Chronic cerebral aspects of long COVID, post‐stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic

The chronic neurological aspects of traumatic brain injury, post‐stroke syndromes, long COVID‐19, persistent Lyme disease, and influenza encephalopathy having close pathophysiological parallels that warrant being investigated in an integrated manner. A mechanism, common to all, for this persistence of the range of symptoms common to these conditions is described. While TNF maintains cerebral homeostasis, its excessive production through either pathogen‐associated molecular patterns or damage‐associated molecular patterns activity associates with the persistence of the symptoms common across both infectious and non‐infectious conditions. The case is made that this shared chronicity arises from a positive feedback loop causing the persistence of the activation of microglia by the TNF that these cells generate. Lowering this excess TNF is the logical way to reducing this persistent, TNF‐maintained, microglial activation. While too large to negotiate the blood‐brain barrier effectively, the specific anti‐TNF biological, etanercept, shows promise when administered by the perispinal route, which allows it to bypass this obstruction.