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IntroductionThe current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss.MethodsThis multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale.ResultsA total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported.ConclusionOlfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.

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.

BackgroundPatients with persistent COVID-19 olfactory dysfunction (OD) commonly report parosmia. Understanding the impact of COVID-19 OD and parosmia is critical to prioritizing research and interventions. In this study we investigate the impact of parosmia and other clinical and disease characteristics on health state utility values (HUVs) for those with persistent COVID-19 OD.MethodsPatients with a history of COVID-19 diagnosis and persistent OD were recruited from a tertiary medical center and a social media support forum for chemosensory dysfunction. Clinical characteristics and disease-specific symptoms were obtained along with self-reported history of smell function and presence of parosmia. HUVs were calculated using indirect (EuroQol 5-Dimension [EQ-5D]) and direct (VAS) measures.ResultsOur study included 286 subjects (75.52% women) with persistent COVID-19-related OD. Results (mean ± standard deviation) of HUVs based on EQ-5D and VAS were 0.81 ± 0.14 and 0.73 ± 0.21, respectively. Mean self-reported smell function (on a 0-10 scale) was 9.67 ± 1.25 pre-COVID-19, 0.93 ± 2.34 at diagnosis, and 3.39 ± 2.32 at most current assessment. A total of 89.16% of the subjects reported parosmia and 24.13% sought medical care for anosmia. Seeing an MD for OD (p

Viral infections have already been implicated with otitis media and sudden sensorineural hearing loss. However, the pathophysiology of COVID-19 as it relates to otologic disorders is not well-defined. With the spread of SARS-CoV-2, it is important to evaluate its colonization of middle ear mucosa. Middle ear and nasal tissue samples for quantitative RT-PCR and histologic evaluations were obtained from post-mortem COVID-19 patients and non-diseased control patients. Here we present evidence that SARS-CoV-2 colonizes the middle ear epithelium and co-localizes with the primary viral receptor, angiotensin-converting enzyme 2 (ACE2). Both middle ear and nasal epithelial cells show relatively high expression of ACE2, required for SARS-CoV-2 entry. The epithelial cell adhesion molecule (EpCAM) was use as a biomarker of epithelia. Furthermore, we found that the viral load in the middle ear is lower than that present in the nasal cavity.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.

This review summarizes the challenges and adaptations that have taken place in rhinology and facial plastics in response to the ongoing coronavirus disease-19 pandemic. In particular, the prolonged exposure and manipulation of the nasal and oral cavities portend a high risk of viral transmission. We discuss evidence-based recommendations to mitigate the risk of viral transmission through novel techniques and device implementation as well as increasing conservative management of certain pathologies.

The association of smell and taste loss with COVID-19 has been well demonstrated with high prevalence rates. In certain cases, chemosensory loss may be the only symptom of COVID-19 and may linger while other symptoms have resolved. The significance of persistent smell and taste loss and its relationship to ongoing viral shedding has yet to be investigated. In this cross-sectional study, of the 316 laboratory test-confirmed COVID-19 cases at our institution, 46 had subsequent test-based confirmation of viral clearance with 2 consecutive negative RT-PCR test results (reverse transcriptase polymerase chain reaction). Olfactory dysfunction was reported by 50% of the patients (23 of 46), with 78% (18 of 23) having subjective persistent smell loss despite negative RT-PCR test results. These preliminary data demonstrate the persistence of self-reported smell loss despite otherwise clinical resolution and undetectable nasal viral RNA.

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

BackgroundEndoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration.ObjectiveTo evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection.MethodsIn this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively.ResultsEighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P = .02 and P = .01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P = .03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P = .04).ConclusionOmega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.MethodsA single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.ResultsA total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.ConclusionIn ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has left many health systems around the world overwhelmed, forcing triaging of scarce medical resources. Identifying indicators of hospital admission for coronavirus disease 2019 (COVID-19) patients early in the disease course could aid the efficient allocation of medical interventions. Self-reported olfactory impairment has recently been recognized as a hallmark of COVID-19 and may be an important predictor of clinical outcome.MethodsA retrospective review of all patients presenting to a San Diego Hospital system with laboratory-confirmed positive COVID-19 infection was conducted with evaluation of olfactory and gustatory function and clinical disease course. Univariable and multivariable logistic regression were performed to identify risk factors for hospital admission and anosmia.ResultsA total of 169 patients tested positive for COVID-19 disease between March 3 and April 8, 2020. Olfactory and gustatory data were obtained for 128 (75.7%) of 169 subjects, of which 26 (20.1%) of 128 required hospitalization. Admission for COVID-19 was associated with intact sense of smell and taste, increased age, diabetes, and subjective and objective parameters associated with respiratory failure. On adjusted analysis, anosmia was strongly and independently associated with outpatient care (adjusted odds ratio [aOR] 0.09; 95% CI, 0.01-0.74), whereas positive findings of pulmonary infiltrates and/or pleural effusion on chest radiograph (aOR 8.01; 95% CI, 1.12-57.49) was strongly and independently associated with admission.ConclusionNormosmia is an independent predictor of admission in COVID-19 cases. Smell loss in COVID-19 may be associated with a milder clinical course.

BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI  16 but  30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2b

A 14-year-old boy had undergone an orbitozygomatic craniotomy for a pontine lesion. There was growth on surveillance imaging with involvement of posterior clinoids, clivus, and left pons suggestive of chordoma (Fernandez-Miranda et al., 2014b). An endoscopic endonasal approach was undertaken involving full upper and midclival exposure including bilateral posterior clinoidectomy (Fernandez-Miranda et al., 2014a; Truong et al., 2019a, 2019b). The internal carotid artery was skeletonized to maximize exposure and facilitate safe resection. The tumor was removed from between the dural layers of the midclivus while preserving the interdural abducens nerve (Barges-Coll et al., 2010). The brainstem component was resected while preserving the pontine perforators. Postoperative diagnosis was chordoma with MRI demonstrating complete resection. The patient was intact postoperatively. The video can be found here: https://youtu.be/g6SQ5JVK0Ko.

BackgroundThere is preliminary evidence that patients with chronic rhinosinusitis (CRS) and comorbid obstructive sleep apnea (OSA) have reduced quality-of-life (QOL) improvements after functional endoscopic sinus surgery (FESS) compared with patients without OSA. The effect of OSA severity on QOL improvement after FESS is unknown.ObjectivesTo better characterize the QOL improvement after FESS for patients with comorbid OSA and to assess whether QOL improvement is dependent on OSA severity.MethodsThis multi-institution, retrospective cohort study evaluated adult patients with CRS who underwent FESS between 2007 and 2015. Preoperative, 1-month, 3-month, 6-month, and 1-year postoperative 22-Item Sino-Nasal Outcome Test scores were used to evaluate QOL. We compared patients without OSA with patients with stratified OSA based on the preoperative apnea-hypopnea index. A multilevel, mixed-effects linear regression model was used for the analysis.ResultsOf 480 participants, 83 (17%) had OSA, and 47 of these patients had polysomnography results available for review. Both patients with OSA and patients without OSA reported significant QOL improvement after surgery (p < 0.0001) relative to baseline. In the unadjusted model, the subjects with OSA demonstrated a statistically worse outcome in 22-Item Sino-Nasal Outcome Test scores at each time point (2.4 points higher per time point, p = 0.006). When controlling for covariates, the adjusted model showed no difference in QOL outcome based on OSA status (p = 0.114). When stratified by OSA disease severity, the adjusted model showed no difference in the QOL outcome.ConclusionsPatients with CRS and comorbid OSA had worse QOL outcomes after FESS; however, when controlling for patient factors, there was no difference in QOL outcome. OSA disease severity did not seem to predict QOL improvement after FESS.

Objective: The anterior ethmoidal artery (AEA) is an important structure to identify during endoscopic sinus surgery. Although identification on imaging is easily taught, a consistent endoscopic landmark for the AEA, independent of anatomic ethmoid cell variation, is lacking, leaving many surgeons unclear about the exact location without dependence on navigation. Here, we describe a consistent endoscopic landmark, regardless of anatomical ethmoid variation. Methods: We prospectively enrolled adult patients undergoing endoscopic surgery involving frontal and ethmoid sinuses in this observational study. The AEA landmark was defined simply as the septation or ridge one step back along the ethmoid skull base from the posterior table of the frontal sinus. The gold standard to calculate the sensitivity of our endoscopic landmark was an image‐navigation system, registered to within 1.5 mm accuracy, locating the AEA within three planes. Both endoscopic and computerized tomography (CT) images of the pointer at the landmark were taken simultaneously. The concordance of endoscopic to navigation images was independently assessed by three blinded rhinologists. Results: Forty patients were included in our study with 73 sides analyzed. Diagnoses included chronic rhinosinusitis without polyps (52.5%), with polyps (22.5%), recurrent acute sinusitis (15%), sinonasal tumors (7.5%), and odontogenic sinusitis (2.5%). The AEA was accurately identified using our endoscopic landmark in 97.3% of the cases (71/73). Of the two cases in which the AEA was not found within the landmark, the artery was located ≤1 mm posteriorly. Conclusion: We describe a consistent endoscopic landmark to identify the AEA, conserved across various clinical diagnoses and anatomic variations in sinus structure. Level of Evidence: 3 Laryngoscope, 134:1096–1099, 2024 [ABSTRACT FROM AUTHOR]

Introduction  Race, ethnicity, and socioeconomic status (SES) are complex, interconnected social determinants of health outcomes. This study uses multivariable analysis on a combination of large national datasets to examine the effects of these factors on 5-year disease-specific survival (DSS) and conditional DSS (CDSS) for nasopharyngeal carcinoma (NPC). Methods  A retrospective study of adults with NPC between 2000 and 2017 from the Surveillance, Epidemiology, End Results (SEER) registry was performed, using the National Cancer Institute Yost Index, a census tract–level composite score of SES to categorize patients. Kaplan–Meier analysis and Cox's regression for DSS and CDSS were stratified by SES. Logistic regression was conducted to identify risk factors for advanced cancer stage at time of diagnosis and receiving multimodal therapy. Results  Our analysis included 5,632 patients. DSS was significantly associated with race and SES (p  < 0.01). Asian/Pacific Islander patients exhibited increased survival when controlling for other variables (hazard ratio [HR] = 0.73, p  < 0.01). Although Black patients were more likely to be diagnosed with advanced disease (Black odds ratio [OR] = 1.47, p  < 0.01), Black patients were also less likely to receive multimodal therapy; however, this relationship lost statistical significance once SES was incorporated into the multivariable analysis. DSS was decreased among the lowest (first) and middle (second) tertiles of SES (first HR = 1.34, p  < 0.01; second HR = 1.20, p  < 0.01) compared with the highest (third). Conclusion  Our results indicate that race, ethnicity, and SES significantly affect survival, stage at diagnosis, and treatment of NPC. An interplay of tumor biology and inequalities in access to care likely drives these disparities. [ABSTRACT FROM AUTHOR]