Abstract
Coronavirus Disease 2019 (COVID-19) pandemic has rapidly spread across the globe while little multi-center research about the epidemiological characteristics of cluster transmission is conducted. To provide a more comprehensive description of the epidemiological characteristics of cluster transmission and the virulence of SARS-CoV-2 carried by asymptomatic carriers, we studied the epidemiological characteristics of 70 clusters. 70 clusters including 311 consecutive subjects from January 20, 2020, to March 10, 2020, were enrolled. Of 70 clusters, 5 were infected by asymptomatic or presymptomatic carriers. We gathered and analyzed information about their demographic, epidemiological, clinical, diagnostic classification, and cluster characteristics. Among the 66 asymptomatic carriers in Jiangsu Province, 49 asymptomatic were observed in 311 subjects distributed in 70 clusters. We demonstrated that there is a significance between the severity of cases infected by asymptomatic carriers and cases infected by symptomatic patients (P=0.033) and the former usually presented with milder symptoms. A significant difference was shown regarding the level distribution of age (P=0.006) and the frequency distribution of gender (P=0.014) and disease severity of COVID-19 (P=0.008) among the seven groups classified by the relationship with the index cases. The average age of infected medical staff was the youngest and the majority of infected medical are females while the infected patients were generally oldest and usually accompanied by severest symptoms. We concluded that asymptomatic carriers are mainly screened out of clusters and the patients infected by asymptomatic carriers present with milder symptoms than those infected by symptomatic patients, which indicated that the SARS-CoV-2 shares decreased virulence among asymptomatic carriers. Effective measures should be taken to prevent transmission in hospitals to protect doctors, nurses, and patients.
Keywords: COVID-19, asymptomatic carrier, clusters, nosocomial infection
Introduction
According to the Situation Report - 100 about coronavirus disease 2019 (COVID-19) released by World Health Organization (WHO), by 10:00 CEST, 01 June 2020, 6,057,853 confirmed cases, including 3018681 (122,917 new) and 371166 deaths (4,000 new) have been reported globally [1]. With an increasing number of infections and deaths, COVID-19 poses a significant threat to public health.
Cluster transmission plays an important role in COVID-19 spreading. Three clusters of COVID-19, containing 28 locally transmitted cases have been reported in Singapore [2]. Another study also reveals the epidemiology features of clusters, including age, gender, and incubation period [3]. Although clusters transmission has been reported before, few pieces of research have been conducted to explain whether the epidemiological characteristics of cluster transmission of COVID-19 presented in the same way in different situations.
With the development of COVID-19 research, it is notable that the asymptomatic carriers are potential sources of COVID-19 infection. Researchers in Germany have reported that the transmission of COVID-19 infection caused by the asymptomatic carrier. Moreover, a 2-family cluster of subjects with COVID-19 infected by having contact with infected but potentially presymptomatic subjects has been demonstrated [4]. Besides, the familial cluster of COVID-19 infection from an asymptomatic case has been reported [5]. According to the recent study, 5% of COVID-19 infection resulted from the asymptomatic case [6]. However, the difference of virulence of SARS-CoV-2 carried by asymptomatic carriers and symptomatic patients and the features of asymptomatic carriers among clusters has not been fully explored.
The purpose of this study was to investigate whether the epidemiological characteristics of cluster transmission of COVID-19 do present the same in different situations and whether the virulence of SARS-CoV-2 between asymptomatic carriers and symptomatic patients is the same. We also aimed to study the features of asymptomatic carriers among clusters. Therefore, we carried out a multi-center study observing 70 clusters across 13 cities in Jiangsu Province, China.
Materials and methods
Subjects and methods
Study participants
From January 20, 2020 to March 10, 2020, 70 cluster outbreaks including 311 consecutive subjects (148 males and 163 females) aged from 1 to 97 years who were laboratory-confirmed asymptomatic carriers, mild cases, ordinary cases, severe and critical cases of Covid-19 from 13 cities across Jiangsu Province, China were enrolled in this study. Of the 311 subjects, 49 (15.8%), 97 (31.2%), 160 (51.4%), and 5 (1.6%) subjects were categorized into asymptomatic carriers, mild cases, ordinary cases, severe and critical cases of Covid-19 respectively. The demographic, epidemiological, clinical, diagnostic classification and cluster characteristics were collected and analyzed.
