Abstract
Objective
To explore the transmission patterns and clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, China in December 2019 as clustered and non-clustered cases of coronavirus disease (COVID-19) emerged in Shenzhen, China.
Methods
This retrospective study included the patients that were confirmed by laboratory detection of SARS-CoV-2 in Shenzen between 19 January 2020 and 21 February 2020. Data on the epidemiological and clinical characteristics were analysed. The patients were divided into non-clustered and clustered groups. The time course, intervals between first and second COVID-19 cases and other transmission patterns were compared between the groups.
Results
The 417 patients were divided into clustered (n = 235) and non-clustered groups (n = 182). Compared with the non-clustered group, the clustered group had significantly more young (≤20 years) and old (>60 years) patients. The clustered group had significantly more severe cases (nine of 235; 3.83%) compared with the non-clustered group (three of 182; 1.65%). Patients with severe disease spent 4–5 more days of hospitalization than patients with moderate and mild disease.
Conclusion
This retrospective study analysed the transmission patterns and clinical course of the first wave of COVID-19 infection in Shenzhen, China.
Introduction
According to the declaration by World Health Organization (WHO), the coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus.1–5 Clustered transmissions are an important transmission route of COVID-19. A cluster is defined as two or more cases associated with the same location, group or event around the same time. Cluster transmission has been used to identify infections that are largely concentrated in a limited locality, often within a family and its extended circle.6,7 Understanding the transmission pattern and the pathogenetic characteristics is of significant importance in preventing outbreaks of COVID-19.8–11
As a heavily populated city with the largest floating population (over 25 million daily) in China, Shenzhen is the city where the first COVID-19 case was imported and diagnosed in China outside of Wuhan. As the spread of the COVID-19 outbreak from Wuhan to other cities in China, Shenzhen ranked among the top cities outside Wuhan with a reported 417 confirmed cases by 21 February 2020. Among all of these laboratory-confirmed COVID-19 cases in Shenzhen between 19 January 2020 and 30 April 2020, there were only three deaths giving a mortality rate of 0.72%.
At present, information regarding the transmission pattern and the clinical course of pneumonia caused by COVID-19 is relatively scarce.6,12 Analyses of patients are particularly useful to determine key epidemiological parameters, such as the incubation between exposure and illness onset, self-observation periods between illness onset and medical visits, diagnosis periods between the medical visit and the reporting of cases, treatment periods between the reporting date and hospital discharge or death. This retrospective study undertook a comprehensive exploration of the transmission patterns and epidemiological time courses for 417 patients with confirmed COVID-19 infection in Shenzhen between 19 January 2020 and 21 February 2020.
Patients and methods
Case collection
This retrospective study enrolled all 417 patients that were diagnosed with COVID-19 infection in Shenzhen between 19 January 2020 and 21 February 2020 according to the Chinese Centre for Disease Control and Prevention interim guidance. The patients were enrolled in the Shenzhen Disease Control Centre, Shenzhen, Guangdong Province, China between 19 January 2020 and 21 February 2020. The grading of COVID-19 infection was mild, moderate, severe and critical; and all of them were accompanied by pneumonia except the mild grade. 13 The patients showed the typical clinical phenotype of COVID-19 infection and were laboratory-confirmed using reverse transcription–polymerase chain reaction (RT–PCR). Patient characteristics and detailed transmission routes of these patients were collected from the official website of the Health Commission of Shenzhen Municipality, including age, sex, occupation, residential district, date of illness onset, date of a first medical visit, date of hospital discharge, date of death, exposure history, the severity of the illness and relationship with other patients. All of the data from included cases have been shared with the WHO.
This study was approved by the Ethics Committee of the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China (no. 20220831001-MC). Individual patient consent was not required due to the retrospective nature of the study.
