Title Page

Global COVID-19 fatality analysis reveals Hubei-like countries

potentially with severe outbreaks

Boyan Lv 1, #, Zhongyan Li 1, #, Yajuan Chen 1, Cheng Long 2, * and Xinmiao Fu 1, *

1 Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation,

College of Life Sciences, Fujian Normal University, Fuzhou City, Fujian Province 350117, China

2 Department of Orthopaedic, Sichuan University West China Hospital, Chengdu City, Sichuan

Province, China

Running title: COVID-19 outbreaks in Hubei-like countries

# These authors contributed to this work equally.

* To whom correspondence should be addressed to Professor Xinmiao Fu

(xmfu@fjnu.edu.cn) and Dr. Cheng Long (longchenghx@126.com).

Keywords: COVID-19; SARS-CoV-2; coronavirus; epidemic; crude fatality ratio,

mortality

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Letter to the Editor 1 2 Global COVID-19 fatality analysis reveals Hubei-like countries potentially 3 with severe outbreaks 4 5 The outbreak of 2019 novel coronavirus diseases (COVID-19) is ongoing in China 1, but appears 6 to reach late stage and also just starts to devastate other countries 2. As of 13 March 2020, there 7 have been 80991 confirmed COVID-19 cases and 3180 deaths in China, much higher than those 8 outside China with 51767 confirmed cases and 1775 deaths 3. However, the daily increase in 9 COVID-19 cases outside China has greatly surpassed that inside China 3 (over 7000 verse 11 on 10 13 March), and therefore people raise deep concerns about the outbreaks outside China. Here we 11 attempted to uncover their characteristics by comparative analysis on crude fatality ratios (CFRs). 12 13 We collected data on the officially released cumulative numbers of confirmed cases and deaths 14 (from 23 January to 13 March 2020) with respect to mainland China, epicenter of the outbreak 15 (i.e., Hubei Province and Wuhan City), outside Hubei (in China) and outside Wuhan (in Hubei), 16 as well as to typical countries reported with a substantial number of deaths including South Korea, 17 Japan, Iran, Italy, USA, France and Spain (Fig. 1). CFRs in Hubei and Wuhan are significantly 18 higher than those outside Hubei and outside Wuhan, and they are relatively higher in the early 19 stage of outbreaks than in the late stage (Fig. 1A), in line with earlier comprehensive reports by 20 China CDC and WHO 4, 5. The outbreaks outside China are overall lagging approximately one 21 month behind China (Fig. 1B vs Fig. 1A). CFR in Iran in the early stage (from 21 February to 22 late March) is extremely high while CFR in Korea is low and stable over time. Notably, CFR in 23 Iran has significantly decreased since 2 March while CFR in Italy increased a lot in the past 10 24 days. 25 26 Next, we performed statistical analysis on CFRs in a period of 10 days in the early stage of 27 outbreaks between outside China and China. In particular, two periods were set for Iran and Italy 28 in order to fully cover their changing trends (for detail, refer to S1.xls file). Results displayed in 29 Fig. 1C revealed i) CFRs in Iran, Italy and USA in the past ten are not significantly different from 30 Hubei (P being 0.24, 0.648 and 0.281, respectively); ii) CFR in USA is not significantly different 31 from Wuhan to marginal degree (P being 0.0504); iii) CFR in Iran from 22 February to 2 March 32 is significantly different from any regions of China (p<0.001; Table S1). In view of the detailed 33 P values among all pairs (Table S1), we suppose the ranking for the severity of COVID-19 34 outbreaks in different countries/regions in terms of CFRs as follows: 35 Iran>Wuhan>Hubei≈USA≈Italy>outside Wuhan ≈Spain≈Japan≈France>South Korea≈outside 36 Hubei. 37 38 As CFR is defined as the number of deaths (numerator) among the number of confirmed cases 39 (denominator), both increase of numerator and decrease of denominator lead to higher CFR. In 40 Hubei/Wuhan there were neither sufficient COVID-19 test kits for infection identification nor 41 enough beds in hospitals for effective treatments in the early stage of the outbreak 6. These 42 shortages led to numerous transmissions in households, reduced the apparent number of 43 cumulative confirmed cases and caused mild patients without treatments to become severe/critical 44 ones and even die, as implicated by earlier reports 4, 7. As such, CFRs in Hubei/Wuhan was 45 relatively high in the early stage 5, 7. Similar CFRs between Hubei and USA/Italy, suggest that 46 these countries may face similar situations at present as Hubei had experienced before. In support 47 of this, recent news reports show that Italy is extremely short of medica resources (beds and acute 48 care equipment) while USA has some problems in COVID-19 test 8. In Iran, these problems might 49 be even more severe such that its CFR is extremely high. To fight against the COVDI-19 50 outbreaks in these Hubei/Wuhan-like countries, governments may need to implement control 51

