key: cord-0926267-ow71hxde authors: Taziki Balajelini, Mohammad Hosein; Rajabi, Abdolhalim; Mohammadi, Masoud; Nikoo, Hadi Razavi; Tabarraei, Alijan; Mansouri, Mohsen; Hosseini, Seyed Mehran title: Virus load and incidence of olfactory, gustatory, respiratory, gastrointestinal disorders in COVID‐19 patients: A retrospective cohort study date: 2021-08-16 journal: Clin Otolaryngol DOI: 10.1111/coa.13844 sha: d2e615ad1718165a10cb3fd6411182a54827b48e doc_id: 926267 cord_uid: ow71hxde OBJECTIVES: This study investigated the relationship between viral load and the incidence of olfactory and gustatory dysfunction (OD and GD), the incidence of respiratory and gastrointestinal symptoms and the recovery of OD and GD in COVID‐19 patients. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: This study was conducted on 599 outpatients' cases in Golestan province between February and June 2020. MAIN OUTCOME MEASURES: The incidence, severity (complete or partial) and recovery time of OD and GD and their associations with cycle threshold (CT) values of SARS‐CoV‐2 polymerase chain reaction were assessed. RESULTS: The mean age of patients was 38.27 ± 13.62 years. The incidence of general symptoms included myalgia 70.1%, headache 51.8%, fever 47.7% and dyspnoea 21.4%. 41.9% of patients had gastrointestinal symptoms, including abdominal pain 26.5%, diarrhoea 25.2%, nausea 20.5% and vomiting 12.9%. 12.2% of patients had comorbidity. The trimester recovery rates of OD and GD were 93.94% and 94.74% respectively. The mean recovery time of OD and GD was 14.56 ± 13.37 and 13.8 ± 3.77 days respectively. The mean CT value in all patients was 27.45 ± 4.55. There were significant associations between the mean of CT value with headache (p = 0.04), GD (p = 0.002) and OD (p = 0.001). CONCLUSIONS: The finding of this study indicates a possible association between viral load with incidence of OD and GD in COVID‐19 patient's cases and assures the recovery of OD/GD in these patients. COVID-19 is caused by severe acute respiratory syndrome virus, SARS-CoV-2. Its cumulative incidence and its morbidity are still growing. 1 Gastrointestinal symptoms, such as diarrhoea, abdominal pain, nausea and vomiting, are also common manifestations in The symptoms of the disease are nonspecific in the early stages and are indistinguishable from the symptoms of the common cold. Even asymptomatic carriers of SARS-CoV-2 can spread the virus and are contagious. 3 Different factors were considered for COVID-19 screening. In summary, they include fever, dry cough, sputum, shortness of breath, sore throat and myalgia, a history of suspected contact with infected individuals, travel to an infected area. OD and GD also received special attention to be used for COVID-19 screening. 4 Following numerous reports of the high prevalence of OD and GD due to COVID-19 in European and American countries, the American Academy of Otolaryngology (Head and Neck Surgery) recommended adding anosmia, ageusia, and dysgeusia to screen for possible COVID-19 infection. 5, 6 But, there are still many questions about pathophysiology and the association between OD and GD with the prognosis of COVID-19. Polymerase Chain Reaction (RT-PCR) test. 7 This test shows the nucleic acid of the virus in the saliva-nasal secretions of the patient. 8 In this test, the cycle threshold value (CT) means the number of amplification cycles required to reach the detection threshold of virus nucleic acids. The value of CT is inversely related to the load of the virus in the sample and indirectly indicates the level of virus replication. 9 Sampling for RT-PCR test can be obtained from nasopharynx, oropharynx and lower respiratory tract. Some studies reported that SARS-CoV-2 virus loads in the nasal samples were more than the pharyngeal samples. 10 Viral loads have also been reported to typically increase during the first week after the onset of symptoms and remain high for subsequent weeks. 11 It has also been reported that the amount of virus in samples collected from the lower respiratory tract is very high, but due to specific conditions for this type of sampling, its application as routine practice in all health centres is limited. Thus, it has not been approved by FDA. 12 There are few studies on virus-related factors that may affect the outcome, and therefore the American Infectious Diseases Association has emphasised quantitative testing as a prognostic factor for the diagnosis of SARS-CoV-2. 13 In this regard, the CT value of the RT-PCR test has been considered as an indicator of virus load in determining the prognosis and outcome of patients and the occurrence of some disorders. Due to the high prevalence of COVID-19 and a large percentage of patients with OD and GD and the importance of determining the predictors of some complications and outcome of patients, this study was performed to determine the relationship between CT value of RT-PCR test and OD and GD in patients with COVID-19 in Golestan province in Iran. The severity of OD and GD was categorised into two types, complete and partial. Patients were classified according to age and three geographical locations in the province, East, Centre and West. • A retrospective analysis of 599 COVID-19 patients was performed to determine the incidence of olfactory and gustatory dysfunction and their recovery. • The association of OD, GD, recovery rate and recovery time with cycle threshold (CT) values of SARS-CoV-2 RT PCR was assessed. • The mean of CT value in patients with complete OD was significantly higher than in patients with partial OD. Also, the mean of CT in patients with or without GD showed a significant difference. • There was no significant relation between a recovery time of OD and GD with the mean of CT value. • There was a strong correlation between the recovery time of OD and GD. TAZIKI BALAJELINI ET AL. Statistical analysis was performed using STATA, version 14.1 (Stata Corp; Stata Corp LLC). Data are presented as mean ±standard deviation (SD) and frequency. Concerning quantitative variables, after variance equality and normal distribution of the values were checked, we used the Mann-Whitney U-test to compare the mean of CT value in binary groups, and to compare the mean of CT values in the categorical variable, we used the Kruskal-Wallis test. The correlation between time of recovery of olfactory and gustatory dysfunctions and CT values was assessed using Spearman's