Epidemiological features and hotspot of COVID-19 in Isfahan province of Iran: Results of a cohort study

Background and Aim: The aim of this study was to description of the epidemiological features and hotspot of COVID-19 in Isfahan province of Iran. Method: In this descriptive, retrospective cohort, multicenter study, all patients admitted to one of the hospitals or health networks of Isfahan province from 3 rd February to 13 th June 2020 due to RT-PCR (Reverse transcription-polymerase chain reaction) test were enrolled to study. Trained staff followed up participants for two weeks by a Telephone number, and the outcome was recorded. Result: Up to 13 June, 41,498 patients recruited and their data were analyzed; the incidence of COVID-19 was 27.5% (95% CI: 27.1, 28.2). Among the participants with the positive test, 93.2% of them, treated by outpatient basis or discharged, 2.1% were hospitalized, and the case fatality rate (CFR) was 4.8%. Khansar and Aradestan was the hotspot of COVID-19 and had the highest incidence among cities of Isfahan province. Najafabad, Khomeinishahr, and Shahinshahr&Meymeh had the highest imported cases of COVID-19 to the capital of Isfahan province, Isfahan city. Also, Charmahal & Bakhtiari, Khuzestan, and Fars provinces had the highest number of imported cases from other provinces to Isfahan city. We found that 77.3% of intra-province imported cases and about 83% of inter-province cases were imported after reducing lockdown. conclusion: The incidence and fatality of COVID-19 in Isfahan province is alarming. Inter-city and inter-provincial unnecessary travels have a high impact on the transmission and spread of the COVID-19. Applying more restrictions will prevent this from happening. It is advised to restrict the inter cities travels again by policy makers for the benet of public health.


Introduction
The novel coronavirus, named as SARS-CoV-2 was rst emerged in Wuhan, China, in December 2019 and caused respiratory illness termed COVID-19. The COVID-19 was highly contagious, and in normal conditions, the R0 level was estimated at 3 (1). Subsequently, the total number of patients has risen sharply around the world in march 2020 and over a hundred countries worldwide become involved (2) On March 11, 2020, the WHO announced COVID-19 as a pandemic aroused emerging global concerns (3).
In Iran, the rst o cial report of COVID-19 diagnosis was coincided with deaths from COVID-19 on February 19, 2020, in the city of Qom (4). On February 24, the Corona Fighting Committee in Iran was formed. Subsequently, schools, universities, religious sites (like the mosque, holy shrine, etc.), sports competitions, public transportation (such as bus, subways, etc.), museums were closed, and travel between cities was restricted until April 20 (5).
According to statistics, in the middle of June 2020, Iran ranks Tenth and ninth in the number of deaths and the number of the infected patients due to COVID-19, respectively (6). Some epidemiological features of COVID-19 have already been reported in China (7-10) and Iran (11)(12)(13). However, further identi cation of the epidemiological characteristics and identify regional spatial clusters of COVID-19 can help to increase knowledge about this disease, make appropriate decisions, and subsequently control epidemics.
The aim of this study was description of the epidemiological features and hotspot of COVID-19 in Isfahan province of Iran with a population of more than 5 million people (14

Outcome and predictor variables
The outcome of participants whom affected by coronavirus, were categorized into ve groups (Discharge, Hospitalized, Died, Outpatient, and Died at home) and trained staff followed up participants for two weeks by telephone number. In addition, the age, gender and place of residence of the participants were assessed as predictors' variable.

Participants and Data collection
All data collected and recorded to either to an online program designed for hospital records, hospital information system (HIS) or at speci c clinics which allocated for the coronavirus patients. According to the Health Network Centers data, patients were admitted from 3 rd February 2020, to 13 th of June 2020.
RT-PCR (Reverse transcription-polymerase chain reaction) using throat and nose swab specimens from the upper respiratory tract examined the patients by trained staff. All patients who had a COVID-19 test were included to the study, and patients with missing test result data or non-native cases (imported cases) were excluded from the geographical analysis. All registered cases at the hospital had a unique national identi cation number so there were no duplicates, and all patient information is kept con dential.

Statistical analysis
The outcome (death or test results) and categorical variables were described by number, percentages and 95% con dence interval (CI); The cumulative incidence of COVID-19 and 95% con dence intervals were calculated overall and across counties subgroups. Mean, standard deviation (SD) and 95% CI, median and inter-quartile range were used to describe age, which nearly normally distributed.
The chi-square and Fisher exact tests were used to examine the association between categorical variables characteristics such as gender, participant's outcome and COVID-19 test results. Also, the Analysis Of Variance (ANOVA) test was used to analyze the differences in mean age of individuals among outcome categories.
Please insert Table 1 here Based on the participant's place of residence, our spatial model of the distribution of cases in a fourmonth time interval showed that Khansar (468 per 100,000) and Aradestan (355 per 100,000) county had the highest incidence of COVID-19 cases of all the Isfahan counties (Kashan and Aran&Bidgol were excluded due to lack of data) (Table 2) (Fig 1).
Also, most Imported cases number were from Najafabad (n= 653), Khomeinishahr (n=335), and Shahinshahr&meymeh (n=331) counties to Isfahan city (Table 3) (Fig 1). Based on the test date as a proxy of importing time, 77.3% cases imported after April 12 (Fig 2).  (Table 4), Charmahal&Bakhtiari (n=166), Khuzestan (n=96), and Fars (n=15) had the highest number of imported cases. Also, based on the test date as a proxy of importing time, our result showed that about 82.9% of cases imported after April 20 (Fig 2).
Please insert Table 2

