Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess

Journal of Clinical Medicine

Editorial Backcalculating the Incidence of Infection with COVID-19 on the Diamond Princess

Hiroshi Nishiura 1,2

1 Graduate School of Medicine, Hokkaido University, Kita 15 Jo Nishi 7 Chome, Kita-ku, Sapporo-shi, Hokkaido 060-8638, Japan; [email protected]; Tel.: +81-11-706-5066 2 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan

Received: 25 February 2020; Accepted: 25 February 2020; Published: 29 February 2020

Abstract: To understand the time-dependent risk of infection on a cruise ship, the Diamond Princess, I estimated the incidence of infection with novel coronavirus (COVID-19). The epidemic curve of a total of 199 conﬁrmed cases was drawn, classifying individuals into passengers with and without close contact and crew members. A backcalculation method was employed to estimate the incidence of infection. The peak time of infection was seen for the time period from 2 to 4 February 2020, and the incidence has abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February on which a movement restriction policy was imposed. Without the intervention from 5 February, it was predicted that the cumulative incidence with and without close contact would have been as large as 1373 (95% CI: 570, 2176) and 766 (95% CI: 587, 946) cases, respectively, while these were kept to be 102 and 47 cases, respectively. Based on an analysis of illness onset data on board, the risk of infection among passengers without close contact was considered to be very limited. Movement restriction greatly reduced the number of infections from 5 February onwards.

Keywords: incidence; forecasting; virus; statistical estimation; emerging infectious diseases

1. Introduction An outbreak of novel coronavirus disease (COVID-19) has occurred on a cruise ship, the Diamond Princess [1]. The primary case remains unknown, but the index case, defined as the first identified case, is a passenger who started coughing from 19 January 2020 on board, disembarking the ship in Hong Kong on 25 January. As the case was diagnosed on 1 February, the ship was requested to remain in the ocean near Yokohama from 3 February onwards. Subsequently, the movement of all passengers was restricted on board from 5 February, for a matter of 14 days of quarantine. Out of a total of 3711 persons (consisting of 2666 passengers and 1045 crew members), 199 symptomatic cases have been diagnosed on board as of 24 February, and additional asymptomatic infections and symptomatic cases after disembarkation have also been reported. One of the critical issues in infectious disease epidemiology is that the time of infection event is seldom directly observable. For this reason, the time of infection needs to be statistically estimated, employing a backcalculation method [2]. Using a sophisticated statistical model with doubly interval-censored likelihood and right truncation with an exponential growth of cases, the mean incubation period has been estimated to be about 5.0 days [3]. To understand the time-dependent risk of infection throughout the course of outbreak and estimate the effectiveness of the quarantine measure from 5 to 19 February 2020, I aimed to estimate the incidence of infection with COVID-19 and also predict the likely number of infections prevented by the quarantine measure.

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2. Backcalculation and Forecasting

