新型冠状病毒肺炎患者的嗅觉障碍[综述]

新型冠状病毒肺炎（coronavirus disease 2019，COVID-19）是由严重急性呼吸综合征相关冠状病毒2（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）引起的疾病。该疾病可能导致从轻度到严重的急性呼吸系统综合征。COVID-19的临床表现包括发热、干咳、乏力、咳痰、气短、咽喉痛、头痛等。伴随着COVID-19的大流行，世界各地的耳鼻咽喉科医师报道相当数量的COVID-19轻症或无症状患者出现嗅觉功能障碍。撰写本文的目的是回顾现有的文献和整理分析文献中COVID-19患者嗅觉减退的症状特点，并分析潜在机制和应对措施。对出现不明原因嗅觉减退的患者予以重视，以指导临床医师的实践。     

SARS-CoV-2感染后嗅觉功能障碍治疗的研究进展

嗅觉功能障碍(olfactory dysfunction, OD)被认为是新型冠状病毒肺炎的主要症状之一。目前,COVID-19相关的OD的发病机制尚不明确,对其患者暂无特异性治疗手段。论文通过回顾近年来OD的相关文献,结合目前COVID-19及COVID-19相关的OD的治疗方法,从安全咨询、嗅觉训练、药物治疗、针灸、中医药、日本汉方药等方面对相关治疗方案进行总结和比较,探讨其在临床应用和开发新的治疗方法方面的挑战,以期为临床治疗COVID-19相关的OD提供参考和帮助。     

新型冠状病毒肺炎患者合并鼻部症状临床分析及诊疗建议

目的调查新型冠状病毒肺炎（COVID-19）患者鼻部相关症状及其临床特点。方法收集2020年2月10日—3月20日华中科技大学同济医院327例确诊COVID-19患者的病例资料，采集鼻塞、流涕、嗅觉改变等鼻部相关症状、全身伴随症状及基础疾病等情况，分析其临床特点。结果在327例纳入研究的COVID-19患者中，轻型、普通型、重型、危重型病例分别为33例（10.1%）、62例（19.0%）、146例（44.6%）、86例（26.3%）；54例（16.5%）COVID-19患者合并鼻部相关症状，按不同症状发生的总例数统计，其中鼻塞35例（10.7%）、鼻腔干燥29例（8.9%）和嗅觉下降21例（6.4%），鼻痒 17例（5.2％）、喷嚏16例（4.9％）、鼻出血14例（4.3％）和流清涕11例（3.4％）。在各不同病情分型患者间，鼻部症状的发生率没有统计学意义（P>0.05)。192例（58.7%）COVID 19患者有高血压、糖尿病等基础疾病存在，经过积极的综合治疗244例（74.6%）痊愈出院。结论COVID-19患者除了发热、咳嗽、咳痰等症状之外，鼻塞、嗅觉下降等鼻腔局部症状并不少见。鼻部疾病的治疗不仅可以改善患者生活质量，同时可以提高患者的治疗效果。因此，临床医师不能忽视COVID-19患者鼻部疾病的处理     

2019新型冠状病毒变异株奥密克戎感染后嗅觉、味觉和听觉障碍的发病率和预后：一项基于网络的调查

目的 了解2019新型冠状病毒变异株奥密克戎（Omicron）感染后嗅觉、味觉及听觉障碍发病率及预后。方法 基于线上问卷的横断面研究,采用视觉模拟量表（VAS）评价嗅觉、味觉及听觉功能。结果 （1）共获得869份有效调查问卷,Omicron感染后耳鼻咽喉科相关症状总体发生率达96.8%,嗅觉、味觉及听觉障碍发生率分别为44.4%、44.2%和10.7%。（2）全体受调查者感染前后嗅觉、味觉、听觉障碍VAS评分,及出现嗅觉、味觉及听觉障碍的受调查者感染前后相应VAS评分均具有统计学差异（P<0.001）。（3）嗅觉、味觉及听觉障碍持续的中位时间分别为5 d、4 d和3 d。结论 Omicron感染后嗅觉、味觉、听觉障碍发生率高,多数可快速自发改善,对于症状长期存在者,耳鼻咽喉科医师需积极干预。     