Study definitions
Asymptomatic carriers who present with no clinical symptoms but with a positive result of the pathogen tests of 2019-nCoV in respiratory tract specimens and so on were found mainly through the investigation of cluster outbreak and tracing of the infectious source. A cluster outbreak means that more than two confirmed cases or asymptomatic carriers are found within 14 days in a small area (such as a family, a building site, a work unit, etc.), and there is a possibility of human-to-human transmission caused by close contact or by exposure to infectious source altogether. The definitions about classifications of COVID-19 of the present study were based on the 6th edition guidance for COVID-19: prevention, control, diagnosis, and management issued by China’s National Health Commission [7].
The incubation period means the time starting from the moment of exposure to severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) until signs and symptoms of COVID-19 appear. Epidemiological data were collected to speculate the latent period of COVID-19. For each subject, the time of exposure to SARS-CoV-2 and appearance of the earliest symptom was recorded as accurately as possible. We would use the time of events when it is precise; otherwise, the upper and lower limits of each event were given according to the case history. When the time of exposure to SARS-CoV-2 is an interval which means uncertain, the median of it was used as the onset of exposure to SARS-CoV-2 [8]. When the time interval of exposure to SARS-CoV-2 could not be determined, we defined it as 7 days according to the previous report [9].
Statistical analyses
Data were analyzed using Statistics Package for Social Sciences (ver. 16.0; SPSS Incorporated, Chicago, IL, USA). Subjects were categorized into two, seven, and ten groups according to the characteristics of the index case, the close contacts’ relationships with the index cases, and manners of being infected respectively. Normally distributed variable of age was presented as mean ± standard deviation (SD), and the comparisons were analyzed using the independent-samples t-test and one-way ANOVA. Variable of incubation period with a skewed distribution were presented as median and quartile ranges, and the comparisons were made using the Mann-Whitney U test and Kruskal-Wallis H test. Categorical variables were compared using chi-square analyses. Statistical significance was considered if the two-tailed p-value was <0.05.
Results
The epidemiological characteristics of cluster transmission of COVID-19
The data source of the cluster transmission of COVID-19 in the present study was shown in Tables S1 and S2. The epidemiological characteristics of index cases and infected patients among 70 clusters were exhibited in Table 1. Among the 70 cluster outbreaks in the present study, clear index cases can be found in 68 cluster outbreaks, and of the 68 cluster outbreaks, 5 clusters were transmitted by asymptomatic infected patients. 66 asymptomatic carriers were found from major hospitals in Jiangsu Province.
