The trend of morbidity and mortality of Coronavirus disease 2019 under the rst-level public health emergency response in China

Background The ongoing outbreak of Coronavirus disease 2019 (COVID-19) has led to declaration of public health emergency of international concern by World Health Organization and the rst-level public health emergency response in China. We aimed to share the Joint Prevention and Control Mechanism taken in Mainland China and evaluate the effectiveness. Methods A powerful Joint Prevention and Control Mechanism was adopted to �ght against COVID-19 in Mainland China. Data were collected from the daily epidemic reports released by the national and provincial health commissions of China from January 21 to April 6, 2020. Global data were collected from daily situation reports by World Health Organization. Results As of April 6, 2020, there were 81,740 con�rmed COVID-19 cases (32 new) in Mainland China. The case fatality ratio was 4.74% and 0.85% in and outside Hubei respectively. It is gratifying to see that there were up to 22 provinces reporting zero new infections, but it can’t be ignored that there were 1,196,651 con�rmed cases (68,700 new) reported in over 221 countries and territories outside China and the total death number were 69,274, nowadays China is facing great challenges of imported cases. Conclusions Great achievements


Background
In late December 2019, clusters of patients with pneumonia of unknown etiology were reported in Wuhan, Hubei Province, China 1 .The causative agent has been identi ed as a novel coronavirus, currently known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which likely originated from bats, according to the gene sequence 2,3 .The Coronavirus disease 2019 (COVID-19) was of clustering onset [4][5][6] , and the estimated basic reproductive number R0 in China ranges from 2.0-4.0 5−8 .Complications like acute respiratory distress syndrome (ARDS) and cytokine storm might be the reason of high intensive care admission rate and death 9 .The outbreak of COVID-19 has led to a public health emergency of international concern declared by World Health Organization (WHO) on January 30, 2020.
China was confronted with multitude challenges in controlling this highly contagious previously unknown disease.The unprecedented pressure posed on the health care system by the exponential patient growth has caused severe shortage of medical resources in Wuhan and even Hubei Province, the epicenter of the outbreak.And coincidentally, the virus strike happened around the Chinese New Year, a traditional national holiday when millions of Chinese migrate in the country.The virus thus began to spread across the country.
The rst-level response to public health emergency in China was promptly started in the nation.The timely and forceful Joint Prevention and Control Mechanism initiated by the State Council, have effectively curbed the spread of the COVID-19 in Wuhan and all of Mainland China.
As of April 6, 2020, there are globally 1,279,722 con rmed COVID-19 cases (68,766 new) in 221 countries and territories, with 32 news in Mainland China and 68, 700 news outside of China.WHO reported that the outbreak of COVID-19 has become a global pandemic, and in fact, COVID-19 is accelerating its spread around the world.Although countries face different stages of epidemic and have different levels of health care, the world is facing the same challenges.This study aimed to explore the change patterns of prevalence and death toll in Mainland China, and more important, to share the measures and China's experience to contain the COVID-19.

Enhancing international cooperation
China has been sharing the latest updates of the epidemic, scienti c research achievements and successful experience with the world since the outbreak.For example, the nucleic acid sequence data of the novel coronavirus was shared with the WHO, so were the results of related randomized clinical trials.Academician Nanshan Zhong, was recently invited to Europe to communicate his experience of the prevention and control of the epidemic.Moreover, the Chinese government has been also donating test kits to other countries, when donations from the government and people of other countries, such as face masks, protective clothing, and etc., were continuously sent to China.

Forming leading groups of COVID-10 response in central and local governments
After the outbreak, Chinese President Jinping Xi personally directed and deployed the prevention and control of the disease.A leading group under the leadership of the Standing Committee of the Political Bureau of the CPC Central Committee was formed to deal with the epidemic, with Chinese Premier Keqiang Li as the head.The leading group is fully responsible for the joint prevention and control of COVID-19 throughout China.Local governments and communities also set up leading groups to response the epidemic.By January 29, all Chinese provinces have declared rst-level response to a major public health emergency.The Chinese New Year holiday was extended; people from high-endemic areas and nonurgent workers were encouraged to delay their return; public places, commercial markets and factories were closed; people were asked to restrain their outdoor activities; tra c between communities and villages were shut down to prevent unnecessary visits.Furthermore, the most stringent control on wildlife selling has been implemented, banning all forms of wildlife trade or transportation.

