Insignificant effect of counter measure for coronavirus infectious disease -19 in Japan

Background: To control COVID-19 outbreak in Japan, sports and entertainment events were canceled in Japan for two weeks from 26 February to 13 March. It has been designated as voluntary event cancellation (VEC). Object: This study predicts the effectiveness of VEC enduring and after its implementation. Method: We applied a simple susceptible–infected–recovery model to data of patients with symptoms in Japan during 14 January to VEC introduction and after VEC introduction to 8 March. We adjusted the reporting delay in the latest few days. Results: Results suggest that the basic reproduction number, R 0, before VEC introduced as 2.29 with a 95% confidence interval (CI) was [2.19, 2.37] and the effective reproduction number, R v, after VEC introduced as 1. 99; its 95% CI was [1.71,2.23]. Discussion and Conclusion: No significant effect of VEC was observed.


Introduction
The initial case of COVID-19 in Japan was that of a patient returning from Wuhan, China who showed symptoms on 3 January, 2020. Subsequently, as of 13 March, 2020, 714 cases were announced, including asymptomatic or those infected at abroad in countries such as China but excluding or those infected on a large cruise ship, the Diamond Princess [1].
Sports and entertainment events were canceled in Japan for two weeks from 26 February to 13 March according to a government advisory. At the same time, it was advised that small business and private meetings be cancelled voluntarily. The policy is designated as voluntary event cancellation (VEC). Moreover, since 3 March, almost all schools have been closed to control the spread until early April. Although schoolchildren are not of pestiferous age, the policy effects remain unknown. These policies must be evaluated as soon as possible. If the effective reproduction number, R v under these measures is less than one, the outbreak can be contained. Alternatively, even given a low R 0 before these measures, if it was greater than one, it might prolong the outbreak. Nevertheless, one could expect to prevent some fatal cases over time by easing burdens on medical resources or developing a vaccine. The entire course of the outbreak might be altered if these measures were able to reduce infectiousness All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. considerably. Therefore, evaluation of these measures must be thorough when these measures are commenced, continued, and ceased. The present study was conducted to evaluate VEC before VEC is cancelled so as to contribute government's decision making whether VEC will be continued or ceased.

Method
We applied a simple susceptible-infected-recovery (SIR) model [2] to the data assuming an incubation period following its empirical distribution in the early stage of the outbreak in Japan. Experiences of Japanese people living in Wuhan until the outbreak provide information related to mild cases because complete laboratory surveillance was administered for them. During January 29 -February 17, 2020, 829 Japanese people returned to Japan from Wuhan. All had received a test to detect COVID-19; of them, 14 were found to be positive for COVID-19 [3]. Of those 14, 10 Japanese people had exhibited mild symptoms; the other 4 showed no symptom as of February 25. Moreover, two Japanese residents of Wuhan exhibited severe symptoms: one was confirmed as COVID-19. The other died, although no fatal case was confirmed as COVID-19 by testing. In addition, two Japanese residents of Wuhan with mild symptoms were refused re-entry to Japan even though they had not been confirmed as All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. infected. If one assumes that the Japanese fatal case in Wuhan and that the two rejected re-entrants were infected with COVID-19, then 2 severe cases, 12 mild cases, and 4 asymptomatic cases were found to exist among these Japanese residents of Wuhan. We therefore apply these proportions to the simulation.
Assuming that the power of infectivity among severe patients and mild patients were equal among the asymptomatic cases, half of the symptomatic cases can be assumed. This assumption about relative infectiousness among asymptomatic cases compared with symptomatic cases was also assumed in simulation studies for influenza [4][5][6][7][8]. We sought R 0 to fit the number of patients during 14 January -28 February and to minimize the sum of absolute values of discrepancies among the reported numbers and the fitted values. Its 95% confidence interval (CI) was calculated using the 10000 iterations of bootstrapping for empirical distribution.
We used data of the community outbreak of patients with COVID-19 who showed any symptom in Japan for 14 January -13 March, 2020. We excluded some patients who had returned from China, and who were presumed to be infected persons from the Diamond Princess. They were presumed to be not community-acquired in Japan. During this period, 544 cases with onset dates occurred.
Published information about COVID-19 patients with symptoms from the Ministry All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. of Labour, Health and Welfare (MLHW), Japan was usually adversely affected with some delay caused by uncertainty during onset to visiting a doctor or in the timing of a physician's suspicion of COVID-19. Therefore, published data of patients must be adjust at least a few days. To adjust it, we applied the following regression. We denote Xt-k|t as the number of patients whose onset date was t-k published on day t. The reporting delay multiplied by the latest published data are expected to be predictions of the number of patients whose onset date was t-k. We used this adjusted number of patients in the latest few days including those after VEC was adopted. We used the published data on 2,5,6, and 9-14 March,2020 by MLHW [1].
First, we estimated R 0 in Japan to fit the data of community outbreak before VEC was introduced. Then, using the adjusted data of patients, we estimated R v after VEC was adopted. We discussed about R v /R 0 through its distribution. We used 5% as All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Results
During 14 January -13 March in Japan, 640 community-acquired cases were identified for whom the onset date was published. Figure 1 showed the empirical distribution of incubation period among 62 cases whose exposed date and onset date were published by MHLW. Its mode and median were six days and average was 6.74 days.  Table 1. The table shows that 1/k, 1/m and 1/km are all significant. When m is sufficiently large, the effects of 1/m and 1/km converge to zero. Therefore, the estimated degree of reporting delay consists of the term of 1/k and a constant term. Based on these results, we predict the degrees of reporting delay as 19.3 for k=1, 9.64 for k=2, 6.42 for All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Discussion
We applied a simple SIR model including asymptomatic cases that had not been incorporated into the model to date. An earlier study [9] estimated R 0 for COVID-19 as 2.24-3.58 in Wuhan. Our R 0 obtained before VEC was similar.
Unfortunately, effectiveness of VEC was not observed even though itreduced infectiousness by 13% in average. .

Conclusion
Results demonstrated that VEC can reduce infectiousness of COVID-19 by 13%, but not significant. However, we have to note that the obtained results were just a preliminary evaluation, and thus it is not a conclusive evaluation. VEC had been extended until March 19 on March 10. We hope that the present study contribute All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted March 23, 2020. . https://doi.org/10.1101/2020.03.19.20037945 doi: medRxiv preprint government's decision making for VEC. The present study is just the authors opinion, but does not reflect any stance of our affiliation.

Conflict of interest
No author has any conflict of interest, financial or otherwise, to declare in relation to this study.
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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  Notes: Bars indicates the number of patients by incubation period among 62 cases whose exposed date and onset date were published by Ministry of Labour, Health and Welfare, Japan. All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.   All rights reserved. No reuse allowed without permission.
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.