新型冠状病毒肺炎与耳鼻咽喉科诊疗的相关研究

2019年末,我国湖北省武汉市暴发了新型冠状病毒肺炎（COVID-19）并在短时间内迅速波及全国。COVID-19患者病情变化迅速,常累及多个器官,需要多学科协作进行综合性诊疗。虽然患者最常见的临床表现为发热、乏力及干咳,但临床数据分析显示有部分患者可以鼻塞、咽痛、嗅觉障碍等耳鼻咽喉科相关症状就诊。同时在标准诊疗方案中也涉及到耳鼻咽喉科的相关内容,故充分认识耳鼻咽喉科与COVID-19诊治的相关性,有助于提高对该疾病的认识与掌握。本文从耳鼻咽喉科角度出发,对二者之间的相关性作一综述,为COVID-19诊断及治疗过程中的耳鼻咽喉科相关问题提供参考。     

国内嗅觉障碍相关研究——基于Citespace的可视化分析

目的 对国内“嗅觉障碍”研究进行可视化分析及合理推测,尝试为学者提供该领域的研究现状及预测未来热点方向。 方法 以“嗅觉障碍”为主题词,检索建库至2020年10月20日中国知网(CNKI)的学术论文并按纳入标准进行筛选,使用Citespace软件对该研究领域所筛选文献的作者、期刊/单位及主题词进行绘制图谱及可视化分析。 结果 整体来讲,“嗅觉障碍”研究的文献发表量呈快速上升趋势。出现频次排名靠前的作者为魏永祥、倪道凤、刘钢、杭伟、姚淋尹、韩德民及刘剑锋,“嗅觉障碍”研究发文排名第1~3例的期刊为:《临床耳鼻咽喉头颈外科杂志》《国际耳鼻咽喉头颈外科杂志》《中华耳鼻咽喉头颈外科杂志》,合作高产单位并具有一定影响力的机构为首都医科大学附属北京安贞医院、中国医学科学院北京协和医院等。主题词聚类分析呈现出7个聚类:慢性鼻-鼻窦炎、帕金森病、kallmann、鼻炎、新型冠状病毒肺炎、超微结构和针刺。 结论 在“嗅觉障碍”领域,早期韩德民、李志春等国内作者对“嗅觉障碍”的研究较深长,而近年来魏永祥、倪道凤等国内作者对“嗅觉障碍”的检测方法、病因、发病机制等进行基础研究及归纳分类,是近年来嗅觉障碍研究的主力,但核心作者中心中介值均小于0.1,这表明关系较稀疏,需加强联络与合作,以期形成学术共同体提高整体影响力。根据聚类分析可知,国内作者目前对“嗅觉障碍”研究热点主要集中在嗅觉障碍与慢性鼻-鼻窦炎伴或不伴鼻息肉、帕金森病、新型冠状病毒肺炎(COVID-19)等原发病之间的联系,探索其生理病理及发病机制;不同类型嗅觉障碍的临床特点及流行病学调查;探索鼻内镜手术、针刺等不同治疗方法对嗅觉障碍的疗效。且从发文突现图可见,以上七大聚类研究范围可能将持续成为该领域重要的热点。其中慢性鼻-鼻窦炎伴或不伴鼻息肉方向是从古至今延续的热点,而COVID-19将成为未来5~10年的热点。另外,不排除COVID-19引起的嗅觉障碍与鼻腔炎症相关,且两者的相关性将会成为嗅觉障碍将来的研究热点与难点。     

