Epidemiological study on COVID-19 virus transmission network in northeast China

Background: to analyze the epidemic situation of COVID-19 in northeast China, Liaoning and Jilin. To study the prevalence of COVID-19 virus in areas other than Hubei province and understand the spread of COVID-19 in Liaoning and Jilin provinces by means of communication network. More in-depth understanding of COVID-19 epidemic, and put forward effective prevention and control recommendations. Methods: We collected the demographic characteristics, exposure history and course of action of patients with laboratory-confirmed infection with COVID-19 published by Liaoning Provincial Health Commission and Jilin Provincial Health Commission as of February 15, 2020. We describe the demographic characteristics, case characteristics, spatial distribution characteristics and related interpersonal network of these patients. To analyze the transmission of COVID-19 in two provinces. Results : By February 15, 2020, the cumulative number of infected people in Liaoning province is 119.The largest number is 27(22.7%) in Shenyang and the smallest in Fushun, with no reported cases of infection. Among them, 55(46.2%) have a history of sojourning in Hubei province. The mainly clinical symptoms of the infected patients are fever, and 67(56.3%) of them developed fever at the time of diagnosis. Cough, sneezing and other respiratory symptoms are less. The cumulative number of infected people in Jilin province is 89, with the highest number in Changchun city at 39(43.8%) and the lowest in Baishan city, with no reported infections. 21(23.6%) people with a history of sojourning in Hubei province. Most of those infected in the two provinces are related to Hubei province, and most of those infected in the second generation or more are infected by close contact with relatives. Conclusion ： The COVID-19 outbreaks in Liaoning and Jilin provinces are gradually stabilizing, but have not yet reached the time required to lower the prevention and control level. The fatality rate of the two provinces is relatively low. There is no evidence of super-spreader in either province.


Background
In December 2019, a case of pneumonia caused by new coronavirus  infection emerged in Wuhan, Hubei province, China [1][2][3][4]. According to the World Health Organization (WHO), a total of 50,580 people have been diagnosed with the virus, with 1,524 deaths. Most of the deaths have been in Wuhan, Hubei province. The number of migrants across Hubei has surged as the country's Spring Festival travel rush peaks.
This has allowed a large number of people who have not yet developed symptoms to spread globally, starting in Wuhan, Hubei province [5,6]. Liaoning and Jilin, two major provinces in northeast China, raised their public health preparedness to the highest level on Jan. 25 and 26, respectively, after the outbreak. Therefore, the situation of the two provinces has certain reference value in the global scope.

Suspected case definition
Epidemiological history: 1. Travel history or residence history of Wuhan and its surrounding areas within 14 days before the onset of the disease, or other communities with cases report;

2.
A history of contact with a confirmed infected person within 14 days prior to onset of illness; 3. Patients with fever or respiratory symptoms from Wuhan and surrounding areas or from communities where cases have been reported were exposed within 14 days prior to the onset of the disease.
Clinical manifestation: 1. Clinical manifestations include fever or respiratory symptoms 2. Imaging features of pneumonia 3. The total number of white blood cells is normal or decreased or the lymphocyte count is decreased.
Will conform to any one of the epidemiological histories and to any two of the clinical manifestations. If there is no obvious history of epidemiology, the patients meeting the three clinical manifestations can be identified as suspected cases.

Confirmed case:
Real time reverse transcriptase polymerase chain assay (rRT-PCR) is used to detect the nucleic acid of COVID-19 virus in respiratory or blood samples. Viral gene sequencing of respiratory or blood samples is highly homologous to the known COVID-19 virus.
Any one of these conditions is considered a confirmed case of COVID-19 infection.

General demographic description
The average age of patients diagnosed in Liaoning province is 45.5 years, with a median age of 45 years. The oldest is an 85-year-old male from Huludao. The youngest, aged 4, is a female returning to Liaoning province from Wuhan.
The average age of patients diagnosed in Jilin province is 43.5 years, with a median age of 42 years. The oldest is an 88-year-old man from Changchun. The youngest 8 years old is a girl from Liaoyuan.

