Effect of intra-nasal nitrilotriacetic acid trisodium salt in lowering elevated calcium cations and improving olfactory dysfunction in COVID-19 patients

Eur Arch Otorhinolaryngol. 2022 Sep;279(9):4623-4628. doi: 10.1007/s00405-022-07424-5. Epub 2022 May 14.


Purpose: An association between COVID-19 and olfactory dysfunction has been noted in many patients worldwide. The olfactory adaptation process leads to an increase in intracellular calcium cation levels. Nitrilotriacetic acid trisodium salt has high selective chelation for calcium cations from olfactory mucus. The aim of this work is to test the effect of an intranasal nitrilotriacetic acid trisodium salt to lower the elevated calcium cations in COVID-19 patients with relevant symptoms of olfactory dysfunction.

Methods: Fifty-eight COVID-19 adult patients with relevant symptoms of olfactory dysfunction were enrolled in a prospective randomized controlled trial. They received a nasal spray containing either 0.9% sodium chloride or 2% nitrilotriacetic acid trisodium salt. Olfactory function was assessed before and after treatment using the Sniffin' Sticks test. Quantitative analysis of calcium cation concentration in nasal secretions was performed using a carbon paste ion-selective electrode.

Results: After the application of nitrilotriacetic acid trisodium salt compared to sodium chloride, a significant improvement from functional anosmia to healthy normosmia with significant decrease in calcium cation concentration was observed.

Conclusions: Further collaborative research is needed to fully investigate the effect of an intranasal nitrilotriacetic acid trisodium salt in the treatment of olfactory disorders.

Keywords: Anosmia; COVID-19; SARS-CoV-2; Smell.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • COVID-19*
  • Calcium
  • Humans
  • Ions
  • Nitrilotriacetic Acid
  • Olfaction Disorders* / diagnosis
  • Olfaction Disorders* / drug therapy
  • Olfaction Disorders* / etiology
  • Prospective Studies
  • Smell
  • Sodium Chloride


  • Ions
  • Sodium Chloride
  • Nitrilotriacetic Acid
  • Calcium