key: cord-0865999-jqmmjwoo
authors: Shi, Ping; Gao, Yumeng; Shen, Yuan; Chen, Enping; Chen, Hai; Liu, Juan; Chen, Yujun; Xiao, Yong; Wang, KeWei; Shi, Chao; Lu, Bing
title: Characteristics and evaluation of the effectiveness of monitoring and control measures for the first 69 Patients with COVID-19 from 18 January 2020 to 2 March in Wuxi, China
date: 2020-10-17
journal: Sustain Cities Soc
DOI: 10.1016/j.scs.2020.102559
sha: c4be154ed77394f27126c526b1ea16b1e7c7ca6e
doc_id: 865999
cord_uid: jqmmjwoo

BACKGROUND: The Coronavirus disease (COVID-19) has caused 91305 confirmed cases and 4746 deaths in China by 13:50 on October 11, 2020. We analyzed data on 69 infections in Wuxi to describe the disease’s characteristics, to analyze factors of cases clinical outcome and to evaluate the prevention and control measures. METHODS: The demographic characteristics, exposure history, time indicators and propagation dynamics in Wuxi were collected. RESULTS: The clinical severity of cases was mostly mild and normal (75.36%). Aging (relative risk [RR] = 1.04, 95% confidence interval [CI]: 1.001-1.08) and fever (RR = 10.33, 95%CI: 2.75-38.78) were risk factors for disease severity. The mean incubation period was estimated to be 4.77 days (95% CI: 3.61-5.94), with a mean serial interval of 6.31 days (95% CI: 5.12-7.50). The controlled reproduction number was estimated to be 1.12 (95%CI: 0.71-1.69). CONCLUSIONS: The incidence of COVID-19 in Wuxi has turned into a lower level, suggesting the early prevention and control measures have achieved effectiveness. Aging and fever of initial symptom were risk factors for severe clinical outcome. The family clusters provided further clues of the risk factors for COVID-19 transmission.

The Coronavirus disease was first reported in December 2019 in Wuhan, China, and now has spread globally [1] . On January 20, 2020, National Health Commission of the People's Republic of China announced that the COVID-19

should be included in the Category B infectious disease stipulated in the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases, and prevention and control measures of Category A infectious disease should be adopted [2] . Wuhan was closed on January 23, 2020. These measures have undoubtedly slowed the growth of the number of COVID-19 cases and limited the scale of the epidemic in China, with studies suggesting that hundreds of thousands of cases were averted as of February 19 [3, 4] . Meanwhile, containment measures such as quarantining suspected patients and their contacts, restricting travel and imposing social isolation on the population were adopted in Wuxi to minimize the spread of the disease. The epidemic situation of Wuxi decreased significantly through such a series of measures after a longest incubation period. Although the results have shown that to fully control COVID-19, the identification and isolation of currently unregistered infections needs to be greatly increased [3] , but it is uncertain which measures are J o u r n a l P r e -p r o o f most effective. The population is generally susceptible to the SARS-CoV-2, and the elderly over 65 years of age are more likely to develop severe illness [5, 6] .

Adolescents and young adults have more opportunities to be exposed because of frequent activities such as study, work, and travel [7] . The patients under the age of 20 in Wuxi accounted for 14.49% (10/69), so a more comprehensive understanding of the characteristics of the disease is very necessary. The manuscript was based on the data from patients with COVID-19 in Wuxi city to describe the characteristics of the disease, to dynamically assess the infectivity of the SARS-CoV-2 in Wuxi and to evaluate the effectiveness of the prevention and control measures. Epidemiologic data were collected through interviews and field reports. Data were collected in standardized forms through interviews of infected persons, relatives, close contacts, and health care workers. All epidemiologic information such as the history of exposure 2 weeks before the onset of illness, timelines of events, and close contacts identification, were collected during the field investigations.

The case definitions according to the updated version (version 7) of COVID-19 diagnosis and treatment program published by National Health Commission of the People's Republic of China. (1) A suspected COVID-19 case was defined as a pneumonia that either fulfilled all the following three criteria -fever, with or without recorded temperature; radiographic evidence of pneumonia; low or normal white-cell count or low lymphocyte count, following standard clinical guidelines or meeting the above mentioned two criteria and had an epidemiologic history. The epidemiologic four criteria were the following: a travel or residence history to Wuhan and surrounding areas or other communities with reported cases within 14 days before illness onset; a history of exposure to people infected with SARS-CoV-2; direct contact with patients from Wuhan and surrounding areas who had fever or respiratory symptoms. (2) A confirmed case was defined as a case with respiratory specimens that tested positive for SARS-CoV-2 by at least one of the following three methods: Close contacts referred to persons who had not effective protection and had close contact (within 1 meter) with suspected or confirmed cases from 2 days before symptom onset or 2 days before sampling of samples of asymptomatic infected persons. Close contacts of the cases were monitored in intensive isolation for 14 days, and nasopharyngeal swabs and serum samples were collected for testing on the first day of observation and on the day before the released or when any symptoms of discomfort not limited to the respiratory system. At the same time, we also performed CT tests on close contacts.