Table 1.
The epidemiological characteristics of index cases and infected patients among 70 clusters
| Cluster | Index case | Infected cases from the index case | |||||
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| Age (years) | Gender | Incubation period (days) | Males | Females | Age (years, mean ± SD) | The incubation period (days, median (interquartile range)) | |
| 1 | 52 | Male | 10 | 0 | 2 | 35.5±16.26 | 3.0 |
| 2 | 49 | Male | 10 | 2 | 1 | 29.0±17.35 | 5.0 |
| 3 | 32 | Female | 8 | 1 | 0 | 36.0 | - |
| 4 | 48 | Male | 4 | 6 | 4 | 38.9±16.02 | 8.5 (5.0-11.0) |
| 5 | 25 | Female | 13 | 5 | 4 | 49.78±18.44 | 11.5 (7.0-14.0) |
| 6 | 57 | Male | 4 | 5 | 1 | 49.1±7.46 | 14.0 (4.0-14.0) |
| 7 | 80 | Female | 16 | 0 | 1 | 73.0 | 14 |
| 8 | 48 | Male | 7 | 11 | 2 | 43.0±15.92 | 9.0 (6.0-11.0) |
| 9 | 2 | Female | 7 | 1 | 0 | 60.0 | 7.0 |
| 10 | 32 | Male | 5 | 1 | 1 | 47.0±22.63 | 6.0 |
| 11 | 2 | 2 | 44.75±27.5 | 6.0 | |||
| 12 | 51 | Male | 8 | 1 | 1 | 36.0±16.97 | 8.0 |
| 13 | 58 | Male | 7 | 1 | 0 | 32.0 | 5.0 |
| 14 | 57 | Male | 4 | 3 | 16 | 55.11±9.81 | 4.0 (4.0-10.0) |
| 15 | 52 | Male | 13 | 2 | 5 | 41.57±8.48 | 8.0 (4.0-14.0) |
| 16 | 46 | Male | 7 | 0 | 2 | 31.5±17.68 | 13.5 (13.0-14.0) |
| 17 | 58 | Male | 5 | 2 | 0 | 45.0±16.97 | 6.0 (5.0-7.0) |
| 18 | 42 | Male | 5 | 2 | 2 | 37.5±9.0 | 1.5 (1.0-2.75) |
| 19 | 50 | Female | 7 | 1 | 3 | 17.75±10.01 | 2.0 (1.0-5.0) |
| 20 | 75 | Female | 7 | 1 | 2 | 39.0±13.89 | 5.0 (2.0-6.0) |
| 21 | 45 | Female | 7 | 2 | 4 | 65.83±15.01 | 6.0 (4.5-6.5) |
| 22 | 36 | Female | 2 | 3 | 1 | 42.5±26.90 | 6.0 (5.0-10.0) |
| 23 | 58 | Female | 4 | 2 | 1 | 67.33±5.03 | 7.0 (4.0-7.0) |
| 24 (A) | 68 | Male | 1 | 1 | 49.5±20.51 | 7.5 (6.0-9.0) | |
| 25 | 34 | Male | 4 | 0 | 2 | 20.0±19.80 | 1.0 |
| 26 | 68 | Female | 7 | 0 | 2 | 80.5±23.33 | 8.0 |
| 27 | 39 | Male | 7 | 0 | 1 | 33.0 | - |
| 28 | 52 | Male | 7 | 1 | 0 | 62.0 | 7.0 |
| 29 | 58 | Female | 10 | 0 | 1 | 53.0 | 10.0 |
| 30 | 50 | Male | 14 | 2 | 4 | 28.83±12.27 | 9.0 (6.75-11.25) |
| 31 | 57 | Male | 7 | 2 | 3 | 49.8±16.81 | 15.0 (10.0-16.0) |
| 32 | 73 | Male | 16 | 0 | 1 | 72.0 | - |
| 33 | 27 | Male | 1 | 1 | 1 | 13.5±17.68 | 6.5 (5.0-8.0) |
| 34 | 30 | Male | 13 | 0 | 1 | 30.0 | 9.0 |
| 35 | 1 | 1 | 74.0±2.83 | 7.0 | |||
| 36 | 42 | Female | 18 | 2 | 2 | 33.75±27.16 | 21.0 (20.0-21.0) |
| 37 (B) | 6 | Male | 0 | 1 | 33.0 | 7.0 | |
| 38 | 25 | Female | 7 | 0 | 1 | 25.0 | 7.0 |
| 39 (C) | 57 | Male | 1 | 1 | 40.0±18.38 | 7.0 | |
| 40 | 57 | Female | 7 | 1 | 1 | 42.5±21.92 | 7.0 |
| 41 | 32 | Male | 8 | 0 | 2 | 48.5±21.92 | - |
| 42 | 52 | Female | 7 | 1 | 1 | 52.0±1.41 | 14.5 (12.0-17.0) |
| 43 | 67 | Male | 5 | 0 | 1 | 66.0 | 9.0 |
| 44 | 63 | Female | 4 | 0 | 1 | 12.0 | 12.0 |
| 45 | 30 | Male | 7 | 1 | 1 | 16.5±17.68 | 7.0 |
| 46 | 9 | Female | 7 | 1 | 1 | 64.0 | 4.5 (1.0-8.0) |
| 47 | 48 | Male | 7 | 0 | 2 | 34.5±17.68 | 7.0 |
| 48 | 50 | Male | 22 | 0 | 3 | 25.33±23.54 | 24.5 (24.0-25.0) |
| 49 | 56 | Female | 16 | 1 | 0 | 55.0 | 17.0 |
