This article is original to the Translational Medicine Network. Please indicate the source when reprinting. Author: Mia Introduction: SARS-CoV-2 can cause changes in the sense of smell, including complete loss of smell. Although changes in smell are usually temporary, many COVID-

This article is original to the Translational Medicine Network. Please indicate the source for reprinting.

Author: Mia

Introduction: SARS-CoV-2 can cause changes in the sense of smell, including complete loss of smell. Although olfactory changes are usually temporary, many COVID-19 patients exhibit olfactory dysfunction that lasts for months to years. Animal and human autopsy studies have proposed mechanisms that cause acute anosmia, but it is currently unclear how SARS-CoV-2 causes long-term loss of smell in a subset of patients.

Recently, researchers at Duke University Medical Center published a research report titled "Scientists find key reason why loss of smell occurs in long COVID-19" in the journal Science Translational Medicine. proposed that the reason why some people are unable to recover their sense of smell after new coronavirus is related to the immune system 's continued attack on olfactory nerve cells and the related decline in the number of these cells. Additionally, while focusing on anosmia, this research also sheds light on potential causes of other long-term symptoms of COVID-19, including general fatigue, shortness of breath, and brain fog, suggesting that these symptoms may be triggered by similar biological mechanisms.

DOI: 10.1126/scitranslmed.add0484

Research background

01

A considerable number of COVID-19 patients will experience loss of smell, and some patients still show olfactory dysfunction that lasts for months to years even after recovery. In previous studies, scientists found that transient gene expression changes in olfactory sensory neurons, changes in the characteristics of the mucus layer surrounding cilia, and inflammation are responsible for acute smell loss. In most patients with anosmia, after the virus is cleared from the body, normal epithelial repair processes rebuild the supporting cell population (and any incidentally damaged neurons), thereby restoring olfactory function.

However, the cause of long-term loss of smell is still unknown. This study from Duke University conducted a direct examination of olfactory tissue in patients with post-acute sequelae of COVID-19 (PASC) who have long-term olfactory dysfunction.

Mechanisms of long-term smell loss after Covid-19

02

The researchers analyzed olfactory epithelial samples collected from 24 biopsies, including nine patients with long-term smell loss after COVID-19, a non-COVID-19 patient control group, and a COVID-19 patient control group without anosmia. The researchers observed extensive infiltration of CD45+ immune cells in the mucous membranes of COVID-19 patients with long-term olfactory loss, but no was found in the control group. Furthermore, T cells identified by CD3 expression appeared to be more widely distributed in PASC samples, with many T cells localized to the upper layers of epithelial cells itself, whereas in controls T cells were mainly distributed in the deep stroma. The

researchers further used scRNA-seq for olfactory biopsy analysis. Biopsies from patients with long-term smell loss show fewer olfactory sensory neurons and altered immune cell populations compared with controls . Among them, diffuse infiltration of γδ T cells expressing the inflammatory cytokine interferon-γ occurred. Furthermore, there is a shift in myeloid cell population composition, including enrichment of CD207+ dendritic cells and , and depletion of anti-inflammatory M2 macrophages. Although no SARS-CoV-2 RNA or the protein was detected in these biopsy samples, gene expression in the olfactory epithelial barrier supporting cells (termed Sertoli cells) appears to reflect a response to ongoing inflammatory signals, with a concomitant reduction in the number of olfactory sensory neurons relative to the olfactory epithelial supporting cells.

These findings indicate that T cell-mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from tissues, suggesting a mechanism for long-term smell loss after COVID-19..

Research Implications

03

Researchers say the mechanistic insights provided by this work suggest potential new treatment strategies. For example, selective blocking of local pro-inflammatory immune cells or direct inhibition of specific signaling nodes may interfere with this circuitry that disrupts olfactory epithelial homeostasis or repair.Furthermore, the location of the olfactory epithelium facilitates localized drug delivery, which may provide a means to avoid systemic or off-target effects of new therapeutic agents.

Reference:

https://www.science.org/doi/10.1126/scitranslmed.add0484#sec-3

Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital.

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