140 J Contemp Med Sci | Vol. 8, No. 2, March-April 2022: 140–146 Original Clinical Features and Upper Airway Symptoms in Association with Severity and Outcome in Patients with COVID-19 Furaq Hussain Hadi1, Iman Jabbar Kadhim2, Falah Abdulhasan Deli3,* 1Department of Internal Medicine, Al-Kafeel General Hospital, Ministry of Health, Kerbala, Iraq. 2Department of Medical Microbiology, Faculty of Medicine, University of Kufa, Najaf, Iraq. 3Department of Internal Medicine, Faculty of Medicine, University of Kufa, Najaf, Iraq. *Correspondence to: Falah Abdulhasan Deli (E-mail: falah.alhasnawi@uokufa.edu.iq) (Submitted: 05 December 2021 – Revised version received: 27 December 2021 – Accepted: 12 January 2022 – Published online: 26 April 2022) Abstract Objectives: To assess the relationship between the early occurrence of upper respiratory tract symptoms and the severity of SARS-COV-2 infection. Methods: A cohort observational study had been conducted on a total of 140 patients [60 mild, 40 moderate, 40 severe], diagnosed with SARS-CoV-2 between 4th of August and 31 of October 2020. Patients diagnosed by PCR or chest CT scan or both of them. A full history was taken from the patients and data including the age of the patient, gender, occupation, residence, height, weight, history of previous comorbidities {cardiovascular, Diabetes mellitus, Hypertension, chronic respiratory disease, chronic renal disease, malignancy, and other diseases}. Smoking and alcoholic history were also taken, clinical features {loss of smell/taste, sore throat, rhinorrhea, fever, cough, shortness of breath, headache, fatigue, myalgia, arthralgia, diarrhea, and vomiting} and temperature, SPO 2 , investigations, the need for respiratory support {O 2 , non-invasive ventilation, invasive ventilation} and any complications developed during illness. Results: Mean age of the patients was 51 (range: 17–82) Males were dominant; (57.1%) with male to female ratio of 1.33 to one, out of the 140 COVID-19 patients, 63 (45%) had upper respiratory symptoms. Regarding biomarkers of severity only S. LDH was significantly lower in cases who did have compared to those who did not have upper respiratory symptoms, 1.3 ± 1.4 vs. 1.7 ± 1.3, respectively. The mean SPO 2 % was significantly higher in patients with upper respiratory symptoms compared to those without. Percent of Pulmonary damage was significantly lower in patients with upper Respiratory symptom compared to those without. Mortalities were significantly lower in patients with upper respiratory symptoms compared to those without; among the 113 patients with upper respiratory symptom compared only 7 (6.2%) died compared to 7 out of 27 (25.9%) patients with no upper respiratory symptom. Conclusion: Early occurrence of upper respiratory tract symptoms predicts less severe form of the disease. Keywords: COVID-19, Anosmia, SARS-CoV-2, Pandemics, Iraq ISSN 2413-0516 Introduction In the early of December 2019, SARS-COV-2 was discovered in China, Wuhan and leads to an ongoing pandemic disease.1,2,3 Corona viruses are RNA viruses and there are four groups of coronavirus virus, are identified; alpha coronavirus, beta coronavirus, gamma coronavirus and delta coronavirus, of these alpha and beta coronaviruses are known to infect the human being.4 SARS-CoV-1 was identified in 2002 in China and MERS-COV was identified in 2013 in Saudi Arabia both are beta COV.5,6 SARS-CoV-2 enters the human cells through angiotensin converting enzyme 2 receptors.7,8 SARS-CoV-2 transmitted between humans by respiratory droplet of infected person [symptomatic or asymptomatic] coming in close (1 meter) or [aerosol particles] contact with person who are not infected with the virus, but this is not the only route of transmission indirect contact can also transmit the virus as touching sur- faces contaminated with the virus and contact with mucous membranes