Chronic Rhinosinusitis and COVID-19
2022; Elsevier BV; Volume: 10; Issue: 6 Linguagem: Inglês
10.1016/j.jaip.2022.03.003
ISSN2213-2201
AutoresConcepció Marı́n, Thomas Hummel, Zheng Liu, Joaquim Mullol,
Tópico(s)Sinusitis and nasal conditions
ResumoThe COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non–type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19. The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non–type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19. INFORMATION FOR CATEGORY 1 CME CREDITCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI: In Practice Web site: www.jaci-inpractice.org/. The accompanying tests may only be submitted online at www.jaci-inpractice.org/. Fax or other copies will not be accepted.Date of Original Release: June 1, 2022. Credit may be obtained for these courses until May 31, 2023.Copyright Statement: Copyright © 2022-2024. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Concepció Marin, MD, PhD, Thomas Hummel, MD, Zheng Liu, MD, PhD, and Joaquim Mullol, MD, PhD (authors); Michael Schatz, MD, MS (editor)Learning objectives: 1.To identify the main characteristics of chronic rhinosinusitis (CRS) in COVID-19.2.To understand the role of type 2 inflammation in CRS and COVID-19.3.To realize the risks of COVID-19 transmission for patients and health professionals during CRS management.4.To improve efficacy and safety in medical and surgical CRS treatment during the COVID-19 outbreak.Recognition of Commercial Support: This CME has not received external commercial support.Disclosure of Relevant Financial Relationships with Commercial Interests: All authors and reviewers reported no relevant financial relationships.IntroductionThe COVID-19 pandemic has raised awareness about olfactory and gustatory dysfunction (frequency ranging from 5% to 98%),1Izquierdo-Domínguez A. Rojas-Lechuga M.J. Mullol J. Alobid I. Olfactory dysfunction in the COVID-19 outbreak.J Investig Allergol Clin Immunol. 2020; 30: 317-326Crossref PubMed Scopus (44) Google Scholar, 2Lechien J.R. Chiesa-Estomba C.M. De Siati D.R. Horoi M. Le Bon S.D. Rodríguez A. et al.Olfactory and gustatory dysfunctions as clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.Eur Arch Otorhinolaryngol. 2020; 277: 2251-2261Crossref PubMed Scopus (0) Google Scholar, 3Moein S.T. Hashemian S.M. Mansourafshar B. Khorram-Tousi A. Tabarsi P. Doty R.L. Smell dysfunction: a biomarker for COVID-19.Int Forum Allergy Rhinol. 2020; 19: 944-950Crossref Scopus (413) Google Scholar, 4Mullol J. Alobid I. Mariño-Sánchez F. Izquierdo-Domínguez A. Marin C. Klimek L. et al.The loss of smell and taste in the COVID-19 outbreak: a tale of many countries.Curr Allergy Asthma Rep. 2020; 29: 61Crossref Scopus (66) Google Scholar, 5Rojas-Lechuga M.J. Izquierdo-Domínguez A. Chiesa-Estomba C. Calvo-Henríquez Ch Villarreal I.M. Cuesta-Chasco G. et al.Chemosensory dysfunction in COVID-19 out-patients.Eur Arch Otorhinolaryngol. 2021; 278: 695-702Crossref PubMed Scopus (24) Google Scholar although loss of smell was commonly present in the general population (5% to 20%) even before COVID-19.6Brämerson A. Johansson L. Ek L. Nordin S. Bende M. Prevalence of olfactory dysfunction: the Skövde population-based study.Laryngoscope. 2004; 114: 733-737Crossref PubMed Scopus (398) Google Scholar, 7Landis B.N. Konnerth C.G. Hummel T. A study on the frequency of olfactory dysfunction.Laryngoscope. 2004; 114: 1764-1769Crossref PubMed Scopus (0) Google Scholar, 8Vennemann M.M. Hummel T. Berger K. The association between smoking and smell and taste impairment in the general population.J Neurol. 2008; 255: 1121-1126Crossref PubMed Scopus (334) Google Scholar Apart from aging, postinfectious (postviral) rhinosinusitis and chronic rhinosinusitis (CRS) are among the most common causes of olfactory dysfunction.9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar Chronic rhinosinusitis can be divided into different phenotypes (ie, with nasal polyps [CRSwNP] and without nasal polyps [CRSsNP]) and endotypes (ie, type 2 and non–type 2 inflammation).9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar Comorbid conditions are often present in those with more severe disease.10Laidlaw T.M. Mullol J. Woessner K.M. Amin N. Mannent L.P. Chronic rhinosinusitis with nasal polyps and asthma.J Allergy Clin Immunol Pract. 