In December 2019, the initialÂ case of COVID-19's disease appeared in Wuhan, Hubei Province, China.Â But it soon caused an outbreak in Chongqing as well. Reasonable estimates for the incubation period distribution and the serial interval distribution would provide timely information to guide intervention policy for the government of Chongqing.Â We collect individual information from Chongqing Center for Disease Control and Prevention(CQCDC).Â We use doubly interval-censored data to estimate the incubation period and the serial interval for confirmed cases exposed to COVID-19 during incubation period,the mean incubation period is estimated to be 7.5(6.6-8.6,95% CI) days and the mean serial interval is estimated to be 6.1 (5.0-7.5,95% CI) days.Â The analysis result show that COVID-19 could spread in the incubation period,which may complicate quarantine work.Â The implementation of control measures is indispensable in reducing the spread of asymptomatic incubation period in high-risk population

Lai, Xinyan

Li, Bosong

Li, Qin

Tang, Weng

Zeng, Qing

Zhao, Han

English

Advanced Emergency Medicine (E-Journal)

Advanced Emergency Medicine- 26 -Estimation of the Incubation Period and the Serial Interval ofCOVID-19 in Chongqing, ChinaXinyan Lai1, Qin Li2, Qing Zeng1*, Weng Tang2, Han Zhao2, Bosong Li21. Chongqing Medical University, Chongqing 400010,Chongqing 400010, China.2. Chongqing Center for Disease Control and Prevention, Chongqing 400010, China.Abstract: In December 2019, the initial case of COVID-19's disease appeared in Wuhan, Hubei Province, China. But it sooncaused an outbreak in Chongqing as well. Reasonable estimates for the incubation period distribution and the serial intervaldistribution would provide timely information to guide intervention policy for the government of Chongqing. We collectindividual information from Chongqing Center for Disease Control and Prevention(CQCDC). We use doubly interval-censored data to estimate the incubation period and the serial interval for confirmed cases exposed to COVID-19 duringincubation period,the mean incubation period is estimated to be 7.5(6.6-8.6,95% CI) days and the mean serial interval isestimated to be 6.1 (5.0-7.5,95% CI) days. The analysis result show that COVID-19 could spread in the incubationperiod,which may complicate quarantine work. The implementation of control measures is indispensable in reducing thespread of asymptomatic incubation period in high-risk population.Keywords: COVID-19; Incubation Period; Serial Interval; Chongqing; CoronavirusKey Massages:1.To estimate the incubation period and the serial interval for confirmed cases exposed to COVID-19 during both theincubation period and symptomatic period.2.To verify that COVID-19 could spread in the incubation period.3.To compare the differences of incubation period and serial interval among patients with different contact periods.IntroductionIn December,2019,an outbreak of novel coronavirus disease COVID-19 broke out in Wuhan, Hubei Province ofChina[1].The novel coronavirus SARS-CoV-2,dubbed COVID-19 (coronavirus disease 2019) by the World HealthOrganization (WHO) is characterized by fever,cough,fatigue, shortness of breath,pneumonia,and other respiratory tractsymptoms[2–4],and in many cases will develop to death. Due to the migration of the annual Spring Festival,the epidemicspread rapidly.As a close neighbor of Wuhan,Chongqing has become one of the cities which was most affected by thecoronavirus disease COVID-19 epidemic, during the early stage. As of January 21st, Chongqing has reported 5 cases ofcoronavirus COVID-19,including 2 cases in Wushan, 2 cases in Wanzhou and 1 case in Changshou[5]. All of the importedcases have lived experience of working in Wuhan. Fortunately, the officials have taken effective measures to control them.As of February 24st,there were no newly confirmed cases in 13 districts and counties in Chongqing for 14 consecutivedays,and there were no newly confirmed cases in 26 districts and counties for 7 consecutive days[6]. At the same time,theglobal