| 50 | 36 | Female | 1 | 1 | 0 | 32.0 | 3.0 |
| 51 | 36 | Male | 7 | 5 | 3 | 52.88±7.61 | 6.6 (3.0-7.5) |
| 52 | 27 | Female | 7 | 1 | 1 | 77.0±2.83 | 2.5 (2.0-3.0) |
| 53 | 49 | Male | 7 | 0 | 2 | 25.5±21.92 | 3.0 (1.0-5.0) |
| 54 | 35 | Male | 7 | 0 | 1 | 63.0 | - |
| 55 | 54 | Male | 10 | 0 | 1 | 52.0 | 8.0 |
| 56 (D) | 21 | Male | 5 | 4 | 37.22±21.21 | 11.0 (7.0-14.0) | |
| 57 | 26 | Male | 4 | 0 | 1 | 23.0 | 4.0 |
| 58 | 56 | Male | 5 | 2 | 4 | 47.0±18.53 | 9.5 (7.5-11.5) |
| 59 | 23 | Male | 4 | 5 | 14 | 41.95±20.32 | 10.0 (8.0-12.0) |
| 60 | 26 | Male | 7 | 0 | 2 | 51.0±35.36 | 5.5 (4.0-7.0) |
| 61 | 60 | Male | 4 | 1 | 2 | 54.67±1.15 | 9.0 (5.0-12.0) |
| 62 | 59 | Female | 7 | 0 | 1 | 62.0 | 6.0 |
| 63 | 27 | Male | 7 | 2 | 0 | 51.5±48.79 | - |
| 64 | 29 | Male | 7 | 5 | 0 | 39.4±24.72 | 7.0 |
| 65 | 73 | Male | 7 | 2 | 1 | 29.67±15.31 | 7.0 |
| 66 | 70 | Male | 7 | 1 | 1 | 25.0±25.46 | 3.0 |
| 67 | 7 | Female | 7 | 0 | 1 | 32.0 | 7.0 |
| 68 | 45 | Male | 5 | 3 | 5 | 42.38±15.46 | 11.0 (8.0-12.5) |
| 69 | 50 | Male | 7 | 1 | 1 | 48.5±2.12 | 16.0 (12.0-20.0) |
| 70 (E) | 36 | Male | 1 | 2 | 47.0±9.54 | 7.0 | |
Clusters A to cluster E illustrated the 5 clusters resulted from asymptomatic carriers, which can be found in Table 1. Cluster A corresponds with the 24th cluster in Table 1. Cluster B can be connected with the 37th cluster in Table 1. Cluster C equals the 39th cluster in Table 1. Cluster D can be linked with the 56th cluster in Table 1. Cluster E corresponds with the 70th cluster in Table 1.
The epidemiological curve (Figure 1) shows the characteristics of persistent cluster transmission from January 19, 2020, to March 10, 2020, in Jiangsu Province. The earliest onset time of the cases that can be traced back is January 19, and there is a peak in the area, which appears on February 3. Also, the epidemic curve suggested that the onset of symptomatic infection is earlier than that of asymptomatic infection.
Figure 1.
Cases admitted in hospital from January 19, 2020, to March 10, 2020, in Jiangsu Province.
The epidemiological characteristics of cluster transmission of COVID-19 grouped by the characteristics of the index case
The independent samples t-test, Mann-Whitney U test, and chi-square test were used to analyze the epidemiological characteristics of cluster transmission of COVID-19 grouped by the characteristics of the index case, and the results were shown in Table 2. The results showed no significant difference was found among the frequency distribution of gender, level distribution of age, and incubation period between the two groups categorized by the characteristics of the index case. However, the frequency distribution of disease severity of COVID-19 significantly differed between the two groups (P=0.033), cases infected by asymptomatic carriers are mainly asymptomaticly infected persons and mildly infected patients, and cases infected by symptomatic infected persons are mainly ordinary cases, severe cases, and critical cases.
Table 2.