病毒感染后嗅觉障碍和慢性鼻窦炎伴嗅觉障碍患者的焦虑抑郁状态及影响因素分析

目的　观察病毒感染后嗅觉障碍（postviral olfactory dysfunction,PVOD）患者和慢性鼻窦炎（CRS）伴嗅觉障碍患者的情绪障碍状况,比较这两种疾病导致的嗅觉障碍引起的患者情绪障碍是否有差异及相关影响因素。方法　自2020年11月～2021年8月在中日友好医院耳鼻咽喉头颈外科,对门诊的PVOD患者（n=20）和住院的CRS伴嗅觉障碍患者（n=43）进行研究。收集患者的年龄、性别、病程、发病方式等人口学和临床资料,采用鼻腔鼻窦结局测试-22（sino-nasal outcome test-22,SNOT-22）、T&T嗅觉功能测试、Zung焦虑自评量表（self-rating anxiety scale,SAS）和Zung抑郁自评量表（self-rating depression scale,SDS）分别评估患者的鼻部症状、嗅觉功能、焦虑和抑郁状态。结果　PVOD患者的平均SNOT-22评分、嗅觉察觉阈及嗅觉识别阈分值均低于CRS伴嗅觉障碍患者（17.64±6.42 vs 30.42±12.08、1.58±3.42 vs 3.40±3.52和3.58±3.07 vs 2.16±3.51）（P 均<0.05）,但PVOD患者焦虑抑郁状态的百分比、SAS评分和SDS评分均高于CRS伴嗅觉障碍患者（45% vs 14%、49.83±6.59 vs 43.97±4.50、52.21±7.83 vs 46.40±9.50）（P 均<0.05）。PVOD和CRS伴嗅觉障碍患者出现轻度焦虑的百分比分别为45.0%和11.63%,轻度抑郁分别 为20%和11.63%,中度抑郁百分比分别为20%和2.33%,焦虑且抑郁分别为30%和2.33%。PVOD患者中多数患者病程＜3个月（75%）、多为突然发病（85%）、鼻腔通气情况多为良好（85%）,而CRS伴嗅觉障碍患者中多数患者病程＞24个月（65.1%）、发病方式多为缓慢发病（76.7%）、鼻腔通气情况多数为差（69.8%）;PVOD患者SNOT-22评分与SDS评分呈正相关（P <0.05）,与SAS评分无显著相关性,CRS伴嗅觉障碍患者SNOT-22评分与SAS、SDS评分均呈正相关（P <0.05）,两种疾病与T&T评分、性别、发病方式及鼻部通气情况均无显著相关性。将PVOD和CRS伴嗅觉障碍患者（n=63）汇集在一起进行Logistic多元回归分析发现嗅觉障碍病程与SAS和SDS评分均呈负相关（P <0.05）;SNOT-22评分与SAS和SDS评分均呈正相关（P <0.01）;年龄与SAS评分呈正相关（P <0.05）,与SDS无显著相关性。结论　相较于CRS伴嗅觉障碍患者,PVOD患者SAS、SDS评分以及 出现焦虑抑郁状态百分比更高,病程、年龄和SNOT-22评分可能会影响嗅觉障碍患者的焦虑抑郁状态。     

单侧全聋型突发性聋患者临床特征及预后分析

目的 分析单侧全聋型突发性聋的一般临床特征,探讨影响预后的相关因素。方法 回顾2019年9月—2021年5月收治住院治疗的127例单侧全聋型突发性聋患者的临床资料,包括一般情况、伴随症状、伴发疾病、实验室检查、治疗效果等,采用χ²检验及二元Logistic回归分析患者性别、年龄、患耳侧别、发病至就诊时间、伴发疾病（高血压、糖尿病、心脏病）、伴随症状（耳鸣、眩晕/头晕）、实验室检查（叶酸、维生素B12、同型半胱氨酸）对预后的影响。结果 127例单侧全聋型突发性聋患者,伴耳鸣者113例（88.98%）,伴眩晕/头晕者91例（71.65%）,总有效率为41.73%。单因素分析显示患者的年龄（P=0.016）、发病至就诊时间（P=0.003）及是否伴眩晕/头晕（P=0.017）与预后相关,差异均具有统计学意义。患者的性别、患耳侧别、伴发基础疾病（高血压、糖尿病、心脏病）、耳鸣、实验室检查（叶酸、维生素B12、高同型半胱氨酸）对预后影响差异无统计学意义。多因素分析显示患者发病至就诊时间（P=0.006）、是否伴眩晕/头晕（P=0.037）为预后的独立危险因素,发病至就诊时间≥3 d组是<3 d组有效率的0.311倍（OR=0.311,95%CI为0.134~0.720,P=0.006）,伴眩晕/头晕者有效率是不伴者有效率的0.385倍（OR=0.385,95%CI为0.157~0.944,P=0.037）。结论 单侧全聋型突发性聋常伴耳鸣、眩晕/头晕,年龄≥40岁、发病至就诊时间≥3 d、伴眩晕/头晕提示预后不佳,其中发病至就诊时间≥3 d以及伴发眩晕/头晕为其独立危险因素,可为临床预后评判及治疗提供理论依据。     

