key: cord-1033619-grwuhlil authors: Kurita, J.; Hata, T.; Sugawara, T.; Ohkusa, Y.; Hata, A. title: Estimating SARS-CoV-2 reproduction number by infection location in Japan date: 2021-04-22 journal: nan DOI: 10.1101/2021.04.13.21255296 sha: d2924f87cc310fe063a645288f365a2b7046cf10 doc_id: 1033619 cord_uid: grwuhlil Background: Infectiousness of COVID-19 by infected place might be different. However, studies of such infectiousness have not been reported. Object: The object of this study was estimation of reproduction numbers by infected place. Method: We ignore patients who infected no one because their reliability might be lower than that of patients who infected more than one person. We estimated the reproduction number from the histogram of the number of the infected people by the same patient, assuming that the histogram follows an exponential distribution. Results: Entertainment at night was the highest and facility for elderly people and hospital followed. Home was the lowest and nursery school and workplace followed. Discussion and Conclusion: The counter measure under the second emergency status declaration targeted restaurant. However, infectiousness at restaurant was not so high and comparable as university or karaoke and not significantly difference from at home which is the lowest infectiousness place. However, these reproduction numbers were for whole populations. Reproduction numbers by location of infection are less known, but infectiousness probably differs among infected places. For instance, countermeasures under the second emergency status declaration on January 7, 2021 clearly stipulate that restaurants close earlier than eight o'clock p.m. This policy was based on an inference that infectiousness at restaurants was higher than at other areas. By contrast, nursery schools and schools were not required to close as a countermeasure, although they had been closed under the first emergency declaration from April 8 to May 24, 2020. The objective of this study was confirmation of differences in infectiousness by infection location. A study conducted to estimate infectiousness in the earlier stage of the outbreak in Japan included patients who were not reported as having infected someone [5]. They estimated a very small reproduction number, 0.6, as of the end of February in Japan. Although they did not designate it as R 0 , they referred to it as the average number of 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 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.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 April 22, 2021. ; https://doi.org/10.1101/2021.04.13.21255296 doi: medRxiv preprint secondary infections. Such a low number indicates that the outbreak of COVID-19 was self-limited. Therefore, any intensive infection control such as school closure or restriction against going out is expected to be unnecessary. The authors of that report apparently misunderstood the meaning of patients who were not reported as having infected someone. They might have been severely underestimated at that time. Therefore, people they infected might have been found and reported. Alternatively, investigation of them cannot simply reveal who had been infected by them. Therefore, we proposed another method of estimating infectiousness that excluded information of patients who were reported as not having infected anyone [6]. When we applied our proposed procedure for the present study to data obtained from an earlier study, we obtained a figure of 4.4273. Its 95% CI was [3.6000, 5.3364]: more than six times greater than the original estimate. That finding was comparable to our results obtained for infections from adults to elderly people and from elderly people to adults. They apparently underestimated R 0. Therefore, the chosen infection-control policy was misguided, with insistence on contact tracing. We adopted a similar method to estimate infectiousness by location of infection, 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. Let x i,j represent the number of cases in which j patients were infected secondarily in place i. Because we do not know the probability by which a patient infected one person, the probability that a person infected two or more people was assumed to follow an exponential distribution as p i , p ij 2 , p ij 3 , and so on. Then R ij= p ij +2p i 2 +3p ij We observed an estimator of p i, as (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 April 22, 2021. ; https://doi.org/10.1101/2021.04.13.21255296 doi: medRxiv preprint of regression of log x i,m on m using ordinary least squares method. In addition, N i * was obtained from an exponential transform for the estimated constant term. The confidence interval (CI) of R i, * was obtained using a bootstrapping procedure Based on the j-th bootstrapped distribution {x i,m (m=1, 2,…)} j , we can obtain R i,j * . We repeated this procedure one million times, thereby obtaining one million bootstrapped R i,j * . We sorted these variables. The duration from R i,25000 * to R i,975000 * is expected to be 95% CI of R i All information used for this study has been published elsewhere [7] . There is therefore no ethical issue related to this study. We inferred significance at the 5% level. Through the end of July, 36,431 patients had been confirmed in 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. Estimation results of R i are presented in Table 1 . Regarding median values, hospitals were found to be the highest, followed by universities and facilities for elderly people. Night entertainment venues were the lowest, followed by nursery schools, schools, and workplaces. However, except for homes and hospitals, the lower bound of 95% CI of all other sites was less than one. In other words, their infectiousness was not significantly different from one. Therefore, their infectiousness at hospitals and homes was considerably higher than one. We used a procedure to estimate the case distributions among numbers of infected cases developed in our earlier study [6] . Although infected cases or unlinked cases for which the infection source was unknown represented a majority of cases, the procedure we used ignores information those cases because it was less credible. However, information about patients who were reported as having infected someone was more reliable than others because, at least, they had been