LOSS OF SENSE OF SMELL AND TASTE AMONG REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION POSITIVE COVID-19 PATIENTS OF A TERTIARY CARE HOSPITAL: A DESCRIPTIVE CROSS-SECTIONAL STUDY

Rajeev Kumar Shah1*, Bipin Koirala2, Sangya Gyawali3 Introduc on Coronavirus disease (COVID-19) is an ongoing global pandemic that results from infec on with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In pa ents with COVID-19, anosmia and ageusia can be the first and only symptoms. Objec ves The aim of the study was to find out the prevalence of Loss of Sense of Smell and Taste among COVID-19 posi ve pa ents. Methodology This was a descrip ve, cross-sec onal study of all pa ents a ending department of otorhinolaryngology of Birat Medical College, Nepal February 5 to April 4, 2020. Ethical approval was obtained from the same hospital. Pa ents with recent onset of loss of smell, taste, or both and pa ents with other COVID-19 suspected symptoms as per WHO guidelines were confirmed by Reverse Transcriptase Polymerase Chain Reac on (RT-PCR) test. Result A total of 166 pa ents were included in the study. The age of the pa ents ranged from 10 to 84 years with a mean age of44.34 ±23.059 years. Out of the 166 RT-PCR posi ve pa ents 103 (62%) had a loss of taste while 114 (68.7%) had a loss of smell. Nearly half of the subjects about 99 (51.6%) had dysfunc on in both taste and smell. Conclusions The present study shows the strong associa on between the olfactory and gustatory dysfunc on with that of COVID infec on. Pa ents with loss of taste and smell should be evaluated properly at the me of COVID pandemic. Olfactory and Gustatory dysfunc on can be the early and only manifesta on of COVID infec on. The prevalence of loss of smell and taste was similar to other studies done in similar se ngs.


INTRODUCTION
Coronavirus disease  is an ongoing global pandemic that results from infec on with the severe acute 2 respiratory syndrome coronavirus-2 (SARS-CoV-2). The clinical spectrum of COVID-19 ranges from an asymptoma c ormild flu-like illness to a severe pneumonia and systemic disease requiring cri cal care. Main symptoms are fever, dry or produc ve cough, and dyspnea. In pa ents with COVID-19, anosmia, and ageusia can be the first and only symptoms if 1 the pa ent is paucisymptoma c. COVID-19 is a highly contagious disease and has human-to-human transmission. COVID-19 was declared a pandemic disease in March 2020 [2][3][4] by WHO. Studies have confirmed different degree of loss of smell (anosmia, hyposmia, dyssomnia) and loss of taste (dysgeusia, hypogeusia, ageusia) as early symptoms of [5][6][7] Covid 19. WHO adopted loss of taste and smell as 8 important discriminatory symptoms of COVID-19. The aim of the study was to find out the prevalence of loss of smell and taste among reverse transcriptase polymerase chain reac on (RT-PCR) posi ve pa ents of a ter ary care hospital in Eastern Nepal. Olfactory dysfunc on can occur following the upper respiratory tract -called postviral anosmia. However, the precise underlying pathogenesis has not been fully iden fied when present in COVID-19 cases.Many viruses can cause olfactory dysfunc on and ageusia through an inflammatory reac on of the nasal mucosa and causes rhinorrhea. When associated with COVID-19 infec ons, though, these altera ons seem to have peculiar characteris cs, as they are not related to rhinorrhea. Ageusia is the loss of the func ons of taste, frequently mistaken for anosmia, since the tongue can only indicate texture and dis nguish the tastes perceived through smell.

METHODOLOGY
This was a descrip vecross-sec onal study of all pa ents a ending otorhinolaryngo logyout pa ent department of Birat Medical College, Nepal from April 5to June 4,2020. This study frame was chosen because the first na onwide lockdown was imposed 24 March 200 when the cases were on the rise and the lockdown was ended on 21 July 2020. Wri en informed consent was taken for the par cipa on in the study from all the pa ents. Ethical approval was obtained from ins tu onal review commi ee of Birat Medical College and Teaching Hospital.
All those pa ents having complaints of recent onset of loss of smell, taste, or both, and pa ents with other COVID-19 suspec ng features like fever, diarrhea, malaise, etc. as per WHO guidelines were included in the study. Nasopharyngeal and oropharyngeal swab for RT-PCR test for COVID-19 was sent as per government protocol and the result was noted. All those pa ents fulfilling the inclusion criteria were included in the study and were evaluated. Exclusion criteria for this study was pa ents not willing to give consent,had trauma, allergic rhini s, chronic rhinosinusi es, nasal polyposis, psychiatric or neurological disorders, previous surgery or radia on of the nasal or oral cavity, exis ng smell or taste disturbances. Relevant history including name, age, gender, address, presen ng complaints, dura on of onset of loss of taste, and the smell was noted. All the data was entered in a prestructured proforma in Microso excel. Results were expressed in frequency, percentage mean and standard devia on.

RESULTS
A total of 166 pa ents were included in the study. The mean age of the pa ents was44.34 ± 23.059 years. The age of the pa ents ranged from 10 to 84 years. There was a male preponderance 101 pa ent (60.84%), with female of 65 (39.15%). 62%(103) pa ents had a loss of taste while 114 (68.7%) had a loss of smell sensa on. Fever was seen in 127 (76.5%) of the pa ents, 86 (51.8%) had a cough, 44 (26.5%) had diarrhea and 42 (25.3%)of subjects had malaise. More than half of the subjects about 98 (59%) had dysfunc on in both taste and smell. Those pa ents who had dysfunc on in both smell and test had higher rates of PCR posi vity sugges ng the study to be sta s cally significant(p-value <0.001). Demographic characteris cs and symptoms profile amongst the studied popula on was studied (Table 1).

