID definition can also support public health, research and policy initiatives. COVID patients with low oxygen saturation levels or multiple co-morbidities should be preferentially watched for the development of long COVID.