of the mouth, nose or eye.9,10,11,12 The symptomatology of SARS-COV-2 infection is wide and reflect different systems involvement, general symptoms as fever, malaise, fatigue, bone pain and back pain are promi- nent, respiratory symptoms like cough, chest tightness and dyspnea are the most important clinical manifestation, upper respiratory symptoms like loss of smell, loss of taste, sore throat and rhinorrhea are occurring next in order, other sys- tems are not an exception, neurological like headache and confusion, gastrointestinal like anorexia, diarrhea and vom- iting, ophthalmic like conjunctivitis and retinitis, cardiovas- cular like acute myocardial injury and atrial fibrillation, rheumatological like arthralgia.9 Fever, cough and fatigue are the three most common manifestation of SARS-CoV-2.13,14 Isolated sudden onset loss of smell is the fourth most common manifestation of the disease.15,16 Surprisingly; sudden loss of smell/taste sense occurs without usual nasal symptoms {as sneezing, rhinorrhea, nasal obstruction and facial pain}, unlike other respiratory diseases caused by respiratory viruses {as influenza, rhinovirus, adenovirus}. There are well described but not fully understood cause of anosmia which is post viral olfactory disorder {PVOD}, some physicians thought it is an inflammatory reaction of nasal mucosa while others thought the virus may damage the olfac- tory neuroepithelium or central olfactory pathway and trans- mitted to the brain directly {central nervous system including olfactory bulbs and olfactory cortex} with the development of micro vascular phenomenon and injury as micro bleeding and blood brain barrier break as demonstrated by MR imaging of patients with SARS-CoV-2 infection.17 Patients with SARS-CoV-2 may have mild symptoms as fatigue, loss of smell with no radiological manifestation or moderate as fever, dry cough but no dyspnea with radiological manifestations less than 50% or severe as having respiratory symptoms of dyspnea, hypoxia, cough, with radiological man- ifestation that is more than 50%.9 https://orcid.org/0000-0002-7605-4529 mailto:falah.alhasnawi@uokufa.edu.iq 141J Contemp Med Sci | Vol. 8, No. 2, March-April 2022: 140–146 F.H. Hadi et al. Original Clinical Features and Upper Airway Symptoms in Association with Severity and Outcome in Patients with COVID-19 The diagnosis of SARS-CoV-2 is done by the detection of the virus by mean of real time-polymerase chain reaction {RT- PCR} assay from nasopharyngeal swab of infected patients,18,19 false negative results may occur. Chest radiography is used as initial imaging method while the computed tomography {CT-scan} is very important in the diagnosis, prognosis and management plan of the disease as it found more sensitive than RT-PCR for detecting SARS-CoV-2 {98% vs. 71%}. Other laboratory tests are helpful in the assessment of severity and complications including: complete blood picture {CBC}, coagulation profile {D-Dimer}, inflammatory markers {C-reactive protein, ferritin}, lactate dehydrogenase, creatine kinase, cardiac troponin and procalcitonin.20 Increase white blood cell count, increase neutrophil count, decrease lymphocyte count, increase lactate dehydroge- nase, increase creatinine, increase D-dimer, increase C-reac- tive protein, CT invasion of more than 50%, SPO2 of less than 93%, are associated with severe disease, unfavorable outcomes and complications.20 Also being old {>65 year}, male sex, BMI >35 kg/m2, have previous comorbidities {as hypertension, car- diovascular, diabetes mellitus, etc.