key: cord-0818492-fcsa8zma authors: Marin, Concepció; Hummel, Thomas; Liu, Zheng; Mullol, Joaquim title: CHRONIC RHINOSINUSITIS AND COVID-19 date: 2022-03-17 journal: J Allergy Clin Immunol Pract DOI: 10.1016/j.jaip.2022.03.003 sha: 81049d8a7ac150b1cc2eb266076947955b6e2eba doc_id: 818492 cord_uid: fcsa8zma The COVID-19 pandemic has raised awareness on olfactory dysfunction, although loss of smell has been found commonly present in the general population even before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease, being also one of the most common causes of olfactory dysfunction. CRS can be classified in different phenotypes (i.e. with and without nasal polyps) and endotypes (i.e. type 2 and non-type 2 inflammation). However, the scientific information regarding CRS in the COVID-19 context is still scarce. This review focuses on: a) the potential effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on CRS symptoms, including loss of smell, and comorbidities; b) the pathophysiological mechanisms involved in the olfactory dysfunction; c) CRS diagnosis in the context of COVID-19, including telemedicine; d) the protective hypothesis of CRS in COVID-19, and e) the efficacy and safety of therapeutic options for CRS in the context of COVID-19. The COVID-19 pandemic has raised awareness of olfactory and gustatory 102 10 i) Nasal endoscopy may be associated with airborne aerosol production irrespective 249 of whether a rigid or flexible scope is used, requires prolonged close proximity to the 250 patient, and carries an unpredictable risk of triggering sneezing. 65 Extreme care 251 should be taken when performing nasal examination with these tools during COVID-252 19. To discard a possible COVID-19 infection, performing a diagnosis analysis, by 253 antigen testing, immediately before the procedure should be considered. Protection 254 protocols developed for endoscopic procedures include complete PPE. 66 During nasal 255 endoscopy, distance between the endoscopist and patient may be maximized by using 256 a tower with a camera, screen, and light source, rather than using an eyepiece. The 257 use of local anesthetic sprays can be replaced by alternatives such as soaked pledgets 258 since atomized anesthesia can aerosolize the virus. 67 259 ii) Acoustic rhinometry, a noninvasive technique for assessing nasal airway 260 obstruction, has a low risk of aerosolization. 68 As the COVID-19 pandemic evolves, and with an unpredictable duration, a shift in 280 the ENT practice in order to protect the patients and the HCWs is required. New systems 281 and protocols will emerge within the field of functional exploration that will replace many 282 of those considered valid to date. Therefore, exploring and implementing strategies to be 283 able to perform ENT procedures safely and effectively is crucial. Telemedicine has become crucial in providing remote access to rhinology medical 292 care while minimizing patient and HCPs exposure to SARS-CoV-2. 71 Other advantages 293 include greater access to specialized care in a cost-effective manner, facilitating timely 294 triage, and broadening geographical practice boundaries. Given the need for incorporating 295 telemedicine into ENT care during COVID-19 pandemics, it is imperative that patients 296 receive the same quality of care as they did prior to restrictions. 297 The applicability and feasibility of telemedicine in rhinology practice have been 298 assessed, studying the outcomes to guide rhinologists on indications for in-office visits 299 during this or future pandemics. 72 The most common diagnosis among the follow-up 300 cases was CRSwNP (38.3%), followed by CRSsNP (13%), allergic rhinitis (10%), and 301 deviated nasal septum (16%). Most cases (98.5%) could be managed remotely during the 302 COVID-19 pandemic, with only a small percentage of patients (1.5%) requiring 303 evaluation in the clinic, most of them in their first visit post-surgery. Regarding the 304 satisfaction questionnaire, 83.3% of responses were "agree or strongly agree" when 305 evaluating their satisfaction about the telemedicine services received. 67% of respondents 306 expressed their trust in telemedicine with preference to use it again. Most of the 307 respondents (90.2%) agreed that telemedicine is cost and time efficient compared to 308 conventional in-office visits, while 85.4% of patients thought it was easy to gain access 309 to specialist care by telemedicine. In contrast, 19% of the respondents showed concern 310 about the clinical assessment via telemedicine considering their conditions should be 311 evaluated face to face in the clinic. 72 312 For CRS patients, telemedicine visits allow HCPs to initiate adequate medical 313 treatments, assess response to therapies, and facilitate discussion of surgical options. 71,73 314 However, a main handicap to incorporating telemedicine visits into clinical practice in 315 CRS patients is the inability to perform a complete physical examination (e.g., nasal 316 endoscopy, olfactory test), which is crucial for the diagnosis and management of the 317 disease. 71 A recent study compared CRS patient satisfaction between telemedicine and 318 in-person clinic visits in rhinology practice, 71 and no significant differences in patient 319 satisfaction were found between telemedicine and clinical visits, measured by the Patient In addition, a negative correlation between ACE2 expression and the levels of 367 cytokines associated with type 2 inflammation, including IL-4, IL-5, and IL-13, in airway 368 epithelial cells has been shown. 