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. 2026 May 29;13:1841690. doi: 10.3389/fmed.2026.1841690

Figure 1.

Mechanism-Anchored Network Model of Long COVID diagram illustrating Long COVID as a multisystem network disorder surrounded by seven blue circles labeled as primary domains: Dysautonomia, Mitochondrial/Bioenergetic Dysfunction, Endothelial/Microvascular Dysfunction, Gut Dysbiosis and Barrier Disruption, Small Fiber Neuropathy, Neuroendocrine Dysregulation, and Mast Cell Activation/Histamine Signaling. Orange rectangles represent secondary amplifiers: Persistent Immune Activation, Viral Antigen Persistence, Autoantibodies/Receptor Modulation, Neuroinflammation, and Small Fiber Neuropathy. There are bidirectional and amplifying influences among these factors. A green section at the bottom presents mechanism-informed stratification: Objective Physiologic Testing, Domain Enrichment, and Targeted Therapeutics.

Primary physiological domains are represented as the central network nodes capable of independently generating multisystem symptoms. Secondary processes such as immune activation, autoantibodies, viral antigen persistence, and neuroinflammation function as amplifiers that may reinforce instability within the network rather than acting as universally dominant initiating mechanisms. Illustrated interactions are representative rather than exhaustive.