} are also associated with severe disease. All these factors were included in our study to assess the severity of the disease and its association with the clinical fea- tures and upper respiratory symptom. Aim of Study In this study we assess the relationship between the early occurrence of upper respiratory tract symptoms and the severity of SARS-CoV-2 infection. Patients and Methods A cohort observational study had been conducted on a total of 140 patients {hospitalized and non-hospitalized} hospitalized patients in Al-Sadder teaching hospital in Najaf Ashraf prov- ince diagnosed with SARS-CoV-2 between 4th of August and 31 of October 2020. Patients diagnosed by PCR or chest CT scan or both of them. A full history was taken from the patients including the age of the patient, gender, occupation, residence, height, weight, history of previous comorbidities {cardiovascular, Diabetes mellitus, Hypertension, chronic respiratory disease, chronic renal disease, malignancy, and other diseases}. Smoking and alcoholic history were also taken, clinical fea- tures {loss of smell/taste, sore throat, rhinorrhea fever, cough, shortness of breath, headache, fatigue, myalgia, arthralgia, diarrhea, and vomiting} and temperature, SPO2, the need for respiratory support {O2, non-invasive ventilation, invasive ventilation} and any complications developed during illness. Chest CT scan was done for symptomatic patients either before confirming the diagnosis with PCR or after confirming the diagnosis with PCR to assess the severity of the disease and treat the patient accordingly. The patients were classified according to clinical presenta- tions into:9 1-Mild: the clinical symptoms were slight and no signs of pneumonia on radiological imaging. 2-Moderate: symptoms of fever and respiratory tract symptoms and signs of pneumonia on radiological imaging. 3-Severe: patients meet any of the following criteria: a-respiratory distress {respiratory rate > = 30 breath/min. b-blood oxygen saturation <93%. c-lung infiltrate >50% of lung field on radiological imaging. Very few patients with moderate, or severe disease con- firmed by CT scan refuse PCR, so, PCR was not done for these patients. Patients were sent for CRP, CBP {neutrophils, lympho- cytes}, renal functions test, ferritin, lactate dehydrogenase and D-dimer. Normal values of these biomarkers are: CRP = <10 mg/l, ferritin = 20–230 ng/ml D-dimer = <400 ng/ml, LDH = 140–280 U/L. The duration of hospitalization and the outcome of the patients whether recovered or died was followed. Ethical consideration: Ethically this study was approved by the ethical committee of the Iraqi Board for Medical Specialization. Statistical Analysis Data of the studied group were entered managed and analyzed using the statistical package for social sciences (SPSS) version 25. Descriptive statistics presented as mean, standard devia- tion, frequencies and percentages according to the type of var- iables. To assess the relationship between categorical variables and severity of SARS-COV-2, chi square test was applied. As an alternative, Fisher’s exact test used when chi square was inapplicable. Analysis of variances (ANOVA) test used to com- pare means across the severity categories, Kruskal-Wallis anal- ysis used when ANOVA test couldn’t be applied (variable did not follow statistical normal distribution), Student’s t and Mann-Whitney tests when applicable, used to compare param- eters according to presence of respiratory symptoms. Level of significance, P. value, of 0.05 or less considered significant. Result A total of 140 SARS-COV-2 patients were enrolled in this study with a mean age of 50.9 ± 15.1 (range: 17–82) Males were dominant; (57.1%) with a male to female ratio of 1.33 to one, other demographic characteristics and distributions are shown in (Table 1 and Figure 1). Table 1. Demographic characteristics of the studied group Variable Age Mean (SD) 50.9 (15.1) Range 17–82 Gender n (%) Male 80 (57.1) Female 60 (42.9) Occupation n (%) Employed 55 (39.3) Unemployed 85 (60.7) Marital status n (%) Married 130 (92.9) Unmarried* 10 (7.1) Smoking n (%) Smoker 24 (17.1) Non-smoker 116 (82.9) BMI category n (%) Normal 35 (25.0) Overweight 71 (50.7) Obese 34 (24.3) SD: standard deviation. Mean (SD) BMI = 27.9 (4.1) (kg/m²). 