Ensuring the supply of medical resources
In order to alleviate the shortage of medical resources in Hubei, there has been 380 medical teams comprising of more than 42,000 doctors, nurses, infection control practitioners and public health experts from all over China to provide their help in Wuhan as of February 25.What's more, each province has been paired with one prefecture-level city of Hubei other than Wuhan to deliver medical aid and vital personal protective equipment to the people of the whole province.In addition, with the help of telemedicine and arti cial intelligence, hundreds of thousands of doctors across the country have been conducting online consultations, greatly easing the pressure on the overall Chinese and Wuhan healthcare system and effectively reducing the number of walk-in patients and thus their risks of infection exposure.
On the other hand, the Leishenshan Hospital and Huoshenshan Hospital, Wuhan versions of Beijing Xiaotangshan Hospital in the ght against SARS in 2003, were established in Wuhan, the design and construction of which was completed in 12 days and 9 days respectively, providing more than 14,000 isolation beds.Another 30,000 beds for mild patients were also managed in mobile cabin hospitals that were remodeled day and night.Moreover, to deal with potential increasing patient volume in other provinces, hospitals for fever patients were designated and regular wards were transformed into isolation wards.In addition to covering all the individual cost of treatment, the government also fully supports the acceleration of basic research and clinical trials of COVID-19, and its vaccine development.

Detecting possible infections early
Since February 6, Wuhan government has worked tremendously on household-to-household daily temperature checks of all of its residents, for the sake of early detection and early treatment.In order to avoid false-negative diagnosis, Hubei Province classi es suspected cases with radiographic features of pneumonia, but with negative nucleic acid test results as con rmed cases.In places outside Hubei, people returning from Hubei Province are accurately identi ed, and home quarantined for 14 days during which temperature check and health condition have to be daily reported.Anyone with fever and/or respiratory discomfort is required to report immediately to local health o cials and would be transferred to the fever clinic of special hospitals by ambulance right away.

Protecting vulnerable people
Individual protection measures includes reducing unnecessary social contact, wearing facemask, washing hands and checking body temperature every day.As for health care workers, hospitals should strictly control nosocomial infection by using different levels of protective equipment in different treatment areas.It is also suggested that the mental health of front-line medical staff shall need proper attention and long hours of heavy workload shall be avoided.

Strengthening the security of supplies
Chinese government promptly organized enterprises to resume production of household goods and medical supplies (including medical protective clothing, N95 masks, medical goggles, negative pressure ambulances and related drugs) to guarantee domestic supply.Also, all national customs have been fully committed to ensuring the rapid clearance of and the exemption of import duties on materials for epidemic prevention and control.In addition, Chinese government urges all drugstores to open normally without raising prices.In sealed-off communities, food are delivered to home by neighborhood committee.Meanwhile, National Grid has promised not to power off Wuhan residents in arrears with their electricity bills.

Information technology assisting prevention and control
Information technology such as big data and arti cial intelligence, has been widely involved in multiple elds.For example, information released by transport authorities help local governments track and manage priority populations.Passengers on the same ight or train compartment with people later con rmed as COVID-19 patients would be picked out, registered in the community's monitoring list and asked to quarantine.Health code are created by tracking individual's travel information (like whether one has been to high-risk areas), people without quali ed health code would be advised to restrain outdoor activities.Zhejiang Province was also the rst to present the epidemic risk of each area to the public on a ve-color map, each color corresponding to a risk level.
On the other hand, information technology keeps people connected in a more precise and effective way amid the outbreak.Online classes and online o ce reduce direct contact while maintain the quality of teaching and work; authoritative and reliable information such as medical guidance can only be found on government website.The use of information technology makes the disease control more scienti c, precise and effective.

Data sources
Data were collected from the daily epidemic reports released by Chinese national and provincial health commissions, including numbers of con rmed, suspected and recovered cases and death toll, etc 10 .The de nition of con rmed case and severe pneumonia is based on the diagnosis and treatment scheme released by the National Health Commission of China.Interested data were collected from January 21 to April 6 (reported on April 7), 2020 in 34 provinces of China including: 1) new, daily and cumulative con rmed cases; 2) new and cumulative death cases; 3) new and cumulative recovered cases; 4) daily severe pneumonia.Outside China, data were collected from daily situation reports by World Health Organization including cumulative con rmed and death cases 11 .

Statistical analysis
Case fatality ratio (CFR) was calculated by dividing the number of cumulative deaths by the number of cumulative con rmed cases in a time.All statistical analyses were conducted using Prism software (version 8, GraphPad).Data collection and analysis were considered as part of a continuing public health outbreak investigation and exempt from institutional review board approval.

Results
The trend of COVID-19 in Wuhan city and Hubei Province As of April 6, 2020, the cumulative con rmed COVID-19 cases are 50,008 in Wuhan and 67,803 in Hubei.The cumulative con rmed cases and death toll in Wuhan accounted for 73.75% and 80.04% of that in Hubei, respectively.Thus the curve of Wuhan is similar to that of Hubei (Fig. 3).The daily number of new con rmed cases signi cantly increased between Jan 21 and Feb 4, 2020, then plateaued between February 4 and February 11.A peak of 14,840 daily increment in Hubei was reported on February 12.The daily number of new con rmed cases continued to decrease in recent days.On April 6, 2020, the daily new con rmed cases was 0 in Hubei.In terms of death, the death toll increment in Hubei peaked and plateaued between February 12 and February 23, and dropped markedly later.Recently the daily new deaths were less than 10 in nationwide.The number of severe pneumonia cases in Hubei continued to decrease signi cantly.The case fatality ratio (CFR) was 5.14% in Wuhan and 4.74% in Hubei.