Analysis of time and space
Overview of COVID-19 infection in Liaoning province.
Since the first case of a 33-year-old male from Wuhan was confirmed on January 22, 2020, a total of 119 patients with COVID-19 have been confirmed in Liaoning province (as of February 15, 2020). The peak occurred on January 31 when a total of 15 people were diagnosed with COVID-19. After that day, the number of new cases in Liaoning province gradually decline and stabilize.
Overview of COVID-19 infection in Jilin province.
Since the first case of a 41-year-old female patient imported from Wuhan was confirmed on January 22, 2020, a total of 89 cases of COVID-19 infection have been confirmed in Jilin province (as of February 15, 2020). The peak occurred on February 4 when a total of 12 people were diagnosed with COVID-19. After that day, the number of new cases in Jilin province gradually declined and stabilized, with only one abnormal increase, nine, on Feb. 8. Since it takes 1-2 days to carry out inspection and compound, the sudden increase on February 8th is the reason for the backlog of samples in the previous days.
After February 15, 2020, the number of newly diagnosed patients in the two provinces was zero for several consecutive days.
According to the regional distribution of the patients in Liaoning province, the largest number of infected patients in Shenyang and Dalian are 27 and 18, respectively. Less distributed cities including Benxi, Anshan, Tieling, the number of patients are 3 to 4.
No cases have been reported in Fushun. The regional distribution of patients in Jilin province is more concentrated than that in Liaoning province, and the geographical distribution shows more obvious aggregation. As can be seen from figure 4, the population of Changchun and Siping is obviously larger than that of other prefectures.

Age distribution and sex ratio
In the age distribution we can see that patients in the two provinces are concentrated between 20 and 69 years old. The proportion of this group of patients in the total number of confirmed cases is 84.1 percent in Liaoning province and 83.1 percent in Jilin province.
The proportion of cases in the elderly group over 60 years old was 21.8% in Liaoning province and 13.4% in Jilin province.

Clinical features of infected person
Fever (56.3%) and cough (16.8%) are the most common symptoms among the 119 infected patients diagnosed in Liaoning province, and the proportion of fever and cough at the time of diagnosis is lower than that in Wuhan [7,8]. Therefore, if only body temperature and cough are selected as the screening criteria for infected patients, it is more likely to be missed. A very small percentage of these patients reported diarrhea and vomiting (6.7%), suggesting that clinical patients with gastrointestinal disease need to be more cautious than ever. Notably, 31 of these confirmed cases are asymptomatic.
These patients did not show significant symptoms when they were diagnosed as infected. This has led to missed cases during screening. One of the 119 confirmed cases was died, with a crude fatality rate of 0.84%. The death occurred on February 12 in an 87-year-old man in Huludao. Prior to infection with COVID-19, the patient had bilateral femoral head necrosis, coronary heart disease and chronic obstructive pulmonary diseases.

History of sojourning in Hubei province
Among the confirmed patients, 55(46.2%) from Liaoning province and 21 (23.6%) from Jilin province had been to Hubei province within 14 days before the onset of disease. None of the patients had been exposed to Huanan seafood market before arriving in Liaoning province and Jilin province.

Propagation network analysis
By analyzing the travel schedule of the patients 14 days before diagnosis published by the Health Committee of the two provinces and the interpersonal relationship between the patients, the communication relationship between the patients is sorted out. Build the propagation network using Gephi0.9.2.
Since this outbreak first occurred in Hubei province, we defined patients from Hubei province as first-generation cases.