rank correlation coefficient. Multivariable analysis was performed for recovery of OD and GD with Cox proportional hazards models, including CT variable. A p value of <0.05 was considered statistically significant. In this study, 599 RT-PCR confirmed COVID-19 cases were included. There were 313 (52.2%) females and 286 (47.74%) males. The mean age 38.27 ± 13.62 years and 50.75% of cases were in the age group of 20-40 years. The clinical characteristics of patients are shown in Table 1 . The mean of CT in patients with complete OD was significantly higher than patients with partial OD (p = 0.02). Also, the mean of CT was 28.16±4.52 in patients with GD and 27.01±4.52 in patients without GD (p = 0.002). However, the difference in mean CT in patients with complete and partial GD was not significant (p = 0.32). In patients, without OD or GD, the mean of CT value was less than cases that had at least one of them (p = 0.001). However, the mean of CT value of OD-recovered patients and OD-unrecovered patients did not show a significant difference (p = 0.62). Also, there was no significant difference between people who had partial recovery and those who had complete recovery (p = 0.38). These comparisons were also carried out for the GD recovery, and the results were similar to the OD recovery. Also, the multivari- Also, the comorbidities of diseases, such as diabetes and hypertension, did not have a significant effect on the mean CT for COVID-19 patients. There was not a significant correlation between OD recovery time and CT and also between GD recovery time and CT. However, there was a strong, direct and significant correlation between the recovery time of OD and GD (r = 0.97, p < 0.001; Figure 1 ). In this study, 599 patients were included in the study, of which 52.2% were female and the mean age of patients was 38.27 ± 3.62 years and the maximum age distribution was in the age group of 20-40 years (50.75%). Comparison of age and sex distribution of our patients who were followed up on an outpatient basis was similar to studies by Zhang-Hu et al. 15 However, the mean age of patients in our study was lower. The lower age of our patients may be because these patients have been followed up on an outpatient basis; however, in other studies, patients were hospitalised, most of whom were older. 16 The mean of CT value in males and females and between age groups had no difference. This finding was similar to others. 17 However, in both studies, the mean of CT value had no statistical difference concerning age groups. This result is similar to the other reports. 18 In that study, it was also reported that the more severe the OD or GD, the higher the CT value, that is, the lower the virus load. At first glance, it may have been thought that people with OD or GD had a higher number of viruses, but the results show the opposite. Anosmia in COVID-19 is known as the main symptom, but its mechanism or pathophysiology remains still unclear. 19 One possibility is that the Mean ± SD p-value* The first reason may be due to an exaggerated utilisation of detergents in the initial phase of the pandemic. Therefore, it may be speculated that the olfactory epithelium damaged secondary to this chemical-induced inflammation and was more vulnerable to viral invasion. The second possible reason may be due to the presence of ACE as viral receptors in the olfactory epithelium. This inevitably increases the vulnerability of olfactory epithelium as one of the first exposed issues to SARS-CoV-2. Another reason may be related to the patient's anxiety due to the possibility of the sudden loss of sense of smell or taste, which can lead to early referral of patients and this anxiety has led to higher CT values. In some studies, a significant relationship was observed between low CT value and an increase in LDH, and a decrease in lymphocytes, indicating a worse prognosis. 21 For quantifying olfactory assessments in the COVID-19 studies, the most reported method was questionnaires, although interviewing or extracting clinical information from the patient's electronic health records were also used; however, these methods are subjective and imprecise. 21, [28] [29] [30] [31] There are several objective methods for the precise assessment of smell and taste. They include tests to determine the olfactory threshold and the type of aromatic substance. Although these two tests are accurate, they are completely nonobjective and are recommended for relative verification of patients. The other test is the olfactory assay, which is completely objective but only used in specialised neurophysiological laboratories. 32, 33 During the pandemic, measuring OD/GD with objective and nonobjective methods was not always possible. This was one of the limitations of the present study. Self-assessed OD/GD has the potential of smell and taste confusion. [34] [35] [36] So, in this study, it is not possible to know how much of your patients had isolated smell, taste or both impaired. The viral load of SARS-CoV-2 is known to vary during the course of infection. 10, 37 However, in most studies, the CT values at the onset of symptoms have been evaluated. 26 The finding of this observational study indicates a possible association between lower viral load with some clinical manifestations, including olfactory dysfunction, severity of olfactory dysfunction, gustatory dysfunction and headache in COVID-19 outpatient cases and assures the recovery of OD/GD in these patients. We would like to acknowledge the clinical laboratory experts who performed the SARS-CoV-2 laboratory testing. None declared. MHT, SMH and AT contributed to the study's concept and design. Study materials and their preparation, data collection provided by HRN, MM and MM. Data acquisition and analysis were performed by AR. The first draft of the manuscript was written by AR, SMH and MHT. However, the comments of all authors on the previous versions of the manuscript have been included in this manuscript. All authors have read and approved the manuscript. This study was approved by the Research Council of Golestan University of Medical Sciences with ethic code IR.GOUMS.REC.1399.031. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Abdolhalim Rajabi https://orcid.org/0000-0002-0698-8166 Seyed Mehran Hosseini https://orcid.org/0000-0002-4783-7428 Multimorbidity -not just an older person's issue. 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