Epidemiological and clinical features of 2019 novel coronavirus diseases (COVID-19) in the South of Iran

In late December 2019, China reported an outbreak of viral pneumonia in Wuhan, Hubei Province, China, which spread rapidly to other areas [1, 2]. It was revealed that the causative agent of the cluster of acute respiratory illness was an RNA enveloped beta coronavirus from the sarbecovirus subgenus of Coronaviridae’s family, which was termed the novel coronavirus disease 2019 (COVID-19) [3‐6]. COVID- 19 counts as the third outbreak of betacoronaviruses in the twenty-first century, causing a public health crisis of global concern [7, 8]. Previous outbreaks of this viral family have been described in 2002 and 2012. The former was a respiratory disease identified as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), involving 37 countries, and the latter, known as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) affected 27 countries. The overall mortality rate of these two epidemics of SARS-CoV and MERS-CoV was 10 and 37%, respectively [4, 9‐12].

COVID-19 is a global concern and has become a significant health problem since the number of infected cases and affected countries has escalated rapidly [13]. On March 11, 2020, the World Health Organization (WHO) confirmed COVID-19 a pandemic. As of March 31, 2020, over 800,000 cases of COVID have been reported with a death toll of over 39,000 patients and only around 141,000 recovered cases in 199 countries and territories worldwide. Among the top-ranking countries, Iran was placed in seventh position with over 35,000 confirmed cases and over 2500 deaths, and only around 11,600 recovered cases [14, 15]. However, the actual number of cases may be much higher because of challenges in confirming the cases due to the limited PCR diagnostic test kits and available staff in the hospitals.

Based on the literature, the incubation period of the disease could be up to 14 days [16]. Most cases have mild symptoms of fever, cough, sore throat, and myalgia. However, some cases can present with severe conditions such as multiple organ failure, acute respiratory distress syndrome, pulmonary edema, and pneumonia [17‐19]. Based on radiological findings in previous studies, the most frequent CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, occasionally with a rounded morphology and a peripheral lung distribution [20, 21]. In respect to laboratory data, a decrease in the absolute value of lymphocytes in most patients can be found [22], indicating that the virus may mainly act on lymphocytes, especially T-cells. Damage to T lymphocytes can be a primary factor resulting in exacerbations of patients [23]. In clinical practice, a low absolute value of lymphocytes could assist as a reference index in diagnosing new cases of coronavirus infections. Due to the severity of the disease, with over 20% critical patients and mortality rate of about 3%, COVID-19 is a global health emergency [24]. Therefore, early detection and appropriate treatment of critical cases are of essential importance.

At present, there is a lack of information regarding the epidemiology and clinical features of COVID-19 patients in the Middle East, especially Iran, a country which is considered as one of the most important focal points of the disease throughout the world. Therefore, this study has been conducted to evaluate the clinical features of COVID-19 patients in Fars province, southern Iran.

Based on the results of this study up to March 30, 2020, a total number of 113 patients were admitted to Shiraz hospitals, the capital of Fars province, Iran, with a diagnosis of COVID-19. The mean age of hospitalized patients was 53 years old, with a male to female ratio of 1.6:1. Of these patients, 29 (25.7%) are still hospitalized, 68 (60.2%) were discharged, 7 (6.2%) were discharged with outpatient treatment and 9 (8%) died. 11 (9.7%) cases were admitted to the ICU due to the severity of the disease.

Virological findings indicated that some Asian populations may potentially be more susceptible to Covid-19 than other races [31‐33]. Chan et al. confirmed the person-to-person transmission of the virus [16]. Our results showed that COVID-19 infects men more than women; these findings are consistent with the findings of the previous studies [1, 34‐36]. In early reports from China, the susceptibility of men contracting the disease was believed to have a relationship with their link to the seafood market as most workers there were men [34]. Nevertheless, as the disease spread to other countries throughout the world, this theory was weakened as men were also more susceptible to the disease in other countries. Several theories have been proposed in this respect; Li et al. reported that the male to female ratio can be attributed to the role of sex hormones and protection of the X chromosome, which plays an essential role in adaptive and innate immunity [36]. However, it may be assumed that due to Iranian culture, men tend to have more person to person contact as they work outside the house more than women who usually stay at home and do household chores.

Taking the patients’ age into consideration, most patients with severe conditions were aged over 50 years. They had comorbid diseases such as hypertension and diabetes, which is aligned with the data that has been previously reported [19, 34]. Fang et al. described a theory stating that since the coronavirus binds to its target through an angiotensin-converting enzyme 2 (ACE-2) expressed by epithelial cells in kidney, lung and blood vessels, the infection can facilitate an increased risk of developing severe COVID-19 in individuals who take ACE inhibitors and angiotensin II Type-I receptor blockers (ARBs) and also among diabetic patients as they tend to have an increase in ACE-2 expression [37‐39].