Discussion
The current study aimed to describe the clinical outcome and report the incidence of COVID-19 in Isfahan province. The incidence of COVID-19 in a four-month time interval was 25.4% among screened patients; this incidence was 2.1 per 1000 person among whole province population.
Authors of the paper believe their results are reliable and valid because of prospective cohort design, relatively large number of screened people, covering of all health centres and in turn, the whole cities and hospitals, and data quality control by two member of research project who are a panel member of province coronavirus data collection team.
The incidence of COVID-19 in a four-month time interval was 25.4% among screened patient that was consistent with the results of the study by Arab-Mazar, which mapped the incidence of COVID-19 in Iran (15).
Our result showed that the median age of the patient was 45.5 years (Table 1) showed that the proportion of men was lower than women's (48.75% male) (17).
The result of our study showed that the CFR of COVID-19 was 4.8% (Table 1)  (18.0%) (26) study. Different reports on CFR was seen in different studies. The difference between the ndings may be due to the age of the participants. In previous studies with higher CFR, the participants age was higher than the present study (23-26). Also, some studies were performed on hospitalized participants (23, 24, 26), while the present study was conducted in health centers, where the cases of the client have a non-severe disease. Some studies may also report low fatality rates due to the high screening rate in the study country and the detection of patients with mild symptoms (22).
Based on the spatial model of the distribution of cases in a four-month time interval, Khansar (469 per 100,000) and Aradestan (355 per 100,000) county had the highest proportion of COVID-19 cases of all the counties (Table 2). This may be due to the lack of enough health facilities and immigration in of suspected cases.
Also, our result showed that most of the imported cases were from the of Najafabad, Khomeini-Shahr, and Shahinshahr&Maymeh. The incidence of COVID-19 in these cities in the four-months was about 246 per 100,000 people (Table3). It seems this migration was due to the proximity of these counties to Isfahan (average distance of 32 km), more facilities in Isfahan (27), and the low capacity of hospitals in these cities (about 126 hospital-beds). Another reason for importing cases was the reduction of travel restrictions since April 15. Our results showed that 77.3% of the cases imported to Isfahan after the reduction of intra province travel restrictions (lockdown) (Figure 2) (28).
The results of our study showed that most of the COVID-19 cases imported from Chaharmahal&Bakhtiari (n=38) and Khuzestan (n=36) provinces (Table 4). Also, our results show that about 83% of cases has been imported since April 20 (Figure 2), That restriction on inter-provincial travel was removed and public transportation such as buses, trains and airlines get started (29).
Despite health advice, there are no restrictions on inter-provincial travel. Isfahan is one of the most famous tourist destinations in Iran. It seems that the trend of importing cases and the prevalence of this disease in the Isfahan will increase in the coming months. Although many cases do not show symptoms, they can spread the virus to susceptible individuals (30). It seems that Isfahan's neighboring provinces have a tremendous impact due to the higher volume of traveling to Isfahan.

Limitation
The study has very strong components including the study design that is prospective cohort study, and the sample size was large enough, so the reproducibility of the results is acceptable. In addition, the use of multi-center data increases the generalizability of the ndings to the population. However, the main pitfall of the study is lack of knowledge on whom migrated to other provinces. The paper also suffers from lack of clinical and lifestyle factors (such as smoking status, comorbidity with other diseases, Socio-Economic Status (SES)) information on coronavirus cases. Other limitations of this study was the high number of invalid PCR tests. We try to collect more background, lifestyle factors, and clinical and biological data and provide a new report soon.

Conclusion
The incidence rate of coronavirus infection (25.4% among screened patients, and 2.1 per 1000 person among whole province population) and fatality of COVID-19 (4.8%, 95% CI: 4.4, 5.2) in Isfahan province which is alarming. It seems that inter-city and inter-provincial unnecessary travels have a high impact on the transmission and spread of the COVID-19. Based on the evidence applying more restrictions will prevent this from happening. It is better for the community health to planners and managers restrict the travels again.

Consent for publication
There no any con ict of interest and all authors approved the nal manuscript and consent for publication.

Availability of data and material
The dataset used and analysed for this paper could be available from the corresponding author on reasonable request.

Con ict of interest
There are no con icts of interest to disclose and any competing nancial interests in relation to the current study.

Funding
No funding was provided for this research.
Authors' contributions MJ contributed in data analysis and writing the paper, FB contributed in writing the proposal, paper, and the literature review, HA & AK contributed in the data collection and data quality control, and GY contributed in data quality control and data analysis, writing and revising the paper.