This line alone should make us cautious: ‘The neuro-invasion of SARS-CoV-2 has been shown to result in brain vascular inflammation, but the long-term impact of COVID-19 neurological sequalae is still unknown’ Hyperinflammationheadaches Yes SARS-Co-V2 invades the brain.

metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache

Long COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache.

Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation.

‘CRP level may not be a right inflammation predictor of long COVID headaches’ I’ve been saying CRP is the wrong marker in many inflammatory disorders for years. Stop relying on it to ‘prove’ someone is inflamed or not.

Despite viral clearance, long COVID patients continued to sustain low-grade inflammation, evidenced by persistent increases of inflammatory markers such as IL-6 and IFN-γ and chemokines such as CXCL10, CCL7 and CCL8 even up to more than 3 months post headache symptom onset.

These findings further supported the critical roles of proinflammatory M1 macrophage-driven sustained inflammation in long COVID, likely contributing to chronic headache

Picture to demonstrate the immuno-metabolic rewriting in long Covid headache

For the millionth time, long Covid is not psychological. End.