Manuscript Click here to view linked References

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measures and timely supply medical resources as Hubei/Wuhan had done in the past month 2, 4. 52 53

Acknowledgments 54 This work is support by the National Natural Science Foundation of China (No. 31972918 and 55

31770830 to XF). Authors declare no conflict of interests. 56

References 57 1. Tang, J.W., P.A. Tambyah, and D.S.C. Hui, Emergence of a novel coronavirus causing respiratory illness from 58

Wuhan, China. Journal of Infection, 2020; https://doi.org/10.1016/j.jinf.2020.01.014. 59 2. WHO: Coronavirus disease (COVID-19) outbreak. Available from: 60

https://www.who.int/emergencies/diseases/novel-coronavirus-2019. 61 3. WHO: Coronavirus disease (COVID-2019) situation reports, 62

https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/. 63 4. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19), 64

https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-65 report.pdf. 2020. 66

5. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Vital surveillances: the 67 epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 68 2020, http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51, in China CDC 69 Weekly. 70

6. Pu et al., Corona Virus Disease 2019, a growing threat to children? Journal of Infection, 2020, 71 https://doi.org/10.1016/j.jinf.2020.02.024. 72

7. Ji, Y., et al., Potential association between COVID-19 mortality and healthcare resource availability. Lancet 73 Global Health, 2020; https://doi.org/10.1016/S2214-109X(20)30068-1. 74

8. CNN: The US is starting to look like Italy on coronavirus lockdown. It could learn a thing or two 75 https://edition.cnn.com/2020/03/13/americas/coronavirus-us-italy-south-korea-lessons-intl/index.html. 76

77 78

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79 80

81 82

Figure 1. CFR comparisons between China and outside China 83

(A, B) CFR for COVID-19 in the indicated regions of China (panel A) or in the indicated countries 84 (panel B) over time (from 23 January to 13 March 2020). (C) Difference analysis of CFRs in the 85 early stages of COVID-19 outbreaks between China and outside China. CFRs in a period of 10-86 day, i.e., from 23 March to 1 February for China and other specific periods for countries outside 87 China (for detail, refer to S1.xls file), were plotted as mean±SD at 95% confidence intervals (in 88 the black box), with median being shown as short lines. Statistics were performed using SPSS 89 with ANOVA algorithm, and significance levels (P value) for all the pairs are shown in Table S1. 90 P values larger than 0.05 between Wuhan/Hubei and other countries are colored in red, indicating 91 no significant difference (i.e., somehow being similar to each other) and the relative severity of 92 the epidemic therein; P value between outside Hubei and South Korea is 0.55 (colored in blue), 93 indicating relatively mild or controllable epidemic in South Korea. 94

A

B

1/27 2/1 2/6 2/11 2/16 2/21 2/26 3/2 3/7 3/120.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

0.16

0.18

0.20

cru

de

fata

lity

ratio

date

South Korea Japan Iran Italy the USA France Spain

-0.05

0.00

0.05

0.10

0.15

0.20

cru

de

fa

talit

y ra

tio

P=0.55

P=0.0504

P=0.24

P=0.648

P=0.281C

1/27 2/1 2/6 2/11 2/16 2/21 2/26 3/2 3/7 3/120.00

0.02

0.04

0.06

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mainland China Hubei Province outside Hubei (in China) Wuhan City outside Wuhan (in Hubei)

