This creates a plausible pathway for motor neuron degeneration, though causality is not yet proven.
We need long-term studies tracking SARS-CoV-2 survivors, neurodegeneration markers, and MND incidence.
The virus’s neurological reach may be wider than we realise.”

Bottom line:
SARS-CoV-2 delivers multiple hits to motor neurons: infection, inflammation, vascular compromise, protein aggregation.

Multiple hits = cumulative vulnerability. This shows how environmental exposures, lifestyle factors, & viral infections can converge on the same neurodegenerative pathways. SARS-CoV-2 may not create MND from scratch, but it could push already vulnerable neurons over the edge.

including motor neuron disease (MND).
Chronic neuronal stress and inflammation can prime cells for degeneration. Conceptually, prior neuronal injury (e.g. from TBI) could lower the threshold for SARS-CoV-2–induced neuronal damage increasing MND risk or hastening its onset.

Systemic immune activation can lead to autoimmune or bystander neuronal injury.
In genetically susceptible people, this could trigger or worsen MND.
Traumatic brain injury (TBI), including repeated concussions from sports like rugby, is a known risk factor for neurodegenerative diseases

Vascular and metabolic stress:
SARS-CoV-2 can cause microthrombi, hypoxia and endothelial dysfunction. Motor neurons are highly metabolically active, so even mild oxygen or nutrient deficits can accelerate degeneration.
Immune-mediated damage:

Neuroinflammation:
Infected neurons trigger microglial activation & astrocyte dysfunction, creating chronic inflammation.
Neuroinflammation is a known driver of MND, especially ALS.
Protein misfolding:
Viral infection causes ER (Endoplasmic Reticulum) stress and oxidative stress,

Let’s break down the neuropathology.
Direct infection of motor neurons:
SARS-CoV-2 enters via ACE2, NRP1, CD147 receptors and can replicate inside neurons.
These long, metabolically demanding cells are highly vulnerable to injury.