Background: The skin prick test (SPT) is the gold standard for diagnosing sensitization to inhalant allergies. The Skin Prick Automated Test (SPAT) device was designed for increased consistency in test results, and captures 32 images to be jointly used for allergy wheal detection and delineation, which leads to a diagnosis. Materials and Methods: Using SPAT data from 868 patients with suspected inhalant allergies, we designed an automated method to detect and delineate wheals on these images. To this end, 10,416 wheals were manually annotated by drawing detailed polygons along the edges. The unique data-modality of the SPAT device, with 32 images taken under distinct lighting conditions, requires a custom-made approach. Our proposed method consists of two parts: a neural network component that segments the wheals on the pixel level, followed by an algorithmic and interpretable approach for detecting and delineating the wheals. Results: We evaluate the performance of our method on a hold-out validation set of 217 patients. As a baseline we use a single conventionally lighted image per SPT as input to our method. Conclusion: Using the 32 SPAT images under various lighting conditions offers a considerably higher accuracy than a single image in conventional, uniform light.

The skin prick test (SPT) is the gold standard for diagnosing allergic sensitization to aeroallergies. The Skin Prick Automated Test (SPAT) device has previously demonstrated reduced variability and more consistent test results compared to manual SPT. The current study aims to develop and validate an artificial intelligence (AI) assisted readout method to support physicians in interpreting skin reactions following SPAT. To train the AI algorithm, 7812 wheals (651 patients) are manually labeled. To validate the AI measurement, the longest wheal diameter of 2604 wheals (217 patients) is measured by the treating physician and compared to the AI measurement. In addition, AI-assisted readout is validated on a separate test cohort of 95 patients (1140 wheals). We demonstrate that the AI measurements of the longest wheal diameter exhibit a strong correlation with the physician's measurements. The AI algorithm shows a specificity of 98·4% and sensitivity of 85·0% in determining positive or negative test results in the validation cohort. In the test cohort, physicians adjust 5·8% of AI measurements, leading to a change in the test interpretation for only 0·5% of cases. AI-assisted readout significantly reduces inter- and intra-observer variability and readout time compared to manual physician measurements. Altogether, the AI-assisted readout method demonstrates high accuracy, with minimal misclassification of test results. Adding AI to SPAT further improves standardization across the SPT process, significantly reducing observer variability and time to readout.

Background:Sinonasal intestinal-type adenocarcinoma (ITAC) is a rare disease entity. In contrast to most previous studies, this cohort study consists of a substantial number of uniformly treated patients undergoing endoscopic surgery and adjuvant radiotherapy and provides updated insights into survival outcomes and tumor and treatment-related prognostic factors. Material and methods:We retrospectively analyzed the medical records of 200 patients primarily treated for ITAC between 1992 and 2022 in our tertiary referral center. Descriptive statistics were applied using Kaplan-Meier method. Cox models were used for univariable and multivariable data analysis. Results:The 5-year overall survival (OS), disease-specific survival (DSS), and local recurrence-free survival (LRFS) rates were 71.4%, 85.1%, and 55.2% respectively. At 10 years, the numbers decreased to 48.2%, 76.2%, and 32.2% respectively. Significant differences were found in OS and DSS between T-groups. Poorly differentiated tumors had decreased DSS compared to well-differentiated tumors (HR: 3.38 [95% CI: 1.20-9.51], p=.0209). Signet-cell differentiation was associated with the poorest survival among poorly differentiated tumors although not reaching significance. In 34.0% of patients, there was local recurrence, with half of the cases detected within the first two years of follow-up but over 10% of recurrence occurring after 10 years. Positive surgical margins (HR: 2.95 [95% CI: 1.29-6.74], p=.0106), local recurrence (HR: 12.28 [95% CI: 5.59-26.99], p<.0001), and distant metastasis (HR: 41.17 [95% CI: 21.58-78.55], p<.0001) negatively affected DSS. Distant metastasis occurred more frequently in poorly differentiated tumors (25.6%) compared to moderately differentiated (9.5%) and well-differentiated tumors (2.5%) (p=.002). Conclusions:This extensive study focusing on sinonasal ITAC primarily managed through endoscopic resection and radiotherapy, demonstrates that T-classification and tumor differentiation are independent prognostic factors influencing survival. Furthermore, local recurrence, distant metastasis, and positive surgical margins negatively affect OS and DSS.