epidemic is getting more and more serious.Key aspects of novel coronavirus disease (COVID-19) transmissiondynamics in 2019 are still unclear [7].Due to the lack of understanding of the key epidemiological and transmission characteristics of newpathogens,especially the limited understanding of their transmission ability and toxicity in the population.Through the estimation of incubation period and serial interval and exposure type analysis, we provide the infectioncharacteristics of COVID-19, that is, incubation period and serial interval, in order to provide clues to containment measuresand reduce the spread of infection.Volume 11 Issue 1·2022 - 27 -1. Method1.1 Case definitionsAccording to standard clinical guidelines,COVID-19 suspected cases are defined as the combination of clinicalcharacteristics and epidemiological histories. Clinical characteristics of suspected case must fit at least 2 of 3 followingcriteria: “fever and/or symptoms in respiratory system; radiographic evidence of pneumonia[8]; The white blood cell count islow or normal, or the lymphocyte count is low. ” Epidemiologic histories must fit at least 1 of 4 following criteria: “a historyof traveling in Hubei Province or other districts that has confirmed cases reported within 14 days of symptom onset; Previouscontact with a patient with fever or respiratory symptoms from Hubei Province or elsewhere who reported a confirmed casewithin 14 days of the onset of symptoms;Anyone who has close contact with confirmed case; cluster cases[8].” A confirmedcase was defined as a case with respiratory specimens that tested positive for the COVID-19 by at least one of the followingtwo methods:positive result by real-time Reverse-Transcription-Polymerase-Chain-Reaction (RT-PCR) assay for COVID-19or a genetic sequence that matches COVID-19.1.2 Data sourcesThe COVID-19 infectious disease report card and close contacts survey were obtained from the China Disease Controland Prevention Information System.The COVID-19 cases reported in Chongqing from January 21,2020 to March 31st wereinvestigated and collected according to the notice of the "Notifications of the Sero-epidemiological Survey Plan for theIssuance of COVID-19 Asymptomatic Infectious Diseases" (National Office of inventions [2020] 14).We collect individualinformation including age, gender, source of infection, onset time of symptoms, diagnosis time, the left and right endpointson the possible exposure interval.We divide patients into three categories:1. Incubation period exposure:When the patient comes into contact with infectious people,the infectious people are in theincubation period without any symptoms;2. Symptomatic period exposure: When the patient contacts the infectious person,the infectious person has developedsymptoms;3. Unsure: the patient has contacted the infectious person who has not yet come into contact with the infectious person whohas already developed the disease,but is not sure which kind of infectious person is infected.The incubation period,that is,the time between infection to onset,is very important in the monitoring and control ofinfectious diseases,but it is usually only a rough observation[9].To estimate the incubation period,we delete the data ofasymptomatic patients. We estimate the incubation period with doubly interval-censored data[10].The serial interval of COVID-19 is defined as the time duration between a primary case-patient injector) havingsymptom onset and a secondary case-patient (infected) having symptom onset [11-12]. As for the serial interval,we use the timeto diagnose the source of infection and the infected person instead of the onset time of symptoms.1.3 Statistical AnalysisThe incubation period is calculated with doubly interval-censored data by using Survival Analysis and the doublyinterval-censored analyses[13].We use Survival Analysis for estimating the serial interval.In order to estimate the incubationperiod and the serial interval accurately,only confirmed cases are retained.2. ResultUp to March 30th,2020,576 cases of