The trend of COVID-19 outbreak outside Hubei Province in Mainland China
The trend of COVID-19 outbreak outside Hubei Province in Mainland China was quite different from that in Wuhan or Hubei due to timely intervention measures.As of April 6, 2020, the numbers of cumulative con rmed and death cases were 13,937 and 119 respectively outside Hubei.The daily number of new con rmed case outside Hubei reached a peak of 880 on February 3 and decreased over time.Recently, the daily numbers of new con rmed cases are very low and mostly cases contracted outside China.The overall death toll outside Hubei is much lower with a CFR of 0.85% as of April 6, 2020.It is gratifying to see that daily number of recovered cases is increasing rapidly both inside and outside Hubei with the latest recover rate as 93.95% and 94.88% as of April 6, 2020, respectively.It is worth noting that there were up to 22 provinces reporting zero new infections, and almost all provinces with new cases are imported cases as of April 6, 2020.

Current geographic distribution of COVID-19 in and outside China
Outside of China, there were 1,196,651 con rmed cases reported in 221 countries and the total death number were 69,274 as of April 6, 2020.The total daily new con rmed case outsides China exceeded those in China on February 26.The highest con rmed case was in U.S.A (333,811), followed by Spain (135,032) and Italy (132,547).The top three death toll were in in Italy (16,525), Spain (13,055) and U.S.A (9,559).The overall CFR varies in countries with Italy (12.48%),Spain (9.67%) and U.S.A (2.86%) to be in detail.

Discussion
In the battle against COVID-19, China has rolled out perhaps the most ambitious, agile and aggressive disease containment effort in history 12 .The rapid spread and the course of this rapidly escalating and deadly epidemic has been changed under the China's powerful and scienti c Joint Prevention and Control Mechanism.The effective control of COVID-19 in China provides at least two prevention and control modes for similar highly contagious diseases, one being the control mode in Wuhan, the epicenter of the outbreak, and the other being the early control mode in regions outside Hubei Province in China.
Consistent with our knowledge about other coronaviruses, SARS-CoV-2 is mainly transmitted via respiratory droplets and contact.In China, interpersonal transmission of COVID-19 occurs mainly in families [4][5][6] , and the relative high basic reproductive number R0 [5][6][7][8] may account for the nationwide outbreak.All populations are susceptible to SARS-CoV-2, including children and infants, and elderly men with underlying diseases are prone to develop severe cases 4,9,13−16 .Despite implementing comprehensive controls in a shorter period of time, the number of con rmed cases of COVID-19 still far exceeds SARS (8,422 cases), suggesting that SARS-CoV-2 may be more contagious than SARS-CoV.Although the case fatality rate (CFR) is much lower than SARS (9%) and MERS (36%) 17 , COVID-19 results in a higher overall death toll due to the large number of cases.It is worth noting that it is widely reported that asymptomatic infected people are also contagious 6,18−23 , which is different from SARS-CoV 24 , greatly enhancing the di culty of outbreak control 25,26 .
The exponential growth of patients nearly crashed down the health care system of Wuhan, even Hubei Province.In order to alleviate the shortage of medical resources in Hubei, as of February 25, 380 medical teams comprising of more than 42,000 health workers from all over China have been providing their help in Wuhan.In addition to increasing isolation wards in existing hospitals and transforming general hospital into infectious disease hospital, Wuhan established the Leishenshan Hospital and Huoshenshan Hospital as designated hospitals of COVID-19.A dozen mobile cabin hospitals were also built overnight to treat mild patients.Meanwhile, apart from lockdown of city and tra c quarantine, Wuhan government has also worked tremendously on household-to-household daily temperature checks of all of its residents and strictly controlled communities.As promising antiviral drugs, Remdesivir and chloroquine prove to effectively inhibit SARS-CoV-2 in vitro 27 , several randomized controlled trials are already underway [28][29][30] , and the successful use of Remdesivir in relieving clinical symptoms in the United States also provides a clinical reference 31 .In addition, Chinese herbal medicine has been proven to greatly relieve patients' condition.The combination of treatment and public health intervention has shown results in recent days.
According to the prediction model of Nanshan Zhong 's team 32 , lifting the Hubei quarantine (such as cancelling lockdown of Wuhan and surrounding cities, returning to normal Spring Festival travel rush) would result in a second epidemic peak in Hubei Province in mid-March and extend the epidemic to late April.But in fact, the number of newly con rmed case in Wuhan has changed from several thousand to 0 on March 18, indicating that the outbreak in Wuhan has been well controlled.Wuhan's experience in control and treatment provides a good reference for other countries/regions with COVID-19 outbreak.
Outside Hubei, China has employed another model of prevention and control, because, unlike Hubei, the other provinces are at the early stage of outbreak.Despite sending medical staff and personal protective equipment to Hubei, many provinces were actually confronted with tough situation.The o cial classi cation of COVID-19 as a Category B infectious disease with the prevention and control methods of Category A, has marked the transition from local-level to central level of disease prevention and control.By January 29, all provinces in Mainland China have launched rst-level response to a major public health emergency.The aim of all enforced public health interventions was to isolate, diagnosis, and treat people coming back from Hubei Province as early, quarantine those having contacts with con rmed case, and reduce the possibility of secondary transmission in other provinces.Take Guangdong and Zhejiang Province for example, as popular destinations for migrant workers, the two provinces effectively prevent the spread of COVID-19 by continuous early detection and early isolation of Hubei-related residents.Nationally, the number of newly con rmed cases outside Hubei increased rapidly from January 20 to February 2, reached a peak on February 3. Since then, it has maintained a steady downward trend, with only an exception peak on February 20.
Although China has made great achievements in this anti-virus combat, the epidemic is still surging worldwide and involving more and more countries 33 .WHO has raised COVID-19 global risk to very high on March 13.And dramatically, the number of con rmed cases worldwide took over three months to reach the rst 100,000 con rmed cases, and only 12 days to reach the next 100,000, even grow exponentially around the world in recent days.In the absence of a speci c antiviral drug or vaccine, other countries could follow China's example to prevent a global outbreak.At the same time, China should stay alert.The focus should be shifted from preventing the spread of domestic epidemics to the importation of international cases.Only when the government pays enough attention together with global effort can epidemic prevention work be better carried out.What's more, Tie Song, deputy director of the Guangdong Provincial CDC, said 14% of discharged patients in Guangdong returned positive nucleic acid results 34 .JAMA also reported that the pharyngeal swab nucleic acid results of 4 medical staff who have been cured turned out to be re-positive 35 .Some experts believe that the virus in the patient has always been positive, the difference is whether it was successfully detected.Therefore, it is of high priority of other countries to con rm the proportion of discharged patients with positive nucleic acid results and whether they are contagious.Whether it is necessary to use more sensitive nucleic acid kits, increase the location of samples, adopt more strict discharge standards or post-discharge isolation measures, all are the focus of our future work.

