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. 2025 Jan;155(1):120-134.
doi: 10.1016/j.jaci.2024.08.027. Epub 2024 Sep 11.

Determinants of persistence and recovery of chronic coronavirus disease 2019 chemosensory dysfunction

Dante G Minichetti  1 , Amelia Boyd  1 , Evan Lemire  2 , Jonathan Hacker  1 , Adam L Haber  2 , Rachel E Roditi  3 , Mark W Albers  4 , Stella Lee  3 , Kathleen M Buchheit  1 , Tanya M Laidlaw  1 , Lora G Bankova  5
Affiliations

Determinants of persistence and recovery of chronic coronavirus disease 2019 chemosensory dysfunction

Dante G Minichetti et al. J Allergy Clin Immunol. 2025 Jan.

Abstract

Background: In 2% to 4% of patients, coronavirus disease 2019 (COVID-19) chemosensory dysfunction (CSD) persists beyond 6 months, accounting for up to 4 million people in the United States. The predictors of persistence and recovery require further exploration.

Objective: We sought to define the predictors of recovery and assess the quality of CSD in registry subjects with self-reported persistent smell and taste dysfunction after COVID-19.

Methods: COVID-19 CSD participants (n = 408) from the 4 major waves of the pandemic completed questionnaires at 4 time points between 2021 and 2023, assessing demographics, sinonasal symptoms, and self-assessed recovery. Objective measurements of smell (UPSIT) and taste (BWETT) were performed on a subcohort (n = 108).

Results: In this chronic CSD cohort, the average symptom duration was 24 ± 5 months, with 70% of those who contracted COVID-19 in 2020 report ongoing dysfunction. Phantosmia and dysgeusia were most prevalent in the early waves of COVID-19, while most participants reported disrupted ability to distinguish scents and flavors as well as undulating chemosensory function. Subjects reported low incidence of subjective sinonasal symptoms but high prevalence of sleep and mood disturbance. Cigarette smoke phantosmia was predictive of persistence of CSD. Conversely, self-reported environmental allergies and hypertension were predictive of recovery, and dust mite allergies specifically were negative predictors of cigarette smoke phantosmia. Finally, no treatment resolved CSD, but nasal steroids were reported to be effective by recovered CSD subjects. Objective measures of both smell and taste were significantly reduced in patients with chronic CSD compared to controls.

Conclusions: Chronic COVID-19 CSD is a syndrome resistant to standard anti-inflammatory therapy. Preexisting environmental allergies and hypertension predict recovery, while cigarette smoke phantosmia predicts persistence.

Keywords: COVID-19; Chemosensory dysfunction; smell disruption; taste disruption.

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Conflict of interest statement

Disclosure statement Supported by grants from the National Institutes of Health: 1R01DC021425 (to L.G.B.), 1R21AI154345 (to L.G.B.), U19 AI095219 (to T.M.L. and IOF to L.G.B.), K23AI139352 (to K.M.B.), and K2 4AI180296 (to T.M.L.). Additional funding was through the Brigham Research Institute Fund to Sustain Research Excellence, Harvard Catalyst The Five Senses: Input & Response pilot fund, and a generous donation by the Vinik family (to L.G.B.). Disclosure of potential conflict of interest: K. M. Buchheit has served on scientific advisory boards for AstraZeneca, Regeneron, Sanofi-Genzyme, and GlaxoSmithKline. S. Lee has received clinical trial funding and has served on the advisory boards for AstraZeneca, Genentech, GSK, Lyra Therapeutics, OptiNose, and SanofiRegeneron. T. M. Laidlaw has served on scientific advisory boards for GlaxoSmithKline, AstraZeneca, Sanofi-Genzyme, Regeneron, and Eli Lilly. R. E. Roditi has received clinical trial funding from AstraZeneca. M. W. Alberts is cofounder of and owns shares in Aromha; has received in-kind contributions from Eli Lilly and research support from TLL Pharma; and is an SAB member of Sudo Therapeutics and consults for BMS and Transposon. The rest of the authors declare that they have no relevant conflicts of interest.

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