Presentation Details
Myeloid cell dysregulation and eicosanoid overproduction define distinct endotypes of chronic COVID19 chemosensory dysfunction

Dante Minichetti1, Amelia Boyd1, Jonathan Hacker1, Caitlin Wong1, Evan Lemire2, Wenjiang Deng2, Kathleen M.Buchheit1, Stella E.Lee3, Rachel E.Roditi3, Reagan w.Bergmark3, Adam L.Haber2, Tanya M.Laidlaw1, Lora Bankova1.

1Division of Allergy and Clinical Immunology, Jeff and Penny Vinik Center for Allergic Disease Research, Brigham & Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA.2Department of Environmental Health, Harvard T.H.Chan School of Public Health, Boston, MA, USA.3Division of Otolaryngology-Head and Neck Surgery, Brigham and Women's Hospital and Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA

Abstract


Chemosensory dysfunction (CSD) persists beyond 6 months in 2-4% of patients recovered from COVID19, accounting for over 4 million people in the US. We aimed to define the mechanistic correlates and characteristics of chronic COVID19 CSD. Study subjects (n=73) with COVID19 CSD and controls with no history of COVID19 CSD (n=21) at the time of enrollment were recruited and underwent objective evaluations of smell (UPSIT) and taste (B-WETT) acuity. Nasal cells and fluid were collected with self-applied Floqswabs and nasosorption strips, respectively. Among study subjects with chronic COVID19 CSD (24±5 months), UPSIT(23±7) and BWETT(16±4) were significantly reduced compared with controls (UPSIT33±4, p<0.001; BWETT19±3, p<0.01). Three endotypes of COVID19 CSD emerged: dysosmia (UPSIT≤25, B-WETT≥17), dysgeusia (UPSIT ≥26, BWETT ≤16), and combined dysosmia and dysgeusia (≤25, ≤16). All COVID19 CSD subjects had significantly increased nasal swab immune cells (53%) compared with normosmic controls (28%, p=0.02). Flow cytometric analysis indicated that the infiltrating immune cells were predominantly macrophages and neutrophils. Transcriptionally, subjects with dysosmia without dysgeusia had a differentially increased signature of myeloid derived suppressor cells. In subjects with dysgeusia or dysgeusia and dysosmia, several linoleic acid metabolites were significantly elevated and negatively correlated with BWETT scores: 9- and 13-HODE, r(64)= -0.4 p<0.01, 12,13di-HOME, r(64)= -0.5, p=0.001. An imprint of dysregulated myeloid immune signature emerges for COVID19 dysosmia, while eicosanoid dysregulation marks and differentiates the dysgeusia endotype. Chronic COVID19 CSD is a multifactorial syndrome with distinct endotypes.

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