Cases definitions
Clustered COVID-19 cases were defined as two or more confirmed cases with contact histories in a defined small area, such as an apartment or house, a working organization and a community. Non-clustered cases were independently confirmed cases. The first case in each cluster was defined as the case with the date of illness onset, but not the date of diagnosis. The onset date was defined as the date when the patient complained of any COVID-19-related symptoms at a medical visit and the confirmation date was defined as the date on which laboratory confirmation was obtained for SARS-CoV-2 infection. The rest of the cases in a cluster group were required to comply with all of the following three criteria: (i) there was a history of contact with the first case within 14 days before the onset of symptoms; (ii) there was no history of travel to Wuhan and surrounding areas or to other communities with reported cases; (iii) there was no other history of contact or exposure to other cases outside of their own cluster of outbreaks.
As the capital city of Hubei Province, Wuhan was the city with the earliest outbreaks and the highest number of infections; and the rest of the cities in Hubei Province, other than Wuhan, had the second highest number of confirmed cases. Therefore, origin-of-case distribution and exposure history were grouped by Wuhan and Hubei other than Wuhan. Based on the contact history, all cases were classified as follows: (i) Wuhan/Hubei residents that came to Shenzhen from Wuhan/Hubei 14 days prior to illness onset; (ii) patients with a travel history to Wuhan/Hubei 14 days prior to illness onset; (iii) patients with a contact history with Wuhan/Hubei residents 14 days prior to illness onset; (iv) patients with no travel history to Wuhan/Hubei or no contact history with Wuhan/Hubei residents 14 days prior to illness onset.
The clustered groups were further divided into family gathering, party or dinner gathering, travel gathering, working gathering, hospital gathering and other close contact gatherings; and there were mixed gatherings consisting of several gathering scenarios. The severity of the illness was reported according to the Chinese interim guidelines for the diagnosis and treatment of COVID-19 patients (version 7 .0). 14
Statistical analyses
All statistical analyses were performed using the SPSS® statistical package, version 16.0 (SPSS Inc., Chicago, IL, USA) for Windows®. Data are presented as mean ± SD, median (interquartile range) and n of patients (%). All data were analysed using descriptive statistics. Comparisons between clustered and non-clustered cases of COVID-19 were undertaken using Pearson χ2-test. If Pearson χ2-test conditions were not met, Fisher's exact test was used. Student’s t-test was used to compare the mean ± SD of two independent samples. All P-values are two-sided. A P-value <0.05 was considered statistically significant.
Results
The baseline clinical and demographic characteristics of the patient population stratified according to clustered or non-clustered cases are shown in Table 1. Between 19 January 2020 and 21 February 2020, there were a total of 417 confirmed cases, including 235 clustered cases and 182 non-clustered cases. The mortality rate of the current cohort of 417 patients was 0.72% (three of 417 patients) and there was a higher susceptibility to COVID-19 in woman than men (1.1:1). However, all three deaths were in males. Compared with the non-clustered group, the clustered group differed significantly in age distribution (P = 0.001); with more young (≤20 years) and old (>60 years) patients in the clustered group. Of the total cohort, 307 (73.62%) patients had a Hubei/Wuhan exposure history and 404 (96.88%) patients had mild or moderate severity disease. There was a higher proportion of patients coming to Shenzhen from Wuhan in the non-clustered group (62 of 182 patients; 34.07%) compared with the clustered group (45 of 235 patients; 19.15%), but the difference was not significant. There was a lower proportion of patients with a Wuhan contact history in the clustered group (103 of 235 patients; 43.83%) compared with the non-clustered group (117 of 182; 64.29%), but the difference was not significant. Disease severity was significantly different between the two groups; with a higher proportion of severe cases in the clustered group (P = 0.01).
The baseline clinical and demographic characteristics of the patients (n = 417) with confirmed COVID-19 infection that were included in a study of the transmission patterns and epidemiological time courses in Shenzhen, China stratified according to clustered or non-clustered cases.
Data presented as mean ± SD, median (interquartile range) and n of patients (%).
Each non-clustered case residing in both Shenzhen and Wuhan was counted as one person coming to Shenzhen from Wuhan.
Comparisons between clustered and non-clustered cases of COVID-19 were undertaken using Pearson χ2-test. If Pearson χ2-test conditions were not met, Fisher's exact test was used; NS, no significant between-group difference (P ≥ 0.05).