变应性鼻炎嗅觉障碍大鼠嗅感受神经元的实验研究

目的　通过锰增强磁共振成像技术（manganese-enhanced magnetic resonance imaging,MEMRI）观察变应性鼻炎（AR）嗅觉障碍大鼠嗅觉传导通路的改变,并用病理学方法观察嗅黏膜形态结构的改变和相关免疫组织化学变化,来探讨AR对嗅黏膜感受神经元的影响。方法　40只SD大鼠,随机分为实验组（30只）和对照组（10只）。实验组应用卵清蛋白致敏并激发SD大鼠,应用埋藏食物小球实验评估AR大鼠嗅觉功能,建立AR嗅觉障碍的大鼠模型。ELISA法测定并比较血清IgE水平。MEMRI观察大鼠嗅球中锰增强的对比显影。HE染色及免疫组化法观察嗅黏膜的组织形态学变化及嗅标记蛋白表达的变化。结果　对成功建模的AR大鼠进行嗅觉功能评估,40%（12/30）的AR大鼠在AR的基础上伴有嗅觉障碍。MEMRI示对照组大鼠嗅球锰增强显影显著,AR伴嗅觉障碍组大鼠嗅球几乎无锰增强显影,AR不伴嗅觉障碍组大鼠嗅球有部分锰增强显影。AR伴嗅觉障碍组大鼠嗅黏膜的上皮层明显变薄,阳性的嗅感受神经元的层数减少,与不伴嗅觉障碍组和对照组相比差异存在统计学意义（P 均<0.05）。结论　通过卵清蛋白致敏激发可以成功建立AR嗅觉障碍的大鼠模型。AR可导致嗅黏膜感受神经元的变化,并由此导致嗅觉传导通路的改变,有可能是AR引起嗅觉障碍的发病机制之一。     

上呼吸道感染后嗅觉障碍的治疗进展

上呼吸道感染是嗅觉障碍最常见的原因之一。一般认为上呼吸道感染后嗅觉障碍主要是由病毒损伤嗅觉通路引起,故又称病毒感染后嗅觉障碍（post-viral olfactory dysfunction,PVOD）。由于PVOD的发病机制尚不明确,到目前为止没有确切的方法可治愈该病,但一些药物和补充疗法已经使用。本文针对该病治疗的研究现状做一综述。     

Alteraciones del olfato en la COVID-19, revisión de la evidencia e implicaciones en el manejo de la pandemia

There is debate as to whether olfactory dysfunction should be considered a symptom of COVID-19 infection. We undertook a systematic literature review of the articles indexed in PubMed on olfactory disorders in viral respiratory tract conditions, with special emphasis on COVID-19. The main objective was to find evidence of clinical interest to support the relationship between anosmia and COVID-19. Olfactory disorders in upper respiratory tract infections are frequent, most caused by obstruction due to oedema of the nasal mucosa. Occasionally, post-viral sensorineural olfactory dysfunction occurs, with a variable prognosis. The evidence on anosmia in COVID-19 patients is extremely limited, corresponding to a level 5 or D of the Centre for Evidence-Based Medicine. According to the available evidence, it seems reasonable to apply isolation, hygiene and social distancing measures in patients with recent olfactory disorders as the only symptom, although the usefulness of diagnostic tests for this type of patient should be studied.     