142 J Contemp Med Sci | Vol. 8, No. 2, March-April 2022: 140–146 Clinical Features and Upper Airway Symptoms in Association with Severity and Outcome in Patients with COVID-19 Original F.H. Hadi et al. Of those 140 patient, 40 had severe disease, 40 had mod- erate disease and 60 had mild disease. The association between chronic diseases from one side and severity of SARS-COV-2 on the other side, no significant association was found between them, in all comparisons, P. value > 0.05), with exception of DM where significant asso- ciation were found, among 37 patients with DM, only 8 had mild disease compared to 17 moderate and 12 severe disease, (P = 0.016). Conversely, chronic use of medication was significantly associated with more severe disease where among 52 chronic medications users (anti-hypertensive, oral hypoglycemic agent, anti-ischemic…) only 21.2% had mild disease com- pared to 46.2% moderate and 32.7% severe disease, (P < 0.001), (Table 2). Among symptoms, presence of headache, sore throat, loss of smell, fatigue and myalgia was significantly associated with mild disease, (P < 0.05), while presence of shortness of breath was significantly associated with more severe disease, (P. value < 0.001), other symptoms did not show significant associations, (P > 0.05), 0020 (Table 3). A significant inverse association was found between SPO2 level and severe disease; patients with mild disease had the higher SPO2 levels with a mean of 97.2 ± 1.1% compared to 92.7% ± 1.2% in moderate disease patients and 74.8% ± 11.3% in severe disease patients, (P. value < 0.001). Similarly, lower temperature was significantly associated with mild disease, 38.1 ± 0.5°C compared to 38.7°C in mod- erate and severe cases, (P < 0.001), (Table 4). As shown in Table 5, CT-scan performed in 118 patients, among them a highly significant difference was found in per- cent of pulmonary damage reported by CT-scan, where mild cases had the lowest pulmonary damage (mean: 20.5% ± 8.8%) followed by moderate (mean: 36.9% ± 8.5%) and the larger percent of pulmonary damage in severe cases with a mean Table 2. History of chronic diseases reported among the studied group (N = 140) Chronic diseases and medi- cation use Total cases Severity P. value (chi-square test/ Fisher’s) Mild (n = 60) Moderate (n = 40) Severe (n = 40) No. % No. % No. % Hyper- tension 50 15 30.0 16 32.0 19 38.0 0.057 NS DM 37 8 21.6 17 45.9 12 32.4 CVD 30 14 46.7 5 16.7 11 36.7 0.235 NS Respiratory disease 7 2 28.6 2 28.6 3 42.9 0.640 NS Renal disease 5 2 40.0 2 40.0 1 20.0 0.827 NS Malignancy 2 0 0.0 0 0.0 2 100.0 0.079 NS Hypothy- roidism 2 0 0.0 1 50.0 1 50.0 0.467 NS Rheu- matoid arthritis 2 0 0.0 0 0.0 2 100.0 0.079 NS Chronic use of medica- tions 52 11 21.2 24 46.2 17 32.7 < 0.001 sig * Some patients had more than one comorbidity. sig: significant association (0.05 or less), NS: not significant. Fig. 1 Age distribution of the studied group. Table 3. Frequency distribution of reported symptoms of the studied group according to severity of COVID-19 (N = 140) Symptom* Severity P. value (chi-square test/Fisher’s) Mild (n = 60) Moderate (n = 40) Severe (n = 40) No. % No. % No. % Fever 58 96.7 38 95.0 37 92.5 0.645 ns Cough 56 93.3 38 95.0 35 87.5 0.415 ns Headache 56 93.3 22 55.0 19 47.5 < 0.001 sig Shortness of breath 23 38.3 36 90.0 36 90.0 < 0.001 sig Sore throat 46 76.7 24 60.0 20 50.0 0.019 sig Loss of smell 38 63.3 25 62.5 15 37.5 0.023 sig Rhinorrhea 5 8.3 3 7.5 1 2.5 0.481 ns Fatigue 44 73.3 19 47.5 25 62.5 0.032 sig Myalgia 49 81.7 14 35.0 9 22.5 < 0.001 sig Vomiting 19 31.7 8 20.0 5 12.5 0.072 ns Arthralgia 8 13.3 8 20.0 13 32.5 0.068 ns Diarrhea 3 5.0 7 17.5 2 5.0 0.058 ns *Majority of patients had more than one symptom. sig: significant association (P = 0.05 or less), NS: not significant. Table 4. Mean values standard deviation (SD) and range of measured temperature and SPO 2 of the studied group (N = 140) Parameter Statistics Severity P. value (ANOVA test) Mild (n = 60) Moderate (n = 40) Severe (n = 40) Spo 2 (%) Mean ± SD 97.2 ± 1.1 92.7 ± 1.2 74.8 ± 11.3 < 0.001 sig Range 95–99 90–94 50–88 Tempera- ture (°C) Mean ± SD 38.1 ± 0.5 38.7 ± 0.7 38.7 ± 0.9 < 0.001 sig Range 37.0–39.0 37.0–40.0 37.0–40.0 SD: standard deviation. sig: significant association (P = 0.05 or less), NS: not significant. 