Clinical subtypes included asymptomatic infection, mild-type (mild clinical symptoms, no pneumonia on imaging), normal-type (with fever, respiratory tract and other symptoms, imaging evidence of pneumonia), severe-type (i.e., dyspnea, respiratory frequency 30/min, blood oxygen saturation 93%, partial pressure of J o u r n a l P r e -p r o o f arterial oxygen to fraction of inspired oxygen ratio <300, and/or lung infiltrates >50% within 24 to 48 hours) and critical-type (i.e., respiratory failure, septic shock, and/or multiple organ dysfunction or failure).

The medical institutions that accepted and treated the cases should collect the relevant clinical specimens in time, including upper respiratory tract specimens (e.g. 

The epidemic curve was constructed by date of illness onset. The general characteristics of the cases were described, including demographic characteristics, exposure history and clinical information. The incubation period distribution (the time delay from infection to illness onset) was estimated by fitting a log-normal J o u r n a l P r e -p r o o f distribution to data on exposure history and onset dates in a subset of cases with detailed information available. Onset-first-medical visit and onset-to-admission distributions were estimated by fitting a Weibull distribution on the dates of illness onset, first medical visit, and hospital admission in a subset of cases with detailed information available. We fitted a gamma distribution to data from cluster investigations to estimate the serial interval distribution, which defined as the delay between illness onset dates in successive cases in chains of transmission.

The basic reproductive number (R0) was defined as the expected number of additional cases that one case would generate, on average, over the course of the infectious period in an otherwise uninfected population [8] . The controlled reproduction number (Rc), which was used to describe the ability of disease spreading after taking the interventions (such as quarantine, isolation, or traffic control), should be used instead of R0. A good measure of any intervention was to reduce Rc and the disease would decline and eventually died out if Rc≤1. We used an informative prior distribution for the serial interval based on the serial interval of SARS with a mean of 8.4 and a standard deviation of 3.8. We used the Exponential growth rate-based (EGR) model to calculate Rc [9] . Analyses of the incubation period, serial interval and Rc were performed with the use of R software (R Foundation for Statistical Computing).

Multivariate logistic regression analysis was used to analyze the factors affecting the outcome of the disease with SPSS version 16.0 (SPSS, Chicago, IL, USA). All testing was two-sided, and a p value < 0.05 was considered statistically significant. Table 1 . There may be cases where the composition ratio is not 1 due to rounding.

The epidemic curve of 69 patients (including 10 cases of asymptomatic infection) was shown in Figure 1 . The last asymptomatic infected person was tested positive for nucleic acid on 12 February (Fig. 1 ).

We examined data on exposures among 46 confirmed cases who had the last exposure time, and we estimated the mean incubation period to be 4.77 days (95% CI:

3.61-5.94); the 95 th percentile of the distribution was 12 days (95%CI: 10.09-13.91) J o u r n a l P r e -p r o o f ( Fig. 2A) . We obtained information from 8 clusters of cases, which was showed in Figure 3 . On the basis of the dates of illness onset of 14 pairs of cases in these clusters, we estimated that the serial interval distribution had a mean (±SD) of 6.31(±3.88) days (95% CI: 5.12-7.50) (Fig. 2B) . The duration from illness onset to first medical visit for 52 patients was estimated to have a mean of 3.47 days (95% CI: 2.68-4.26) (Fig. 2C) . The mean duration from onset to hospital admission was estimated to be 4.43 days (95% CI: 3.45-5.40) among 51 cases with illness (Fig. 2D) . Of the 69 infections, 12 cases had a unique history of exposure, and 3 cases were asymptomatic at discharge, so we analyzed 9 cases of them and estimated another mean incubation period of 8.59 days (95% CI: 7.56-9.62) (Fig. 2E) . We calculated Rc to evaluate the transmission dynamics of the disease using the Exponential growth rate-based (EGR) model. From January 18th to February 9th, the mean Rc value was 1.12 (95% CI: 0.71-1.69), meaning that each patient could spread infection to 1.12 other people on average (Fig. 4) . Thirty-six percent (21/59) of the patients had underlying diseases, including diabetes (9 patients), hypertension (11 patients), and cardiovascular disease (4 patients). We divided the infected patients into the non-pneumonia group (asymptomatic and mild) and the pneumonia group (common, severe and critical), and found that elder people (RR=1.04, 95%CI: 1.001-1.08) and people with fever (RR=10.33, 95%CI: 2.75-38.78)

were more likely to develop pneumonia and severe illness ( Table 2) . 