investigated by public health authorities. Results demonstrated that the estimated infectiousness at hospitals and homes was significantly greater than one. Infectiousness at facilities for elderly people was 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 April 22, 2021. ; https://doi.org/10.1101/2021.04.13.21255296 doi: medRxiv preprint marginally higher than one. Infectiousness at the other considered places was not significantly higher than one. Particularly, the estimated infectiousness in restaurants was not high. Therefore, rather than restaurants, countermeasures for COVID-19 should specifically examine hospitals, some other considered places, or homes. It is noteworthy that infectious areas found from the present study do not represent a hot spot at which numerous people were infected. The total number of people infected in a type of place represents the product of infectiousness and people who are infectious visiting and staying at a place. For example, although infectiousness at homes was less than at other places, a huge number of patients stayed at home and shared contact with family members. For those reasons, one would expect that the number of people infected at home would be quite larger than at other places: and it was. When interpreting the obtained results, one must be reminded that infectiousness represents an average number of secondarily infected people per infectious person. We have examined advanced bootstrapping procedures with special consideration for some particle numbers of secondary infection recording zero cases. For estimation in the present study, information about the number of secondary infections was ignored because log transformation of the number of cases was used. However, the likelihood of one case at a particular number of secondary infections actually leading to zero cases 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 April 22, 2021. ; https://doi.org/10.1101/2021.04.13.21255296 doi: medRxiv preprint was probably less but an almost comparable likelihood to that of one case at a particular number of secondary infections actually recording one case in a bootstrapping procedure. Therefore, we treat those numbers of secondary infections recording zero cases with special consideration. The present study has some limitations. First, because infectiousness in all places were not significantly different as results, data might be insufficient to do our procedure. When we accumulate the data, it might be solved partially. Second, because of data limitations, we cannot analyze characteristics such as those of patients or hospital staff, residents or staff at a facility for elderly persons, or students and teachers at a school. For example, infectiousness among students in school or among kids in nursery school, or of medical staff to patients are probably very important factors to control the outbreak. To resolve that difficulty to some degree, data accumulation is expected to be necessary in the near future. Thirdly, seasonality of infectiousness might be fundamentally important, as it has come to be for influenza. Because data used for this study were accumulated through July, we are unable to evaluate them. In winter, data must also be analyzed similarly. Risk related to location must be evaluated. 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 April 22, 2021. ; This study demonstrated that effective reproduction numbers at restaurants were not high. Results show that they were comparable to data from universities or karaoke and were not significantly different from data related to infection at home: the least infectious place. Therefore, countermeasures taken under the second emergency status declaration targeting infection at restaurants might not be based on evidence. We can find no significant difference in infectiousness among the places considered. The present study is based on the authors' opinions: it does not reflect any stance or policy of their professionally affiliated bodies. We acknowledge the great efforts of all staff at public health centers, medical institutions, and other facilities who are fighting the spread and destruction associated with COVID-19. All information used for this study was collected under the Law of Infection Control, Japan and published data was used. There is therefore no ethical issue related to this study. 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. (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 April 22, 2021. ; c a n c e l l a t i o n a n d s c h o o l c l o s u r e a s c o u n t e r m e a s u r e s a g a i n s t C O V I D -1 9 o u t b r e a k i 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. (cases) (Number of secondarily infected) Note: Blue bars represent the number of the infected cases at hospitals. Orange bars represent those at facilities for elderly people. Gray bars represent those at workplaces. Infections at hospitals include cases in which 21, 34, or 57 were secondarily infected. In the figure, these three cases were added together as 20 secondarily infected. 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 April 22, 2021. ; Figure 3 : Histogram showing the numbers of people infected at schools, nursery schools, and universities. (cases) (Number of secondarily infected) Note: Blue bars represent the number of the infected cases in school, Orange bars represent those at nursery school. Gray bars represent those at university. Schools do not include nursery schools or universities, but include kindergartens, elementary, junior high, and high schools. 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. The copyright holder for this preprint this version posted April 22, 2021. ; https://doi.org/10.1101/2021.04.13.21255296 doi: medRxiv preprint Note: "School" includes kindergartens, elementary schools, junior high schools, and high schools. "Restaurant" excludes "Night entertainment" and "Karaoke." 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 April 22, 2021. ; https://doi.org/10.1101/2021.04.13.21255296 doi: medRxiv preprint 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 The reproductive number of COVID-19 is higher than SARS coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus disease-2019 (COVID-19): The Epidemic and the Challenges No author has any conflict of interest, financial or otherwise, to declare in relation to this study.