Putting aside the typical symptoms such as fever, cough, and myalgia [6, 40, 41], our data revealed that many patients presented with atypical symptoms such as abdominal pain, diarrhea, nausea, vomiting, and vertigo. In a study carried out by Lechien et al. [42] in Europe, headache, loss of smell, rhinorrhea and nasal obstruction were among the most common symptoms of patients following typical symptoms. Moreover, Spinato et al. stated that out of 202 confirmed COVID-19 patients, 130 (64.4%) reported to have an altered sense of smell or taste [43]. However, due to the design of our study and incomplete hospital records these data were not collected in our study. These data suggest that aside from the focus on typical symptoms, atypical presentations of the disease must be kept in mind as most of our patients developed gastrointestinal symptoms observed in earlier diagnosis and facilitated prevention of the spread of the disease. Moreover, these differences in the presentation of the virus might be due to alterations in the virus genotype or the level of expression of the virus receptors, including ACE2, in which necessitates further studies and evaluation.

Based on our data, those who had lower O₂ saturation on admission and presented with rales on physical examination were significantly associated with being severely ill and achieving poorer prognosis. Furthermore, those who were severely ill had lower heart rates and blood pressure. These findings can be explained by the theory that coronavirus affects not only the respiratory system but also the cardiovascular system. Based on published studies, COVID-19 patients have had high levels of myocardial injury biomarkers in their blood samples [4, 34]. Furthermore, Zheng et al. stated that this myocardial injury might be related to ACE2 which is widely expressed in the cardiovascular system as well as the respiratory system [44].

In terms of laboratory data, abnormalities included leukocytosis in 10.8%, lymphopenia in 12.6%, thrombocytopenia in 15.6%, PT and PTT in 77.9 and 45.8% were seen in the patients. Patients with severe conditions had higher increases in C - reactive protein and ESR levels, and those who died had higher levels of lactate dehydrogenase. Furthermore, severe cases of COVID-19 had more laboratory abnormalities than those who were admitted in general wards. The same results have been reported in previous studies, except for the fact that the number of cases with lymphopenia in our study was lower than other studies [1, 28, 34, 45, 46].

It is worth mentioning that in our study, the NLR ratio was significantly higher in those who were admitted to the ICU and those who died, but the average level of NLR in most patients was higher than 3.13. Therefore, we assume that a higher cut off in approach to COVID-19 patients based on the NLR ratio might be beneficial as Lie et al. reported the appropriate cutoff of 3.13 [47]. The overall results of laboratory data suggest that the novel coronavirus infection is associated with the activation of immune system responses with an impact on lymphocytes and the activation of the coagulation cascade. Thus, further studies in this area can be beneficial in the treatment of COVID-19.

Based on our data, 4 (4.9%) of our patients, who were under 50 years old and not severely ill, had normal chest CT scans. Hu et al. also reported that 29.2% of the younger asymptomatic patients in his study had normal radiologic findings [48]. Most abnormal radiologic findings consisted of ground-glass opacities, consolidation, and crazy paving presented mostly in both lungs and peripheral areas. These data, which is consistent with other publications, suggest that CT scan can play a crucial role in the diagnosis and evaluation of the severity of the disease [28, 34, 40].

The fatality rate of patients included in the current study was 8%, which is quite near to the national mortality rate in Iran which was reported to be 7% based on documented COVID-19 patients but was significantly higher compared to most studies from China [34, 49, 50], although some of which reported higher or equal mortality rate in hospitalized patients [36, 41]. Given that China had a history of SARS outbreak in 2003, they were able to successfully control the disease with the help of their previous experience and appropriate leadership. Inadequate awareness towards the disease in the early stages, lack of medical protection, high infectivity of the virus, and lack of treatment measures in Iran led to a rapid increase in the number of patients and mortality rate [51]. Moreover, since those who developed mild symptoms did not seek medical treatment, the actual mortality rate in the society might be even lower.

Controlling the source of infection, taking preventive measures, early diagnosis, isolation of suspicious cases, and supportive care have been taken into consideration to cease the spread of the virus. Although many randomized controlled trials have been initiated around the world, no specific treatment or vaccine has of yet been proposed for COVID-19. Antiviral and antibiotic therapies have been used to treat COVID-19; however, none of them were found to be properly beneficial [34, 46]. In the present study, all of the patients received antiviral therapy, all except one received antibiotic treatment, and 5 cases (4.4%) received corticosteroids.

As with any hospital-based study, this study has its own limitations. Firstly, we encountered some missing data as there were variations in patients’ documents in two hospitals due to the limited time and shortage of trained medical staff. Secondly, some patients were still being admitted to the hospital during the time of writing the manuscript, which could have affected the outcome results. Thirdly, due to the limited number of patients and given the fact that most patients with mild symptoms were not hospitalized and were not included in the study, further community-based studies are justified to explore and clarify the different aspects of this disease in Iran, as one of the most important focal points of the disease.

In this multicenter case series of 113 hospitalized patients, an 8% mortality rate for the COVID-19 patients in south of Iran was reported. Some patients developed atypical symptoms at the time of admission which makes the diagnosis difficult. Finding the source of infection and studying the behavior of COVID-19 is crucial for understanding the pandemic. Furthermore, early diagnosis, improving detection methods, timely isolation, and proper treatment are the key factors in fighting this infection.