2021; 9: 1133-1141Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar However, scientific information regarding CRS within the COVID-19 context remains scarce (Figure 1).Since March 2020, the COVID-19 outbreak imposed drastic changes in daily ear, nose, and throat (ENT) and allergy clinical practice. During the first phase of the epidemic, the suspension of deferable consultations was necessary. The gradual restoration of daily ENT and allergy activities begun, which must be performed avoiding viral transmission and protecting health care providers (HCPs) from infection.11de Bernardi F. Turri-Zanoni M. Battaglia P. Castelnuovo P. How to reorganize an ENT outpatient service during the COVID-19 outbreak: report from northern Italy.Laryngoscope. 2020; 130: 2544-2545Crossref PubMed Scopus (20) Google ScholarThis review focuses on the potential effects of COVID-19 pandemic on CRS symptoms, including the loss of smell, and comorbidities; the use of telemedicine in CRS diagnosis and management; the possible role of CRS as a protective factor for COVID-19, and the therapeutic options for CRS within the COVID-19 pandemic context.Chronic Rhinosinusitis Symptoms and COVID-19Chronic rhinosinusitis and olfactory lossChronic rhinosinusitis is a disorder with a multifactorial etiology characterized by chronic inflammation of the sinonasal mucosa, affecting 5% to 15% of the general population.9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar The disease is characterized by heterogeneity in the clinical phenotypes and inflammatory profile. Basically, according to the nasal endoscopic findings, CRS is phenotypically classified as CRSsNP and CRSwNP.9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar Chronic rhinosinusitis with nasal polyps accounts for approximately 18% to 20% of CRS and has a greater disease severity and higher levels of morbidity than does CRSsNP.9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar,12Stevens W.W. Peters A.T. Hirsch A.G. Nordberg C. Scheartz B.S. Mercer D. et al.Clinical characteristics of patients with chronic rhinosinusitis with nasal polyps, asthma and aspirin exacerbated respiratory disease.J Allergy Clin Immunol Pract. 2017; 5: 1061-1070Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar The prevalence of CRSwNP is thought to be around 2% to 4% of the general population, in which symptoms (anteroposterior rhinorrhea, nasal congestion or obstruction, loss of smell, and/or facial pain or pressure) persist for greater than 12 weeks.9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google ScholarBased on the degree of eosinophil infiltration in nasal tissue, CRSwNP can be further classified into eosinophilic and noneosinophilic with distinct immunoinflammatory characteristics.13Cao P.-P. Li H.-B. Wang B.-F. Wang S.-B. You X.-J. Cui Y.-H. et al.Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese.J Allergy Clin Immunol. 2009; 124: 478-484Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar Specifically, and mainly in Western countries, eosinophilic CRSwNP has a predominantly type 2 inflammation, whereas noneosinophilic CRSwNP is characterized by non–type 2 inflammation.9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar Type 2 inflammation has high levels of activated TH2 cell-released cytokines, such asIL-4, IL-5, and IL-13, innate lymphoid cell 2 (ILC2), and infiltrating eosinophils and mast cells, which are more resistant to therapy and exhibit a high rate of recurrence. Non–type 2 is related to TH1/TH17 immune response characterized by ILC1/ILC3, TH cell-released cytokines such as IL-17A, IL-8, and IL-22, IFN-gamma, TNF-α, as well as neutrophilic inflammation (Figure 2).9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar,14Wang X. Zhang N. Bo M. Holtappels G. Zheng M. Lou H. et al.Diversity of T(H) cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania.J Allergy Clin Immunol. 