A scoping review of 2019 Novel Coronavirus during the early outbreak period: Epidemiology, causes, clinical manifestation and diagnosis, prevention and control

Background: The 2019-nCoV has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. This epidemic had spread to 19 countries with 11791 confirmed cases, including 213 deaths, as of January 31, 2020. The World Health Organization declared it as a Public Health Emergency of International Concern. Methods: A scoping review of 65 research articles published until January 31, 2020 were analyzed and discussed for a better understanding of the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, publishing dates, journal language, and authors’ affiliations, as well as methodological characteristics were analyzed. All findings and statements that are mentioned regarding the outbreak in this review are based on published information as listed in the references. Results: Most of the publications were in English language (89.23%). The largest proportion of articles were related to causes (38.46%) and majority (67.69%), and were published by Chinese scholars. Research articles initially focused on causes while there was an increase of the articles related to prevention and control over time. Studies thus far have shown origination in connection to a seafood market in Wuhan, but specific animal association has not been confirmed. The reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines are being discussed for reducing the transmission. To date, no specific antiviral treatment is proven effective, hence, infected people primarily rely on symptomatic treatment and supportive care. Conclusions: There has been a rapid surge in research in response to the outbreak of 2019-nCoV. During this early period, published research primarily explored the

epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies had relevance to the control of a public emergency, more high-quality research need to be conducted to provide valid and reliable ways to manage this kind of public health emergency in both short-and longterms.

Background
The Coronavirus belongs to the family of virus that causes viral pneumonia including fever, breathing difficulty, and lung infection [1]. These viruses are common in animals worldwide, but very few cases of them are known to affect humans. The World Health Organization (WHO) used the term 2019 novel coronavirus (2019-nCoV) to refer to the coronavirus that was diagnosed from the lower respiratory tract of patients with pneumonia in Wuhan, China on 29 December, 2019 [2][3][4]. It was reported that the human infection of the virus originated from the local Huanan South China Seafood Market in Wuhan, Hubei Province, China [5]. Consequently, The Chinese Center for Disease Control and Prevention (China CDC) dispatched a rapid response team to accompany Hubei provincial and Wuhan city health authorities to conduct epidemiological and etiological investigations. The WHO reported that the outbreak of the coronavirus epidemic was associated with the marketplace, but no specific animal association has been identified [6]. Scientists immediately started to research the source of coronavirus. The first genome of 2019-nCoV was published by the research team led by Prof. Yong-Zhen Zhang, on January 10, 2020 [7]. Within one month, this virus spread quickly throughout China and globally during the Chinese New Year when there was high level of human mobility among Chinese. Although it is still early to predict the susceptible population, early patterns have shown a similar trend with Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus. The susceptibility of the virus seems to be associated with age, biological sex and other health conditions [8]. 2019-nCoV has now been declared as Public Health Emergency of International Concern by WHO [9].
Given the spread of the new coronavirus and its impacts on human health, the research community has responded rapidly to the new virus and many preliminary research articles have already been published about this epidemic (Appendix Table). We conducted a scoping review to summarize and critically analyze all the published scientific articles regarding the new coronavirus in January 2020. This review aims to provide the evidence of early findings on the epidemiology, causes, clinical diagnosis, as well as prevention and control of 2019-nCoV in relation to time, location and source of publication. This review can provide meaningful information for future research related to the topic and may support government decision-making on strategies to handle this public health emergency at the community, national and international levels.

Study design
A scoping review was conducted following the methodological framework suggested by Arksey and O'Malley [10]. The five stages followed for conducting this scoping review include: a) identifying clear research objective and search strategies, b) identifying relevant research articles, c) selection of research articles, d) extraction and charting of data, and e) summarizing, discussing, analyzing and reporting the results.

Literature search strategies
Literature for this review was identified by searching the following online databases: bioRxiv, medRxiv, ChemRxiv, Google scholar, Pubmed, as well as CNKI and Wan Fang (the two primary databases for biomedical research in mainland China). These online databases contain archives of most English and Chinese biomedical journals. In addition, some white papers published online by the National Health Commission of China, National Center of Disease Prevention and Control, and WHO were also searched and included in the analysis. We searched scientific publications from 1 January to 31 January 2020. The  Table). Figure 1

presents a Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram showing the process of searching and selecting the research articles [11].

Data extraction from the included studies
After the articles were selected, data were extracted and recorded in the excel

Results And Disucssion
Characteristics of published studies  Table 2). Methodological characteristics of those publications were analyzed. The majority of the articles are based on mathematical modeling (44.62%) followed by cross -sectional study designs (18.46%). Around half of the research include targeted population (49.23%) for their analysis followed by species (36.92%). Among the 32 articles with population as the target of study, 34.38% had a sample size less than 10, 31.25% were conducted in hospital setting, and 50% used secondary data. Quality control activities for data collection were mentioned in 56.25% of the population study (Table 3).   [2]. In this publication it was suggested that the population at most risk may be people with poor immune function such as older people and people with renal and hepatic dysfunction [2].  (1), Thailand (14), United States of America (6), United Arab Emirates (4) and Vietnam (5) ( Figure 5) [21].