On January 23, 2020, Wuhan was closed. On January 25, 2020, the prevention and control strategy of "external defense input and internal non-proliferation" was J o u r n a l P r e -p r o o f adopted in Wuxi [10] . After a maximum incubation period of 14 days (from January 23, 2020), the number of cases decreased significantly, proving that the blockade of Wuhan was effective [4, 11] . COVID-19 was susceptible to infection in all age groups, and we found that most (80%) of the 10 cases under 20 years old were mild and asymptomatic, whereas the critical cases were all over 60 years old, which was similar to the national situation reported earlier [12] . The analysis of the characteristics of different age groups showed that the early imported cases in Wuxi were young and middle-aged, and the clinical severity was mainly normal type. All children cases, who were mainly asymptomatic infections and mild cases, were found in close contacts. All of them were the secondary cases of clusters in families,

indicating that parents and family members were the main source of infection in children. Most cases aged 60 years or above were associated with underlying diseases, as well as the deterioration of immune function, resulting in relatively rapid disease progression and more severe clinical symptoms. Analysis of the risk factors for clinical outcomes of cases also confirmed that people with older age and fever were prone to cause pneumonia and severe illness, which was consistent with the previous studies [13, 14] .

Here we provided an assessment of time indicators and propagation dynamics to prove the effectiveness of our prevention and control measures. In our study, the mean time of the serial interval distribution was 6.31 day, which was similar to the previous study (7.5 day) [15] . The delays between the onset of illness and seeking medical attention in our city were generally shorter than that of Wuhan, with 65% of patients J o u r n a l P r e -p r o o f seeking attention within 1 day after onset, and the delays to hospitalization were 50% of patients being hospitalized 3 days after illness, which indicated that our measures of early detection of cases and asymptomatic infections through close screening were effective. In our study, we calculated two incubation periods. We estimated a mean incubation period of 4.77 days, which was slightly lower than previous studies (5.2 days and 5.1 days) [15, 16] , when the last exposure date was used as the first infection date. We also selected 9 patients infected after single exposure and calculated the mean incubation period to be much higher than that of the former, which might be more accurate. Although the sample size is small, these results might provide a clue for future research. The value of Rc was 1.12 in our manuscript, which was lower than the previously published estimates, ranging from 2.2 (95% CI: 1.4-3.9) to 3.58

(95%CI: 2.89-4.39) [15, 17, 18] . In general, an epidemic would increase as long as Rc was greater than 1, and the control measures should reduce it to less than 1. [19] . We found that 26 infections, who were the close contacts of the cases, were asymptomatic at the beginning, and 16 of them appeared symptoms after an average of 2.25 days (between 0 to 6 days), and 4 of them developed CT abnormalities first, and the rest developed symptom such as fever and cough. We isolated positive infections and further screened their close contacts to stop the infection chain. It showed that early concentrated isolation and screening of close contacts could effectively detect potential sources of infection, cut off transmission and effectively avoid community transmission. We also found that 85.71% (6/7) of the third-generation cases were asymptomatic. It indicates that the virulence of the SARS-CoV-2 might decrease as it spreads.

In conclusion, our data supported the effectiveness of prevention and control measures. Through epidemiological investigations, we quarantined and tested all those exposed and in close contact with the infected persons, which could effectively prevent community transmission. Our study of family clusters provided further clues to the path of COVID-19 transmission, such as single exposure to meals in the family, playing cards in confined spaces, and eating and living together in the family. At the same time, we found that the third-generation cases had a higher proportion of asymptomatic cases. Our manuscript could provide some suggestions for policy adjustments in the prevention and control process of COVID-19, which was conducive to reduce the burden of disease and promote the healthy development of cities. However, to reduce panic and economic loss, and to manage and save the J o u r n a l P r e -p r o o f infected, much remains to be done. The goal is to break the transmission chain of COVID-19.

The COVID-19 epidemic in Wuxi city was mainly imported cases. The cases were mainly 20-60 years old. The clinical severity was mostly mild and normal, and asymptomatic infection accounted for 14.49%. We found that aging and fever were risk factors for severe clinical outcome. Our study of family clusters provided further clues of the risk factors for COVID-19 transmission. Our data supported the effectiveness of prevention and control measures. The two results of incubation period were useful for current proposals of the length of quarantine, although longer monitoring periods might be justified.

This research was supported by Wuxi Project of Health Commission (No.

Clinical Characteristics of Coronavirus Disease 2019 in China

National Health Commission of the People's Republic of China

People's Republic of China on the Prevention and Treatment of Infectious Diseases

Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2)

A Novel Coronavirus Emerging in China -Key Questions for Impact Assessment

The efficacy of social distance and ventilation effectiveness in preventing COVID-19 transmission. Sustainable cities and society

COVID-19 epidemic in China

Epidemiological and clinical characteristics of COVID-19 in adolescents and young adults

Infectious Diseases of Humans: Dynamics and Control

How generation intervals shape the relationship between growth rates and reproductive numbers

Wuxi Municipal People's Government

Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease

Clinical characteristics of fatal and recovered cases of coronavirus disease

China: a retrospective study

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application

Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions

Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak

SARS-CoV-2 presented in the air of an intensive care unit (ICU)

We thank seven Districts Center for Disease Control and Prevention and Wuxi No.5People's Hospital for their help and contributions to this study.J o u r n a l P r e -p r o o f