Neurological Symptoms of COVID-19: The Zonulin Hypothesis

Front Immunol. 2021 Apr 26:12:665300. doi: 10.3389/fimmu.2021.665300. eCollection 2021.

Abstract

The irruption of SARS-CoV-2 during 2020 has been of pandemic proportions due to its rapid spread and virulence. COVID-19 patients experience respiratory, digestive and neurological symptoms. Distinctive symptom as anosmia, suggests a potential neurotropism of this virus. Amongst the several pathways of entry to the nervous system, we propose an alternative pathway from the infection of the gut, involving Toll-like receptor 4 (TLR4), zonulin, protease-activated receptor 2 (PAR2) and zonulin brain receptor. Possible use of zonulin antagonists could be investigated to attenuate neurological manifestations caused by SARS-CoV-19 infection.

Keywords: SARS-CoV-2; Toll-like receptor4; blood-brain barrier; gastrointestinal symptoms; haematogenous route; neurological symptoms; tight junctions; zonulin.

Publication types

  • Review

MeSH terms

  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / virology
  • Brain / metabolism
  • Brain / virology
  • COVID-19 / complications*
  • COVID-19 / metabolism
  • COVID-19 / virology
  • Complement System Proteins / metabolism
  • Gastrointestinal Diseases / complications
  • Gastrointestinal Diseases / metabolism
  • Gastrointestinal Diseases / virology
  • Haptoglobins / metabolism*
  • Humans
  • Nervous System Diseases / complications*
  • Nervous System Diseases / metabolism
  • Nervous System Diseases / virology
  • Protein Precursors / metabolism*
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / pathogenicity
  • Toll-Like Receptor 4 / metabolism

Substances

  • Haptoglobins
  • Protein Precursors
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • zonulin
  • Complement System Proteins