Otorhinolaryngological Manifestations in COVID-19: Review of Recent Evidence

Objectives: In this review we provide an updated concise review about the most common Otorhinolaryngological symptoms in COVID-19 patients. Methods: A searched strategy designed on published literature in different large medical databases and journals using various keywords to get the recent described manifestations. Results: 25 included studies that focused on ENT symptoms and involved the confirmed cases only. 6276 patients were accounted for the results which showed that the most prevalent ENT manifestation were cough in 3498 (56%) patients, headache in 2013 (32%) patients, sore throat in 1966 (31%) patients, anosmia in 1340 (21%) patients, loss of taste in 914 (15%) patients, and rhinorrhea in 196 (3%) patients. Conclusion: Cough was the commonest symptoms which should raise the suspicion to do COVID19 swab especially if associated with smell and taste disorder. Review Article Alherabi et al.; JPRI, 33(58A): 505-510, 2021; Article no.JPRI.79249 506


INTRODUCTION
A new pneumonia-causing virus outbreak occurred in Wuhan, China at the end of December 2019. Since then, Severe Acute Respiratory Syndrome Coronavirus-2 has been identified as a novel member of the coronavirus family and it has quickly become a global pandemic. On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak an international public health emergency [1]. By April 6, 2021, the WHO had recorded 131,487,572 reported cases of COVID-19, with 2,857,702 confirmed deaths [2]. It is a highly contagious virus, causing severe respiratory failure and, in the worst case, death among infected patients, as it spreads rapidly, it continues to do so because it can cause mild or even no symptoms in most cases [3,4]. Early studies reported that the most frequent manifestations of COVID-19 are cough, fever, sputum production, shortness of breath, arthralgia, myalgia, rhinorrhea, sore throat, headache, and diarrhea [5,6].
COVID-19 patients exhibit a diverse variety of manifestations globally. In addition to otorhinolaryngological symptoms, the loss of smell and/or taste has been documented as a common symptom in COVID-19-positive patients in several studies, mainly from Europe [7,8]. Additionally, reports indicate COVID-19 may present as only isolated anosmia [9]. Similarly, Aguseia had a sudden onset and a higher frequency among young populations [10]. Since otolaryngologists works in the upper respiratory tract, which is a major reservoir for SARS-CoV-2, they are extremely vulnerable to SARS-CoV-2 infection.
As a result, COVID-19 is a highly infectious disease, and the early detection and isolation of the infected individual is one of the most effective strategies to prevent transmission. Thus, the aim of this review is to summarize recent evidence to identify and address the various otorhinolaryngological (ORL) manifestations identified in COVID-19-positive patients in reviewed and published works.

MATERIALS AND METHODS
We viewed and searched articles published in April 2021 from medical databases, including Web of Science, PubMed, Springer, the JAMA network, the New England Journal of Medicine, the American Journal of Roentgenology, the Wiley online library, and Elsevier. We used the following keywords: ENT; otorhinolaryngology; loss of taste; loss of smell; COVID-19; coronavirus; and SARS-CoV-2. This review

Fig. 1. Flow diagram showing the included articles
concentrated on the most common ENT manifestations of COVID-19, mainly sore throat, rhinorrhea, anosmia, and headache. We included studies that establish the incidence of ENTrelated manifestations such as sore throat, cough, decreased sense of smell, and running nose in laboratory-confirmed positive COVID-19 patients. We included studies that collected data through self-administered questionnaires, retrospective data from medical records, and prospective studies. We excluded studies that did not reveal ear, nose, and throat symptoms at the time of presentation and studies that focused on one manifestation only. The data were collected, analyzed, and demonstrated in this review using tables and figures.

RESULTS
There are many studies regarding COVID-19 and ENT manifestations recently, however we only included 25 studies that met our eligibility criteria from different countries with total number of 6276 COVID-19 positive patients; Table 1. One casecontrol, ten retrospective, nine prospective and three cross-sectional observational studies, and two case series. Results showed that the common reported ENT manifestation were cough in 3498 (56%) patients, headache in 2013 (32%) patients, sore throat in 1966 (31%) patients, anosmia in 1340 (21%) patients, loss of taste in 914 (15%) patients, and rhinorrhea in 196 (3%) patients.

DISCUSSION
The coronavirus pandemic increased hospitalizations of patients with pneumonia and multi-organ diseases. It originated from the novel severe acute respiratory syndrome. The coronavirus is transmitted among humans via droplets and direct contact with oral, nasal, and eye mucous membrane. COVID-19 infection may be asymptomatic or cause a broad spectrum of symptoms, ranging from mild to severe respiratory distress syndrome and even death in infected patients. Based on a systematic review and meta-analysis, the rate of asymptomatic cases was 17.9% and 15.6%, respectively [11]. This review aims to detect the most common ENT manifestations of COVID-19, mainly sore throat, rhinorrhea, anosmia, loss of taste, and headache.
The results of the current review agree with those of previous reports [9,10]: cough, and headache are the most common ENT symptoms of SARS-CoV-2 infection, followed by sore throat. However, it was found that a loss of smell and loss of taste are significant manifestations in other specialized studies that spotlight them and do not include other manifestations. El-Anwar et al. [12] found that the most common ENT manifestations for COVID-19-positive patients are sore throat (11.3%) and headache (10.7%). By contrast, Aremu et al. [13] found cough in 799 patients, headache in 189 patients, loss of smell in 171 patients, rhinitis in 87 patients, loss of taste in 80 patients, and sore throat in 49 patients.
In the current review, anosmia and ageusia were reported in 21% and 15% of patients, respectively, while Qiu et al. [14] found that of the 394 COVID-19 patients screened for the study, 161 (41%) exhibited sudden olfactory and/or gustatory dysfunction. Lechien et al. [15] reported 85.6% olfactory dysfunction, whereas Mao et al. [16] found anosmia in 5.1% of their studied cases. Moreover, Kaye et al. [17] found that anosmia was noted in 73% of COVID-19 patients prior to diagnosis, and in 26.6% of cases, it was the initial symptom. Although anosmia and ageusia does not seems to be specific for COVID-19, as in Menni et al. [18] they found that COVID-19-positive patients reported loss of smell and taste at a rate of 59%, compared with 18% of COVID-19-negative patients.

CONCLUSION
This study provides insights into the most common ENT manifestations described in COVID-19-positive patients in the reviewed and published literature. Extensive symptoms, ranging from no symptoms to moderate and lifethreatening symptoms, to be related to the novel coronavirus with many non-ENT manifestations. However, the most frequent otolaryngological symptoms are sore throat, headache, anosmia, a loss of taste, cough, and rhinorrhea. Further studies are needed using a global form to collect data on ENT manifestations in COVID-19 patients.

RECOMMENDATION
Our recommendation is to consider a global form to collect complete, reliable, and accurate data on ENT manifestations in COVID-19. We also call for the consideration of a new monitoring system for COVID-19-confirmed patients regarding ENT manifestations during the viral prodromal period.

LIMITATIONS
This study's limitations include the potential for information bias during data collection by the included studies (i.e., receiving answers using an electronic self-administered questionnaire); there is also huge variation in the approaches to clinical data collection from one study to another. Moreover, most studies in this review did not mention asymptomatic or COVID-19 cases with mild symptoms that did not need hospitalization. Further, there was no endoscopic or radiological data on otolaryngology in the published papers. The RT-PCR test, on which the COVID-19 diagnosis is based, is not entirely accurate. Furthermore, the studies included in this review were conducted among participants from a limited number of countries, while COVID-19 is a worldwide pandemic.

CONSENT AND ETHICAL APPROVAL
It is not applicable.