2016; 138: 1344-1353Abstract Full Text Full Text PDF PubMed Scopus (262) Google ScholarFigure 2Impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (left) in patients without chronic rhinosinusitis with nasal polyps (type 1 predominant) and (right) in those with chronic rhinosinusitis with nasal polyps (type 2 predominant). Type 2 eosinophilic inflammation may decrease angiotensin converting enzyme 2 (ACE2) expression in sinonasal epithelial cells, which potentially represents a protective effect for SARS-CoV-2 infection. ILC, innate lymphoid cell.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Olfactory dysfunction is present in 56% to 78% of CRS patients.15Kohli P. Naik A.N. Harruff E.E. Nguyen S.A. Schlosser R.J. Soler Z.M. The prevalence of olfactory dysfunction in chronic rhinosinusitis.Laryngoscope. 2017; 17: 309-320Crossref Scopus (51) Google Scholar,16Passali G.C. Passali D. Cingi C. Ciprandi G. Smell impairment in patients with chronic rhinosinusitis: a real-life study.Eur Arch Otorhinlaryngol. 2022; 279: 773-777Crossref PubMed Scopus (4) Google Scholar It has a progressive and fluctuant course and is strongly associated with the type 2 inflammatory endotype.17Stevens W.W. Peters A.T. Tan B.K. Klinger A.I. Poposki J.A. Hulse K.E. et al.Associations between inflammatory endotypes and clinical presentations in chronic rhinosinusitis.J Allergy Clin Immunol Pract. 2019; 7: 2812-2820Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar Patients with eosinophilic CRSwNP report a higher degree of loss of smell,18Thompson C.F. Price C.P.E. Huang J.H. Min J.-Y. Suh L.A. Shintani-Smith S. et al.A pilot study of symptom profiles from a polyp vs an eosinophilic-based classification of chronic rhinosinusitis.Int Forum Allergy Rhinol. 2016; 6: 500-507Crossref PubMed Scopus (34) Google Scholar and the degree of smell function is positively correlated with the inflammatory condition of the sinonasal mucosa.9Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar Moreover, the frequency and severity of olfactory dysfunction increase when CRSwNP is associated with asthma19Alobid I. Cardelús S. Benítez P. Guilemany J.M. Roca-Ferrer J. Picado C. et al.Persistent asthma has an accumulative impact on the loss of smell in patients with nasal polyposis.Rhinology. 2011; 49: 519-524Crossref PubMed Scopus (40) Google Scholar,20Rhyou H.-I. Bae W.Y. Nam Y.-H. Association between olfactory function and asthma in adults.J Asthma Allergy. 2021; 14: 309-316Crossref PubMed Scopus (3) Google Scholar or aspirin- or nonsteroidal anti-inflammatory drug–exacerbated respiratory disease.21Gudziol V. Michel M. Sonnefeld C. Koschel D. Hummel T. Olfaction and sinonasal symptoms in patients with CRSwNP and AERD and without AERD: a cross-sectional and longitudinal study.Eur Arch Otorhinolaryngol. 2017; 274: 1487-1493Crossref PubMed Scopus (20) Google Scholar,22Spielman F.B. Overdevest J. Gudis D.A. Olfactory outcomes in the management of aspirin exacerbated respiratory disease related chronic rhinosinusitis.World J Otorhinolaryngol Head Neck Surg. 2020; 6: 207-213Crossref PubMed Google ScholarCOVID-19 and olfactory lossOlfactory dysfunction is an official World Health Organization symptom of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with a frequency of 5% to 85%, depending on the country of study.1Izquierdo-Domínguez A. Rojas-Lechuga M.J. Mullol J. Alobid I. Olfactory dysfunction in the COVID-19 outbreak.J Investig Allergol Clin Immunol. 2020; 30: 317-326Crossref PubMed Scopus (44) Google Scholar,2Lechien J.R. Chiesa-Estomba C.M. De Siati D.R. Horoi M. Le Bon S.D. Rodríguez A. et al.Olfactory and gustatory dysfunctions as clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.Eur Arch Otorhinolaryngol. 2020; 277: 2251-2261Crossref PubMed Scopus (0) Google Scholar,23Von Bartheld C.S. Hagen M.M. Butowt R. Prevalence of chemosensory dysfunction in COVID-19 patients: a systematic review and meta-analysis reveals significant ethnic differences.ACS Chem Neurosci. 2020; 19: 2944-2961Crossref Scopus (78) Google Scholar Sudden olfactory loss without nasal congestion is among the characteristic early symptoms of COVID-19.24Haehner A. Draf J. Dräger S. de With K. Hummel T. Predictive value of sudden olfactory loss in the diagnosis of COVID-19.ORL J Otorhinolaryngol Relat Spec. 2020; 82: 175-180Crossref PubMed Scopus (72) Google Scholar, 25Parma V. Ohla K. Veldhuizen M.G. Niv M.Y. ChE Kelly Bakke A.J. et al.More than smell-COVID-19 is associated with severe impairment of smell, taste, and chemesthesis.Chem Senses. 