key: cord-0879131-n7k4va9k authors: Yen, Yung-Feng; Lai, Hsin-Hao; Chan, Shang-Yih; Yi-Fong Su, Vincent; Chiu, Ting-Fang; Huang, Chiao-Yu; Hung, Chia-Chun; Kuo, Tzu-Ling; Lee, Ya-Ling; Chu, Dachen title: Olfactory disorder in patients infected with SARS-CoV-2 date: 2020-08-20 journal: J Microbiol Immunol Infect DOI: 10.1016/j.jmii.2020.08.010 sha: 1e7bc41faa4ef2bd62165af63aed33dcb1327000 doc_id: 879131 cord_uid: n7k4va9k Abstract Three (60%) of five patients with coronavirus disease 2019 (COVID-19) had olfactory disorder. Two exhibited anosmia at the onset of COVID-19, while one had hyposmia 4 days after the onset of COVID-19. All patients with olfactory disorder were completely recovered with a mean recovery length of 11.3 days. As of the end of May, 2020, more than 5 million individuals have been infected with SARS-CoV-2 in 216 countries. 1 In Taiwan, by the end of May, 429 laboratory-confirmed COVID-19 cases were reported to Taiwan Centers for Disease Control (CDC). 2 SARS-CoV-2 is a human respiratory coronavirus and enters human cells through binding the host's angiotensin-converting-enzyme 2 (ACE2) receptor. 3 High ACE2 expression has been identified in type II alveolar cells 3 suggesting that the lungs are the major site of SARS-CoV-2 infection. ACE2 receptors also exist in the olfactory epithelium, 3 providing SARS-CoV-2 with an entry site into the olfactory bulb and neurons. The invasion of SARS-CoV-2 into the olfactory bulb could cause the olfactory epithelium apoptosis and a decreased volume of the olfactory bulb, 4 thereby possibly inducing the symptom of olfactory disorder. A case report indicated that COVID-19 patients could manifest the loss of olfactory function. 5 According to two cross-sectional studies, the prevalence of olfactory disorder in COVID-19 patients ranged from 23.7% to 85.6%. 6, 7 Although several reports showed that olfactory disorder is one of the COVID-19-related symptoms, the clinical course of olfactory J o u r n a l P r e -p r o o f disorder in COVID19 patients has not been well studied. Therefore, we conducted this cohort study to characterize the clinical course of olfactory disorder in COVID-19 patients in Taiwan. This cohort study included COVID-19 patients who were admitted to Taipei City Hospital (TCH) Yangming Branch between March 22 and April 3, 2020. The diagnosis of COVID-19 patients was confirmed by a positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR). All COVID-19 patients admitted to TCH were followed up until their discharge from hospital or the end of April 2020. This study was approved by the Institutional Review Board of TCH (no. TCHIRB- When COVID-19 patients were admitted to TCH, their demographic data and clinical symptoms (e.g., olfactory disorder) were recorded. Radiologic assessments and laboratory testing in COVID-19 patients were performed according to the World Health Organization's guidelines on clinical management of COVID-19 patients. Laboratory assessments on admission consisted of a complete blood cell count, tests of kidney and liver function, and measurement of electrolyte, C-reactive protein, and ferritin levels. cases (80%) were identified through home quarantine screening, compared to one case (20%) through airport screening. Three of the five patients (60%) manifested olfactory disorder, including two anosmia and one hyposmia. Characteristics and clinical features of COVID-19 patients are summarized in the were more likely to have gustatory disorder, rhinorrhea, and cough than those who did not suffer from this disorder. Imaging and laboratory testing in the five COVID-19 patients showed that abnormal chest radiograph findings were found in one patient, while no patients This case series cohort study found that the proportion of COVID-19 patients complicated with olfactory disorder was 60%. Two patients exhibited anosmia as the main symptom at the onset of SARS-CoV-2 infection, while one patient had hyposmia 4 days after the onset of COVID-19. All patients with olfactory disorder were completely recovered with a mean recovery length of 11.3 days. The proportion of COVID-19 patients complicated with olfactory disorder in our present study (60%) was higher than that in a study conducted in Italy (23.7%) 6 but lower than that in a multicenter European report (85.6%). 7 Although respiratory symptoms, such as cough, sore throat, and fever, are those most commonly reported in COVID-19 patients, 8 Sensory neuronal damage due to SARS-CoV-2 may account for the olfactory disorder in COVID-19 patients. SARS-CoV-2 is a neurotropic and neuroinvasive virus that enters human cells through ACE2 receptors. 9 A previous animal study found that SARS-CoV could invade the olfactory nerves by binding with ACE2 receptors on the olfactory bulb. 10 The invasion of SARS-CoV-2 into the olfactory bulb could cause the olfactory epithelium apoptosis and a decreased volume of the olfactory bulb, 4 which may result in olfactory disorder. Our present study found that the mean recovery time for patients with olfactory disorder was 11.3 days. Two thirds of the patients with olfactory disorder in our study had olfactory disorder for more than 4 days, which was comparable to that of a European study (67%). 7 All patients with olfactory disorder in our study fully recovered their olfactory function before the RT-PCR results for SARS-CoV-2 turned negative. This cohort study was the first to characterize the clinical course of olfactory disorder in COVID-19 patients. Nevertheless, the present study has three limitations. First, since Taiwan CDC successful contained the spreading of SARS-CoV-2 in the community, limited patients were diagnosed with SARS-CoV-2 infection during the COVID-19 pandemic. 2 Limited COVID-19 cases in this study may preclude this J o u r n a l P r e -p r o o f analysis from estimating the precise prevalence of olfactory disorder in patients infected with SARS-CoV-2. However, consistent with a current report, 7 the findings of our study suggest that olfactory disorder is not an uncommon symptom in COVID-19 patients. Second, the diagnosis of olfactory disorder in COVID-19 patients was not confirmed by the electrophysiologic test. 9 Since SARS-CoV-2 is highly contagious, inessential invasive tests were not recommended while COVID-19 patients were under care. Finally, the external validity of our findings may be a concern because all of our patients were Taiwanese. The generalizability of our results to other non-Asian ethnic groups requires further verification. In conclusion, this study findings show that olfactory disorder is not an uncommon World Health Organization: Coronavirus disease (COVID-19) Pandemic Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Frontiers of medicine Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virologica Sinica Sudden and Complete Olfactory Loss Function as a Possible Symptom of COVID-19. JAMA otolaryngology--head & neck surgery Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology -Head and Neck Surgery Clinical Characteristics of Coronavirus Disease 2019 in China Olfactory dysfunction and its measurement in the clinic. World journal of otorhinolaryngology -head and neck surgery Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2 The authors are grateful to the members of the Research Office for Health Data, No conflict of interest exists for the author.