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      From severe acute respiratory syndrome-associated coronavirus to 2019 novel coronavirus outbreak: similarities in the early epidemics and prediction of future trends


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          Emerging infectious diseases represent a serious threat for human public health worldwide.[1,2] The 2019 novel coronavirus (2019-nCoV) caused a pneumonia outbreak, which is spreading around the country and has affected 32 provinces and regions of China as of January 27, 2020.[3,4] Countries outside China, including Japan, the United States, Thailand, and South Korea, have also reported cases imported from other countries.[5] With the joint efforts of Chinese scientists, health workers, and related departments, the pathogen causing this epidemic was quickly identified as a new type of coronavirus, 10 days after the first official report. After confirming the pathogen, specific detection methods were rapidly developed, with improvement in etiological diagnosis. As of January 22, 2020, it has been confirmed that the new coronavirus came from wild bats and belonged to group 2b of the beta coronavirus, which includes severe acute respiratory syndrome-associated coronavirus (SARS-CoV).[6] Although 2019-nCoV and SARS-CoV belong to the same sub-group of beta coronaviruses, the similarity at the genome level is only 80%,[7,8] meaning that the new virus is genetically different from SARS-CoV [Supplementary Figure 1A]. Rapid discovery of the causative agent and development of diagnostic reagents demonstrated that technology has greatly improved in the 17 years since the SARS outbreak. However, no effective anti-viral medication or vaccines are available for this new virus, and many of its aspects remain to be explored. Similar to the SARS outbreak, this outbreak also occurred during the spring festival, the most important of the Chinese traditional festivals, when 3 billion people travel throughout the country.[9] This unexpectedly provides beneficial conditions for the transmission of this highly infectious disease and correspondingly poses great challenges for the prevention and control of the outbreak. Although technology has greatly improved since the 2003 SARS outbreak, the basic laws and characteristics of the occurrence and development of infectious diseases have not fundamentally changed.[10] Therefore, the epidemic laws and characteristics of the SARS outbreak and the painful lessons we learned in responding to the epidemic are of great value currently and in the future. Due to concerns about controlling the impact of the epidemic and the relatively less developed information exchange tools of that time, the early epidemics and characteristics of the early SARS cases were not reported. However, as we had participated in the epidemiological investigations of early SARS cases in 2003, we had collected important data about the early stages of the outbreak. Using these valuable data, we analyzed the characteristics of the early SARS cases and the progression of the outbreak. By comparing the epidemic situations of the two outbreaks, we found some strikingly similar characteristics and trends, providing lessons for better responses to the present and future epidemics. On January 2, 2003, a hospital in Heyuan city, Guangdong Province, reported two strange cases of severe pneumonia, which were then transferred to a larger hospital for further treatment. Several days later, seven medical staff members in the department that treated these patients developed symptoms. Retrospective investigation found that a hospital in Foshan had treated a similar case on November 25, 2002 [Supplementary Figure 2A]. This patient developed symptoms on November 16, 2002, and subsequently, five family members also developed symptoms. This indicated that SARS-CoV emerged with high human-to-human transmission capability, characterized by familial and medical staff infections.[11,12] An investigation of family clustering identified 35 clusters involving 105 patients, in families with two or more family members in Guangzhou. The largest cluster was derived from a female patient. A total of 91 persons were infected due to visiting or nursing the female patient, and two of these people died[13] [Supplementary Figure 2B]. This indicated that the super virus spreader emerged at the earliest stage of the outbreak, confirming the high infection capability of the virus.[14,15] Subsequent case investigations also showed that SARS-CoV had the capability to multiply and continuously undergo human-to-human transmission [Supplementary Figure 2C]; at least four generations of cases were identified from one original patient. Among the clusters of cases, healthcare workers were common victims.[16] As of April 13, 2003, a total of 48 medical institutions had medical staff with SARS-CoV infection, and 33 medical institutions in Guangzhou reported a total of 283 cases. The incidence among medical staff in the respiratory care department of a university affiliated hospital in Guangzhou was 61.7% (29/47), that is, more than half of the medical staff were infected while treating their patients.[17] As for the 2019-nCoV outbreak, the first patient with unexplained pneumonia was identified on December 12, 2019. On December 31, 2019, 27 cases of viral pneumonia were officially announced; seven of these patients were in a severe condition.