DISCUSSION
The first cases of the COVID-19 out break started in December 2019 in Wuhan (China) in pa ents with complicated 9 pneumonia. COVID-19 is a highly contagious disease andhas human-to-human transmission. COVID-19 was 2-4 declared a pandemic disease in March 2020 by WHO. According to The American Academy of Otolaryngology-Head and Neck Surgery (AAHNS) and by the Bri sh Rhinology Society (BRS), anosmia, ageusia, and dysgeusia [10][11][12][13] have been reported as symptoms of COVID-19 disease. These two symptoms are also some of the earliest and indicators of COVID-19 and may be er predict posi vity compared with other symptoms such as fever and cough. Viral infec ons (common cold, acute rhinosinusi s) of the upper airway can cause olfactory dysfunc on. However, the frequency of sensory disorder (taste and /or smell) in the pa ent affected with COVID-19 is much higher. Pa ents with COVID-19 gene rally present with symptoms of general malaise, fever, cough, and shortness of breath along with muscle and joint pain, sore throat, headache, nausea orvomi ng, diarrhea, and some nasal symptoms (smell and taste dysfunc on). Similar to other upper airway viral infec ons (URTI), such as common cold or flu, the loss of smellis a frequent symptomin COVID-19 pa ents. However, a sudden, severe, and isolated loss of smell and/or taste mayalso be presen n COVID-19 pa ents who are otherwise 14 asymptoma c. Many theories have been postulated on the loss of smell and taste in pa ents with COVID-19. COVID-19 infec ons use the same receptor [cellular angiotensin-conver ngenzyme 2 (ACE2)] as SARS-CoV. This enzyme is found in the tongue. COVID-19 causes taste dysfunc on in the same way as ACE2 15 inhibitors. Among all the symptoms related to COVID-19, both losses of taste and smell were present in more than 50% of the pa ents in our study. Our study is supported by Agyeman AAin which 47%(up to 80%)of the pa ents who test posi ve for COVID19 had a subjec ve loss of smell and 15 taste. COVID-19 and SARS-COV uses same receptors (Cellular ACE2) and causing degrada on of enzymes related to smell and taste sensa on. However, the exact mechanism is not yet proven. Of the many theories 3 major theories has been put forward and is explained in a following way for the loss of smell. First, viral infec on triggers inflamma on of both respiratory and olfactory mucosa and create a barrier between the dendri c cells of the olfactory sensory neurons and olfactory mucosa, 16 thereby leading to disrup on in odor detec on. The other mechanism for the loss of smell is by viral infec on on the olfactory receptors, which causes the damage with resultant 17,18 inhibi on of transmission of odor signals. The last accepted mechanism explains that the virus is neurotropic and can penetrate through the cribriform plate and can infect the olfactory bulb. It then infects the olfactory cortex of the temporal lobe which is responsible for smell. The coronavirus footprint has been found in the cerebrospinal fluid and brain of COVID-19 pa ents, thereby clinically 19 verifying viral encephali s.
Similar study was conducted in Italy in which 60.42% (113/187) of the pa ents with COVID-19 had an altera on in 20 taste and smell. Full recovery was seen in 55 pa ents, 46 pa ents had improvement and no change was seen in 12 20 pa ents. A study conducted in Saudi Arabia also found out 21 64.59% (177/274) of the pa ents had a loss of smell. Many studies have shown that recent loss of taste and smell is a good predictor forearly diagnosis of COVID-19. Loss of taste and smell tend to recover with me inpa ents suffering from COVID-19. This recovery is because of some transient inflammatory response over the nasal or oral epithelium 22,23 and the sensory receptors by the virus. A retrospec ve study was conducted those pa ents with normal smell func on appeared to have a worse course of the disease and were more likely to be hospitalized and placed on a 24 ven lator. This suggests that the pa ents with smell dysfunc on have a milder form of the disease.
This study was conducted in a limited number of pa ents in three months dura on. This study would have been more effec ve if would have been done in large popula on and at mul ple centers. However, this study will help in knowing the associa on of olfactory and gustatory dysfunc on and provide some data for further studies.

CONCLUSIONS
Our study shows a strong associa on between the loss of smell and taste with that of COVID-19 infec on. Olfactory and gustatory disturbances can be the early presenta ons of COVID-19. So, in country like Nepal with limited resources of number of beds, medical staff, lack of oxygen, RT-PCR machine, etc. it is be er to self-isolate when one suffers from olfactory and gustatory dysfunc on as this can be the earliest symptoms. The prevalence of loss of smell and taste was similar to other studies done in similar se ngs.

RECOMMENDATIONS
This study was conducted in a limited number of pa ents in three months dura on. This study would have been more effec ve if would have been done in large popula on and at mul ple centers. However, this study will help in knowing the associa on of olfactory and gustatory dysfunc on and provide some data for further studies.

LIMITATIONS OF THE STUDY
The research was conducted in a small group of pa ents and over a short period of me. RCT and Mul centric study has to be conducted over a longer period of me and larger popula on to know the exact prevalence of Loss of Sense of Smell and Taste among COVID-19 posi ve pa ents.