143J Contemp Med Sci | Vol. 8, No. 2, March-April 2022: 140–146 F.H. Hadi et al. Original Clinical Features and Upper Airway Symptoms in Association with Severity and Outcome in Patients with COVID-19 Table 6. Frequency distribution of hospitalization, duration of hospital stays and need for respiratory support among patients with moderate and severe disease Moderate (n = 40) Severe (n = 40) P. value Hospitalization no. (%) 27 (67.5%) 40 (100.0) < 0.001 sig Chi square Duration hospital stay (day) Mean ± SD (range) 4.3 ± 2.1 (2–8) 13.8 ± 8.2 (3–55) < 0.001 sig t test Respiratory support no. (%) 23 (57.5) 40 (100.0) < 0.001 sig Chi square SD: standard deviation, sig: significant difference sig: significant association (P = 0.05 or less), NS: not significant. Table 7. N Hematological WBC differential count regarding neutrophils & lymphocyte in pt. with COVID-19 (N = 140) Parameter Severity P. value Fisher’s test Mild (n = 60) Moderate (n = 40) Severe (n = 40) No. % No. % No. % Neutrophil count High 18 30.0 31 77.5 32 80.0 < 0.001 sig Normal 42 70.0 9 22.5 8 20.0 Lympho- cyte count High 2 3.3 0 0.0 0 0.0 < 0.001 sigLow 17 28.3 31 77.5 32 80.0 Normal 41 68.3 9 22.5 8 20.0 sig: significant (0.05 or less). *Result taken at presentation (before management). Table 9. Distribution of biomarkers according to disease severity (N = 140) Parameter Severity P. value Mild (N = 60) Moderate (N = 40) Severe (N = 40) CRP Mean ± SD 3.0 ± 1.7 4.1 ± 3.5 7.3 ± 4.8 < 0.001 sig Range 1–10 2–28 3–28 S. Ferritin Mean ± SD 1.2 ± 1.0 1.1 ± 1.1 4.2 ± 2.6 < 0.001 sig Range 1–3 1–5 1–10 S. LDH Mean ± SD 1.0 ± 1.0 1.0 ± 1.0 2.6 ± 1.4 < 0.001 sig Range 1.0–2.0 1.0–3.0 1.0–6.0 D-Dimer Mean ± SD 1.3 ± 0.9 2.2 ± 1.6 9.0 ± 4.1 < 0.001 sig Range 1–6.0 1–11.0 1–34 CRP: C-reactive protein, S. LDH: serum lactate dehydrogenase, all parameters presented in mean folds elevated than normal, sig: significant association (P = 0.05 or less), NS: not significant. Table 5. Radiological findings of the studied group according to disease severity (N = 140) Parameter Statistics Severity P. value Mild (n = 60) Moderate (n = 40) Severe (n = 40) CT scan (percent of pulmonary damage)* Mean ± SD 20.5 ± 8.8 36.9 ± 8.5 64.6 ± 11.3 < 0.001 sig ANOVARange 10–35 20–50 50–85 Chest X-ray Finding no (%) Infiltrate 21 (35.0) 14 (35.0) 15 (37.5) < 0.001 sig Fisher’s Normal 28 (46.7) 0 (0.0) 0 (0.0) Not available 11 (18.3) 26 (65.0) 25 (62.5) SD: standard deviation, sig: significant difference Fisher’s exact test, chi square couldn’t be applied *CT scan performed in 118 patients only sig: significant association (P = 0.05 or less), NS: not significant. Table 8. Distribution of blood urea and serum creatinine levels according to disease severity of among studied group (N = 140) Parameter Severity P. value Chi square test Mild (n = 60) Moderate (n = 40) Severe (n = 40) No. % No. % No % Blood urea High 6 10.0 8 20.0 16 40.0 0.002 sig Normal 54 90.0 32 80.0 24 60.0 S. Cre- atinine High 4 6.7 3 7.5 5 12.5 0.570 ns Normal 56 93.3 37 92.5 35 87.5 sig: significant association (P = 0.05 or less), NS: not significant. percent of pulmonary damage of (64.6% ± 11.3%), (P. value < 0.001). With regard to chest X-ray findings, none, of the cases with moderate or severe disease form had normal X-ray findings, compared to 46.7% of mild cases (P. value < 0.001). Hospitalization needed in 67.5% of moderate cases and all