The epidemiological characteristics of cluster transmission of COVID-19 grouped by the characteristics of the index case
| Index case | Infected cases from the index case | ||||||
|---|---|---|---|---|---|---|---|
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| Age (years, mean ± SD) | The incubation period (days, median (interquartile range)) | Males | Females | Asymptomatic carrier | Mile case | Ordinary case, severe case, critical case | |
| Asymptomatic cases | 40.47±4.28 | 7 (7-9.50) | 8 | 9 | 4 | 10 | 3 |
| Symptomatic cases | 44.41±1.31 | 7 (5-11) | 97 | 129 | 40 | 74 | 112 |
| Statistical parameter | -0.799 | -0.365 | 0.11 | 6.810 | |||
| P value | 0.425 | 0.715 | 0.740 | 0.033 | |||
The epidemiological characteristics of cluster transmission of COVID-19 grouped by the close contacts’ relationships with the index cases
The One-Way ANOVA test, Kruskal-Wallis H test, and chi-square test were used to analyze the epidemiological characteristics of cluster transmission of COVID-19 grouped by the close contacts’ relationships with index cases, and the results were shown in Table 3. The significant difference was not found among the seven groups giving the level distribution latent period. However, the significant difference was found regarding the level distribution of age (P=0.006) and the frequency distribution of gender (P=0.014) and disease severity of COVID-19 (P=0.008) among the seven groups respectively. Among the close contacts of COVID-19 cases, the infected medical staff is the youngest group and is mainly composed of females, and the infected patients group is the oldest one, the majority of which are ordinary cases, severe cases, critical cases.
Table 3.
The epidemiological characteristics of cluster transmission of COVID-19 grouped by the close contacts’ relationships with the index cases
| Close contacts | Infected cases from the index case | ||||||
|---|---|---|---|---|---|---|---|
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| Age (years, mean ± SD) | The incubation period (days, median (interquartile range)) | Males | Females | Asymptomatic carrier | Mile case | Ordinary case, severe case, critical case | |
| Family members | 42.36±20.86 | 7 (5-10) | 41 | 65 | 19 | 37 | 50 |
| Relatives | 42.11±23.19 | 8 (7-11) | 11 | 17 | 7 | 8 | 13 |
| Friends | 45.17±11.07 | 5 (1.5-7.50) | 4 | 2 | 0 | 4 | 2 |
| Colleagues/Classmates | 49.88±16.24 | 8 (4-11) | 22 | 29 | 10 | 27 | 14 |
| Medical staff | 26.82±4.67 | 8 (4.5-11.5) | 1 | 10 | 2 | 2 | 7 |
| Patients | 53.71±17.38 | 8.5 (4.75-11.75) | 7 | 7 | 2 | 0 | 12 |
| Others | 44.19±17.40 | 9 (6-12) | 19 | 8 | 6 | 4 | 17 |
| Statistical parameter | 6724.035 | 7.289 | 16.006 | 26.992 | |||
| P value | 0.006 | 0.295 | 0.014 | 0.008 | |||
The epidemiological characteristics of cluster transmission of COVID-19 grouped by manners of being infected
Table 4 presented the epidemiological characteristics of cluster transmission of COVID-19 grouped by manners of being infected analyzed via the One-Way ANOVA test, Kruskal-Wallis H test, and chi-square test. The difference in age among the 10 groups of close contacts was statistically significant (P=0.041), providing medical service infected with the youngest. And, no significant difference was found concerning the level distribution of the latent period (P=0.175) and the frequency distribution of gender (P=0.120) and disease severity of COVID-19 (P=0.394).
Table 4.