COVID-19 have been reported in Chongqing,and we collect personal informationon 552 confirmed cases.Among the 552 confirmed cases,the median age is 48 years (38-56) and 283 cases(51.2%) arefemale.In addition, we also analyzed the time interval from symptoms to diagnosis. The mean interval of 4.3 days.2.1 Estimation of incubation periodFor confirmed cases infected with COVID-19 during the incubation period,the Lognormal distribution provides the bestAdvanced Emergency Medicine- 28 -match with the data by using Survival Analysis (Tab. 1). We estimate that the mean incubation period in Chongqing is 7.5(6.6-8.6,95% CI) days. The incubation period in Chongqing ranged from 1.1 to 23.4 days ( topercentile).Then we used the Lognormal distribution to fit the coarse data for estimating the incubation period. This time,themean incubation period was estimated at 7.5 days (6.3-8.7 days, 95% CI).For confirmed cases infected with COVID-19 during symptomatic period,the Gamma distribution provides the best fit tothe data by using Survival Analysis(Tab. 2). The mean incubation period in Chongqing was estimated to be 6.0(4.9-7.2,95%95% CI) days. The incubation period in Chongqing ranged from 0.9 to 19.3 days ( to percentile).Then weused the Gamma distribution to fit the coarse data for estimating the incubation period.The mean incubation period inChongqing was estimated to be 6.0 (5.0-7.2,95% CI) days.Tab. 1 Estimated incubation period for confirmed casesaMean (Days)Distribution Estimate (95% CI) AIC*Lognormal 7.5 (6.6,8.6) 356.9Weibull 8.4 (3.5,17.9) 359.1Gamma 8.1 (7.0.9.3) 357.0AIC*:Short for Akaike information criterion; this indicates the goodness-of-fit,where lower values indicate a better fit.confirmed casesa:The confirmed cases exposed to COVID-19 during incubation period.Tab. 2 Estimated incubation period for confirmed casesbMean (Days)Distribution Estimate (95% CI) AIC*Lognormal 5.4 (4.4,6.6) 244.3Weibull 6.1 (4.7,8.1) 243.5Gamma 6.0 (4.9,7.2) 241.7AIC*: Short for Akaike information criterion; this indicates the goodness-of-fit,where lower values indicate a better fit.confirmed casesb:The confirmed cases exposed to COVID-19 during symptomatic period.2.2 Estimation of serial intervalFor confirmed cases infected with COVID-19 during the incubation period,the Lognormal distribution provides the bestfit to the data by using Survival Analysis (Tab. 3). The mean serial interval in Chongqing was estimated to be 6.1 (5.0-7.5,95% CI) days. The incubation period in Chongqing ranged from 1.9 to 20.1 days ( to percentile).Forconfirmed cases infected with COVID-19 during symptomatic period,the Weibull distribution provides the best fit to the databy using Survival Analysis(Tab. 4). The mean serial interval in Chongqing was estimated to be 4.9(3.9-6.0,95% CI) days. Theincubation period in Chongqing ranged from 0.4to 17.8 days ( to percentile).Tab. 3 Estimated serial interval for confirmed casesaMean (Days)Distribution Estimate (95% CI) AIC*Lognormal 6.1 (5.0,7.5) 189.9Weibull 6.7 (5.4,8.3) 194.8Gamma 6.5 (5.3,8.0) 192.1AIC*: Short for Akaike information criterion; this indicates the goodness-of-fit,where lower values indicate a better fit.confirmed casesa:The confirmed cases infected with COVID-19 during incubation period.Volume 11 Issue 1·2022 - 29 -Tab. 4 Estimated serial interval for confirmed casesbMean (Days)Distribution Estimate (95% CI) AIC*Lognormal 4.1 (3.3,5.2) 382.4Weibull 4.9 (3.9,6.0) 377.6Gamma 4.7 (3.8,5.6) 378.3AIC*: Short for Akaike information criterion; this indicates the goodness-of-fit,where lower values indicate a better fit.confirmed casesb:The confirmed cases infected with COVID-19 during symptomatic period.2.3 Comparison of COVID-19 incubation period to other studyA comparison to the estimated incubation period distribution for COVID-19(Tab. 5) shows that there are differencebetween these values, but the differences are not significant.The estimated mean incubation periods for COVID-19 inChongqing are slightly longer.Tab. 5 Estimated incubation periods for coronaviruses from different