I analyzed the epidemic curve, ct, on day t, illustrated by the number of confirmed cases by the date of illness onset. The confirmatory diagnosis was made, using the reverse transcriptase polymerase J. Clin. Med. 2020, 9, x FOR PEER REVIEW 2 of 4 chain reaction (RT-PCR). The date of illness onset was defined as the first date of fever. In addition to the date2. Backcalculation of illness onset, and cases Forecasting were classified by contact history inside the cabin and also by the type of membership, i.e., crew or passenger. Close contact was defined as having at least one cabinmate who I analyzed the epidemic curve, ct, on day t, illustrated by the number of confirmed cases by the was confirmed by RT-PCR. date of illness onset. The confirmatory diagnosis was made, using the reverse transcriptase Wepolymerase estimate chain the numberreaction (RT-PCR). of cases by The time date of of infection, illness onsetit. Usingwas defined the probability as the first date mass of function fever. of the incubationIn addition period to the date of length of illnesss, f sonset,, the incidence cases were of classified infection by is contact known history to satisfy inside the cabin and also by the type of membership, i.e., crew or passenger. Close contact was defined as having at least t 1 one cabinmate who was confirmed by RT-PCR. X− E(ct) = it s fs, (1) We estimate the number of cases by time of infection,− it. Using the probability mass function of s=1 the incubation period of length s, fs, the incidence of infection is known to satisfy where E(.) represents the expected value. As for f s, it is known that the mean and standard deviation are 5.0 and 3.0 days, respectively, best fitted( by lognormal)= distribution, [3]. Employing a step function,(1) the incidence of infection was statistically estimated via a maximum likelihood method. The estimation was implementedwhere E(.) represents independently the expected by thevalue. history As for of fs, contactit is known and that type the of mean membership. and standard deviation Regardingare 5.0 and 3.0 the days, real-time respectively, forecasting, best fitted we by employed lognormal the distribution so-called [3]. Richards Employing model, a step an function, analogue to the incidence of infection was statistically estimated via a maximum likelihood method. The the generalized logistic model [4,5]: estimation was implemented independently by the history of contact and type of membership. Regarding the real-time forecasting, we employedZ the so-called Richards model, an analogue to ( ) = the generalized logistic model [4,5]:E C t 1 , (2) (1 + s exp( a(t t )) s − − i ()= , (2) where Ct is the cumulative incidence on day t(,1+exp(−(−Z is the cumulative)) incidence at the end of the outbreak, s is the parameter that governs the flexibility of the logistic curve, a is the early growth rate of cases and where is the cumulative incidence on day t, Z is the cumulative incidence at the end of the ti is theoutbreak, inflection s is the point parameter of the cumulative that governs incidence the flexibility curve. of the Assuming logistic curve, that a the is the cumulative early growth incidence rate is Gaussianof cases distributed, and ti is thefour inflection unknown point of parameters the cumulative were incidence estimated. curve. The Assuming Richards that model the cumulative was fitted to two diincidencefferent datasets,is Gaussian i.e., distributed, (i) the dataset four unknown of the entire parameters course were of the estimate epidemicd. The and Richards (ii) the model dataset by 4 Februarywas fitted 2020 to. two The different latter dataset datasets, corresponds i.e., (i) the dataset to the of time the entire period course without of the any epidemic impact and of movement(ii) the restrictiondataset that by 4 was February in place 2020. from The 5 latter February dataset onwards. corresponds to the time period without any impact of movement restriction that was in place from 5 February onwards. 3. Estimated Incidence 3. Estimated Incidence Figure1 shows the epidemic curve by contact history and type of membership. The highest incidenceFigure of illness 1 shows onset the was epidemic observed curve on 7by February. contact history The epidemic and type curveof membership. in a latter The half highest period was incidence of illness onset was observed on 7 February. The epidemic curve in a latter half period was dominated by crew members whose movement was not strictly controlled due to the need to continue dominated by crew members whose movement was not strictly controlled due to the need to continue serviceservice on the on ship.the ship. The The second second dominating dominating group group was passengers passengers with with close close contact contact history. history. The last The last illnessillness onset onset date date on boardon board of aof passenger a passenger without without closeclose contact contact was was on on 14 14 February. February.

FigureFigure 1. The 1. The number number of confirmedof confirmed cases cases of of COVID-19COVID-19 by by contact contact history history and and thethe type type of membership of membership fromfrom 20 January 20 January to 20 toFebruary 20 February 2020 2020 on on the the Diamond Diamond PrincessPrincess ( (nn == 199).199). Close Close contact contact waswas defined defined as as passengerspassengers with with a confirmed a confirmed case case among among their their cabinmates. cabinmates.

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EstimatingEstimating thethe incidenceincidence ofof infection,infection, thethe peakpeak inincidencecidence waswas identifiedidentified forfor thethe periodperiod fromfrom 22 toto 4 February among passengers both with and without close contact (Figure 2). The incidence of 4 FebruaryEstimating among the incidencepassengers of infection,both with the and peak with incidenceout close was contact identiﬁed (Figure for the2). periodThe incidence from 2 to of 4 infection abruptly dropped after 5 February, the date of movement restriction. Among passengers Februaryinfection amongabruptly passengers dropped bothafter with5 February, and without the date close of contact movement (Figure restriction.2). The incidence Among ofpassengers infection without close contact, the incidence was estimated to be zero, except for 8–10 February 2020, during abruptlywithout close dropped contact, after the 5 February,incidence was the dateestimated of movement to be zero, restriction. except for Among 8–10 February passengers 2020, without during which 0.98 persons (95% confidence intervals (CI): 0, 7.74) per day were estimated to have been closewhich contact, 0.98 persons the incidence (95% confidence was estimated intervals to be (CI): zero, 0, except 7.74) per for 8–10day were February estimated 2020, duringto have which been infected. The epidemic peak among crew members was seen for the period from 8 to 10 February 0.98infected. persons The (95%epidemic conﬁdence peak among intervals crew (CI): members 0, 7.74) wa pers dayseen were for the estimated period from to have 8 to been 10 February infected. 2020. The2020. epidemic peak among crew members was seen for the period from 8 to 10 February 2020.