Discussion
Here we report the symptoms and interpersonal relationships of 208 laboratory- As a result, the number of imported cases is higher than that of other cities in the two provinces. In addition, these three cities have better medical conditions than other cities. Therefore, it is easier to find infected patients in the process of patient admission and testing. By contrast, Siping, as the third largest city in Jilin province, has a smaller floating population than Changchun, but it does not have the infrastructure and medical level of Changchun. It is difficult to identify and treat infected people in time. Therefore, it is more difficult to prevent and control the epidemic in Siping.
From the perspective of clinical symptoms, most of these patients had different degrees of relevant clinical symptoms at the initial stage of diagnosis. Fever is the most common clinical manifestation. So using a high body temperature as a standard for community screening is still a relatively reliable screening at the moment, even though it may miss a lot of people who are not symptomatic. It is therefore recommended that in persons with a highly suspicious epidemiological history, continuous observation and management are required after the monitoring temperature has not developed fever. Of those diagnosed, six had diarrhea that had no apparent cause. Since the receptor used by the COVID-19 virus is the angiotensin-converting enzyme 2(ACE2). This receptor is not only widely distributed in the respiratory tract, but also highly expressed in the kidney, liver and digestive tract [10]. So the COVID-19 virus has the ability to replicate massively in the digestive system. The first American case of COVID-19 infection, published in the New England journal of medicine, was found to have the nucleic acid sequence of COVID-19 in the stool [11]. Subsequently, Nanshan Zhong's team successfully isolated live viruses from the feces of patients infected with COVID-19 virus on February 13, indicating that there may be a path of fecal-oral transmission of COVID-19 virus [12,13]. Therefore, hospitals should be more careful in handling patients' feces to prevent potential fecal-oral transmission. In the course of the investigation, the confirmed cases in Liaoning province have included many asymptomatic patients who did not show significant clinical symptoms when they were laboratory confirmed to be infected. Studies have shown that asymptomatic or preclinical infections can be highly contagious, so the potential for transmission cannot be ignored [14].

The New Coronavirus Pneumonia Prevention and Control Plan
Issued (4th edition) by the National Health Commission of China clearly states that the management and identification of asymptomatic or preclinical infections should be strengthened.
One 87-year-old man died in Liaoning province, out of 119 people infected with the COVID-19 virus. The patient had severe underlying disease prior to infection with COVID-19. This is the only death from COVID-19 in Liaoning province, which is similar to that in other Chinese provinces (except Hubei) [15]. Looking at other studies, it is not difficult to find that people infected with serious underlying diseases are more likely to die. Therefore, timely treatment should be given to patients with underlying diseases that co-infect COVID-19, and priority should be given to those susceptible before infection occurs.

Limitations
Due to the limited degree of details of the public data, the specific clinical treatment process and treatment effect of patients in the two provinces cannot be described in detail.

Declarations Ethics approval and consent to participate
The National Health Commission of the People's Republic of China has determined that data collection and analysis of cases and close contacts are part of ongoing investigations into public health outbreaks and are therefore exempt from the approval requirements of the agency review committee.

Source of map
The map is our own. No copyright issues.

Consent for publication
All authors agree to publish.

Availability of data and material
The data used in this study are all public data. Contact the author if necessary.

Competing interests
The author declared no competing interests.  the number of daily con rmed cases and the cumulative con rmed cases in Jilin province Figure 3 distribution of con rmed patients in Liaoning province. Note: The designations employed and the presentation of the material on this map do not imply the expression of any opinion whatsoever on the part of Research Square concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. This map has been provided by the authors. distribution of patients in Jilin province. Note: The designations employed and the presentation of the material on this map do not imply the expression of any opinion whatsoever on the part of Research Square concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. This map has been provided by the authors.  Relationship of transmission among con rmed infected persons in Liaoning province. The arrow line represents an infected person with a transmissive relationship. The nodes connected by the arrowless wires indicate that they belong to the same family or participate in the same activity together.

Figure 7
Relationship of transmission among con rmed infected persons in Jilin province. The arrow line represents an infected person with a transmissive relationship. The nodes connected by the arrowless wires indicate that they belong to the same family or participate in the same activity together

Supplementary Files
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