Overactive immune cells might drive nerve pain in long COVID

Publication date: Jul 29, 2026

According to this report, long COVID, or post-acute sequelae of SARS-CoV-2 infection, affects over 60 million individuals globally, often presenting with persistent nerve pain, fatigue, and cognitive issues. A key focus of the research centers on mast cells ? specialized immune cells heavily concentrated near nerves ? as a potential driver of this ongoing damage. The study suggests that the SARS-CoV-2 spike protein directly binds to receptors on mast cells, triggering an excessive release of inflammatory chemicals like histamine and tryptase. These chemicals then irritate pain receptors in small nerve fibers, leading to neuropathy characterized by burning pain, numbness, and tingling, particularly affecting the tiny, unmyelinated nerve endings in the skin and organs. The research indicates that this mast cell hyperactivity can also disrupt autonomic nervous system function, contributing to conditions like postural orthostatic tachycardia syndrome, alongside potentially compromising the blood-brain barrier and exacerbating brain inflammation.

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