FigureFigure 2.2.2. EstimatedEstimated incidenceincidence ofof infectioninfection COVID-19COVID-19 byby contactcontact historyhistory andand thethe typetype ofof membershipmembership fromfromfrom 202020 JanuaryJanuaryJanuary tototo 202020 FebruaryFebruaryFebruary 2020 20202020 on onon the thethe Diamond DiamondDiamond Princess PrincessPrincess ( (n(nn= == 199).199).199). CloseClose contactcontact waswas deﬁneddefineddefined asas passengerspassengerspassengers with withwith a aa conﬁrmed confirmedconfirmed case casecase among amongamong their theirtheir cabinmates. cabinmates.cabinmates. Figure3 compares the cumulative incidence with and without movement restriction policy from FigureFigure 33 comparescompares thethe cumulativecumulative incidenceincidence withwith andand withoutwithout movementmovement restrictionrestriction policypolicy fromfrom 5 February. In the presence of intervention, the cumulative incidence among passengers with and 55 February.February. InIn thethe presencepresence ofof intervention,intervention, thethe cumulativecumulative incidenceincidence amongamong passengerspassengers withwith andand without close contact and crew members were 102, 47 and 48 cases, respectively, as of 24 February 2020. withoutwithout closeclose contactcontact andand crewcrew membersmembers werewere 102,102, 4747 andand 4848 cases,cases, respectively,respectively, asas ofof 2424 FebruaryFebruary These were well realized by the Richards model. Without intervention from 5 February onwards, it 2020.2020. TheseThese werewere wellwell realizedrealized byby thethe RichardsRichards model.model. WithoutWithout interventionintervention fromfrom 55 FebruaryFebruary was predicted that the cumulative incidence with and without close contact would have been 1373 onwards,onwards, itit waswas predictedpredicted thatthat thethe cumulativecumulative inincidencecidence withwith andand withoutwithout closeclose contactcontact wouldwould havehave (95% CI: 570, 2176) and 766 (95% CI: 587, 946) cases, respectively. beenbeen 13731373 (95%(95% CI:CI: 570,570, 2176)2176) andand 766766 (95%(95% CI:CI: 587,587, 946)946) cases,cases, respectively.respectively.

Figure 3. Comparisons between observed and predicted cumulative incidence of cases with COVID-19 Figure 3. Comparisons between observed and predicted cumulative incidence of cases with COVID- onFigure the Diamond3. Comparisons Princess. between The intervention, observed and i.e., predicted movement cumulative restriction, incidence was in placeof cases from with 5 February COVID- 19 on the Diamond Princess. The intervention, i.e., movement restriction, was in place from 5 onwards.19 on the Dashed Diamond lines Princess represent. The predictions intervention, without i.e., accounting movement for restriction, the dataset was from in 5 Februaryplace from 2020. 5 February onwards. Dashed lines represent predictions without accounting for the dataset from 5 CloseFebruary contact onwards. was deﬁned Dashed as lines passengers represent with predic a conﬁrmedtions without case among accounting their cabinmates. for the dataset from 5 FebruaryFebruary 2020.2020. CloseClose contactcontact waswas defineddefined asas papassengersssengers withwith aa confirmedconfirmed casecase amongamong theirtheir cabinmates.cabinmates.

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4. Discussion and Conclusions A large outbreak of COVID-19 occurred on a cruise ship. Estimating the incidence, the peak time of infection was shown to have been from 2 to 4 February, and the incidence abruptly declined afterwards. The estimated number of new infections among passengers without close contact was very small from 5 February, on which the movement restriction policy was imposed, and at most there was, on average, one case of infection per day from 8 to 10 February. Other than continued exposure among crew members, the estimated incidence in this study indicates that the movement restriction policy from 5 February 2020 was highly successful in greatly reducing the number of secondary transmissions on board. Based on an analysis of illness onset data on board (and before the disembarkation of a large number of passengers), the risk of infection among passengers without close contact was considered to be very limited Among disembarked passengers, symptomatic cases have started to be reported on the ground in and outside of Japan. In particular, cases arising from passengers without close contact indicate a possible pathway of infection via mechanisms that were not covered by the abovementioned analysis that relied on symptomatic cases. Although the transmission via direct human-to-human contact was prevented by movement restrictions, the role of other modes of transmission, e.g., environmental and asymptomatic transmissions, should be further explored.

Funding: H.N. received funding from the Japan Agency for Medical Research and Development (AMED) [grant number: JP18fk0108050]; the Japan Society for the Promotion of Science (JSPS) KAKENHI [grant numbers, H.N.: 17H04701, 17H05808, 18H04895 and 19H01074], the Inamori Foundation, and the Japan Science and Technology Agency (JST) CREST program [grant number: JPMJCR1413]. Conﬂicts of Interest: The author declares no conﬂict of interest.

References

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