key: cord-0735784-4a5zy5wu authors: Yuan, Jing; Li, Minghui; Lv, Gang; Lu, Z. Kevin title: Monitoring Transmissibility and Mortality of COVID-19 in Europe date: 2020-03-28 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.03.050 sha: 03cda737465b68fbf1a76dafe2e3788961f986be doc_id: 735784 cord_uid: 4a5zy5wu OBJECTIVES: As a global pandemic is inevitable, real-time monitoring of transmission is vital for containing the spread of COVID-19. The main objective was to report real-time effective reproduction numbers (R(t)) case fatality rate (CFR). METHODS: Data were mainly obtained from WHO website, up to 9 March 2020. R(t) was estimated by exponential growth rate (EG) and time dependent (TD) methods. “R0” package in R was employed to estimate R(t) by fitting the existing epidemic curve. Both naïve CFR (nCFR) and adjust CFR (aCFR) were estimated. RESULTS: In EG method, R(t) was 3.27 [3.17-3.38] for Italy, 6.32 [5.72-6.99] for France, 6.07 [5.51-6.69] for Germany, 5.08 [4.51-5.74] for Spain. With TD method, the R value for March 9 was 3.10 [2.21-4.11] for Italy, 6.56 [2.04-12.26] for France, 4.43 [1.83-7.92] for Germany, and 3.95 [0-10.19] for Spain. CONCLUSIONS: This study provides important findings on an early outbreak of COVID-19 in Europe. Due to the recent rapid increase in new cases of COVID-19, real-time monitoring of the transmissibility and mortality in Spain and France is a priority The continued outbreak of coronavirus disease 2019 in Europe is a significant public health concern. Several European countries have reported imported cases of COVID-19 from Italy, the epicenter in Europe. Local transmission of COVID-19 has been confirmed in certain European countries. As of 10 March 2020, confirmed cases of COVID-19 have reached 10,000 in Italy, exceeded 1,000 in Spain, France, and Germany, and grew quickly in other European countries. (1) In terms of deaths caused by COVID-19, more than 800 were reported in Italy, approximately 50 were reported in Spain and France, but only 3 were reported in Germany. Based on the diversity in the number of infected cases and deaths, European and local authorities should adopt country-specific measures to prevent onward transmission of COVID- Working with the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC) has provided several recommendations to national and regional authorities in Italy to contain the further spread of COVID-19. Italian governments have locked down its northern region of Lombardy, where several clusters of COVID-19 cases were found, on (2) Little attention has been paid to European countries. Given the rapid increase of COVID-19 in Europe, it is urgent to understand the transmissibility and mortality in key European countries to guide the implementation of prioritized prevention and control measures. The realtime reproduction number (R(t)), defined as the number of secondary cases one case would produce over the course of the outbreak, is useful to monitor the transmissibility of COVID-19 over time.(3) Therefore, R(t) calculates the effective reproduction number when immunity intervention measures are implemented. By contrast, the basic reproduction number (R0) is the reproduction number when no immunity from past exposures or vaccination, nor any deliberate intervention in disease transmission has been carried out. As a result, it is more appropriate to use R(t) to monitor the real-time transmissibility when public measures are in place. The case fatality rate (CFR) can be used to measure the mortality rate. Data were obtained from daily laboratory-confirmed cases of COVID-19, made publicly available In the abovementioned methods, generation time (GT), measured by the onset time lag between primary and secondary cases, is required but cannot be easily obtained. Here, we assumed the GT is equal to the incubation period, which was estimated to be 5.8 days (standard deviation [SD]=2.6),(7) based on previous research. We also used the assumption of 4 days (SD = 2.4) in the sensitivity analysis.(8) The R0 package, an R-language coded statistical package, was carried out to estimate the reproduction numbers of COVID-19. (11) As shown in Appendix Figure 1 , TD method provides a good fit for epidemic curve. During the early outbreak, naïve CFR (nCFR), the ratio of reported deaths to cases, tends to underestimate the true CFR because final outcomes are unknown for some cases. 2. aCFR = CFR3=D(t)/C(t-interval); division of the number of cumulative deaths by the number of cumulative cases at time (t-T). Here, T is the average time from case confirmation to death. We assumed 1, 3, and 5 days due to the lack of data. In EG method, we have tested all possible combinations of begin and end dates that might yield a good fit. For Italy, the period starting on 23 February and ending on 9 March yielded the best fit for exponential growth, with daily growth rate r=0.21 (Table 1) Spain, corresponding R(t) for those dates were zero. As of 9 March 2020, there were 366 deaths in Italy, 19 in France, and 10 in Spain, respectively. No death was reported in Germany. nCFR for Italy was 4.96 %, 1.70% for both France and Spain. The magnitude of CFRs depended on the calculation methods: aCFR yielded a higher estimate ( Figure 3 ). Based on different models, the reproduction numbers in Italy, Spain, France, and Germany were all higher than 2, indicating that the outbreak of COVID-19 will continue. More strict prevention and control measures are recommended in these countries to slow the spread of COVID-19. The mortality rate of COVID-19 in Italy was higher than in China. (12) The higher mortality rate can be attributed to the ongoing nature of the outbreak, different age distributions of the population, and different treatment strategies. The epidemic in Italy started in Lombardy and using the entire Italy tend to underestimate the burden of Lombardy. Although this study focused on R(t)s at country level, we also calculated the Rt of Lombardy, which ranged from 6.39 (6.13-6.65) to 3.26 (2.70-3.86), suggesting that Lombardy is a higher-epidemic province. Continued monitoring of deaths caused by COVID-19 in Italy is required to better care patients. The mortality rates of COVID-19 in Spain and France were lower than in China but higher than in Critical revision of the manuscript for important intellectual content Ethical Approval: This research does not involve human subjects. It is not required to obtain Institutional Review Board (IRB) approval. 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