studiesMean (Days)Study Distribution Estimate(95% CI)This study(Incubation period contact) Lognormal 7.5 (6.6,8.6)This study(Incubation period contact) Weibull 8.4 (3.5,17.9)This study(Incubation period contact) Gamma 8.1 (7.0.9.3)This study(Symptomatic period contact) Lognormal 5.4 (4.4,6.6)This study(Symptomatic period contact) Weibull 6.1 (4.7,8.1)This study(Symptomatic period contact) Gamma 6.0 (4.9,7.2)This study(Unsure) Lognormal 5.7 (4.9,6.5)This study(Unsure) Weibull 6.4 (5.0,8.3)This study(Unsure) Gamma 6.2 (5.4,7.1)Li Q[8] Lognormal 5.2 (4.1,7.0)Chun,J. Y. [14] Lognormal 2.87(2.33,3.50)Ren,X. [15] Lognormal 5.3 (4.6,6.0)Du Z C [16] Lognormal 4.958(3.472,7.318)Du Z C [16] Gamma 5.083(3.511,7.314)Du Z C [16] Weibull 5.695(3.675,7.674)Yang,L. [17] Weibull 5.5 (4.8,6.0)3. DiscussionThis study provides an initial analysis among epidemiologic characteristics and two typical transmission phenomena ofCOVID-19 in Chongqing. The mean incubation period in Chongqing was estimated to be 7.5(6.6-8.6,95% CI)and 6.0(4.9-7.2,95% CI) days and the mean serial interval is estimated to be 6.1 (5.0-7.5,95% CI)and 4.9(3.9-6.0,95% CI) days.It can beseen from the results that both the estimation of incubation period and the estimation of serial interval,the cases exposed toinfection in the incubation period were slightly longer than those in the symptomatic period. When collecting data,theexposure time range filled in by confirmed patients exposed to infected individual during the incubation period may be longerthan the actual one,and it is difficult to recall the exact date. As for the serial interval,we replace the onset time of symptomswith the time of diagnosis of the source of infection and the infected person,because we found that the interval between theonset time and the diagnosis time of most patients is too long. Considering the imperfection of medical examination methodsin the early stage of the epidemic and the patients' lack of active seeking medical treatment,we finally decided to use thediagnosis time to estimate the serial interval. In any case, there may be some unreasonable aspects in our way ofAdvanced Emergency Medicine- 30 -processing data in this way, but whether there is a more sensible way of data processing remains to be considered. Theincubation period that we calculate is slightly longer according to other studies(Tab. 5).It’s not hard to find out that the estimated values of serial interval is shorter than the incubation period.This result canpreliminarily prove the possibility of COVID-19 spreading in the incubation period.The infectivity of incubation periodincreases the difficulty of control and the risk of infection,which indicates that personal protective measures are necessary.We estimate a mean serial interval for COVID-19 of 4.9 (3.9-6.0,95% CI) days and 6.1 (5.1-9.2,95% CI) days. Li et al. [8]estimated the serial interval distribution to have a mean of 7.5 days (5.5-19,95% CI) based on 6 observations,and theincubation period distribution has a mean of 5.2 days (4.1-7.0,95% CI) based on 10 observations. Other studies estimate theincubation period distribution to have a mean of 6.4 days (5.6-7.7 95% CI) [18],median of 5 days (4.0-5.8 95% CI)[19],mean of5.2 days (range 1.8-12.4 days) [20],and a mean of 4.8 days (range 2-11 days) [21]. After comparison,our estimated results areclose to those of other studies.It indicates that our estimation results have a certain reference value.Although many scholars have found novel coronavirus pneumonia epidemiological characteristics,many countries havenot effectively controlled the epidemic situation. Even after the successful control of the epidemic in China,some countriesare still dissatisfied with such important measures as wearing masks and isolation,which is also the reason why it is difficultto effectively control the epidemic abroad.In recent years,mankind has been faced with new crises,such as SARS,H1N1,Ebola COVID-19 pneumonia etc. Thereason why we can control the epidemic so quickly is that we have studied SARS and gained experience before.Although thenew epidemic in the future may be different from the COVID-19 pneumonia,it has left us with experience and knowledge onhow to deal with sudden epidemic again.Volume 11 Issue 1·2022 - 31 -References[1] Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China,2019. N Engl JMed,2020,382: 727-733.