severe cases, (P < 0.001). The mean duration of hospital stay was significantly longer in severe cases, 13.8 ± 8.2 days, than moderate disease group, (4.3 ± 2.1 days), (P < 0.001). All cases with severe disease needed respiratory support compared to 57.5% of moderate cases, (P < 0.001), it is worth mentioned that none of mild cases hospitalized or needed res- piratory support, (Table 6). Neutrophil count was significantly higher in severe cases while Lymphocyte count was significantly lower in severe cases, (P < 0.001), (Table 7). A significantly higher blood urea reported in severe cases (P = 0.002), where 40% of severe cases had elevated blood urea compared to 20% of moderate cases and 10% of mild ones. No significant differences were reported in S. Creatinine (P > 0.05), (Table 8). The comparison of biomarkers according to disease severity revealed that severe cases had significantly higher CRP, S. ferritin, S. LDH and D-dimer, in all comparisons, (P < 0.001), (Table 9). All mild and moderate cases recovered, however, only 2 moderate cases developed complications and recovered later, among severe cases complications occurred in 50%, and unfortunately, 14 (35%) died, the differences in outcomes, were statistically significant, (Table 10). The mean S. LDH level was significantly lower in cases who did have compared to those who did not have upper res- piratory symptoms, 1.3 ± 1.4 vs. 1.7 ± 1.3, respectively, (P. value = 0.011). Neither CRP, S. Ferritin nor D-Dimer level significantly different across the presence of upper respiratory symptoms, (P > 0.05), (Table 11). 144 J Contemp Med Sci | Vol. 8, No. 2, March-April 2022: 140–146 Clinical Features and Upper Airway Symptoms in Association with Severity and Outcome in Patients with COVID-19 Original F.H. Hadi et al. Table 12. Relationship between of Upper Respiratory symptom with SPO 2 and CT scan findings of the studied group Parameter Upper Respiratory symptom P. valueYes No Mean SD Mean SD Spo 2 (%) 90.7 9.7 84.3 15.5 0.007 sig Chest CT scan (%) of pulmonary damage 34.6 20.2 49.1 21.2 0.001 sig Table 13. Relationship between of Upper Respiratory symptom with complication and mortality of COVID-19 patients (N = 140) Upper respiratory symptoms P. Value Yes (n = 113) No (n = 27) No. % No. % Complications Yes 15 13.3 7 25.9 0.105 NsNo 98 86.7 20 74.1 Outcome Recovered 106 93.8 20 74.1 0.002 SigDied 7 6.2 7 25.9 sig: significant association (P = 0.05 or less), NS: not significant. Table 10. Outcomes of moderate and severe Covid-19 patients Outcome Moderate (N = 40) Severe (N = 40) P. value Chi square test No. % No. % Recovered 40 100.0 26 65.0 < 0.001 sig Complications developed 2 5.0 20 50.0 < 0.001 sig Died 0 0.0 14 35.0 < 0.001 sig Table 11. Relationship between Upper Respiratory symptom and markers of diseases severity Parameter Upper Respiratory symptom P. valueYes (N = 113) No (N =27) Mean ± SD* Mean ± SD CRP level 4.4 ± 3.2 5.0 ± 3.8 0.552 ns S. LDH 1.3 ± 1.4 1.7 ± 1.3 0.011 sig S. Ferritin 1.8 ± 2.1 3.0 ± 2.6 0.175 ns D-Dimer 2.8 ± 1.7 5.1 ± 3.4 0.070 ns SD: standard deviation. The mean SPO2% was significantly higher in patients with upper respiratory symptom compared to those without, (P = 0.007). Percent of Pulmonary damage was significantly lower in patients with upper Respiratory symptom compared to those without, (P = 0.001), (Table 12). No significant association was found between complica- tions and presence of upper respiratory symptom, (P > 0.05). Mortalities were significantly lower in patients with upper res- piratory symptom compared to those without; among the 113 patients with upper respiratory symptom compared only 7 (6.2%) died compared to 7 out of 27 (25.9%) patients with no upper respiratory symptom, (P = 0.002), (Table 13). Discussion The clinical manifestations associated with SARS-COV-2 share some features with other respiratory viral infection