The epidemiological characteristics of cluster transmission of COVID-19 grouped by manners of being infected
| Close contact style | Infected cases from the index case | ||||||
|---|---|---|---|---|---|---|---|
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| Age (years, mean ± SD) | The incubation period (days, median (interquartile range)) | Males | Females | Asymptomatic carrier | Mile case | Ordinary case, severe case, critical case | |
| Living with the case | 42.98±20.88 | 7 (5-10) | 30 | 60 | 17 | 35 | 38 |
| Dining together | 48.71±18.15 | 7 (4-10) | 39 | 34 | 15 | 28 | 30 |
| Working/Studying together | 44.29±16.90 | 10 (2-14) | 3 | 4 | 0 | 2 | 5 |
| Taking the same transportation | 43.17±22.36 | 6 (3.75-6.75) | 3 | 3 | 2 | 2 | 2 |
| Providing medical service | 31.45±14.10 | 8.5 (4.75-11.25) | 2 | 9 | 1 | 2 | 8 |
| Same ward | 48.0 | 12 (7.50-14) | 0 | 1 | 0 | 0 | 1 |
| Same diagnosis and treatment environment | 54.5±17.57 | 12 (7.5-14) | 9 | 5 | 4 | 2 | 8 |
| Short conversation | 38.67±11.15 | 8 (3.75-10.25) | 2 | 4 | 0 | 3 | 3 |
| Same building | 32.63±13.07 | 9 (7.5-12) | 3 | 5 | 3 | 1 | 4 |
| Same activity environment | 40.04±21.10 | 7 (6-9) | 14 | 13 | 2 | 9 | 16 |
| Statistical parameter | 6636.211 | 12.745 | 14.064 | 18.972 | |||
| P value | 0.041 | 0.175 | 0.120 | 0.394 | |||
The epidemiological characteristics of cluster transmission of coronavirus disease 2019 (COVID-19) from asymptomatic cases
Cluster A (Cluster 24 in Table 1)
Patient-Index is a 68-year-old otherwise-healthy man and was tested positive by nucleic acid test on January 03, 2020. He went to Wuxue, Hubei province to apply for a medical insurance card on January 19, 2020, and returned to Nanjing the following day. He suggested that he was totally asymptomatic and well since he came from Hubei. Patient 1 is the son of the patient index and reported that the first symptom that appeared on him was dizziness and tiredness with a fever of 38.4°C on January 16, 2020, after which he received clinical treatment in a local hospital. The confirmation test of the SARS-CoV-2 infection was positive on February 02, 2020. His mother was tested positive by RT-PCR assays on February 03, 2020. Patient 2 is the wife of the index patient and cohabited with the index patient since he came back from Wuxue, Hubei province on January 19, 2020. She had a fever of 38.7°C accompanied by tiredness and vomiting since January 31, 2020. She was then treated in a local clinic and the RT-PCR assays were identified as positive. The chronology of the symptom onset of Cluster A is shown in Figure 2.
Figure 2.
Timeline of Exposure to Index case with Asymptomatic COVID-19 Infection of the cluster A in the present study. Boxes filled in red are the dates on which patients traveled in Wuhan or had close contacts with the index case. The blue boxes mean the dates on which patients separated from the index case. The arrows point to the date of symptom onset or the date of RT-PCR Positive.
Cluster B (Cluster 37 in Table 1)
The index patient is a 7-year-old boy visiting Wuhan relatives with his parents before the Spring Festival and returning to Nanjing on January 21, 2020. He showed no symptoms of infection but was tested positive on the qRT-PCR assay. Patient 1 is the index patient’s mother and went to Wuhan with her husband and son. She developed a sore throat on January 18, 2020, but still returned to Nanjing on January 21, 2020. She received treatment on January 26, 2020, in a local hospital and was tested positive on nucleic acid testing on February 5, 2020. Her husband, son, and parents were also tested positive on the qRT-PCR assay. The chronology of the symptom onset of Cluster B is revealed in Figure 3.
Figure 3.
Timeline of Exposure to Index case with Asymptomatic COVID-19 Infection of cluster B in the present study. Boxes painted with red are the dates on which patients traveled in Wuhan or had close contacts with the index case. The blue boxes mean the dates on which patients separated from the index case. The arrows point to the date of symptom onset or the date of RT-PCR Positive.
Cluster C (Cluster 39 in Table 1)
The index patient is a 57-year-old Nanjing resident working in Wuhan who drove back to Nanjing together with his son and a colleague on January 22, 2020, and was reported being asymptomatic but was nonetheless tested positive for SARS-CoV-2 on January 22, 2020. Patient 1 is the index patient’s wife living and working in Nanjing. She had close contact with her husband and son after their arrival. He presented with no symptoms but was tested positive on RT-PCR assays on January 28, 2020. A short conversation was conducted with his parents and mother-in-law but none of them showed any symptoms. Patient 2 is the index patient’s 27-year-old son living in Wuhan with his father. His father drove back to Nanjing together with him and his father’s colleague on January 22, 2020. He developed a fever of 37.5°C on January 25, 2020, and tested positive by RT-PCR assays on January 27, 2020. None of the families he had contacted showed COVID-19-relevant symptoms. The chronology of symptom onset of Cluster C is presented in Figure 4.