[18] Respiratory infectious diseases, including influenza, SARS, and Middle East respiratory syndrome, were screened for and excluded.[19] On January 3, 2020, only 1 week later, a new type of coronavirus was discovered. The identification of pathogenic nucleic acids was completed on January 10,[20] and on January 12, the World Health Organization officially named the new coronavirus the “2019 novel coronavirus.” It took less than 10 days from the first official announcement to the identification of the pathogen. In contrast to that of SARS-CoV, the discovery of human-to-human transmission of 2019-nCoV came relatively late. On December 31, 2019, 27 confirmed pneumonia cases were officially reported, no human-to-human transmission case was identified.[18] On January 19, 2020, a cluster of cases, including 15 healthcare workers, were confirmed to have been infected via patients, confirming that 2019-nCoV also has human-to-human transmission capability.[21] Based on these results, it was concluded that 2019-nCoV also has high human-to-human transmission capability. It remains unclear whether earlier cases also showed this capability, and if so, how many victims were not identified. The close contacts of these unidentified patients might act as new infection sources and could become super-spreaders. The incidence and development process of the SARS outbreak has valuable implications for the 2019-nCoV outbreak. After discovering the earliest case identified on November 16, 2002, the incidence remained low until January 2, 2003. The peak of the incidence was observed between January 3 and February 4, 2003, and the number of cases accounted for 54.7% of the total cases (Wikipedia). According to the case numbers and the developmental characteristics, the SARS epidemic can be roughly divided into four stages: stage 1, from November 16, 2002 to January 31, 2003; stage 2, from February 1 to March 2, 2003; stage 3, from March 3 to April 2; and stage 4, after April 4 [Supplementary Figure 2D]. Coincidentally, the SARS outbreak duration also coincided with the Chinese spring festival. Each year, the Chinese government launches a 40-day spring festival transport support system, and during this period, billions of people migrate around China. In 2003, the spring festival transport period started from January 17 to February 25, 2003 and coincided with the peak incidence [Supplementary Figure 2D, purple box]. The spring festival travel period in 2020 started from January 10 to February 18, which coincided with the rapid increase in 2019-nCoV cases between January 10 and 22, 2020 [Supplementary Figure 2D, red box]. Both outbreaks happened in the winter, when the two provinces have similar climate patterns suitable for virus survival and spread. Temperature and weather are risk factors of natural infectious diseases, and those in Wuhan and Guangzhou seem to be suitable for disease transmission. Given previous trends, this is unlikely to be the incidence peak of this new virus outbreak. The daily counts of 2019-nCoV cases were higher than the daily counts of SARS cases during its peak in 2003, implying a possibly higher number of cumulative cases.[10] We analyzed the transportation between different and large cities. High frequency transportation is mainly distributed among megacities [Supplementary Figure 2E]. The highest ranked cities include Beijing, Guangzhou, and Shanghai.[22] Wuhan has a population of 10 million and is also a major hub of the spring festival transportation network.[23] The predicted number of passengers traveling during the 2020 spring festival is 3.11 billion, 1.7 times the total number in 2003 (1.82 billion) [Supplementary Figure 2F]. This large-scale migration has brought favorable conditions for disease spread that are difficult to control. Because we are now in the early stage of the outbreak, we must be prepared for subsequent larger-scale outbreaks and predict the scale of the outbreak. Since 2019-nCoV is highly similar to SARS-CoV, some important characteristics of SARS-CoV could be used for this prediction. By combining the reported daily counts of 2019-nCoV cases and data from the SARS outbreak, we constructed a logistic model and predicted the incidence of 2019-nCoV over time. During the 2003 SARS outbreak, a total of 8000 cases were reported.[24] With this data and the present situation, we predict that the cumulative number of 2019-nCoV cases might be 60,000 to 70,000. Logistic models were fitted to these data, and the cumulative and daily counts of 2019-nCoV cases were predicted. As shown in Supplementary Figure 1B and 1C, we also calculated the time needed to reach the peak of incidence under different scenarios. Setting the upper limit of cumulative incidence (K) to 50,000, 60,000, or 70,000, the end date of incidences will be in 56 days (March 6, 2020), 60 days (March 10, 2020), or 62 days (March 12, 2020), respectively. Using valuable epidemiological data from the SARS outbreak, we systematically evaluated and compared the characteristics of the 2019-nCoV and SARS-CoV outbreaks. The two outbreaks share many similarities, and the ongoing 2019-nCoV outbreak situation seems to be a repetition of the SARS-CoV outbreak situation. Fortunately, the Chinese government is implementing many efficient measures, including shutting down public transportation in Wuhan and other cities, reducing population migration, and encouraging personal protection such as face mask-wearing. With these measures, case numbers could be reduced significantly. However, due to the lack of awareness regarding the human-to-human transmission capability of 2019-nCoV in the early stages, there is a possibility that super-spreaders exist.