but there are many areas of differences including the absence or minimal occurrence of rhinorrhea, severe and distressing cough and marked involvement of lung with severe destruc- tion observed in many patients.21,22 Radiographic imaging has a significant role in confirma- tion of diagnosis and the assessment of severity of pulmonary damage and this helps in early recognition of critically ill patients to prevent unnecessary delay in intensive manage- ment and consequently increasing mortality.23–30 The present study is planned to assess the clinical features, in particular, upper respiratory symptoms and their associa- tion with CT findings and severity of disease in group of Iraqi patients. In this study there was no significant association between having chronic diseases and severity of SARS-COV-2, with the exception of diabetic patients and chronic medication users had significantly more severe disease. Similar findings were also reported in previous studies; in large scale case-control study, Yan et al. found that chronic drug users had significant higher susceptibility and severity of disease,31 Erener S docu- mented that diabetic patients at high risk of infection and poor glycemic control are a major risk factor for infection and con- tributed that to the alteration in the immune function in dia- betic patients.32 On the other hand, other studies reported strong correlation between comorbid chronic disease and severity of SARS-COV-2;33 Wang et al. found that comorbid chronic disease and acute organs injury was strongly and sig- nificantly associated with severe disease and higher mortality among patients with SARS-COV-2.34 Expectedly, in the present study, lower SPO2% was signifi- cantly associated with more severe disease, similar findings reported in many other studies;35–37 Xie et al. found a signifi- cant association between hypoxemia and higher mortalities.35 Rubin et al. supported these findings.36 Li et al.37 found that oxygen saturation of less than 93% was significant predictor of poor prognosis and higher body temperature on admission was significantly associated with more severe disease. Petrelli et al.38 found that body temperature on admis- sion was good predictor for viral infection and that higher temperature of 38°C or more would be good diagnostic indi- cator implies severe and critically ill patients, on the other hand, Petrelli et al.38 documented higher proportion of patients with severe disease with temperature of more than 38°C compared to those with milder disease and non- hospitalized patients. Conversely, Guan et al.39 from China studied the clinical characteristics of 1909 SARS-COV-2 patients, among their findings no significant difference in the mean body tempera- ture on admission between cases with non-severe and severe disease. The differences between studies could be due to the criteria that depended for admission and classification of dis- ease severity in different countries, where in most studies, cli- nician not much rely on body temperature as indicator of severe disease, but some authors stated that patients with severe or critical illness, had significantly longer duration of 145J Contemp Med Sci | Vol. 8, No. 2, March-April 2022: 140–146 F.H. Hadi et al. Original Clinical Features and Upper Airway Symptoms in Association with Severity and Outcome in Patients with COVID-19 higher body temperature than the mild or non-severe cases. Furthermore, the duration of high body temperature in patients who transferred to ICU was almost 31 days compared to 9 days in other patients.40 The present study found that higher CT scan percent of pulmonary damage associated with severe disease this finding supported that in other studies,41,42 where these studies docu- mented that CT-scan detected pulmonary damage was signifi- cantly associated with disease severity and the proportion of pulmonary