Figure 4.
Timeline of Exposure to Index case with Asymptomatic COVID-19 Infection of cluster C in the present study. Boxes filled in red are the dates on which patients traveled in Wuhan or had close contacts with the index case. The blue boxes mean the dates on which patients separated from the index case. The arrows point to the date of symptom onset or the date of RT-PCR Positive.
Cluster D (Cluster 56 in Table 1)
All patients of cluster D went to Hubei province to visit relatives but on different dates, including index patient, patient 2, patient 3, patient 4 on January 13, 2020, patient 1 on January 7, 2020, patient 5, patient 6, patient 7 on January 16, 2020, after which they all came back to Wuxi on January 7, 2020, in two separate cars. They were all found to be positive on qRT-PCR assays but not on the same day, patient 5, patient 6 and patient 7 on February 5, 2020, and the rest of patients on February 6, 2020. Patient 3 got a headache on February 2, 2020 while patient 4 presented with headache on January 31, 2020, and dry cough on February 2, 2020. The symptom of dry cough appeared in patient 6 on January 28, 2020. Patient 7 showed the symptom of snuffle on February 3, 2020, and patient 9 developed a fever on February 1, 2020. Among the cluster, index patient, patient 1, patient 2, and patient 8 presented no symptoms of infection except having laboratory-confirmed SARS-CoV-2-infection. Figure 5A and 5B show the chronology of the symptom onset of Cluster D.
Figure 5.
A. Timeline of Exposure to Index case with Asymptomatic COVID-19 Infection of the cluster D in the present study. Boxes filled in red are the dates on which patients traveled in Wuhan or had close contacts with the index case. The blue boxes mean the dates on which patients separated from the index case. The arrows point to the date of symptom onset or the date of RT-PCR Positive. B. Timeline of Exposure to Index case with Asymptomatic COVID-19 Infection of the cluster D in the present study. Boxes filled in red are the dates on which patients traveled in Wuhan or had close contacts with the index case. The blue boxes mean the dates on which patients separated from the index case. The arrows point to the date of symptom onset or the date of RT-PCR Positive.
Cluster E (Cluster 70 in Table 1)
From Wuhan to Nanjing with four other friends on January 21, 2020. He was placed under home quarantine upon his return. He developed no symptoms while testing positive on laboratory confirmation of SARS-CoV-2-infection on February 1, 2020. Patient 1 is a 53-year-old male who drove from Wuhan to Nanjing with Index patient on January 21, 2020, and then developed a fever on January 23, 2020. Patient 2 is a Yangzhou resident living in Wuhan. She took the car back to Yangzhou with the index patient on January 21, 2020, and was under home quarantine after her arrival. She presented with symptoms of fever and cough on January 27, 2020. The laboratory confirmation of SARS-CoV-2-infection is on February 3, 2020. Patient 3 is a Yangzhou resident working in Wuhan. The date of departure with the other three friends from Wuhan was January 21, 2020. The symptom of cough was shown on January 27, 2020, accompanied by tiredness. Timeline of Exposure to Index case with Asymptomatic COVID-19 Infection of the cluster E was shown in Figure 6.
Figure 6.
Timeline of Exposure to Index case with Asymptomatic COVID-19 Infection of the cluster E in the present study. Boxes filled in red are the dates on which patients traveled in Wuhan or had close contacts with the index case. The blue boxes mean the dates on which patients separated from the index case. The arrows point to the date of symptom onset or the date of RT-PCR Positive.
Discussion
In China, cases of COVID-19 were initially found in Wuhan, Hubei Province, in December 2019 and January 2020. From the report, the evidence of human-to-human transmission among close contacts has been confirmed since mid-December 2019 [10]. Subsequently, on Jan 2, 2020, and Jan 10, 2020, one family cluster of COVID-19 was found in Wuhan, China [11], and a family of six patients who traveled to Wuhan from Shenzhen [12] respectively. Subsequent studies suggested that cluster transmission of COVID-19 had occurred in China [13] and outside of China [14]. However, to date, the studies that focused on the cluster transmission of COVID-19 are mostly single-center studies, and the large sample multi-center study has not been reported.