The comparisons of dates of exposure, illness onset, medical visit, confirmed cases and hospital discharge/death between the clustered and the non-clustered groups are shown in Figure 1. The first COVID-19 patient in Shenzhen was admitted on 9 January 2020 with a reported illness onset date of 1 January 2020 and an exposure date of 26 December 2019 in Wuhan. The number of confirmed cases of COVID-19 began to be released daily from 19 January 2020. Most of the patients were exposed before 25 January 2020, especially between 10 January 2020 and 25 January 2020 (Figure 1a). The date of illness onset for both the non-clustered (181 of 182 patients; 99.45%) and clustered groups (225 of 235 patients; 95.74%) were mainly between 18 January 2020 and 6 February 2020 (Figure 1b). The illness onset time peak of the non-clustered group (22 January 2020) was 1–2 days earlier than that of the clustered group (24 January 2020). The peak time of the medical visit for the non-clustered group (22–24 January 2020) was earlier than that of the clustered group (29–31 January 2020) (Figure 1c). The peak date of confirmed cases for the non-clustered and clustered groups were similar (between 29 January 2020 and 6 February 2020) (Figure 1d). The overall discharge peak time of non-clustered patients (11 February 2020) was earlier than that of the clustered patients (17 February 2020 and 21 February 2020) (Figure 1e).
Comparison of the date of exposure, illness onset, medical visit, confirmed cases and hospital discharge/death in patients (n = 417) with confirmed COVID-19 infection that were included in a study of the transmission patterns and epidemiological time courses in Shenzhen, China stratified according to clustered (n = 235) or non-clustered (n = 182) cases: (a) date of exposure in clustered and non-clustered cases; (b) date of illness onset in clustered and non-clustered cases; (c) date of the medical visit in clustered and non-clustered cases; (d) date of confirmed cases in clustered and non-clustered cases and (e) date of hospital discharges/death in clustered and non-clustered cases. The colour version of this figure is available at: http://imr.sagepub.com.
Figure 2a shows the dates of illness onset in each clustered group identified in this study. The first case onset in Shenzhen was 1 January 2020, which resulted in five clustered cases through family transmission. On 19 January 2020, the National Health Commission of China officially confirmed the first imported COVID-19 case in Shenzhen. There were already 10 groups of clustered cases before that time. Then 27 clustered groups appeared in the following weeks: three groups (seven cases) occurred on 18 January 2020, three groups (eight cases) on 19 January 2020, five groups (18 cases) on 20 January 2020, seven groups (25 cases) on 23 January 2020 and nine groups (30 cases) on 24 January 2020. After 20 February 2020, the origins of the clustered cases were basically under control. The 235 clustered cases consisted of 86 clustered groups. Of these, 160 cases (69 clustered groups) had a Hubei/Wuhan exposure history. Among 86 clustered groups, there was one group with nine clustered cases, two groups with six clustered cases, four groups with five clustered cases, eight groups with four clustered cases, 20 groups with three clustered cases and 51 groups with two clustered cases (Figure 2a).
Characteristics of the patients (n = 235) with confirmed COVID-19 infection in different clusters that were included in a study of the transmission patterns and epidemiological time courses in Shenzhen, China: (a) dates of illness onset in each clustered group and (b) a diagram of the typical transmission path of the clustered cases. The colour version of this figure is available at: http://imr.sagepub.com.
For the transmission pattern analysis, the number of cases of transmission from family, colleagues and friends was 227, five and three, respectively (Figure 2b). In clustering group 1 (the familial clustering case), the first case was a 36-year-old man. He and his family members had driven to Wuhan to visit relatives on 29 December 2019 and returned to Shenzhen on 4 January 2020. He got infected on 1 January 2020, and thereafter his family members were all diagnosed with COVID-19 and hospitalized. His family became the first epidemic cluster in Shenzhen and was also the first group of COVID-19 patients diagnosed outside of Wuhan. In clustering group 2 (the friend-gathering clustering case), the first case was a 34-year-old male resident of Wuhan that has left Wuhan on 20 January 2020 (he had been ill before this trip) for Shenzhen to meet friends, spreading the infection to three friends in a row on 23 January 2020, 25 January 2020 and 26 January 2020, all of which were hospitalized on 27 January 2020. In clustering group 3 (the multiple clustering case: family + workmates), the patients in this group were permanent residents of Shenzhen that denied a history of traveling 14 days prior to symptom onset. The first case was a 25-year-old female that fell ill on 23 January 2020 and was admitted to a designated hospital for COVID-19 treatment on 28 January 2020. Her parents developed severe pneumonia on 24 January 2020. From 25 January 2020 to 30 January 2020, six close contacts with her family members got infected. This was the only example of four-generation transmission among the familial clustered cases. The transmission routes in other clustered groups are depicted in Supplementary Figure S1 (see supplementary materials, Figure S1).