[25] These super-spreaders may be distributed in different places and are difficult to track. This represents the most important problem for this outbreak. Acknowledgements The authors thank the collaborators who participated in the original investigations during the 2002 to 2003 SARS outbreak. Funding This work was supported by grants from the National Key Research and Development Program Projects of China (No. 2017YFD0500305), the National Key Program for Infectious Disease of China (No. 2018ZX10101002-002), the State Key Program of National Natural Science of China (No. U1808202), Guangdong Province Key Area R & D Plan Project (No. 2018B020241002), and the Guangdong Provincial Science and Technology Project (No. 2018B020207013). Conflicts of interest None. Supplementary Material Supplemental Digital Content

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

            Summary Background An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Funding The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
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              The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China

              The city of Wuhan in China is the focus of global attention due to an outbreak of a febrile respiratory illness due to a coronavirus 2019-nCoV. In December 2019, there was an outbreak of pneumonia of unknown cause in Wuhan, Hubei province in China, with an epidemiological link to the Huanan Seafood Wholesale Market where there was also sale of live animals. Notification of the WHO on 31 Dec 2019 by the Chinese Health Authorities has prompted health authorities in Hong Kong, Macau, and Taiwan to step up border surveillance, and generated concern and fears that it could mark the emergence of a novel and serious threat to public health (WHO, 2020a, Parr, 2020). The Chinese health authorities have taken prompt public health measures including intensive surveillance, epidemiological investigations, and closure of the market on 1 Jan 2020. SARS-CoV, MERS-CoV, avian influenza, influenza and other common respiratory viruses were ruled out. The Chinese scientists were able to isolate a 2019-nCoV from a patient within a short time on 7 Jan 2020 and perform genome sequencing of the 2019-nCoV. The genetic sequence of the 2019-nCoV has become available to the WHO on 12 Jan 2020 and this has facilitated the laboratories in different countries to produce specific diagnostic PCR tests for detecting the novel infection (WHO, 2020b). The 2019-nCoV is a β CoV of group 2B with at least 70% similarity in genetic sequence to SARS-CoV and has been named 2019-nCoV by the WHO. SARS is a zoonosis caused by SARS-CoV, which first emerged in China in 2002 before spreading to 29 countries/regions in 2003 through a travel-related global outbreak with 8,098 cases with a case fatality rate of 9.6%. Nosocomial transmission of SARS-CoV was common while the primary reservoir was putatively bats, although unproven as the actual source and the intermediary source was civet cats in the wet markets in Guangdong (Hui and Zumla, 2019). MERS is a novel lethal zoonotic disease of humans endemic to the Middle East, caused by MERS-CoV. Humans are thought to acquire MERS-CoV infection though contact with camels or camel products with a case fatality rate close to 35% while nosocomial transmission is also a hallmark (Azhar et al., 2019). The recent outbreak of clusters of viral pneumonia due to a 2019-nCoV in the Wuhan market poses significant threats to international health and may be related to sale of bush meat derived from wild or captive sources at the seafood market. As of 10 Jan 2020, 41 patients have been diagnosed to have infection by the 2019-nCoV animals. The onset of illness of the 41 cases ranges from 8 December 2019 to 2 January 2020. Symptoms include fever (>90% cases), malaise, dry cough (80%), shortness of breath (20%) and respiratory distress (15%). The vital signs were stable in most of the cases while leucopenia and lymphopenia were common. Among the 41 cases, six patients have been discharged, seven patients are in critical care and one died, while the remaining patients are in stable condition. The fatal case involved a 61 year-old man with an abdominal tumour and cirrhosis who was admitted to a hospital due to respiratory failure and severe pneumonia. The diagnoses included severe pneumonia, acute respiratory distress syndrome, septic shock and multi-organ failure. The 2019-nCoV infection in Wuhan appears clinically milder than SARS or MERS overall in terms of severity, case fatality rate and transmissibility, which increases the risk of cases remaining undetected. There is currently no clear evidence of human to human transmission. At present, 739 close contacts including 419 healthcare workers are being quarantined and monitored for any development of symptoms (WHO, 2020b, Center for Health Protection and HKSAR, 2020). No new cases have been detected in Wuhan since 3 January 2020. However the first case outside China was reported on 13th January 2020 in a Chinese tourist in Thailand with no epidemiological linkage to the Huanan Seafood Wholesale Market. The Chinese Health Authorities have carried out very appropriate and prompt response measures including active case