81,97 Moreover, IL-13 stimulation suppresses ACE2 369 expression in nasal and bronchial epithelial cells cultured with an air-liquid interface 370 method. 81,88,97 All these data suggest that increased type 2 inflammation reduces ACE2 15 airway epithelial expression as a potential mechanism by which type 2 inflammation may 372 be responsible for a putative protective effect, and may explain less severe outcome from 373 COVID-19 infection. between eosinophil levels and ACE2 expression has been also described. 105 Thus, an 391 increase in ACE2 gene expression in bronchial epithelial cells has been observed in 392 asthmatic patients with low peripheral blood eosinophil counts when compared with those 393 with high eosinophil counts. 105 394 In summary, all these findings provide evidence that type 2 inflammation 395 decreases ACE2 expression in the upper and lower respiratory and olfactory epithelium, Loss of smell in COVID-19 patients, characterized as one of the most early and 472 common symptoms, has a sudden onset and variability in severity ranging from hyposmia 473 to anosmia. 3 Rates of patients' self-reported subjective smell and taste loss range from 474 40% to 80%. 118 In most cases, olfactory dysfunction seems to be self-limited, and has 475 been reported to be improved in the first 30 days after disease onset. 119,,120 Olfactory 476 dysfunction is also a common symptom in CRS patients, particularly in those with 477 CRSwNP. Whether COVID-19 patients with pre-existing CRS have higher risk of loss of 478 smell and poorer prognosis compared to those without CRS remains unclear. Olfactory dysfunction in the Diversity of T(H) cytokine profiles 572 in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and Oceania The prevalence of olfactory 575 dysfunction in chronic rhinosinusitis Smell impairment in patients with chronic 23 Prevalence of chemosensory dysfunction in COVID-19 596 patients: A systematic review and meta-analysis reveals significant ethnic differences Predictive value of sudden olfactory loss in 599 the diagnosis of COVID-19 More than smell-601 COVID-19 is associated with severe impairment of smell, taste, and chemesthesis Corona viruses and the 604 chemical senses: Past, present, and future Recent smell loss is 606 the best predictor of COVID-19 among individuals with recent respiratory symptoms Objective sensory 609 testing methods reveal a higher prevalence of olfactory loss in COVID-19-positive patients 610 compared to subjective methods: A systematic review and meta-analysis Comparison 613 of COVID-19 and common cold chemosensory dysfunction Ratings of overall olfactory function Clinical usefulness of self-rated olfactory performance-A data science-based 617 assessment of 6000 patients SCENTinel 1.0: 619 Development of a rapid test to screen for smell loss Psychophysical testing of smell and taste function Updated Sniffin' Sticks normative 623 data based on an extended sample of 9139 subjects Assessment of olfaction and gustation Management of smell and taste disorders: A practical guide for 626 clinicians A systematic review of olfactory related questionnaires 628 and scales Olfactory disorders and quality of life-an updated review A study of depression, 632 partnership and sexual satisfaction in patients with post-traumatic olfactory disorders COVID-19-related 635 anosmia is associated with viral persistence and inflammation in human olfactory epithelium and 636 brain infection in hamsters The olfactory nerve is not a likely route to 638 brain infection in COVID-19: a critical review of data from humans and animal models More that ACE2? NRP1 may play a central role in the 641 underlying pathophysiological mechanisms of olfactory dysfunction in COVID-19 and its 642 association with enhanced survival Expression of the SARS-CoV-2 entry 644 proteins, ACE2 and TMPRSS2, in cells of the olfactory epithelium: identification of cell types and 645 trends with age Non-neuronal 647 expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying 648 COVID-19-associated anosmia Neuropilin-1 650 facilitates SARS-CoV-2 cell entry and infectivity Neuropilin-1 652 is a host factor for SARS-CoV-2 infection Risk management 663 during COVID-19: safety procedures for otolaryngologists Increased 665 transmissibility and global spread of SARS-CoV-2 variants of concern as at COVID-19 and otorhinolaryngology: Returning to practice Impact of coronavirus 670 disease 2019 on ENT clinical practice and training: the resident's perspective Back to the future: principles on resuming out-patient services in the 673 COVID-19 era A 675 compendium answering 150 questions on COVID-19 and SARS-CoV-2 Safe surgical tracheostomy during 677 COVID-19 pandemic: a protocol based on experiences with Middle East respiratory syndrome and 678 COVID-19 outbreaks in South Korea Recommendations for 680 prehospital airway management in patients with suspected COVID-19 infection Risk of SARS-CoV-2 transmission 683 during flexible laryngoscopy: A systematic review Bronchoscopy, laryngoscopy, and esophagoscopy during the 686 COVID-19 pandemic World Health Organization, Rational use of personal protective equipment (PPE) for coronavirus 688 disease (COVID-19) and considerations during severe shortages. Interim guidance Functional examination of the upper and lower airways in asthma and respiratory 692 allergic diseases: Considerations in the post-SARs-CoV-2 era Transmission routes of respiratory 695 viruses among humans Visualizing speech-generated oral