key: cord-349912-em1abdrg authors: Meng, Xiangming; Deng, Yanzhong; Dai, Zhiyong; Meng, Zhisheng title: COVID-19 and anosmia: A review based on up-to-date knowledge date: 2020-06-02 journal: Am J Otolaryngol DOI: 10.1016/j.amjoto.2020.102581 sha: doc_id: 349912 cord_uid: em1abdrg 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. In December 2019, Coronavirus Disease 2019 (COVID-19) outbreak occurred in Wuhan, Hubei Province, China and spread rapidly throughout China, and then emerged around the world [1] [2] [3] . On February 12, 2020, WHO named the disease caused by the novel coronavirus as COVID-19 [4] . Clinical evidence has shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted by person-to-person [1] . Recently, the number of COVID-19 cases has skyrocketed worldwide. As of May 3, 2020, WHO reports that 3,349,786 people have been diagnosed with COVID-19 worldwide, with 238,628 deaths, including 214 countries and territories [3] . COVID-19 pandemic has had a massive impact on global health-care systems and economic stability. In COVID-19 patients, the main manifestations were fever and cough and characterized by Lymphocytopenia and ground-glass opacity changes on chest computed tomography [2] . Patients with severe infection can also develop J o u r n a l P r e -p r o o f 5 Multiple pieces of evidence confirmed that the nasal cavity is a vital area susceptible to SARS-CoV-2 infection. Using rhesus macaques model of coronavirus infection, the researchers compared the pathology and virology of SARS-CoV-2, SARS-CoV and MERS-CoV [14] . The study revealed that these pathogenic coronaviruses have different mainly pathogenic sites: SARS-CoV-2(nose and throat); SARS-CoV(lung); MERS-CoV(type II pneumocytes) [14] . Viral loads in the patient's nasal cavity were higher than the viral loads in the pharynx, both symptomatic individuals and asymptomatic ones, hinting the nasal cavity as the first gateway for the initial infection [15] . The researchers investigated the expression of SARS-CoV-2 entry-associated genes, ACE2 and TMPRSS2, in single-cell RNA-sequencing datasets from different tissues in the human body [16] . Goblet cells and ciliated cells in the nasal mucosa may be the initial site of SARS-CoV-2 infection, implicating primary SARS-CoV-2 transmission is through infectious droplets [16] . Furthermore, SARS-CoV-2 was detected in the tears of COVID-19 patient and can cause nasal infection via the nasolacrimal duct [17, 18] . Therefore, these findings could explain J o u r n a l P r e -p r o o f 7 Kingdom, France, Belgium, the United States and Iran [29] [30] [31] [32] [33] . These surveys were typically handled through non-contact methods such as online questionnaires and telephone interviews [23, 30, 33] . Incidence of OD in COVID-19 patients varied widely among these cross-sectional studies, with rates ranging from 33.9 to 68% [29] [30] [31] [32] [33] . The studies showed that individuals with smell disorders tend to have a taste disorder, suggesting a probable association between the two [29] [30] [31] [32] [33] . Also, most studies have found that the incidence of smell disorders in COVID-19 patients is higher in females than males [29, 30, 33] . The characteristic of female preponderance is consistent with the findings of previous studies about the OD caused by upper respiratory infection [34] . To date, two case-control studies on the relationship between OD and COVID-19 have been carried out [35, 36] . Moein et al. performed the olfactory function test (OFT)of 60 SARS-CoV-2 positive patients and took 60 subjects from previous studies as a control group matching the age and gender of the patient's group [35] . The study revealed that the COVID-19 patients presented a pronounced OD, matched the control group and the published normative data [35] . Another investigation, using a self-reported questionnaire, analyzed the prevalence of smell and/or taste disorders in J o u r n a l P r e -p r o o f 8 OFT has been the mainstay for diagnosis of OD; however, the patients in most studies were untested by OFT. So far, OFT was available only in several studies [35, 37, 38 focus on the associations between OD and COVID-19 inpatients [35] . The study found that 59(98%) out of 60 COVID-19 subjects exhibited some OD, only 21(35%) of them were aware before testing, revealing the exact incidence is much higher than the self-reported rate [35] . Notably, this study provided firm evidence that OD is often [51] . They suggested that SARS-CoV-2 may have the potential to transmit via aerosols [51] . Except for emergency illnesses, online telemedicine in Otolaryngology is a good option for reducing COVID-19 cross-infection [52] . The destructive power and the exact mechanism of the SARS-CoV-2 on the patient for ultrastructural observation to better understand the pathology of OD in COVID-19 patients [34] . After containing the COVID-19 pandemic, the multicenter epidemiological investigation, including different countries and races, should be carried out. Limitations in the original researches also yield limitations of the present review. In some cross-sectional studies, patients were identified by the reported questionnaire submitted by themselves, which were not verified by the researchers. OD was based on self-report rather than OFT in most studies. Besides, some essential information, such as gender and age, did not appear in some studies. For covering the latest knowledge, this review also uses data from several preprints literature that has not been undergone full peer review. OD is a characteristic sign of COVID-19 patient, which can occur independently or with other symptoms, but its pathogenesis is not well understood. In-depth studies are needed to elucidate clinical features and pathogenesis of COVID-19 patient with J o u r n a l P r e -p r o o f 14 OD. Otolaryngologists should be aware of anosmia to avoid delaying the diagnosis of COVID-19 and thus contributing to an epidemic. Not applicable. Not applicable. Not applicable. Not applicable. The authors declare that they have no competing interests. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia Clinical characteristics of coronavirus disease 2019 in China World Health Organization World Health Organization. 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