The diagnostic value of detecting sudden smell loss among asymptomatic COVID-19 patients in early stage: The possible early sign of COVID-19

ImportanceThe newly emerged coronavirus disease 19 (COVID-19), is threatening the world. Olfactory or gustatory dysfunction is reported as one of the symptoms worldwide. As reported so far, different clinical features have been reported according to outbreak sites and gender; most of the patients, who complained of anosmia or hyposmia, were Europeans. We had a fast review for novel articles about COVID-19 infection and olfactory function.ObservationsRapid reviews for COVID-19 or other viral infection and olfactory and/or gustatory dysfunctions were done in this review. Up to date, a lot of reports have shown that olfactory dysfunction is related to viral infections but no exact mechanism, clinical course, and definite treatment have been discovered, which is also same in COVID-19. In general, intranasal steroid (INS) and oral steroid for short time help improve the recovery of the olfactory function in case of olfactory dysfunction after virus infection. Considering severe respiratory complications and immunocompromised state of COVID-19, the use of steroid should be limited and cautious because we do not have enough data to support the usage of steroid to treat olfactory dysfunction in the clinical course of COVID-19.Conclusions and relevanceIn the days of pandemic COVID-19, we should keep in mind that olfactory dysfunctions, even without other upper respiratory infection or otolaryngologic symptoms, might be the early signs of COVID-19.     

COVID-19 and anosmia: A review based on up-to-date knowledge

The pandemic of Coronavirus Disease 2019 (COVID-19) has caused a vast disaster throughout the world. There is increasing evidence that olfactory dysfunction can present in COVID-19 patients. Anosmia can occur alone or can be accompanied by other symptoms of COVID-19, such as a dry cough. However, the pathogenic mechanism of olfactory dysfunction and its clinical characteristics in patients with COVID-19 remains unclear. Multiple cross-sectional studies have demonstrated that the incidence rate of olfactory dysfunction in COVID-19 patients varies from 33.9–68% with female dominance. Anosmia and dysgeusia are often comorbid in COVID-19 patients. Otolaryngologists should be mindful of the symptom of anosmia in outpatients so as not to delay the diagnosis of COVID-19. In this paper, we have reviewed the relevant knowledge based on up-to-date literature.     

Objective evaluation and predictive value of olfactory dysfunction among patients hospitalized with COVID-19

ObjectivesOlfactory dysfunction is a frequent feature of COVID-19. Despite the growing evidence, current knowledge on the subject remains insufficient, so that data obtained with different tools, from multiple centers and in distinct scenarios are welcome. Yet, the predictive value of olfactory dysfunction in terms of the overall prognosis of COVID-19 is unknown. This study aims to evaluate the olfactory function of hospitalized patients with COVID-19 and the impact of the results on their clinical outcomes.MethodsPatients with severe acute respiratory distress syndrome (ARDS) admitted to a university tertiary hospital were recruited and divided into those with ARDS due to COVID-19, and those with ARDS of any other cause. Sociodemographic and clinical data were collected at baseline and the patients had their objective olfactory function evaluated by the Alcohol Sniff Test on admission and during hospital stay. The participants were then followed up until reaching an endpoint: hospital discharge, endotracheal intubation, transfer to the intensive care unit, or death. Patients with COVID-19 were also subgrouped and compared according to their olfactory thresholds and to their overall clinical outcomes. The obtained data was analyzed using R software. Level of significance was set at 0.05.ResultsEighty-two patients were included (of which 58 had COVID-19). 87.93% of the patients with COVID-19 had diminished olfactory dysfunction on admission. The mean length of hospital stay among patients with olfactory dysfunction was greater (7.84 vs 6.14 days) and nine individuals in this subgroup had poor overall outcomes. None of those with normal olfactory function developed critical COVID-19. The mean olfactory function was significantly worse among patients with COVID-19 and poor outcomes (3.97 vs 7.90 cm, P = .023).ConclusionObjective olfactory dysfunction is frequent in ARDS caused by SARS-CoV-2 infection. Patients with longitudinal poorer outcomes present worse olfactory thresholds on admission.     

Olfactory dysfunction in COVID-19: a marker of good prognosis?

