Paper says Long COVID should be grouped by biology, not symptoms

A new Frontiers in Medicine paper from Plano-based physician Robert Groysman argues Long COVID research has been too symptom-focused and should instead classify patients by six measurable biological mechanisms. The author says that approach could improve trial results and explain why many treatments have only mixed or modest effects.

Why it matters: - Long COVID trials and clinics may be missing important differences between patients if they group people only by shared symptoms. - A biology-first approach could help researchers match treatments to the mechanism driving each patient’s illness. - The paper argues that better patient stratification may improve the odds of finding therapies with clear effects.

What happened: - Robert Groysman, MD, founder of The COVID Institute in Plano, Texas, published a Hypothesis and Theory paper in Frontiers in Medicine in late May 2026. - The paper proposes that Long COVID should be sorted by underlying biology rather than symptoms alone. - Groysman says symptom-based grouping can blur clinical-trial results and may help explain why many Long COVID treatments have produced mixed or modest outcomes.

The details: - The framework identifies six recurring and testable domains: autonomic dysfunction, mitochondrial dysfunction, endothelial and microvascular dysfunction, gut dysbiosis and barrier disruption, mast cell signaling, and neuroendocrine dysregulation. - Each domain can be assessed with established physiological testing or lab markers. - The paper describes these domains as interacting nodes in a single network. - The model says dysfunction in one system can spread to others and create self-reinforcing loops. - The paper presents this network view as one explanation for why symptoms can continue long after the original infection has cleared. - The study reports no funding and no commercial conflict of interest. - The paper includes a prototype screening tool that Groysman describes as unvalidated and for research use only. - The full paper, Long COVID as a network disorder, is open access in Frontiers in Medicine.

Between the lines: - The paper is a hypothesis, not a proven treatment guide. - It says the model is falsifiable and will need prospective studies to test whether biologically defined groups respond differently to therapy. - Groysman says the framework reflects the mechanism-based method he has used in his Plano clinic for more than five years. - The argument is aimed at shifting Long COVID research from broad symptom categories to measurable biological subgroups.

What's next: - The paper calls for trials that enroll patients by biology rather than by symptoms. - Future studies will need to test whether the six-mechanism model improves diagnosis, trial design and treatment response. - Researchers will also need to validate the screening tool before it can be used beyond research settings.

The bottom line: - Groysman is trying to turn Long COVID from a symptom-defined condition into a mechanistically defined one, with the goal of making treatment research more precise and more effective.