Exposure-history Type and Characteristics of SARS-CoV-2 Infected Patients in Wuhan (cid:0) Epicenter (cid:0) Neighboring Shaanxi Province of China

The whole outbreak period in Shaanxi Province (from to Feb 20, 2020) was split into two consecutive stages. Epidemiological feature like exposure-history type and characteristics of the conrmed SARS-CoV-2 infected patients in Shaanxi Province were analyzed.


Introduction
In December 2019, cases of pneumonia associated with a novel coronavirus (SARS-CoV-2; previously known as 2019-nCoV) emerged in Wuhan, Hubei Province. To date the virus has spread to more than 150 countries, areas or territories [1]. Earlier epidemiological studies have reached the consensus that the transportation between Wuhan (Epicenter) and other major cities in China played critical role in the domestic spreading of the SARS-CoV-2 infection in China [2][3][4][5]. Moreover the massive population migration before the Spring Festival has aggregated the spread of the virus. By the date of Feb 20, 2020 75,465 con rmed SARS-CoV-2 cases were reported in all 31 provinces of mainland China [6].
Shaanxi Province is an adjoining province northwest to Hubei Province, with a population of 38.64 million. The moderate travel load between the two provinces makes Shaanxi Province one ideal observation site for both epidemiology study and control-effectiveness observation of SARS-CoV-2 epidemic [7,8]. As the major attention was on clinical and major epidemiological features in Wuhan and surrounding areas of Hubei Province in earlier epidemic [9][10][11], other epidemiological features including patients' exposure-history type and characteristics in epic-center neighboring areas during the whole breakout period were rarely reported.
On January 19, 2020 the rst con rmed case outside Hubei Province in China was reported in Shenzhen, Guangdong Province. Meanwhile with more exported cases outside Hubei Province in mainland China were reported, both nationwide and provincial measures were taken [12]. On Jan 22 China announced a travel quarantine of Wuhan and next day on Jan 23 Wuhan was locked down. By January 30 a total of 16 major cities in mainland China were included in the list of travel quarantine. The rst con rmed case of SARS-CoV-2 infection was reported in Shaanxi Province on Jan 23, 2020. Control measures including case isolation, contact tracing, and surveillance were taken on the same day. On Jan 25 Provincial Primary Level (the highest level) Health Emergence Response was launched and travel quarantine was applied (restricted to Hubei Province). Further upgrading of travel quarantine (restricted to areas outside Shaanxi Province) was announced on January 31. On February 4 new series of measures including social distancing and community limitations were active in Shaanxi Province.
In this study retrospectively we performed a descriptive analysis on exposure-history type and characteristics of the con rmed SARS-CoV-2 infected patients and evaluated the control effects of provincial level measures on local transmission in epi-center neighboring Shaanxi Province.

Settings
Shaanxi Province (31°42′N-39°35′N, 105°29′E-111°15′E ) is located in northwestern China (Fig. 1). It is comprised of 11 prefecture-level cities, with a land area of 205,600 km 2 and a population of 38.64 million in 2018 [13]. With a population of 10, 00 million (2018) and land area of 10,108 km 2 , the population density of Xi'an is 989 persons/km 2 . Xi'an is the regional center for Shaanxi Province and center city for northwestern China.

Data collection and case de nition
Patients' data including exposure-history type and other characteristics including demographic features were obtained from public online data announced by Health Commission of Shaanxi Province (http://sxwjw.shaanxi.gov.cn/). As the public health is the major concern for both the study and publication, ethical approval is deemed unnecessary for the study.
The diagnosis of SARS-CoV-2 infection (or COVID-19) was established based on respiratory specimen detection by uorescence quantitative polymerase chain reaction assay for SARS-CoV-2 nucleic acid combined with or without clinical characteristics and/or chest imaging throughout the outbreak period.

Mapping
A spatial distribution map was made to analyze the spatial association of SARS-CoV-2 infection. The incidence rate (calculated by total infected number divided by the population of the prefecture-level city) in each prefecture-level city was mapped and different level of incidence rate was marked with a corresponding color on the city-level digital map.

Statistical Analysis
Categorical variables were presented as frequencies and proportions, and differences between groups were evaluated with chi-square test or Fisher's exact test. Continuous variables were reported as means with 95% con dence interval and were compared with Wilcoxon rank-sum test between groups. A twosided P value of ≤ 0.05 was considered to be statistically signi cant. All analyses were performed using SPSS.