BACKGROUND:Double-blinded placebo-controlled trials have revealed the efficacy of mepolizumab and omalizumab in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). However, real-world efficacy (RWE) data, data on therapeutic response and level of disease control for both biologicals are lacking. METHODOLOGY:167 patients with uncontrolled severe CRSwNP, meeting national reimbursement criteria, were included with follow-up over 24 weeks. Primary outcomes included changes in nasal congestion (NCS), nasal polyp score (NPS), VAS-scores, SNOT-22, ACQ-5, and AQLQ scores. Secondary outcomes were therapeutic response and disease control according to EUFOREA/EPOS criteria. RESULTS:Of the 167 CRSwNP patients, 144 received mepolizumab and 23 omalizumab. After 24 weeks, Patient reported outcomes and NPS significantly improved for both biologicals, with significant effects seen at 12 weeks, with further reduction in NPS by 24 weeks in mepolizumab patients. 74% of patients on omalizumab and 81% of patients on mepolizumab continued their therapy beyond 24 weeks, with 47% and 45% of patients on omalizumab and mepolizumab respectively showing an excellent therapeutic response, with only one out of seven having no/poor response. Disease control was reached in one third of the patients at 24 weeks. CONCLUSIONS:Both mepolizumab and omalizumab significantly improved patient-reported outcomes after 24-weeks, with major effects already observed at 12 weeks. Follow-up beyond 24-weeks might reveal additional effects on both control and remission.

We present a protocol for the rapid postmortem bedside procurement of selected tissue samples using an endoscopic endonasal surgical technique that we adapted from skull base surgery. We describe steps for the postmortem collection of blood, cerebrospinal fluid, a nasopharyngeal swab, and tissue samples; the clean-up procedure; and the initial processing and storage of the samples. This protocol was validated with tissue samples procured postmortem from COVID-19 patients and can be applied in another emerging infectious disease. For complete details on the use and execution of this protocol, please refer to Khan et al. (2021)1 and Khan et al. (2022).2

We aimed to examine the correlation between clinical characteristics and the pathogenic gene variants in patients with Primary Ciliary Dyskinesia (PCD). We conducted a retrospective single-center study in patients with PCD followed at the University Hospitals Leuven. We included patients with genetically confirmed PCD and described their genotype, data from ultrastructural ciliary evaluation and clinical characteristics. Genotype/phenotype correlations were studied in patients with the most frequently involved genes. We enrolled 74 patients with a median age of 25.58 years. The most frequently involved genes were DNAH11 (n = 23) and DNAH5 (n = 19). The most frequent types of pathogenic variants were missense (n = 42) and frameshift variants (n = 36) and most patients had compound heterozygous variants (n = 44). Ciliary ultrastructure (p < 0.001), situs (p = 0.015) and age at diagnosis (median 9.50 vs 4.71 years, p = 0.037) differed between DNAH11 and DNAH5. When correcting for situs this difference in age at diagnosis was no longer significant (p = 0.973). Patients with situs inversus were diagnosed earlier (p = 0.031). Respiratory tract microbiology (p = 0.161), lung function (cross-sectional, p = 0.829 and longitudinal, p = 0.329) and chest CT abnormalities (p = 0.202) were not significantly different between DNAH11 and DNAH5 variants. This study suggests a genotype–phenotype correlation for some of the evaluated clinical characteristics of the two most frequently involved genes in this study, namely DNAH11 and DNAH5.

BACKGROUND: Nasal hyperreactivity (NHR) is prevalent in all chronic upper airway inflammatory phenotypes, including allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Although NHR in patients with non-allergic rhinitis is mediated by neuronal pathways, AR and CRSwNP are mainly characterized by type 2 inflammation. METHODS: Eighteen healthy controls and 45 patients with symptomatic AR/CRSwNP underwent a cold, dry air (CDA) provocation test for objective diagnosis of NHR. Before and after, questionnaires were filled out and nasal secretions and biopsies were collected. Markers for neurogenic inflammation (substance P, calcitonin gene-related peptide, neurokinin A), epithelial activation (IL-33), and histamine were measured in secretions by ELISA; and expression of neuronal markers PGP9.5, TRPV1, and TRPM8 was studied in biopsies by RT-q-PCR. Effects of histamine on TRPV1/A1 were studied with Ca2+-imaging using murine trigeminal neurons. RESULTS: CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/ patients (p