The median time interval of illness onset between the first and second case was 3 days and the mean ± SD time intervals of illness onset were 4.0 ± 4.0 days (Figure 3a). The median time interval of the first medical visit between the first and second case was 1 day and the mean ± SD time interval of illness onset was 2.4 ± 4.0 days (Figure 3b). The median time interval of diagnosis confirmation between the first and second case was 1 day and the mean ± SD time interval of diagnosis confirmation was 1.5 ± 3.4 days (Figure 3c). The median time interval of hospital discharge/death between the first and second case was –1.0 day and the mean ± SD time interval of hospital discharge/death was –0.6 ± 6.9 days (Figure 3d).
Median time intervals between the first and the second case in the clustered group of patients (n = 235) with confirmed COVID-19 infection that were included in a study of the transmission patterns and epidemiological time courses in Shenzhen, China: (a) time intervals of illness onset; (b) time intervals of the first medical visit; (c) time intervals of diagnosis confirmation and (d) time intervals of hospital discharge/death.
The median time intervals between illness onset and hospital discharge for the patients with severe, moderate and mild symptoms were 25 days, 26 days and 22 days, respectively (Figure 4a). The median time intervals between medical visits and hospital discharge/death date were 22, 17 and 18 days for patients with severe, moderate and mild disease (Figure 4b). The median time intervals between case confirmation and hospital discharge/death date were 19, 15 and 15 days for patients with severe, moderate and mild disease, respectively (Figure 4c). Due to the relatively severe clinical condition of critically ill patients, the time intervals between symptom onset and a hospital visit were relatively short, with the median time interval being 3 days (Figures 4a and 4b). Due to the relatively stable condition of patients with moderate and mild disease, the time interval between illness onset and medical intervention was relatively long, with median time intervals of 9 days and 4 days, respectively. The median time intervals between diagnosis confirmation and discharge for patients with severe, moderate and mild disease were 19 days, 15 days and 15 days, respectively (Figure 4c), indicating that patients with severe disease needed 4–5 more days of medical intervention compared with patients with moderate and mild disease.
Time course of the patients with mild, moderate and severe disease in a study of the transmission patterns and epidemiological time courses of COVID-19 in Shenzhen, China: (a) time intervals between the illness onset and hospital discharge/death; (b) time intervals between the medical visit and hospital discharge/death; (c) time intervals between the case confirmation date and hospital discharge/death date; (d) age distribution; (e) dates of the number of patients with moderate and severe disease and (f) dates of the proportion of patients with moderate and severe disease. The colour version of this figure is available at: http://imr.sagepub.com.
There was a higher proportion of severe disease in the >60 s, which indicates that COVID-19 infection occurred more frequently in older patients (Figure 4d). Figure 4e shows the total number of patients with moderate and severe disease on each day between 29 January 2020 and 21 February 2020 (Figure 4e). Figure 4f shows the dates of the proportion of patients with moderate and severe disease.
Timely implementation of various control measures effectively prevented cross infections and epidemic transmission in Shenzhen. The first COVID-19 case was confirmed on 19 January 2020 and the epidemic situation was under control by 9 March 2020 (0 new COVID-19 cases within 24 h). During this 50-day period, no healthcare workers were infected. As of 9 March 2020, there were only three deaths caused by COVID-19 (giving a mortality rate of 0.72%). After the implementation of all these strategies and measures, the COVID-19 cases started to decline from 6 February 2020.