IntroductionIn May 2020, the World Health Organization recognized olfactory dysfunction as a COVID-19 symptom. The presence of hyposmia/anosmia may be a marker of good prognosis in COVID-19.ObjectiveTo associate the presence of olfaction disorder to the clinical condition severity in patients with COVID-19.MethodsIndividuals with the flu syndrome caused by SARS-CoV-2, diagnosed from March to June 2020, were recruited. They were divided into three groups: mild flu syndrome, severe flu syndrome (admitted to hospital wards) and critical illness (admitted to the ICU). Inpatients were interviewed by telephone contact after hospital discharge and their medical records were also evaluated regarding complementary test results. Outpatients answered an electronic questionnaire containing only clinical information.ResultsA total of 261 patients participated in the study: 23.75% with mild flu syndrome, 57.85% with severe flu syndrome and 18.40% with critical illness. A total of 66.28% patients with COVID-19 had olfaction disorders. In approximately 56.58% of the individuals the smell alterations lasted between 9 days and 2 months. There was a significantly higher proportion of individuals with olfactory dysfunction in the group with mild flu syndrome than in the severe flu syndrome group (mild × severe – p < 0.001; Odds Ratio = 4.63; 95% CI [1.87–10.86]). This relationship was also maintained between patients with mild flu syndrome and critically-ill patients (mild × critical – p < 0.001; Odds Ratio = 9.28; 95% CI [3.52–25.53]).ConclusionOlfaction dysfunction was significantly more prevalent in patients with mild flu syndrome in COVID-19. It may be a predictor of a good prognosis for this infection. New population-based studies must be carried out to corroborate these findings.     

Patterns and clinical outcomes of olfactory and gustatory disorders in six months: Prospective study of 1031 COVID-19 patients

ObjectiveThis study aims to comprehensively evaluate olfactory and gustatory dysfunctions during the COVID-19 pandemic regarding onset, course, associated symptoms, prognosis and relation to patients' demographics, treatment received and other symptoms.Patients& methodsThis is a prospective study conducted on patients proven to be infected with COVID-19 and with olfactory/gustatory dysfunction symptoms. Detailed history was taken from each patient about the onset of this dysfunction, associated symptoms. Then follow-up survey was done after 6 months to evaluate the prognosis.Results1031 patients were included in the study, aged 18 to 69 years old, with 31.8% were male. Olfactory/gustatory dysfunctions occurred after other COVID-19 symptoms in 43.5% of cases, occurred suddenly in 80.4% and gradually in 19.6%. These dysfunctions were anosmia & ageusia in 50.2%, hyposmia & hypogeusia in 23.3%, anosmia alone in 17.7%, phantosmia in 18%, Parosmia in 28.4%. In terms of recovery 6-month follow up, 680 patients (66%) recovered completely, 22.1% recovered partially while 11.9% did not recover. Most improvement occurred in the first two weeks. Headache, malaise, nasal obstruction and rhinorrhea were the commonest COVID-19 symptoms associated.ConclusionMost recovery of olfactory/gustatory dysfunction in COVID-19 infection occurs at the first two weeks and is unrelated to patient demographics, treatment or olfactory training. Parosmia is an independent predictor for complete recovery, while phantosmia is significantly associated with lower probability of complete recovery.     

Olfactory and taste disorders in COVID-19: a systematic review

IntroductionThe SARS-CoV-2 virus causes COVID-19, and it is responsible for the largest pandemic since the 1918 H1N1 influenza outbreak. The classic symptoms of the disease have been well defined by the World Health Organization; however, olfactory/gustatory disorders have been reported in some studies, but there are still several missing points in the understanding and in the consensus about the clinical management of these cases.ObjectiveTo identify evidence in the scientific literature about olfactory/gustatory disorders, their clinical presentation, prevalence and possible specific treatments associated with COVID-19.MethodsA systematic review of articles published up to April 25, 2020 was performed in Medline, Cochrane Clinical Trials, ScienceDirect, Lilacs, Scopus and Google Schoolar, OpenGrey.eu, DissOnline, The New York Academy of Medicine and Reasearch Gate. Inclusion criteria: (1) Studies on patients with COVID-19; (2) Records of COVID-19 signs/symptoms, and olfactory/gustatory functions. Exclusion criteria: (1) Studies on non-human coronavirus; (2) Review articles; (3) Experimental studies (in animals or in vitro); (4) Olfactory/gustatory disorders initiated prior to SARS-CoV-2 infection. The risk assessment of bias of the selected studies was performed using the Newcastle-Ottawa scale.ResultsSix articles from the 1788 records met the inclusion criteria and were analyzed. A total of 1457 patients of different ethnicities were assessed; of them, 885 (60.7%) and 822 (56.4%) had smell and taste disorders, respectively, with women being most often affected. There were olfactory/gustatory disorders even without nasal obstruction/rhinorrhea and beginning even before the signs/symptoms of COVID-19; the recovery of smell/taste, when it occurs, usually happened in the first two weeks after COVID-19 resolution. There is evidence that olfactory/gustatory disorders are strong predictors of infection by SARS-CoV-2, and it is possible to recommend patient isolation, as early as of the medical consultation, preventing the spread of the virus. No scientific evidence has been identified for effective treatments for any of the disorders.ConclusionOlfactory/gustatory disorders may occur at varying intensities and prior to the general symptoms of COVID-19 and should be considered as part of the clinical features of COVID-19, even in mild cases. There is still no scientific evidence of specific treatments for such disorders in COVID-19 disease.     