[2]Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronaviruspneumonia in Wuhan,China: a descriptive study. Lancet 2020;published online Jan 30. DOI:10.1016/S0140-6736(20)30211-7.[3] Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan,China. JAMA. 2020. DOI:10.1001/jama.2020.1585.[4] Yang, Yang Y, Lu Q, et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China.doi:10.1101/2020.02.10.20021675.[5] Chongqing Center for Disease Control and Prevention http://www.cqcdc.org/index.php?a= shows&catid=71&id=698(January 2020,date last accessed).[6] CNR News http://news.cnr.cn/native/city/20200222/t20200222_524986421.shtml (February 2020, date last accessed).[7] Cowling BJ,Leung GM. Epidemiological research priorities for public health control of the ongoing global novelcoronavirus (2019-nCoV) outbreak. Euro Surveill. 2020;25.[8] Li Q,Guan X,Wu P,et al. Early Transmission Dynamics in Wuhan,China,of Novel Coronavirus–Infected Pneumonia. NewEngland Journal of Medicine,2020.[9] Brookmeyer R. Incubation period of infectious diseases. Encyclopedia of Biostatistics,vol. 3. Wiley: New York,1998;2011–2016.[10] Reich Nicholas G,Lessler Justin,Cummings Derek A T et al. Estimating incubation period distributions with coarsedata.Stat Med,2009,28: 2769-84.[11] Fine PEM. The interval between successive cases of an infectious disease. Am J Epidemiol 2003;158(11):1039–1047.[PubMed: 14630599].[12] Lipsitch M,Cohen T,Cooper B,et al. Transmission dynamics and control of severe acute respiratory syndrome.Science2003;300(5627):1966–1970. [PubMed: 12766207][13] Lessler J,Reich NG,Cummings DAT,et al. Outbreak of 2009 pandemic influenza A (H1N1) at a New York City school. NEngl J Med 2009;361:2628-36.[14] Chun,J. Y.,Baek,G.,& Kim,Y. (2020). Transmission onset distribution of COVID-19. International Journal of InfectiousDiseases. doi:10.1016/j.ijid.2020.07.075.[15] Ren,X.,Li,Y.,Yang,X.,Li,Z.,Cui,J.,Zhu,A.,… Li,Z. (2020). Evidence for pre‐symptomatic transmission of coronavirusdisease 2019 (COVID‐19) in China. Influenza and Other Respiratory Viruses. doi:10.1111/irv.12787.[16] Du Z C,Gu J,Li J H et al. Estimating the distribution of COVID-19 incubation period by interval-censored dataestimation method.Zhonghua Liu Xing Bing Xue Za Zhi,2020,41: 1000-1003.[17] Yang,L.,Dai,J.,Zhao,J.,Wang,Y.,Deng,P.,& Wang,J. (2020). Estimation of incubation period and serial interval ofCOVID-19: analysis of 178 cases and 131 transmission chains in Hubei province,China. Epidemiology and Infection,148.doi:10.1017/s0950268820001338.[18] J. A. Backer,D. Klinkenberg,and J. Wallinga. “Incubation period of 2019 novelcoronavirus (2019-nCoV) infectionsamong travellers from Wuhan,China,20 – 28 January 2020”.In: Eurosurveillance 25 (5 2020). doi: 10.2807/1560-7917.ES.2020.25.5.2000062.[19] N. M. Linton,T. Kobayashi,and Y. Yang et al. “Epidemiological characteristics of novel coronavirus infection: Astatistical analysis of publicly available case data”.In: medRxiv preprint (2020). doi: 10.1101/2020.01.26.20018754.[20] J. Zhang et al. “Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of localtransmission outside Hubei Province in China: a descriptive and modeling study”. In: medRxiv preprint (Feb 2020). doi:10.1101/2020.02.21.20026328.[21] T. Liu,J. Hu,and L. Lin et al.“Transmission dynamics of 2019 novel coronavirus(2019-nCoV)”. In: bioRxiv preprint(2020). doi: 10.1101/2020.01.25.919787.

Estimation of the Incubation Period and the Serial Interval of COVID-19 in Chongqing, China

https://aem.usp-pl.com/index.php/aem/article/download/220/214

Estimation of the Incubation Period and the Serial Interval of COVID-19 in Chongqing, China

Abstract

Similar works

Full text

Available Versions

Advanced Emergency Medicine (E-Journal)