2020; 45: 609-622Crossref PubMed Scopus (187) Google Scholar, 26Pellegrino R. Cooper K.W. Di Pizio A. Joseph P.V. Bhutani S. Parma V. Corona viruses and the chemical senses: past, present, and future.Chem Senses. 2020; 45: 415-422Crossref Scopus (43) Google Scholar, 27Gerkin R.C. Ohla K. Veldhuien M.G. Joseph P.V. Kelly ChE. Bakke A.J. et al.Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms.Chem Senses. 2021; 46: bjaa081Crossref PubMed Scopus (44) Google Scholar At the beginning of the SARS-CoV-2 pandemic, the diagnosis of olfactory loss was frequently based on unvalidated questionnaires in many countries,4Mullol J. Alobid I. Mariño-Sánchez F. Izquierdo-Domínguez A. Marin C. Klimek L. et al.The loss of smell and taste in the COVID-19 outbreak: a tale of many countries.Curr Allergy Asthma Rep. 2020; 29: 61Crossref Scopus (66) Google Scholar and few studies tested the dysfunction with psychophysical smell tests.25Parma V. Ohla K. Veldhuizen M.G. Niv M.Y. ChE Kelly Bakke A.J. et al.More than smell-COVID-19 is associated with severe impairment of smell, taste, and chemesthesis.Chem Senses. 2020; 45: 609-622Crossref PubMed Scopus (187) Google Scholar,28Hannum M.E. Ramírez V.A. Lipson S.J. Herriman R.D. Toskala A.K. Lin C. et al.Objective sensory testing methods reveal a higher prevalence of olfactory loss in COVID-19-positive patients compared to subjective methods: a systematic review and meta-analysis.Chem Senses. 2020; 45: 865-874PubMed Google Scholar,29Huart C. Philpott C. Konstantinidis I. Altundag A. Whitcrift K.L. Trecca E.M.C. et al.Comparison of COVID-19 and common cold chemosensory dysfunction.Rhinology. 2020; 58: 623-625Crossref PubMed Scopus (55) Google Scholar Because many studies found self-ratings of olfactory function to be unreliable and inaccurate,4Mullol J. Alobid I. Mariño-Sánchez F. Izquierdo-Domínguez A. Marin C. Klimek L. et al.The loss of smell and taste in the COVID-19 outbreak: a tale of many countries.Curr Allergy Asthma Rep. 2020; 29: 61Crossref Scopus (66) Google Scholar,30Landis B.N. Hummel T. Hugentobler M. Giger R. Lacroix J.S. Ratings of overall olfactory function.Chem Senses. 2003; 28: 691-694Crossref PubMed Scopus (244) Google Scholar,31Lötsch J. Hummel T. Clinical usefulness of self-rated olfactory performance-a data science-based assessment of 6000 patients.Chem Senses. 2019; 44: 357-364Crossref PubMed Scopus (52) Google Scholar short screening tools27Gerkin R.C. Ohla K. Veldhuien M.G. Joseph P.V. Kelly ChE. Bakke A.J. et al.Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms.Chem Senses. 2021; 46: bjaa081Crossref PubMed Scopus (44) Google Scholar,32Parma V. Hannum M.E. O'Leary M. Pellegrino R. Rawson N.E. Reed D.R. et al.SCENTinel 1.0: development of a rapid test to screen for smell loss.Chem Senses. 2021; 46: bjab012Crossref PubMed Scopus (3) Google Scholar and individual smell tests are needed to assess the related chemosensory dysfunction during the infection as well as to learn about recovery rates after infection. For such testing, numerous alternatives exist that have been shown to be valid and reliable.33Doty R.L. Psychophysical testing of smell and taste function.Handb Clin Neurol. 2019; 164: 229-246Crossref PubMed Scopus (0) Google Scholar,34Oleszkiewicz A. Schriever V.A. Croy I. Hähner A. Hummel T. Updated Sniffin' Sticks normative data based on an extended sample of 9139 subjects.Eur Arch Otorhinolaryngol. 2019; 276: 719-728Crossref PubMed Scopus (0) Google Scholar Smell tests also enable tracking of olfactory sensitivity at threshold levels,35Hummel T. Hummel C. Welge-Luessen A. Assessment of olfaction and gustation.in: Welge-Luessen A. Hummel T. Management of smell and taste disorders: a practical guide for clinicians. Thieme, Stuttgart, Germany2013: 58-75Google Scholar which appears to be important in addressing more detailed reports of patients with olfactory loss. At the same time, it is important to obtain an in-depth medical history of patients covering the subjective burden of patients with a loss of smell,36Han P. Su T. Qin M. Chen H. Hummel T. A systematic review of olfactory related questionnaires and scales.Rhinology. 