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Related Experiment Video

Updated: Jul 17, 2025

Author Spotlight: Assessing the Olfactory Effects of Airborne Pollutants — Buried Food and Social Odor Tests
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Pro-inflammatory markers associated with COVID-19-related persistent olfactory dysfunction.

Sophie S Jang1, Kwang S Pak1, Allyssa Strom2

  • 1Department of Otolaryngology, Head and Neck Surgery, University of California San Diego, La Jolla, California, USA.

International Forum of Allergy & Rhinology
|September 7, 2023
PubMed
Summary
This summary is machine-generated.

Persistent olfactory dysfunction after COVID-19 may be linked to elevated interferon (IFN) pathway cytokines in the olfactory cleft. This study identified specific biomarkers in mucus samples predicting long-term smell loss in COVID-19 survivors.

Keywords:
COVID‐19long haulersmucusolfactory dysfunctionpersistent smell losspro‐inflammatory

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Area of Science:

  • Immunology
  • Virology
  • Otolaryngology

Background:

  • Localized inflammation is implicated in acute COVID-19 olfactory dysfunction (OD).
  • Persistent COVID-19 OD (>3 months) pathophysiology and therapeutics remain poorly understood.
  • Olfactory cleft (OC) mucus biomarkers were prospectively evaluated as predictors of persistent OD.

Purpose of the Study:

  • To investigate olfactory cleft (OC) biomarkers as predictors of persistent olfactory dysfunction (OD) in COVID-19 patients.
  • To compare inflammatory and anti-viral biomarker profiles in the OC mucus of COVID-19 survivors with and without persistent OD, and non-infected individuals.

Main Methods:

  • Prospective study comparing COVID-19 subjects with persistent OD (>3 months) to COVID-19 subjects with no OD and non-infected controls.
  • Olfactory cleft (OC) mucus samples analyzed for 13 anti-viral and inflammatory biomarkers.
  • Biomarker levels compared using ANOVA and Mann-Whitney tests; viral RNA assessed via RT-PCR (COVID-19 N2 primer).

Main Results:

  • Significant differences in Interferon-lambda 1 (IFN-λ1) and Interferon-gamma (IFN-γ) expression were found across the three groups (p = 0.007 and p = 0.006, respectively).
  • Highest cytokine concentrations, particularly IFN-γ, were observed in COVID-19 patients with persistent OD.
  • IFN-α2 levels were elevated in COVID-19 OD versus no OD (p = 0.026); no significant difference in IL6 or detected N2 gene expression.

Conclusions:

  • Interferon (IFN) pathway cytokines are elevated in the olfactory microenvironment of COVID-19 patients with persistent olfactory dysfunction.
  • These findings suggest a potential role for IFN pathway dysregulation in the pathophysiology of long-term smell loss post-COVID-19.
  • OC mucus biomarkers, specifically IFN cytokines, may serve as predictors for persistent COVID-19 related olfactory dysfunction.