Discussion
The transmission of COVID-19 in Shenzhen, China demonstrated epidemic characteristics such as a rapid increase in the number of cases over a short period of time. The epidemiological patterns and the clinical time course of the overall cohort of 417 patients with confirmed COVID-19 infection between 19 January 2020 and 21 February 2020 were systematically analysed in this current study. The clustered cases were mainly due to familial clustering with the subsequently infected patients having had close contact with the previous generation of cases when they were in the symptomatic phase. Therefore, preventing clustered cases from rapid growth helps to reduce the general severity of the disease. Regarding COVID-19 prevention and quarantine, concerns must be paid to home quarantine and in-house quarantine, which is effective in severe disease prevention. There was no difference in incubation periods between clustered and non-clustered cases. Due to the rapid intervention response in Shenzhen, China, the secondary infected cases were quickly diagnosed using RT–PCR testing and isolated after the diagnosis of the first case in the clustered groups.
The mortality rate of SARS-CoV has been reported as more than 10%, MERS-CoV at more than 35% and SARS-nCoV-2 at more than 10%, with men more likely to be affected than women.15–18 The mortality rate of the current cohort of 417 patients was 0.72% and there was higher susceptibility for COVID-19 in woman than men (1.1:1). However, all three death cases were in males. The reduced mortality of females could be attributed to the protection from sex hormones that play an important role in innate and adaptive immunity. 19 The reasons for the low mortality rates were mainly attributed to the early treatment of patients with severe disease, the timely identification of patients with aggravated conditions and the early intervention with screening and diagnosis performed by experts in critical care medicine, respiratory medicine, infection control and medical imaging. The government conducts screening, evaluation, timely adjustment of diagnosis and treatment measures and correction of potentially reversible factors that aggravate the condition of patients with COVID-19 at least once a day, with the aim of alleviating the condition to avoid aggravation and death.
The following results were demonstrated for the group of clustered cases: (i) the median time interval of illness onset between the first and second case was 3 days; (ii) the median time interval of the first medical visit between the first and second case was 1 day; (iii) the median time interval for confirmation of diagnosis between the first and second case was 1 day: (iv) the median time interval of hospital discharge/death between the first and second case was –1.0 day. These findings indicate an immediate tracking of the suspected cases. Compared with the time intervals between infection and recovery in the patients with severe, moderate and mild conditions, a shortened clinical duration was observed for mild cases, which suggests that a prolonged time course of viral elimination was associated with poor prognosis. There were some minor differences in the number of days of hospitalization between the three groups based on disease severity (22, 17 and 18 days for patients with severe, moderate and mild disease, respectively), which might be due to the following reasons. From the perspective of disease treatment, patients with severe disease obviously need longer medical care than mild and moderate patients. However, the discharge time depends not only on the degree of recovery from the disease, but also on community control policies and hospital discharge standards. Due to strict management and control policies, patients need to have resolution of their symptoms and a negative RT–PCR before being discharged from hospital, which reduced the difference in length of hospital stay between the mild, moderate, and severe groups. Quick diagnosis and timely patient isolation were effective measures to improve the prognosis of these patients.
Timely and effective prevention measures can quickly cut the routes of transmission that lead from the development of clusters to community transmissions, which then returns the clustered transmission status to a non-clustered transmission status until the new disease cases are resolved. This reversal of the state from clustered transmissions to non-clustered transmission can significantly reduce the infection rate and the severity rate, thereby reducing mortality.
