Abstract:Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

Recent reports suggest an association between COVID-19 and altered olfactory function. Here we analyze bulk and single cell RNA-Seq datasets to identify cell types in the olfactory epithelium that express molecules that mediate infection by SARS-CoV-2 (CoV-2), the causal agent in COVID-19. We find in both mouse and human datasets that olfactory sensory neurons do not express two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. In contrast, olfactory epithelial support cells and stem cells express both of these genes, as do cells in the nasal respiratory epithelium. Taken together, these findings suggest possible mechanisms through which CoV-2 infection could lead to anosmia or other forms of olfactory dysfunction.

SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how SARS-CoV-2 causes persistent smell loss in a subset of patients. To address this question, we analyzed olfactory epithelial samples collected from 24 biopsies, including from nine patients with objectively quantified long-term smell loss after COVID-19. This biopsy-based approach revealed a diffuse infiltrate of T cells expressing interferon-γ and a shift in myeloid cell population composition, including enrichment of CD207 + dendritic cells and depletion of anti-inflammatory M2 macrophages. Despite the absence of detectable SARS-CoV-2 RNA or protein, gene expression in the barrier supporting cells of the olfactory epithelium, termed sustentacular cells, appeared to reflect a response to ongoing inflammatory signaling, which was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells. These findings indicate that T cell–mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post–COVID-19 smell loss.

Objectives/Hypothesis Responsible prescribing of postoperative pain medications is necessary in combatting the current opioid epidemic in the United States. The goal of this study was to determine which clinical factors affect opioid usage following functional endoscopic sinus surgery (FESS). Study Design Retrospective medical records study. Methods This is a single‐institution retrospective study of subjects undergoing FESS by the senior author between September 2016 and December 2017. Opioid usage was assessed for each patient at the first postoperative visit. Univariate and multivariable analyses were performed to investigate factors associated with pain medication usage. Patients using opioids prior to surgery were excluded. Results A total of 136 patients were stratified into three groups based on number of opioid tablets taken during the first week after surgery: 31 patients (23%) took no opioids, 61 patients (45%) took one to five tablets, and 44 patients (32%) took more than five tablets. Gender, extent of surgery, revision surgery, polyp status, and cystic fibrosis did not significantly vary between the three groups. Multinomial logistic regression analysis with backward stepwise variable selection method revealed that those who had septoplasty (odds ratio [OR]: 4.84, 95% confidence interval [CI]: 1.68‐13.98; P < .01) or were of younger age (OR 0.96, 95% CI: 0.93‐0.99; P = .01) had significantly higher odds of taking >5 tablets. Conclusions The majority of patients undergoing FESS did not take more than 5 opioid tablets after surgery. Concurrent septoplasty and younger age were associated with increased opioid usage. Knowledge of such factors can help surgeons to assess opioid prescribing patterns and to counsel their patients on postoperative pain.Laryngoscope, 129:1751–1755, 2019

This technique permits endoscopic endonasal inset and placement of reliable, well vascularized free tissue that may be utilized for complex, secondary reconstruction of the skull base.