Incomplete and late recovery of sudden olfactory dysfunction in COVID-19

IntroductionSudden olfactory dysfunction is a new symptom related to COVID-19, with little data on its duration or recovery rate.ObjectiveTo characterize patients with sudden olfactory dysfunction during the COVID-19 pandemic, especially their recovery data.MethodsAn online survey was conducted by the Brazilian Society of Otorhinolaryngology and Cervico-Facial Surgery, and Brazilian Academy of Rhinology, including doctors who assessed sudden olfactory dysfunction patients starting after February 1st, 2020. Participants were posteriorly asked by e-mail to verify data on the recovery of sudden olfactory loss and test for COVID-19 at the end of the data collection period.Results253 sudden olfactory dysfunction patients were included, of which 59.1% were females with median age of 36 years, with a median follow-up period of 31 days. 183 patients (72.3%) had been tested for COVID-19, and of those 145 (79.2%) tested positive. Patients that tested positive for COVID-19 more frequently showed non-specific inflammatory symptoms (89.7% vs. 73.7%; p = 0.02), a lower rate of total recovery of sudden olfactory dysfunction (52.6% vs. 70.3%; p = 0.05) and a longer duration to achieve total recovery (15 days vs. 10 days; p = 0.0006) than the ones who tested negative for COVID-19. Considering only positive-COVID-19 patients, individuals with sudden hyposmia completely recovered more often than the ones with sudden anosmia (68.4% vs. 50.0%; p = 0.04).ConclusionPositive-COVID-19 patients with sudden olfactory dysfunction showed lower total recovery rate and longer duration than negative-COVID-19 patients. Additionally, total recovery was seen more frequently in positive-COVID-19 patients with sudden hyposmia than the ones with sudden anosmia.     

Pathophysiological relationship between COVID-19 and olfactory dysfunction: A systematic review

IntroductionSARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia.ObjectiveThis article aims to analyze current scientific evidence intended to elucidate the pathophysiological relationship between COVID-19 and the cause of olfactory disorders.MethodsPubmed, Embase, Scopus and ScienceDirect were used to compose this article. The research was conducted on November 24th, 2020. Original articles with experimental studies in human, animal and in vitro, short communications, viewpoint, published in the English language and between 2019 and 2020 were included, all related to the pathophysiological relationship between olfactory disorders and COVID-19 infection.ResultsBoth human cell receptors ACE2 and TMPRSS2 are essential for the SARS-CoV-2 entrance. These receptors are mostly present in the olfactory epithelium cells, therefore, the main hypothesis is that anosmia is caused due to damage to non-neuronal cells which, thereafter, affects the normal olfactory metabolism. Furthermore, magnetic resonance imaging studies exhibit a relationship between a reduction on the neuronal epithelium and the olfactory bulb atrophy. Damage to non-neuronal cells explains the average recovery lasting a few weeks. This injury can be exacerbated by an aggressive immune response, which leads to damage to neuronal cells and stem cells inducing a persistent anosmia. Conductive anosmia is not sufficient to explain most cases of COVID-19 induced anosmia.ConclusionOlfactory disorders such as anosmia and hyposmia can be caused by COVID-19, the main mechanism is associated with olfactory epithelium damage, targeting predominantly non-neuronal cells. However, neuronal cells can also be affected, worsening the condition of olfactory loss.