Clinical and Epidemiological Characteristics of Hospitalized COVID-19 Patients in Hormozgan, Iran: A Retrospective, Multicenter Study

1Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran 2Health Information Technology, Faculty of Paramedicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran 3Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran 4Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran 5Department of Health Information Management, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran


Introduction
A series of pneumonia cases with unknown etiology appeared in Wuhan, China, in December 2019. The clinical symptoms were very similar to those of viral pneumonia. 1 However, more precise research studying the lower respiratory tract led to the discovery of a new virus, later named coronavirus 2019. 2 Being highly contagious for the human-to-human infection and the rapid spread of the virus attracted global attention. Soon enough, the World Health Organization (WHO) declared the coronavirus 2019 disease  as an emergency for public health and international concern. 3,4 Iran is one of the countries with the highest cases of COVID-19. As of October 6, 2020, there have been 479 000 confirmed cases and 27 000 deaths. 5 To manage COVID-19 data, Hormozgan University of Medical Sciences (HUMS), Iran, established a regional registry program (RCovidRH) in March 2020 6 and started to collect the related data.
Although the number of studies addressing COVID-19 is increasing in the world, these studies are mainly from China, the US, and European countries, [7][8][9][10][11][12][13][14][15][16] few studies from developing countries such as Iran have also reported the clinical and epidemiological features of the disease. In the present report of RCovidRH, 6 we characterized the features of patients with COVID-19 admitted to hospitals affiliated to HUMS in the Hormozgan province.

Study Design and Population
This retrospective study was carried out based on the data obtained from the RCovidRH. 6 This registry has been collecting data related to patients with a definite or suspected diagnosis of COVID-19 for both outpatients and hospitalized patients referring to 20 hospitals and healthcare facilities throughout Hormozgan province in southern Iran since March 25, 2020. There are 14 cities in Hormozgan in which more than 1,750,627 people live. RCovidRH has already collected the data from more than 5000 patients. We extracted the data related to hospitalized patients with a definite diagnosis of COVID-19 according to CT-scan or real-time reverse transcriptase-polymerase chain reaction (RT-PCR) results until September 25, 2020.

Data Collection
RCovidRH collects data both prospectively and retrospectively. The variables collected in the RCovidRH were selected based on the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) , the US Center for Disease Prevention and Control (CDC), and WHO case reporting forms. [17][18][19] The registry extracts the required data from patients' medical records as well as PCR lab test results from the reference laboratory of the province assigned for the diagnosis of COVID-19. Two trained nurses supervised by an infectious diseases specialist review the medical records, and subsequently fill out the data extraction forms, and finally register them in a web-based software. Quality control staff in the registry control the quality of the data continuously and provide required feedback for the collection of shortcomings and completion of data. More details were provided in an earlier study. 6 For this study, we extracted data of 2393 hospitalized patients with a definite diagnosis of COVID-19 from the registry. There were 42 re-admissions. For this study, the researchers solely considered the admission leading to the worst outcome (death); otherwise, the first admission was considered for the analysis. Finally, we analyzed the data from 2351 inpatients.

Outcomes
The main outcome was intensive care unit (ICU) admission. We also reported demographics, signs and symptoms on admission, comorbidities, treatments, clinical outcomes (recovery/death), and length of hospital stay.

Data Analysis
We used frequency and percentage for non-numerical data, and mean, median, and interquartile range (IQR) for numerical variables. Age categories were made based on previous studies. 9,20 We used the Pearson Chi-Square or Fisher's Exact Test for non-numerical variables, and the t-test or Mann-Whitney for numerical variables for the normally distributed data. Normality of distribution was tested with the Kolmogorov-Smirnov test. The analyses were carried out using SPSS software (edition 25) and P < 0.05 was considered as the level of significance. The most common symptoms on admission included cough (57.1%), fever (45.1%), shortness of breath (52.1%), fatigue (18.1%), muscle aches (17.7%) and chills (11.3%). Although there was no significant difference for most symptoms between ICU and non-ICU patients, cough, seizure, shortness of breath, fever, fatigue, headache, lost sense (of smell or taste), and vertigo were significantly different between ICU and non-ICU patients ( Table 2, Figures 1 and 2).

