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

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. Design- Case-Crossover Population-based study Setting- Veterans Affairs medical centers across the United States between January 1 2020 and August 18 2022. Participants- 367148 individuals with positive COVID-19 tests and preexisting ICD-10-CM codes recorded in the VA electronic health record were enrolled. Trigger- SARS-CoV2 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 at least 1 to 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 ICD10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based upon a patients' demographics, Elixhauser score, vaccination status, and COVID disease severity. 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 367148 patient post-COVID population. In our long COVID definition at a proportion of at least 59.7 percent (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 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-comorbidities should be preferentially watched for the development of long COVID. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work has been supported in part by grants from NIH NLM T15LM012495, R25LM014213, NIAAA R21AA026954, R33AA0226954 and NCATS UL1TR001412. This study was funded in part by the Department of Veterans Affairs. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was granted by our UB IRB I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data can be made available to VA researchers with IRB approval.