Long-COVID subtypes may help stratify patients, inform treatment strategies: Study

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Researchers have uncovered distinct long-COVID subtypes they believe may help stratify patients and inform treatment strategies.

The investigators, from numerous organizations, recently published their findings in eBioMedicine, saying the semantic phenotypic clustering they identified “provides a foundation for assigning patients to stratified subgroups for natural history or therapy studies” on long COVID.

Study investigators Dr. Peter Robinson, a professor at the Jackson Laboratory in Farmington, CT, and Ben Coleman, a predoctoral associate at the lab, have been investigating long COVID using electronic health record (EHR) data from U.S. healthcare systems as part of the National COVID Cohort Collaborative (N3C).

N3C has one of the largest collections of deidentified clinical data in the U.S. for COVID-19 research.

Following the introduction of a diagnostic code for long COVID, Robinson, Coleman, and their colleagues analyzed clinical data for patients diagnosed with the condition. They sought to better define its characteristics and determine whether it is possible to identify and define subtypes.

Long COVID has highly variable duration, symptoms, and severity, making its diagnosis challenging. A code used in its diagnosis was made available on October 1, 2021, allowing patients to be formally diagnosed by a physician and enabling a record of the diagnosis to be entered into EHR systems.

Evaluating this data, the eBioMedicine study investigators saw so-called “similarity metrics” between a patient and a computational disease model and between pairs of patients. They adapted an algorithm called Phenomizer that calculates semantic similarity between a pair of patients based on their phenotypic features. With further calculations, they grouped patients into six distinct clusters, each representing a different long-COVID subtype.

The subtypes are defined by the following predominant clinical manifestations:

  1. Multi-system + lab, which is associated with severe initial infection and a high frequency of multiple symptoms. These symptoms include neuropsychiatric, pulmonary, constitutional (such as general fatigue), cardiovascular, and vertigo as well as lab test abnormalities.
  2. Hypoxemia and cough
  3. Neuropsychiatric (headache, insomnia, depression, and movement abnormalities)
  4. Cardiovascular
  5. Pain/fatigue 
  6. Multi-system pain (similar to the first subtype without the lab results)

Each subtype has different age, gender, and race frequencies as well as different prior comorbidities and conditions. The findings underscore the possibility that the mechanisms of long COVID may vary among individuals based on a collection of baseline risk factors, according to the Jackson Laboratory. Clinical research studies will be needed to define sub-cohorts and identify candidate therapeutics, it added.

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