Vital Signs and Laboratory Results
According to the available vital signs and laboratory results, the values of temperature, blood pressure, platelets, APTT, sodium and potassium did not show any significant difference between ICU and non-ICU patients. The levels of hematocrit, hemoglobin, lymphocyte, and oxygen saturation of ICU patients were significantly lower than non-ICU patients while the reverse was true for other laboratory and vital sign values (Table 3).

Treatments
In total, 47.1% of the patients underwent oxygen therapy. Moreover, this procedure was applied for 95.6% of ICU patients (P < 0.0001). Non-invasive and invasive ventilation were respectively used for 4.5% and 6.8% of         (Table 5). Figure 3 shows the distribution of outcomes (discharge and death) between male and female patients classified by age groups. As is shown, in both sexes, more deaths occurred among patients in the age groups of more than 70, 60-69, and 50-59 years, in decreasing order of frequency.

Discussion
The present study is the first descriptive study addressing clinical and epidemiological characteristics of COVID-19 in southern Iran. The mean and median age for our patients was 47 and 46 years, respectively. In a study from China, the mean age and the most frequent age groups were 55.5, and 50-59 years (30%), respectively. 10 Studies from the UK, Germany and Italy reported median age values of 73, 73 and 71 years, respectively. [7][8]15 A study in Tehran, Iran, showed that the mean age was 55.5, and the majority of patients were in the age group of 50-70 years. 21 This indicates that our patients are younger. Our ICU patients were significantly older than non-ICU patients (53 vs. 46 years). Another study showed that there was no difference between ICU and non-ICU patients in terms of patients' age 12 and another reported that ICU patients were older. 22 We found that this disease infected men more than women. Furthermore, male patients were hospitalized in the ICU more than women. Other studies have reported similar results. 7-8,10,21 Some studies have suggested that this might be related to the X chromosome and sex hormones as factors for stimulating adaptive immunity. 10 Most of our cases suffered from comorbidities including hypertension, chronic cardiac diseases, diabetes, and asthma. Our findings confirm earlier studies. 8,21,[23][24] A study from China reported cardiovascular and cerebrovascular diseases (40%), endocrine system diseases such as diabetes (13%), and digestive system disease (11%) as common comorbidities. 10 A UK study reported that the most common comorbidities were chronic cardiac disease (30.9%), diabetes without complications (20.7%), chronic pulmonary disease excluding asthma (17.7%), chronic kidney disease (16.2%), and asthma (14.5%), which was almost similar to our study in terms of common comorbidities. However, our patients suffered from fewer comorbidities than the UK report. 7 A systematic review on 10 articles and 76,993 patients indicated that hypertension (16.37%), cardiovascular disease (12.11%), smoking history (7.63%), and diabetes (7.87%) were the most common comorbidities in people infected with COVID-19. Chronic obstructive pulmonary disease (COPD), malignancy, and chronic kidney disease were other common comorbidities. 25 Another systematic review shows that hypertension (15.6%), diabetes (7.7%), cardiovascular disease (4.7%), malignancy (1.2%) were the most prevalent comorbidities. 26 These studies confirm our findings.
We found that hypertension, chronic cardiac disease, diabetes, chronic neurological disorders, chronic kidney disease, chronic hematologic disease, malignant neoplasm, moderate or severe liver disease, dementia and fauvism were more common in ICU patients than non-ICU patients. Another study showed that diabetes, hypertension and cardiovascular disease were the most common comorbidities and there were no differences between ICU and non-ICU patients in this respect 12 ; however, a study reported that hypertension, cardiovascular disease, diabetes, and cerebrovascular disease were significantly more common in ICU patients. 22 In our patients, the most common reported symptoms were cough, shortness of breath, fever, fatigue, and muscle aches. Chen reported fever (83%), cough (82%), shortness of breath (31%), and muscle ache (11%) as common symptoms of patients in China. 10 A recent UK study confirms our findings and presents cough (68.9%), fever (71.6), and shortness of breath (71.2%) as the most common symptoms. 7 A systematic review analyzed 43 studies involving 3600 patients found that fever (83.3%), cough (60.3%), and fatigue (38.0%) were the most common clinical symptoms. 27 Another systematic review indicated that fever (85.6%), cough (65.7%), fatigue (42.4%), and dyspnea (21.4%) were the most common symptoms. 26 A systematic review also showed that fever (88.7%), cough (57.6%), and dyspnea (45.6%) were the most common symptoms. 28 These studies are almost similar to our study.