BACKGROUND:The introduction of CFTR modulators has changed the landscape in the treatment of cystic fibrosis (CF) and early case series have shown improvements in sinonasal outcomes in this patient population. METHODOLOGY:A real-word data study was performed to evaluate the impact of dual therapy with tezacaftor/ivacaftor (TEZ/IVA) and triple therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CF-related chronic rhinosinusitis (CRS), by comparing subjective and objective outcome measures at baseline, 12 months after treatment with TEZ/IVA and six months after treatment with ELX/TEZ/IVA. RESULTS:In total, 43 CF patients, with a mean age of 32 years, were included. After triple therapy, significant improvements in overall visual analogue scale, SNOT-22, Lund Kennedy, nasal polyps, and Lund-Mackay scores were observed, whereas no beneficial effect could be seen in patients treated with dual therapy. Bacterial upper airway colonization did not differ pre- and postmodulator therapy in the present study. The number of responders to dual and triple therapy is 23.8% and 63.2% of the patients, respectively. CONCLUSIONS:Triple therapy with ELX/TEZ/IVA is superior to dual therapy with TEZ/IVA in the treatment of CF-CRS, as significantly reduced sinonasal complaints, nasal endoscopy and CT scores were observed after triple therapy, whereas this was not the case for dual therapy.

BACKGROUND:Recent advances in endoscopic endonasal transsphenoidal approaches (EETA) for skull base lesions have resulted in a significant increase in extent and complexity of skull base defects, demanding more elaborate and novel reconstruction techniques to prevent cerebrospinal fluid (CSF) leakage and to improve healing. Currently, commercially available fibrin sealants are often used to reinforce the skull base reconstruction. However, problems have been reported regarding hypersensitivity reactions, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) membranes as an alternative for commercially available fibrin glues in EETA-related skull base reconstruction reinforcement. METHODS/DESIGN:This multicenter, prospective randomized controlled trial aims to demonstrate non-inferiority of L-PRF membranes compared to commercially available fibrin sealants in EETA cases (1) without intra-operative CSF-leak as dural or sellar floor closure reinforcement and (2) in EETA cases with intra-operative CSF-leak (or very large defects) in which a classic multilayer reconstruction has been made, as an additional sealing. The trial includes patients undergoing EETA in three different centers in Belgium. Patients are randomized in a 1:1 fashion comparing L-PRF with commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage. Secondary endpoints are identification of risk factors for reconstruction failure, assessment of rhinological symptoms, and interference with postoperative imaging. Additionally, a cost-effectiveness analysis is performed. DISCUSSION:With this trial, we will evaluate the safety and efficacy of L-PRF compared to commercially available fibrin sealants. TRIAL REGISTRATION:ClinicalTrials.gov NCT03910374. Registered on 10 April 2019.

BACKGROUND: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics. OBJECTIVE: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology. METHODOLOGY: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion. RESULTS: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security as-pects. Up to 300 patients have already been included. CONCLUSIONS: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE. (c) 2022 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:431-8)

OBJECTIVES:Chronic rhinosinusitis (CRS) is prevalent in people with cystic fibrosis (PwCF) and is often refractory to treatments. Uncontrolled CRS might negatively impact the lower airways and the quality of life. The aim of this study is to evaluate the burden of cystic fibrosis (CF)-related CRS in the era of CF transmembrane conductance regulator (CFTR) modulators.METHODS:Adult PwCF were asked to fill in a questionnaire on sinonasal complaints, they underwent a nasal endoscopy, bacteriological sampling, and a CT scan. Afterwards, these outcome measures were compared between patients treated with and without modulators.RESULTS:In the 122 included patients, CRS was present in 83%. CFTR modulators were prescribed in 48% of the patients, with a median of 10 months since the start of the treatment. Subjectively, the median SNOT-22 score was 16/110. Objectively, a median Lund-Kennedy score of 6/12 and modified Lund-Mackay score of 10/24 were observed. No correlation could be found between SNOT-22 score and other outcome measures including endoscopy and radiology. Altogether, 21% of the patients had controlled disease. When comparing patients treated with and without modulators, significantly lower CT scores (p = 0.0018) and less bacterial colonization (p = 0.0082) were observed in patients receiving modulators.CONCLUSION:CF-CRS is highly prevalent in our cohort and only the minority of PwCF has a well-controlled disease. A multidisciplinary ENT-pneumology clinic would be beneficial, as there is a high discrepancy between patient-reported symptoms and the extent of the disease. CFTR modulators are promising, as lower CT scores and less bacterial colonization were observed in the modulator group.LEVEL OF EVIDENCE:Level 3 Laryngoscope, 133:2898-2909, 2023.

