SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury

Area of Science:

• Neuroscience
• Virology
• Pathology

Background:

• Coronavirus disease (COVID-19), caused by SARS-CoV-2, presents with diverse clinical manifestations, ranging from asymptomatic cases to severe pneumonia and multi-organ failure.
• SARS-CoV-2 can infect various organs, including the brain, yet viral detection in blood is rare, posing a challenge to understanding systemic spread.
• Neurological involvement is observed in over a third of COVID-19 cases, often without clear respiratory pathology.

Purpose of the Study:

• To propose a novel model for SARS-CoV-2 neuroinvasion and systemic dissemination.
• To explain the mechanisms behind the wide spectrum of COVID-19 clinical presentations, including neurological symptoms and multi-organ injury.

Main Methods:

• The study proposes a theoretical model based on existing knowledge of viral behavior and cellular transport mechanisms.
• It hypothesizes nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium as entry points for brain invasion.
• It suggests viral dissemination from the brain to peripheral organs via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula.

Main Results:

• The proposed model explains neurological symptoms in COVID-19 patients, even without significant lung involvement.
• It accounts for the protracted presence of SARS-CoV-2 in some patients post-recovery.
• It provides a framework for understanding exaggerated immune responses and multi-organ failure in severe COVID-19 cases.

Conclusions:

• SARS-CoV-2 can invade the brain via nerve terminals and spread systemically, independent of respiratory infection.
• This neurocentric model clarifies diverse COVID-19 pathologies and offers insights into potential long-term sequelae.
• The model establishes a basis for future research into SARS-CoV-2 pathogenesis and therapeutic strategies.