We also found that only cough, seizure, shortness of breath, fever, fatigue, headache, lost sense (of smell or taste), and vertigo were significantly different between ICU and non-ICU patients. According to a study, only dyspnea was significantly more common in ICU patients 12 ; however, another study reported significantly higher anorexia, dyspnea, pharyngalgia, dizziness, and abdominal pain among ICU patients. 22 In our study, 47.1% of the patients (95.6% of ICU patients) received oxygen therapy. Only 4.5% and 6.8% of patients received non-invasive and invasive ventilation, respectively. Antibiotics (80.1%) and antiviral agents (82.5%) were common medications. In the UK, 55% received high flow oxygen, while 16%, and 10% received non-invasive and invasive ventilation, respectively. 7 Similarly, 76% of patients reported in a Chinese study received oxygen therapy. Non-invasive and invasive ventilation were used for 13% and 4%, respectively. Also, 71% and 76% of patients received antibiotics and antiviral treatment, respectively. 10 The use of antibiotic therapy (100%) and antiviral therapy (93%) reported in another study is similar to our findings. The authors also reported the use of non-invasive ventilation (24%) or invasive mechanical ventilation (5%) among Chinese patients. 12 Prescribing antibiotics for our patients was similar to an Italian study. 8 In our study, 9.7% of patients were hospitalized in ICU. It was lower than New York (14.2%), 13 the UK (17%), 7 France (31%), 14 Italy (20.5%) 8 and Germany (21%). 15 According to a systematic review, 20.3% of patients required ICU services. 28 This study may indicate that our patients were infected with a less severe disease. Additionally, the mortality rate was 12.5% among all patients and 64.5% among ICU patients. Mortality was higher among older male patients. The mortality was reported at 11% and 15% in Chinese studies, 10,12 20% in France, 14 26% in the UK 7 , 43.6% in Italy 8 and 16.6% in Germany. 15 A systematic review indicates that 13.9% of hospitalized patients have fatal outcomes and the case fatality rate is > 13%. 28 In a study from Tehran, the case fatality rate was 8.06% among hospitalized patients and most deceased patients were ≥ 60 years of age (mean = 65.38). Additionally, the fatality rate was 8.54% and 7.13% for men and women, respectively. 21 Although the age of patients who died was almost similar in our and the UK 7 and Tehran 21 studies, mortality was lower in our population. Conversely, in the UK, 32% of patients who received a high level of care such as ICU services died, while this rate was 64.5% in our population, which was higher than the UK 7 , Italy (26%), 29 China (38%) 12 and Germany (29%). 15 This study had some strengths. The data was extracted from a multi-center registry with considerable quality control. This registry is currently enrolling patients and enables us to analyze more patients in the future and compare the trends. Furthermore, this registry applied ISARIC case report form that improved the comparability of findings. Despite these strengths, some limitations should be considered. Our analysis did not include homequarantined cases and outpatients. Although we collected data regarding outpatients, these data were not complete and were under the quality improvement process. Therefore, we excluded these patients from the study.
In conclusion, this study is the first epidemiologic investigation with quite a high sample size in southern Iran. It shows that hypertension, chronic cardiac disease, diabetes, and asthma are the most prevalent comorbidities, and cough, shortness of breath, fever, fatigue, and muscle aches are the most common signs and symptoms. ICU and non-ICU patients are different in terms of some comorbidities and symptoms. The mortality rate is 12.5% in general and 64.5% in ICU patients and is higher in older men. These findings may play a major role in healthcare policy-making for this disease.

Ethical Statement
This study received ethical approval from the Ethics Committee of Hormozgan University of Medical Sciences (HUMS. REC.1398.482).

Funding
This study was financially supported by a grant provided by Hormozgan University of Medical Sciences (Main project number at HUMS-Vice Chancellor for Research and Technology: 980464). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.