damage increased with severity. In the current study, presence of infiltrate on chest x-ray was significantly associated with severe disease. It had been adopted that Chest-X-ray findings is helpful in monitoring the course and severity of SARS-COV-2.43 Yasin and Gouda from Egypt found that severity score was significantly associated with abnormal X-ray findings and concluded that radio- graphic findings were good predictor for long term monitoring of SARS-COV-2 cases. In the current study, patients with severe disease needed longer duration of hospitalization than the cases with mod- erate disease and all patients with severe disease needed res- piratory support compared to only 57.5% of moderate cases, these findings were not unexpected due to nature of disease, and similar findings reported in most other studies,36,38,40–42,44 in the present study none of mild cases were admitted, and this is according to the management recommendations of MOH in Iraq that mild cases send for home quarantine and followed up. The blood count results of this study show increase neu- trophils count and decrease lymphocytes count was found in severe cases compared to moderate and mild cases, Knong et al. reported that higher neutrophil and lower lymphocyte counts as demonstrated by higher neutrophil to lymphocyte ratio (NLR) was significantly associated with severe form of SARS-COV-2 and that patients with increased NLR should be admitted to an isolation ward with respiratory monitoring and supportive care.45 A meta-analysis conducted by Li et al.46 proved good value of NLR in prediction of severe and critical disease. Another study indicated that high neutrophil and lower lym- phocyte counts had good prognostic implications in SARS-COV-2, the higher NLR has been hypothesized to be associated with underlying endothelial dysfunction which favor cellular damage and then endothelial cell death particu- larly in patients with pre-existing endothelial dysfunction.47 Biomarkers including CRP, S. ferritin, S. LDH and D-Dimer were all significantly and proportionately increased with severity of SARS-COV-2; patients with severe disease had significantly higher mean values of these biomarkers than those with moderate disease while the level in mild cases were the lowest and these findings were consistent with other studies.24,25,48–50 Regarding the association between symptoms and severity of disease, the present study found that patients with head- ache, sore throat, loss of smell, fatigue and myalgia had signif- icantly milder disease and those with shortness of breath had significantly more severe disease, while other symptoms did not show significant associations with severity of SARS-COV-2, the patients with upper respiratory symptoms had lower levels of CRP, S. ferritin, S. LDH and D-Dimer, higher SPO2% and lower CT scan percent of pulmonary damage, these findings indicated less severe disease in patients with upper respiratory symptoms compared to those without. Although the exact pathophysiology of post-viral anosmia is unclear, it is believed that damage to the receptor cells of the olfactory neuroepithelium is one of the probable causes. Objective assessment of loss of smell was not done because of risk of infection transmission. Conclusion Early occurrence of upper respiratory tract symptoms predicts less severe form of the disease and good outcome of the patient. Conflicts of Interest None.  References 1. Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. “The continuing 2019-nCoVepidemic threat of novel coronaviruses to global health—The latest 2019 novel corona virus outbreak in Wuhan, China”. International Journal of Infectious Diseases. (February 2020) 91:264–266. 2. Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study [published correction appears in Lancet. 2020 Feb 4;]. 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