2021; 59: 133-143PubMed Google Scholar because olfactory loss can have a significant impact on quality of life leading to social isolation, changes in sexuality and partnership, and depression.37Croy I. Nordin S. Hummel T. Olfactory disorders and quality of life-an updated review.Chem Senses. 2014; 39: 185-194Crossref PubMed Scopus (0) Google Scholar,38Kamrava S.K. Tavakol Z. Talebi A. Farhadi M. Jalessi M. Hosseini S.F. et al.A study of depression, partnership and sexual satisfaction in patients with post-traumatic olfactory disorders.Sci Rep. 2021; 11: 20218Crossref PubMed Scopus (3) Google ScholarIn COVID-19, although olfactory loss usually recovers in the first weeks after viral infection, in a significant proportion of patients it may persist for months or even become permanent (long COVID-19).39de Melo G.D. Lazarini F. Levallois S. Hautefort Ch Michel V. Larrous F. et al.COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.Sci Transl Med. 2021; 13eabf8396Crossref PubMed Scopus (68) Google Scholar The underlying mechanisms of COVID-19–induced olfactory loss remain controversial and incompletely understood. Several pathophysiologic mechanisms have been proposed for olfactory dysfunction caused by COVID-19,40Butowt R. Meunier N. Bryche B. von Bartheld C.S. The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from humans and animal models.Acta Neuropathol. 2021; 141: 809-822Crossref PubMed Scopus (14) Google Scholar,41Hopkins C. Lechien J.R. Saussez S. More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanisms of olfactory dysfunction in COVID-19 and its association with enhanced survival.Med Hypotheses. 2021; 146: 110406Crossref PubMed Scopus (19) Google Scholar including (1) epithelial edema and obstruction of the olfactory cleft; (2) epithelial injury and infection of the sustentacular supporting cells, which are known to express angiotensin converting enzyme 2 (ACE2), an entry receptor for SARS-CoV-242Bilinska K. Jakubowska P. Von Bartheld S. Butowt R. Expression of the SARS-CoV-2 entry proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: identification of cell types and trends with age.ACS Chem Neurosci. 2020; 11: 1555-1562Crossref PubMed Scopus (198) Google Scholar,43Brann D.H. Tsukahara T. Weinreb C. Lipovsek M. Van den Berge K. Gong B. et al.Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia.Sci Adv. 2020; 6eabc5801Crossref PubMed Scopus (374) Google Scholar; and (3) injury of olfactory sensory cells via neuropilin-1 receptor (NRP1), which can also bind with the spike protein.44Cantuti-Castelvetri L. Ojha R. Pedro L.D. Djannatian M. Franz J. Kuivanen S. et al.Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.Science. 2020; 370: 856-860Crossref PubMed Scopus (657) Google Scholar,45Daly J.L. Simonetti B. Klein K. Chen K.-E. Williamson M.K. Antón-Plágaro C. et al.Neuropilin-1 is a host factor for SARS-CoV-2 infection.Science. 2020; 370: 861-865Crossref PubMed Scopus (459) Google ScholarAlthough accumulating evidence supports olfactory epithelial injury as a key mechanism,46Khan M. Yoo S.-J. Clijsters M. Backaert W. Vanstapel A. Speleman K. et al.Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb.Cell. 2021; 184: 5932-5949Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar this does not explain all features of loss of smell in COVID-19, such as the duration of loss in some patients, neuroimaging changes, the possible presence of viral particles in the olfactory bulbs (OBs), and the inverse association between COVID-19 severity and the prevalence of olfactory loss.41Hopkins C. Lechien J.R. Saussez S. More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanisms of olfactory dysfunction in COVID-19 and its association with enhanced survival.Med Hypotheses. 2021; 146: 110406Crossref PubMed Scopus (19) Google Scholar The recent description of a viral entry mediated by NRP1 addresses some of these inconsistencies. Neuropilin-1 receptor is expressed in olfactory neurons and in neuronal progenitor cells.44Cantuti-Castelvetri L. Ojha R. Pedro L.D. Djannatian M. Franz J. Kuivanen S. et al.Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.Science. 