Conclusion
China made a great achievement in control the spread of COVID-19 through the enforced nationwide intervention even suspension of normal social and economic operations and sacri ce by China and its people in both human and material terms.However, there are still many challenges and a lot of work need to do to curb the new disease since outbreak occurred internationally now, such as explore the source of infection, transmissibility, pathogenesis and virulence of the virus, risk factors for infection and disease progression, surveillance, diagnostics, the effective drugs and vaccine development.China has shared successful model of joint prevention and management experience against COVID-19 with international community.In face this previous unknown disease, all countries need to unite, learn from the excellent prevention and control model, adopt the method suitable for their own countries and regions, to control the new pneumonia.

List Of Abbreviations
Prevention and Control for COVID-19 taken by China At the early stage of COVID-19 outbreak in Wuhan, the communist party of China (CPC) Central Committee and the State Council launched the national emergency response.Timeline of ghting against SARS-CoV-2 outbreak was described in Fig. 1.A central leadership team was established for Epidemic Response and the Joint Prevention and Control Mechanism was determined by the State Council.Control of the COVID-19 outbreak was given the top priority of government at all levels.National measures against COVID-19 could be summarized as blow but not limited to Fig. 2.

3 .
Launching rst-level response to a major public health emergency in 31 provinces January 15, the Chinese CDC announced a national-level emergency response.January 20, the National Health Commission issued the Guideline for the Prevention, Diagnosis and Treatment of COVID-19 that has been updated to the 7th version until recently.COVID-19 was classi ed by the commission as a Category B infectious disease but should be controlled with Category A's prevention and control methods under the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases.Since then, number of con rmed cases in each province has been reported on a daily basis by the National Health Commission.

COVID- 19 :
Coronavirus disease 2019 SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2 ARDS: acute respiratory distress syndrome WHO: World Health Organization CPC: the communist party of China CFR: Case fatality ratioDeclarations -Ethics approval and consent to participateNo ethics approval consent participate was required.We only report the numbers of patients according to the WHO daily report but don't include the detailed individual information.

Figure 4 Distribution
Figure 4