finding, and retrospective investigations of the current cluster of patients which have been completed; The Huanan Seafood Wholesale Market has been temporarily closed to carry out investigation, environmental sanitation and disinfection; Public risk communication activities have been carried out to improve public awareness and adoption of self-protection measures. Technical guidance on novel coronavirus has been developed and will continue to be updated as additional information becomes available. However, many questions about the new coronavirus remain. While it appears to be transmitted to humans via animals, the specific animals and other reservoirs need to be identified, the transmission route, the incubation period and characteristics of the susceptible population and survival rates. At present, there is however very limited clinical information of the 2019-nCoV infection and data are missing in regard to the age range, animal source of the virus, incubation period, epidemic curve, viral kinetics, transmission route, pathogenesis, autopsy findings and any treatment response to antivirals among the severe cases. Once there is any clue to the source of animals being responsible for this outbreak, global public health authorities should examine the trading route and source of movement of animals or products taken from the wild or captive conditions from other parts to Wuhan and consider appropriate trading restrictions or other control measures to limit. The rapid identification and containment of a novel coronavirus virus in a short period of time is a re-assuring and a commendable achievement by China’s public health authorities and reflects the increasing global capacity to detect, identify, define and contain new outbreaks. The latest analysis show that the Wuhan CoV cluster with the SARS CoV.10 (Novel coronavirus - China (01): (HU) WHO, phylogenetic tree Archive Number: 20200112.6885385). This outbreak brings back memories of the novel coronavirus outbreak in China, the severe acute respiratory syndrome (SARS) in China in 2003, caused by a novel SARS-CoV-coronavirus (World Health Organization, 2019a). SARS-CoV rapidly spread from southern China in 2003 and infected more than 3000 people, killing 774 by 2004, and then disappeared – never to be seen again. However, The Middle East Respiratory Syndrome (MERS) Coronavirus (MERS-CoV) (World Health Organization, 2019b), a lethal zoonotic pathogen that was first identified in humans in the Kingdom of Saudi Arabia (KSA) in 2012 continues to emerge and re-emerge through intermittent sporadic cases, community clusters and nosocomial outbreaks. Between 2012 and December 2019, a total of 2465 laboratory-confirmed cases of MERS-CoV infection, including 850 deaths (34.4% mortality) were reported from 27 countries to WHO, the majority of which were reported by KSA (2073 cases, 772 deaths. Whilst several important aspects of MERS-CoV epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, have been defined, there remain many unanswered questions, including source, transmission and epidemic potential. The Wuhan outbreak is a stark reminder of the continuing threat of zoonotic diseases to global health security. More significant and better targeted investments are required for a more concerted and collaborative global effort, learning from experiences from all geographical regions, through a ‘ONE-HUMAN-ENIVRONMENTAL-ANIMAL-HEALTH’ global consortium to reduce the global threat of zoonotic diseases (Zumla et al., 2016). Sharing experience and learning from all geographical regions and across disciplines will be key to sustaining and further developing the progress being made. Author declarations All authors have a specialist interest in emerging and re-emerging pathogens. FN, RK, OD, GI, TDMc, CD and AZ are members of the Pan-African Network on Emerging and Re-emerging Infections (PANDORA-ID-NET) funded by the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Programme for Research and Innovation. AZ is a National Institutes of Health Research senior investigator. All authors declare no conflicts of interest.

                Author and article information

                Chin Med J (Engl)
                Chin. Med. J
                Chinese Medical Journal
                Wolters Kluwer Health
                5 May 2020
                05 May 2020
                : 133
                : 9
                : 1112-1114
                [1 ]One Health Center, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
                [2 ]Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Shenyang Agricultural University, Shenyang, Liaoning 110866, China
                [3 ]Department of Biological Science and Technology, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
                [4 ]Department of Health Law, Policy and Management, School of Public Health, Boston University, Boston, MA 02215, USA
                [5 ]Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
                [6 ]Animal Experiment Center, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
                Author notes
                Correspondence to: Prof. Jia-Hai Lu, One Health Center, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China E-Mail: lujiahai@ 123456mail.sysu.edu.cn
                CMJ-2020-295 00017
                Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                : 11 February 2020
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