The epidemiological characteristics of cluster transmission of COVID-19 from asymptomatic cases in Jiangsu Province have been reported in our study. The main findings from our study are as follows: the persistent cluster transmission was found from January 19, 2020, to March 10, 2020, in Jiangsu Province; among the 70 cluster outbreaks in our study, 5 clusters were transmitted by asymptomatic infected patients; the frequency distribution of disease severity of COVID-19 significantly differed between the two groups according to the characteristics of the index case (P=0.033); cases infected by asymptomatic carrier are mainly asymptomatic infected carriers and mildly infected patients, and cases infected by symptomatic infected persons are the mainly ordinary cases, severe cases, and critical cases.
In our study, the epidemiological characteristics of 70 cluster outbreaks of COVID-19 from 13 cities across Jiangsu Province, China have been reported. According to our research, 49 (15.8%) patients are asymptomatic carriers which is much higher than the results from the previous study [6]. And the number of all the asymptomatic carriers collected from major hospitals in Jiangsu Province is 66, 49 (74.2%) of which distributed among the 70 clusters. This difference suggests that asymptomatic carriers are mainly screened out of clusters, which is similar to the findings in Jinan, China [15]. Our study also demonstrated that the symptoms of patients infected by asymptomatic carriers are usually milder than those infected by symptomatic patients. This reinforces the work of others who have shown that asymptomatic carriers share a lower reproduction potential than symptomatically infected hosts [16]. And, the results from our study confirmed that the infected medical staff tend to be younger than other infected population and the majority of them are females and the oldest population are patients among which ordinary cases, severe cases, critical cases account for more than that in other groups. The findings of the present study are consistent with cluster transmission of COVID-19 in hospital settings, the reports of infected medical staff (mostly are nurse) and patients in other studies [17]. Therefore, a comprehensive and objective identification strategy of nosocomial infection is necessary to be designed to prevent and control the epidemic effectively.
Our study suffers from some limitations although it is multi-center research. The results are concluded from 13 cities in Jiangsu Province. Thus, our results must be interpreted with some caution when applied in other cities or other countries. Moreover, the data collected from the website is incomplete and there are still 2 index patients we could not find despite all of our might. Once these presymptomatic carriers developed any symptoms, we would classify them into the symptomatic group. However, we still could not ensure that all the asymptomatic or presymptomatic carriers will not present any discomfort in the next following days. From the data presented in this investigation, we only enrolled the patients who were involved in clusters and their epidemiological characteristics may be inconsistent with those not in clusters. Therefore, we cannot completely exclude the possibility that these results are biased.
Overall, our study has demonstrated the epidemiological characteristics of cluster transmission of coronavirus disease 2019 (COVID-19) from asymptomatic cases by conducting multi-center research in Jiangsu Province, China. We reveal that cases infected with SARS-CoV-2 by asymptomatic patients would present with milder symptoms in comparison with those infected by symptomatic patients. Medical staff suffering from COVID-19 were observed to be the youngest groups while patients tend to be the oldest infected group and once patients got infected with SARS-CoV-2 they developed more severe syndromes than average ones. As the COVID-19 pandemic challenges the world, here we do our best to show its characteristic more comprehensively.
Conclusion
In this study, we showed the characteristics of cluster transmission among 70 clusters across Jiangsu Province. These findings suggest that we screened the asymptomatic carriers mainly out of clusters and patients infected by symptomatic patients showed more severe symptoms than those infected by asymptomatic patients. We also found that in the infected groups, the medical staff is the youngest one and mainly composed of females. Infected patients tend to be older than other close contacts and most of them were ordinary cases, severe cases, critical cases. The results demonstrate that effective measures should be taken to prevent cluster transmission in hospitals to protect the medical staff and patients.
Acknowledgements
This study was supported by the National Natural Science Foundation of China (No. 81170180, 30400173, 30971257, and 81970302). A project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. We would like to acknowledge colleagues for helpful comments.
Disclosure of conflict of interest
None.
Supporting Information
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