Results
From Jan 23, 2020 to Feb 20, 2020 a total of 245 patients were con rmed with SARS-CoV-2 infection in Shaanxi Province. In general the average age of the con rmed patients was 46.02 (95% CI, 43.96 to 48.09) ( Table 1). 133 (54.29%) were male and 112 (45.71%) were female (Table 1). 5 patients (2.04%) were children under the age of 12 and the youngest was 3 years old (Table 1). 42 (17.14%) and 5 (2.04%) patients were above the age of 65 and 80 respectively, while the majority (n = 162, 66.12%) were aged 30 to 65 years (Table 1).  . 2), the capital city of Shaanxi Province and the main transport port (both ight and train). Other relatively high incident areas include Hanzhong and Ankang (Fig. 2), both of which were in southern part of Shaanxi Province and have closer transportation connections with Hubei Province by trains, buses, and private transportation.
To investigate the shift of the epidemic, the whole outbreak period was split into two consecutive stages: before Feb 6 since rst reported con rmed case on January 23 (earlier stage, rst 14 days period) and after Feb 5 till last reported con rmed case on February 20 (second stage, 15 days period) (Fig. 3).
89 (53.94%) patients in earlier stage (Jan 23-Feb 5, 2020) had a history of living or travelling in either Wuhan or neighboring cities of Hubei Province after the onset of the SARS-CoV-2 epidemic (Imported cases) (Fig. 4). 24 (14.55%) patients were local inhabitants con rmed to have direct contact with the imported cases (Local primary cases) (Fig. 4). 6 (3.65%) patients were local inhabitants con rmed to have direct contact with the local primary cases (Local secondary cases) (Fig. 4). 46 patients (27.88%) were patients with no de nite exposure history and other types (Exposure inde nite and other types) (Fig. 4).
During the second stage (Feb 6-Feb 20, 2020) the percentage of the imported cases dropped from 53.94-16.25% while that of inde nite exposure history and other types increased from 27.88-70.00% (Fig. 4). Meanwhile the percentage of local primary and secondary cases decreased from 18.15-13.75% (Fig. 4).
The mean age of the con rmed patients in the second stage was 52.29 (95% CI, 48.57 to 56.02), higher than that in earlier stage (42.98, 40.61 to 45.35) (P < 0.001) ( Table 2). It was also noticed that percentage of female patients increased from 42.42% in earlier stage to 52.50% in second stage (P > 0.05) ( Table 2).  Table 2). We noted that a total of 31 cases (18 in earlier stage and 13 in second stage) became symptomatic or asymptomatically con rmed during the quarantine observation period as close-contacts of the con rmed cases (due to lack of symptom or direct diagnosis post symptom onset these 31 cases were excluded from the calculation of the duration to con rm).
Obvious family clustering phenomenon was also observed, with a total of 117 cases clustered in 39 families (2-6 cases/cluster) and accounting for 43.67% of the total con rmed cases.

Discussion
As the control measures were taken during late-January in succession the effectiveness on local transmission of SARS-CoV-2 infection was demonstrated by the declining number of daily con rmed SARS-CoV-2 infected cases during mid-February in second stage.
From Jan 23 through Feb 5, 2020 the Hubei-area imported cases took the majority of the con rmed cases. However, as the epidemic was evolving more contact-origin unidenti ed cases, including cases with no de nite exposure history were con rmed during the second stage (Feb 6, 2020 to Feb 20, 2020).
On the one hand, the results demonstrated the effect of city knockdown and travel quarantine. On the other hand, the transition also suggested an increased risk for community or environmental transmission as the epidemic was evolving. Though some local primary and secondary cases were con rmed, no local third-generation cases were reported during the whole outbreak period. Moreover from Feb 20 to Mar 10, 2020 no new cases were con rmed in Shaanxi Province. The above results validated the timeliness and effectiveness of the control measures in response to SARS-CoV-2 epidemic in Shaanxi Province.
In terms of average age of the con rmed cases, our results were similar to those reported in other areas in mainland China [14,15]. The small number of infected children and absence of infant case was also consistent with previous reports [16,17]. It was speculated that the low rate of children and infant infection was due to a lower risk of exposure or di culty in identi cation due to mildness or lack of their symptom [18,19]. However, we noted a lower percentage of old-age infected patients compared with the earlier report in Wuhan [9], which was related to the lower rate of mortality (one case in 245 by the date of March 10, 2020) in Shaanxi Province. The phenomenon of obvious family clustering observed in both Liu's and our study alarm us the high probability of intra-family transmission during the outbreak period [20].
As the imported cases were mostly migrant workers back for the celebration of Chinese Spring Festival, the lower average age and more male percentile in earlier stage was observed, which was consistent with the results in other provinces [14,15]. With the continuous implementation of control measures mentioned above, a shortened span from symptom onset to diagnosis should be expected. However, the duration to con rm in second stage was 3 days longer than that in earlier stage. We speculated the epidemic evolvement of exposure type might be the cause of the delay in second period, as patients with no de nite exposure history were more unlikely to be identi ed and hospitalized. Moreover the asymptomatic or mild-symptom cases were more likely to accumulate and be con rmed in the second stage, thus contributing to the observed longer duration to con rm.
Our study also demonstrated the spatial heterogeneity of SARS-CoV-2 infected cases in Shaanxi Province, as shown by the higher incident rate in central areas (capital city and its surrounding areas) and southern part (adjoining areas to Hubei) of the province. Factors like geographical distance, transport accessibility and economic activity all might account for this heterogeneity [5,21]. Districts that display high-level mutual communication with epic-center areas should adapt more comprehensive and proactive containing measures [22].
One limitation of our study is that the incubation period of SARS-CoV-2 infected patients in Shaanxi Province was not calculated due to lack of complete data and uncertainty of exact date concerning patients' exposure time.

Conclusions
In conclusion, we analyzed epidemiological feature like exposure-history and characteristics of SARS-CoV-2 infected patients in Wuhan, Hubei neighboring Shaanxi Province during the whole outbreak period. From the view of public health's point the serial measures taken by local government in China like Shaanxi Province set an example for the world, given the abruptness of the epidemic and the pandemic situation globally [23,24].

Declarations
Ethical Approval and Consent to participate Not applicable.

Figure 1
The location of Shaanxi and Hubei Province in China were marked with color. Circles indicate the capital cities. 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.

Figure 2
The SARS-CoV-2 infection incident rate in 10 prefecture-level cities of Shaanxi Province Figure 3 Major daily event and the number of daily con rmed SARS-CoV-2 infected cases in Shaanxi Province during the outbreak period