fluid droplets with 697 laser light scattering Ventilation control for airborne transmission of human exhaled bio-aerosols in 699 buildings Airborne 703 aerosol generation during endonasal procedures in the era of COVID-19: Risks and 704 recommendations Precautions for 706 endoscopic transnasal skull base surgery during the COVID-19 pandemic Personal protection and delivery of 25 Evaluation of nasal 712 obstruction in children by acoustic rhinometry: A prospective study Nasal nitric oxide measurements in the assessments of nasal allergen 715 challenge COVID-19 pandemic: 717 Practical considerations in the organization of an allergic clinic-an EAACI/ARIA Position Paper Telemedicine, patient 720 satisfaction, and chronic rhinosinusitis care in the era of COVID-19 Utilization of 723 telemedicine in rhinologic practice during COVID-19 pandemic Telehealth opportunities for the otolaryngologist: A silver lining during the COVID-19 pandemic Isolated sudden onset anosmia in COVID-19 infection. A novel 729 syndrome? Clinical features of patients infected with 731 2019 novel coronavirus in Wuhan, China Workman AD, Bhattacharyya N. Do patients with chronic rhinosinusitis exhibit elevated rates of 735 COVID-19 infection? Laryngoscope The characterization of chronic 739 rhinosinusitis in hospitalized patients with COVID-19 Prevalence and 742 characterization of asthma in hospitalized and non-hospitalized patients with COVID-19 Association of 745 respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2 The effect of allergy and asthma 748 as a comorbidity on the susceptibility and outcomes of COVID-19 COVID-19 infections and asthma SARS-CoV-752 2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease 753 inhibitor Composition of coronavirus spike proteins and 755 host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2 Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps Structure, function and 761 antigenicity of the SARS-CoV-2 spike glycoprotein Type 2 and 763 interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium SARS-CoV-2 receptor angiotensin-converting enzyme 2 in nasal mucosa receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and enriched in 779 specific cell subsets across tissues ACE2 781 downregulation in olfactory mucosa: Eosinophilic rhinosinusitis as COVID-19 protective factor? 782 Coronavirus disease 2019 and 784 asthma, allergic rhinitis: molecular mechanisms and host-environmental interactions ACE2, TMPRSS2, 787 and furin gene expression in the airways of people with asthma-implications for COVID-19 Type 2 790 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells Behavior of eosinophil counts in recovered and deceased 794 COVID-19 patients over the course of the disease Eosinophil responses during COVID-19 infections 796 and coronavirus vaccination Protective effects of eosinophils against COVID-19: More than 798 and ACE() in the hole? The relationship between 800 asthma, eosinophilia, and outcomes in coronavirus disease 2019 infection Patients with COVID-19 may benefit from 803 sustained Lopinavir-combined regimen and the increase of eosinophil may predict the outcome of 804 COVID-19 progression Eosinophil count in severe coronavirus disease 2019 Eosinophilia in 807 asthma patients is protective against severe COVID-19 illness Expression of SARS-CoV-2 receptor 810 ACE2 and coincident host response signature varies by asthma inflammatory phenotype International 813 consensus statement on allergy and rhinology rhinosinusitis 2021 Systemic corticoids 816 in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view Glucocorticosteroids enhance 819 replication of respiratory viruses: effect of adjuvant interferon Angiotensin-converting enzyme II 821 expression and its implication in the association between COVID-19 and allergic rhinitis Estimating COVID-19 infection 824 and severity risks in patients with chronic rhinosinusitis: A Korean nationwide cohort study Management of patients with 832 chronic rhinosinusitis during the COVID-19 pandemic-An EAACI position paper COVID-19 in a patient with severe chronic 835 rhinosinusitis with nasal polyps during therapy with dupilumab Clinical and 838 inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort Highlights in the advances of chronic rhinosinusitis COVID-19 and the 843 Otolaryngologist: Preliminary evidence-based review Taste and 845 smell as chemosensory dysfunctions in COVID-19 infection Patterns 847 of smell recovery in 751 patients affected by the COVID-19 outbreak Self-reported taste and smell disorders 850 in patients with COVID-19: Distinct features in China Olfactory training for 852 postviral olfactory dysfunction: Systematic review and meta-analysis Olfactory dysfunction in COVID-19: Diagnosis and management Efficacy and safety of 857 oral corticosteroids and olfactory training in the management of COVID-19-related loss of smell Impaired 860 humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis 861 patients Dupilumab does not 863 affect correlates of vaccine-induced immunity: A randomized, placebo-controlled trial in adults 864 with moderate-to-severe atopic dermatitis TFH 2 cells associate with enhanced 866 humoral immunity to SARS-CoV-2 inactivated vaccine in patients with allergic rhinitis Reduced COVID-19 vaccine response in patients treated with biologic therapies for asthma COVID-19 872 vaccination of patients with allergies and type-2 inflammation with concurrent antibody therapy 873 (biologicals) -A Position Paper of the German Society of Allergology and