At the beginning of the outbreak of COVID-19, regardless of the severity, all infected patients will be isolated and treated, which was the control policy in China during this period. Patients with mild disease were usually isolated in mobile cabin hospitals and other patients were admitted to hospitals that specialized in infectious diseases or intensive care units for treatment. Because many patients were discharged or transferred in batches, the discharge time of mild and moderately affected patients was almost the same. It only took 50 days for Shenzhen to control the epidemic situation (i.e. no new domestic cases) from diagnosis of the first case. There was also no infection of healthcare workers reported throughout this period. As of 9 March 2020, there were only three deaths, giving a mortality rate of 0.72%. After the occurrence of this COVID-19 epidemic in Wuhan, Shenzhen municipal government and related agencies responded quickly and implemented a number of public epidemic prevention measures in a timely manner. On 19 January 2020, the first COVID-19 patient was diagnosed in Shenzhen. As early as 31 December 2019,20–22 Shenzhen Disease Control Centre launched an epidemic control programme and its epidemic response strategy has been fully recognized and praised by WHO. 23 A series of early preventive strategies were implemented, which included the measurement of body temperature at all entrances to the main traffic and buildings and an outpatients service, especially for patients with fever in all main hospitals in Shenzhen. All the patients with fever were screened with nasal/throat swab RT–PCR detection of COVID-19, chest computed tomography scans and blood lymphocyte counts to find cases of COVID-19 as quickly as possible. Medical observation was established in every public hospital and Shenzhen Third People’s Hospital, Shenzhen, Guangdong Province, China was responsible for the admission and medical care of all confirmed cases. A protection procedure was established for all medical staff that undertook the screening and cared for the suspected and confirmed cases. A 14-day period of isolated observation of all subjects that arrived at Shenzhen with a travel history was implemented from 2 February 2020. The Main preventive policies and strategies for COVID-19 in Shenzhen can be found on the website of the National Health Commission of China, Health Commission of Guangdong Province and Shenzhen Municipal Health Commission. It might be worthwhile for other cities and areas to learn about the public healthcare prevention strategy of Shenzhen.
Many countries and regions conducted research on their transmission patterns and clinical courses when the epidemic first broke out in order to better formulate effective prevention and control measures to avoid the spread of the epidemic.24–26 Similar to them, this current study investigated the earliest outbreak of the COVID-19 pandemic in Shenzhen.
This current study had several limitations that should also be acknowledged. Firstly, the majority of the most severe patients that were tracked and included in the analyses shown in Figure 4 were severely ill when they were diagnosed as COVID-19 positive. Since there were a few patients with moderate disease that developed more severe disease during the treatment period, the timeline information of this subgroup of patients remains unknown and they were not included in these analyses. Secondly, among the clustered cases, 100% of the clustered infection chains were tracked. Due to timely isolation and tracking, most clustered cases were in 2–3 clustered infections. However, some clusters included transmission across several generations. The clinical features between those different clusters are worth further investigation. Future research will also focus on the transmission patterns, clinical course and effect of vaccines on disease control from 2020 to 2022.
In conclusion, this current study retrospectively analysed the transmission patterns and clinical course of the first wave of COVID-19 infection in Shenzhen, China, which has provided valuable data for future disease prevention and control.
Supplemental Material
sj-pdf-1-imr-10.1177_03000605231174303 - Supplemental material for The transmission pattern and clinical course of the first 417 patients with COVID-19 infection in Shenzhen, China
Supplemental material, sj-pdf-1-imr-10.1177_03000605231174303 for The transmission pattern and clinical course of the first 417 patients with COVID-19 infection in Shenzhen, China by Yizi Zheng, Zhenhan Deng, Feijuan Huang, Yu Zhang, Yuanzhe Cai, Jingyue Su, Zhengzhi Wu and Shiwei Yang in Journal of International Medical Research
Footnotes
Acknowledgements
The authors acknowledge the Health Commission of Shenzhen Municipality for their great support and provision of data about patients diagnosed with COVID-19.
Author contribution
S.W.Y., Y.Z.Z. and Z.Z.W. conceived and designed the study; Y.Z. and F.J.H. contributed to data collection and data entry; Y.Z.C. contributed to figure production and performed the statistical analyses; J.Y.S. and Z.H.D. had roles in the study design, clinical management, data collection, data analysis, data interpretation, literature search and writing of the manuscript. All authors reviewed and approved the final version of the manuscript.
Declaration of conflicting interest
The authors declare that there are no conflicts of interest.
Funding
This study was supported by Shenzhen Science and Technology Project (no. JCYJ20190806170418445) and the National Natural Science Foundation of China (no. 82273397).
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