BackgroundThe skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of having an inhalant allergy. Recently, it was demonstrated that SPT using a novel skin prick automated test (SPAT) device showed increased reproducibility and tolerability compared to the conventional SPT, among other benefits.ObjectiveThis study aimed to evaluate prick location bias using the novel SPAT device.MethodsA total of 118 volunteers were enrolled in this study and underwent SPATs with histamine (nine pricks) and glycerol control (one prick) solutions on the volar side of their forearms. Imaging of the skin reactions was performed using the SPAT device, and the physician determined the longest wheal diameter by visually inspecting the images using a web interface. Prick location bias was assessed along the medial vs. lateral and proximal vs. distal axes of the forearm.ResultsIn total, 944 histamine pricks were analyzed. Four medial and four lateral histamine pricks were grouped, and wheal sizes were compared. The longest wheal diameters were not significantly different between the medial and lateral prick locations (p = 0.41). Furthermore, the pricks were grouped by two based on their position on the proximal–distal axis of the forearm. No significant difference was observed among the four groups of analyzed prick locations (p = 0.73).ConclusionThe prick location on the volar side of the forearm did not influence wheal size in SPAT-pricked individuals.

To the Editor, Respiratory allergies affect 30%–40% of individuals worldwide and represent a major health-economic problem.1 Identification of the triggering or causative allergens in symptomatic patients is based on skin prick test or serum-specific IgE analysis in addition to a detailed medical history by the physician.2, 3 Skin prick test (SPT) is the first choice diagnostic instrument according to international guidelines because of reduced cost, faster results, less invasiveness and a better sensitivity-specificity profile compared to extract-based specific IgE analysis.4, 5 However, there is a need for standardized automation of the entire SPT procedure given that SPT exhibits both operator and device-dependent variability.6, 7 A monocentric, prospective diagnostic test accuracy study (ISRCTN14098475) was performed at the University Hospitals of Leuven (UZ Leuven, Belgium) to compare reproducibility, tolerability and safety of a newly developed Skin Prick Automated Test or SPAT (Figure S1A–C) to the Skin Prick Manual Test or SPMT (Figure S1D–F). The full methodology can be found in the Appendix S1. In brief, SPAT was performed on the right arm and SPMT was performed on the left arm. On both arms, pricks were applied with 10 mg/ml histamine (N = 9) and glycerol-saline (N = 1) as respectively positive and negative control (HAL Allergy) in line with previous device validation studies (also Appendix S1). In total, 118 healthy volunteers (49 males – 69 females; mean ± standard deviation age: 40.1 ± 13.3) were enrolled in the study (Figure S2). SPAT showed significantly lower coefficient of variation of the histamine wheal sizes (SPAT median (IQR): 13.6% (10.4%–17.7%)) compared to SPMT (SPMT median: 17.6% (13.6%–22.9%); p < 0.0001; Figure 1). Similar findings were obtained in all but one of the pre-defined age decades (Figure S3). Wheal sizes were significantly larger in SPAT compared to SPMT for both control (p = 0.002) and histamine prick (p < 0.0001; Figure 2A). The wheal size difference between histamine and control wheals was equal between SPAT and SPMT (p = 0.13; Figure 2B). The 97.5% percentile (=4.5 mm) in controls was used to determine the cut-off that defines a positive wheal with SPAT. Sensitivity and specificity profiles of SPAT (respectively 1.00 (0.96–1.00); 0.99 (0.95–1.00)) and SPMT (respectively 0.93 (0.86–0.96); 1.00 (0.96–1.00)) were comparable (Table S1). Subjective scoring of discomfort as assessed by VAS was significantly lower in the SPAT (median (IQR): 2 cm (1–2 cm)) compared to the SPMT (2 cm (1–4 cm)) group (p = 0.0009; Figure S4). No adverse events were reported during the study for either test. Prick failures were analysed on a total number of 1180 pricks (Table S2). Overall, prick failures occurred significantly less frequently during SPAT compared to SPMT (p < 0.0001). The time needed to execute the SPAT pricks per participant (20 s) was markedly less compared to the time needed to execute the SPMT pricks per participant (on average 144 s). The amount of histamine required to carry out the pricks of the entire study with SPAT (4.5 ml) was 2.7 times less compared with SPMT (12.0 ml). Even though the SPAT produces larger histamine wheal sizes, it exhibits lower intra-subject wheal variability compared to SPMT. Larger histamine wheal sizes could be attributed to the combination of vertical pressure and 90° clockwise rotation of the lancet.8 Lower intra-subject test variability represents a major advancement in the field of allergy diagnostics because skin-prick test reproducibility is one of the biggest issues in current clinical practice.9 This study also demonstrated that the ability to discriminate a histamine from a control wheal is as good as with SPMT. In near future, new studies with SPAT in allergic and non-allergic individuals will shed a light on the precision of the device to detect allergy to inhalant allergens. In conclusion, SPAT showed increased reproducibility and tolerability compared to SPMT. SPAT is able to limit the number of prick failures due to human errors during SPMT. The fact that SPAT is time saving and consumes less allergen solution when dropping glasses are used to run the SPT makes it an interesting cost-effective instrument for future allergy diagnostics. We would like to thank Leen Cools and Els Costermans for their coordination of the study on site. We would also like to thank all volunteers who participated in the study. SG, SFS and LVG hold shares of Hippocreates who developed the SPAT device. MJT received consulting fees for statistical advice for the study. SG, DL and SFS are employees of Hippocreates. RS is supported by a FWO senior clinical investigator fellowship (1805518N). SU, WB, MJ, PWH have nothing to disclose. The study was supported by a grant from SmartHub Vlaams Brabant. Appendix S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Objective: Juvenile angiofibromas are benign tumors that almost exclusively affect male adolescents. Over the last decades, there is an evolution from open surgery to less-invasive endoscopic techniques. Methods: The medical records of 39 consecutive patients who underwent endoscopic sinus surgery for a juvenile angiofibroma were retrospectively analyzed. Results: The distribution of the tumor stages according to the classification system of Radkowski was asfollows: 1 in stage IA, 5 in IB, 7 in IIA, 13 in IIB, 5 in IIC, 4 in IIIA, and 4 in IIIB. Preoperative angiography with embolization was performed in all but 1 patient. The mean postoperative follow-up time was 32 months. Five patients (12.8%) had a recurrence after a mean period of 9 months (range 3-24 months), of which 2 initially had incomplete macroscopic tumor removal due to intracranial extension. The mean operating time was 106 minutes (range 35-400 minutes). The mean duration of hospitalization was 4.3 days (range 1-9 days). Two patients (5.1%) had postoperative bleeding out of the internal maxillary artery for which a reintervention and blood transfusion was needed. Conclusions: Endoscopic surgery for juvenile angiofibromas is an effective and safe technique with good outcomes and low postoperative morbidity. This technique should be used as the first choice in the treatment of small to medium-sized tumors (I-IIB) and is a worthy alternative to open surgery for advanced tumor stages (IIC-IIIB) when performed by an experienced surgeon.

Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) often requires surgery, but recurrence even after surgery is common. Recurrence rates largely vary in literature and asthma seems to be a comorbid factor. Objective In this study, we aim to estimate disease recurrence during a long-term follow-up, together with the investigation of possible predicting and/or influencing parameters. Methods Out of 196 patients operated for CRSwNP between 01/2000 and 01/2006, 133 patients had a follow-up of at least 10 years and could be included. The inflammatory profile at surgery was determined on nasal tissue and sinonasal secretions, and included analysis of eosinophils, eosinophilic-rich mucus (ERM) typically containing Charcot-Leyden crystals (CLC), and fungal hyphae (FH). During follow-up, recurrence, received treatments and comorbidities were collected. Results Out of the 133 included patients, local eosinophilia was present in 81% and ERM in 60%. Recurrence during follow-up was observed in 62%, and was associated with local eosinophilia and ERM (both p < 0.001). Asthma was present in 28% at inclusion, and 17% developed asthma after surgery during follow-up. The presence of asthma, at inclusion as well as developed during follow-up, was significantly associated with recurrence of CRSwNP (p = 0.001 for group comparison). Conclusion Recurrence after CRSwNP surgery is common when a long-term follow-up is taken into account. ERM detected in sinonasal secretions at surgery seems to be a predictive factor for recurrence and need for revision surgery. Asthma is a frequently found comorbid factor in CRSwNP, develops even at higher age despite surgical treatment for CRSwNP, and is also associated with a higher recurrence rate. Sustained medical care after surgery is mandatory.

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.