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Supporting information file

Global COVID-19 fatality analysis reveals Hubei-like countries potentially

with severe outbreaks

Boyan Lv, Zhongyan Li, Yajuan Chen, Cheng Long and Xinmiao Fu

Methods

Sources of data We collected the cumulative number of confirmed cases and deaths (from 23 Jan 2020 to 7 March 2020) of COVID-19 from the official websites of the National Health Commission of China (http://www.nhc.gov.cn/xcs/yqtb/list_gzbd.shtml) and Hubei Provincial Health Commissions (http://wjw.hubei.gov.cn/fbjd/dtyw/) and WHO’s website (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). Crude fatality ratio was calculated as the cumulative number of COVID-19 deaths among the cumulative number of confirmed cases with respect to each region or country. It should be pointed out that for USA, only five-day data points are available because its first COVID-19 death was reported on 3 March 2020. We noticed that: i) In the WHO Situation Report-48 (i.e., on 8 March), the data of USA are the same with those on 7 March [1], apparently no update; ii) The data of USA from the real-time COVID-19 website (https://news.sina.cn/project/fy2020/yq_province.shtml?country=SCUS0001&wm=6109&wm=6109) of Sina, a top internet corporation in China, are substantially different from the data released by WHO [2] (for detail, refer to Table S2), but consistent with the data from Baidu, another top internet corporation in China (https://voice.baidu.com/act/newpneumonia/newpneumonia/?from=osari_pc_3#tab4). In view of these, the data for USA were also downloaded from Sina and analyzed.

supplementary data file including data source and Table S1 Click here to access/download;Video Still;SOM (globalcomparison of COVID fatality).pdf

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Results

Table S1 Significance levels for CFR comparisons between different geographic regions a China Hubei outside

Hubei

Wuhan outside

Wuhan

South

Korea

Japan Iran-1 b Iran-2 b Italy-1

b

Italy-2

b

USA France Spain

China 0.024 0.002 0 0.091 0.01 0.349 0 0.274 0.908 0.007 0.001 0.231 0.155

Hubei 0.024 0 0.003 0 0 0.002 0* 0.24 0.032 0.648 0.281 0.001 0

outside

Hubei

0.002 0 0 0.131 0.55 0.024 0 0 0.001 0 0 0.046 0.091

Wuhan 0 0.003 0 0 0 0 0* 0 0 0.011 0.054 0 0

outside

Wuhan

0.091 0 0.131 0 0.36 0.448 0 0.006 0.071 0 0 0.62 0.823

South

Korea

0.01 0 0.55 0 0.36 0 0 0.007 0 0 0.159 0.265

Japan 0.349 0.002 0.024 0 0.448 0.095 0.095 0.044 0.293 0 0 0.792 0.607

Iran-1 0 0 0 0 0 0 0 0 0 0 0 0 0

Iran-2 0.274 0.24 0 0 0.006 0 0.044 0 0 0.104 0.025 0.023 0.014

Italy-1 0.908 0.032 0.001 0 0.071 0.007 0.293 0 0.328 0.328 0.001 0.189 0.125

Italy-2 0.007 0.648 0 0.011 0 0 0 0 0.104 0.01 0.01 0 0

USA 0.001 0.281 0 0.054 0 0 0 0 0.025 0.001 0.533 0.533 0 0

France 0.231 0.001 0.046 0 0.62 0.159 0.792 0 0.023 0.189 0 0 0.796

Spain 0.155 0 0.091 0 0.823 0.265 0.607 0 0.014 0.125 0 0 0.796

a P values between countries and Hubei/Wuhan, if >0.05, indicate relative severe outbreaks therein and are colored in red; P values between countries and outside Hubei, if >0.05, indicate less severe outbreaks therein and are colored in blue; P values between Hubei/Wuhan and Iran-1 is less than 0.001 (colored in purple, indicating the extremely severe outbreak. a Two sets of data for Iran and Italy in different periods were analyzed (for detail, refer to Table S2). 1. WHO: Coronavirus disease (COVID-2019) situation reports,

https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/.

2. Sina: Real-time data of the COVID-19 outbreaks worldwide (in Chinese)

https://news.sina.cn/project/fy2020/yq_province.shtml?country=SCUS0001&wm=6109&wm=61

09.