2020; 370: 856-860Crossref PubMed Scopus (657) Google Scholar Binding to NRP1 could facilitate direct entry and damage to olfactory neurons, causing loss of smell and the loss of progenitor cells, leading to the delayed recovery of olfactory dysfunction and enabling axonal transport to the OBs.It has been suggested that all three mechanisms might have a role in SARS-CoV-2–induced olfactory dysfunction.41Hopkins C. Lechien J.R. Saussez S. More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanisms of olfactory dysfunction in COVID-19 and its association with enhanced survival.Med Hypotheses. 2021; 146: 110406Crossref PubMed Scopus (19) Google Scholar An early olfactory cleft obstruction resulting from olfactory epithelial injury and inflammation mediated by ACE2-related sustentacular cells infection may occur. In addition, in patients with more persistent olfactory loss, a direct injury to olfactory neurons and consequently to the OB, mediated by NRP1 may be present, in which the loss of the progenitor cells is the cause of permanent smell loss.41Hopkins C. Lechien J.R. Saussez S. More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanisms of olfactory dysfunction in COVID-19 and its association with enhanced survival.Med Hypotheses. 2021; 146: 110406Crossref PubMed Scopus (19) Google Scholar Along this line, the persistence of the inflammatory process in the olfactory mucosa, with consequent damage to the olfactory neurons and alteration of the neurogenesis process, has been associated with persistent olfactory dysfunction in COVID-19.39de Melo G.D. Lazarini F. Levallois S. Hautefort Ch Michel V. Larrous F. et al.COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.Sci Transl Med. 2021; 13eabf8396Crossref PubMed Scopus (68) Google ScholarRelationships between CRS and COVID-19 symptomsThe severity of CRS symptoms and the quality of life of CRS patients involved with COVID-19 was assessed using the Sino-Nasal Outcome Test-22 questionnaire.47Akhlaghi A, Darabi A, Mahmoodi M, Movahed A, Kaboodkhani R, Mohammadi Z, et al. The frequency and clinical assessment of COVID-19 in patients with chronic rhinosinusitis. Ear Nose Throat J. Published online August 20, 2021. https://doi.org/10.1177/01455613211038070Google Scholar No differences were found in the four domains (nasal, otologic, sleep and emotional symptoms) of Sino-Nasal Outcome Test-22 in CRS patients with COVID-19 compared with CRS patients without COVID-19.47Akhlaghi A, Darabi A, Mahmoodi M, Movahed A, Kaboodkhani R, Mohammadi Z, et al. The frequency and clinical assessment of COVID-19 in patients with chronic rhinosinusitis. Ear Nose Throat J. Published online August 20, 2021. https://doi.org/10.1177/01455613211038070Google Scholar Thus, COVID-19 did not aggravate sinonasal symptoms, including olfactory function, in patients with CRS.In addition, the severity of symptoms of COVID-19 in patients with CRS was studied,47Akhlaghi A, Darabi A, Mahmoodi M, Movahed A, Kaboodkhani R, Mohammadi Z, et al. The frequency and clinical assessment of COVID-19 in patients with chronic rhinosinusitis. Ear Nose Throat J. Published online August 20, 2021. https://doi.org/10.1177/01455613211038070Google Scholar and the results showed that hypoxemia and pulmonary system involvement in patients with CRSwNP were not different from those with CRSsNP. 47Akhlaghi A, Darabi A, Mahmoodi M, Movahed A, Kaboodkhani R, Mohammadi Z, et al. The frequency and clinical assessment of COVID-19 in patients with chronic rhinosinusitis. Ear Nose Throat J. Published online August 20, 2021. https://doi.org/10.1177/01455613211038070Google ScholarChronic Rhinosinusitis Diagnosis in the Context of COVID-19Risk for COVID-19 transmission to HCPs and patientsThe COVID-19 pandemic has had a profound impact on the ENT outpatient clinical practice, which is at high risk for respiratory SARS-CoV-2 transmission because of the close contact between the examiner and the patient's upper respiratory tract.11de Bernardi F. Turri-Zanoni M. Battaglia P. Castelnuovo P. How to reorganize an ENT outpatient service during the COVID-19 outbreak: report from northern Italy.Laryngoscope. 2020; 130: 2544-2545Crossref PubMed Scopus (20) Goo
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