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South Korea Japan Iran-1date cumulative casesdeaths CFR date cumulative casesdeaths CFR date2020.02.21 204 1 0.004902 2020.02.26 164 1 0.0060976 2020.02.22

2020.02.22 346 2 0.0057803 2020.02.27 186 3 0.016129 2020.02.23

2020.02.23 602 5 0.0083056 2020.02.28 210 4 0.0190476 2020.02.24

2020.02.24 763 7 0.0091743 2020.02.29 230 5 0.0217391 2020.02.25

2020.02.25 977 10 0.0102354 2020.03.01 239 5 0.0209205 2020.02.26

2020.02.26 1261 12 0.0095163 2020.03.02 254 6 0.023622 2020.02.27

2020.02.27 1766 13 0.0073613 2020.03.03 268 6 0.0223881 2020.02.28

2020.02.28 2337 13 0.0055627 2020.03.04 284 6 0.0211268 2020.02.29

2020.02.29 3150 17 0.0053968 2020.03.05 317 6 0.0189274 2020.03.01

2020.03.01 3736 18 0.004818 2020.03.06 349 6 0.017192 2020.03.02

original data file Click here to access/download;Video Still;S1.xls.xlsx

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Iran-2 Italy-1cumulative casesdeaths CFR date cumulative casesdeaths CFR date cumulative cases

18 2 0.1111111 2020.03.04 2336 77 0.0329623 2020.02.24 124

28 5 0.1785714 2020.03.05 2922 92 0.0314853 2020.02.25 229

43 8 0.1860465 2020.03.06 3513 107 0.0304583 2020.02.26 322

61 12 0.1967213 2020.03.07 4747 124 0.0261218 2020.02.27 400

95 15 0.1578947 2020.03.08 5823 145 0.0249013 2020.02.28 650

141 22 0.1560284 2020.03.09 6566 194 0.0295461 2020.02.29 888

245 26 0.1061224 2020.03.10 7161 237 0.0330959 2020.03.01 1128

388 34 0.0876289 2020.03.11 8042 291 0.036185 2020.03.02 1689

593 43 0.0725126 2020.03.12 9000 354 0.0393333 2020.03.03 2036

978 54 0.0552147 2020.03.13 10075 429 0.0425806 2020.03.04 2502

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Italy-2 USAdeaths CFR date cumulative casesdeaths CFR date cumulative casesdeaths

2 0.016129 2020.03.04 2502 80 0.0319744 2020.03.03 64 2

6 0.0262009 2020.03.05 3089 107 0.034639 2020.03.04 108 6

11 0.0341615 2020.03.06 3858 148 0.0383618 2020.03.05 129 9

12 0.03 2020.03.07 4636 197 0.0424935 2020.03.06 148 10

17 0.0261538 2020.03.08 5883 234 0.0397756 2020.03.07 213 11

21 0.0236486 2020.03.09 7375 366 0.0496271 2020.03.08 213 11

29 0.0257092 2020.03.10 9172 463 0.0504797 2020.03.09 213 11

35 0.0207223 2020.03.11 10149 631 0.0621736 2020.03.10 472 19

52 0.0255403 2020.03.12 12462 827 0.0663617 2020.03.11 696 25

80 0.0319744 2020.03.13 15113 1016 0.0672269 2020.03.12 987 29

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France SpainCFR date cumulative casesdeaths CFR date cumulative casesdeaths CFR0.03125 2020.03.04 212 4 0.0188679 2020.03.05 198 1 0.0050505

0.0555556 2020.03.05 282 4 0.0141844 2020.03.06 257 3 0.0116732

0.0697674 2020.03.06 420 6 0.0142857 2020.03.07 374 5 0.013369

0.0675676 2020.03.07 613 9 0.0146819 2020.03.08 430 5 0.0116279

0.0516432 2020.03.08 706 10 0.0141643 2020.03.09 589 10 0.0169779

0.0516432 2020.03.09 1116 19 0.0170251 2020.03.10 1024 28 0.0273438

0.0516432 2020.03.10 1402 30 0.021398 2020.03.11 1639 36 0.0219646

0.0402542 2020.03.11 1774 33 0.018602 2020.03.12 2140 48 0.0224299

0.0359195 2020.03.12 2269 48 0.0211547 2020.03.13 2965 84 0.0283305

0.029382 2020.03.13 2860 61 0.0213287

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