Virology and Pathogenesis
Coronaviruses are enveloped single-stranded RNA viruses that are zoonotic in nature and cause symptoms ranging from those similar to the common cold to more severe respiratory, enteric, hepatic and neurological symptoms [5,22]. indicated that it originated from wild animals sold in the market [27]. Then, researchers used the lung fluid, blood, and throat swab samples of 15 patients to conduct laboratory tests. These laboratory tests found the virus-specific nucleic acid sequences in the sample, which has a different coronavirus-specific nucleic acid sequences from known human coronavirus species. Laboratory results also indicated that 2019-nCoV is similar to some of the beta (β) coronaviruses genera identified in bats [12,18,28], which is situated in a group of SARS/ SARS-like CoV [12].
To conduct next-generation sequencing from bronchoalveolar lavage fluid and cultured isolates, researchers enrolled nine inpatients with viral pneumonia and negative in common respiratory pathogens in Wuhan. The results of this next-generation sequencing indicated that 2019-nCoV was more distant from SARS-CoV (with about 79% sequence identity) and MERS-CoV (with about 50% sequence identity) than from two bat-derived SARS-like coronaviruses--bat-SL-CoVZC45 (with 87.99% sequence identity) and bat-SL-CoVZXC21(with 87.23% sequence identity) [29]. Studies also reported that 2019-nCoV Sprotein supported strong interaction with human ACE2 molecules despite its sequence diversity with SARS-CoV [12,30]. these three routes, one study also indicated the digestive system as a potential transmission route for 2019-nCoV infection. Since patients had abdominal discomfort and diarrhea symptoms, researchers analyzed 4 datasets with single-cell transcriptomes of digestive system and found that ACE2 was highly expressed in absorptive enterocytes from ileum and colon [32].

Clinical manifestation and diagnosis
The complete clinical manifestation is not clear yet, as the reported symptoms range from mild to severe, sometimes even resulting in death [3]. The most commonly reported symptoms are fever, cough, myalgia or fatigue, pneumonia and complicated dyspnea, whereas less common reported symptoms include headache, diarrhea, hemoptysis, runny nose, and phlegm-producing cough [3,16]. Patients with mild symptoms were reported to be usually recovered after 1 week while severe cases were reported to experience progressive respiratory failure due to alveolar damage from the virus, which may lead to death [13]. Cases resulting in death were primarily middle-aged and elderly patients with pre-existing diseases (tumor surgery, cirrhosis, hypertension, coronary heart disease, diabetes, and Parkinson's disease) [13]. Case definition guidelines mention the following symptoms: fever, decrease in lymphocytes and white blood cells, new pulmonary infiltrates on chest radiography, and no improvement in symptoms upon three days of antibiotics treatment [2].
For patients with suspected infection, the following procedures have been suggested for diagnosis: performing real-time fluorescence (RT-PCR) to detect the positive nucleic acid of 2019-nCoV in sputum, throat swabs, and secretions of the lower respiratory tract samples [13,14,31].

Prevention and Control
Prevention and control strategies and methods are reported at three levels: national level, case-related population level, and general population level. At the national level, the National Health Commission of the People's Republic of China issued the "No.1 announcement" on January 20, 2020, which officially included the 2019-nCoV into the management of class B legal infectious diseases, and allowed for class A infectious diseases preventive and control measures to be implemented [33]. disinfection" during the Chinese Spring Festival [35]. National-level strategies have also been issued with targeted measures for rural areas (issued on January 28, 2020) and the elderly population (issued on January 31, 2020) [36,37]. Several public health measures were mentioned that may prevent or slow down the transmission of the 2019-nCoV; these include case isolation, identification and follow-up of contacts, environmental disinfection, and use of personal protective equipment [38].
To date, no specific antiviral treatment has been confirmed to be effective. Regarding infected patients with 2019-nCoV, it has been recommended to apply appropriate symptomatic treatment and supportive care [3,16]. Studies have also explored the prevention of nosocomial infection and psychological health issues associated with the 2019-nCoV. A series of measures have been suggested to reduce nosocomial infection, including knowledge training for prevention and control, isolation, disinfection, classified protection at different degrees in infection areas, and protection of confirmed cases [18,38,39]. Concerning psychological health, some suggested psychological intervention for confirmed cases, suspected cases, and medical staffs [18,40].
For the general population, at this moment there is no vaccine preventing 2019-nCoV. The best prevention is to avoid being exposed to the virus [41]. WHO discussed the detailed advice on the use of face masks in the community, during care at home, and in the health care settings in 2019-nCoV [42]. In this document, health care workers are recommended to use the particulate respirator such as certified N95 or FFP2 when performing aerosols generating procedures, and to use medical masks while providing any care to suspected or confirmed cases. According to this document, individuals with respiratory symptoms are advised to use medical masks both in health care and home care settings properly following the infection prevention guidelines.
According to this advice, in the community, individual without respiratory symptoms do not require a medical mask. Individuals should cover nose and mouth with tissues or flexed elbow while coughing and sneezing. Regular hand hygiene is recommended. Proper use and disposal of masks are important to avoid any increase in risk of transmission [42].
In addition to articles published in research journals, the China CDC published a guideline to raise awareness of the prevention and control of 2019-nCoV among the general population. This guideline contains plenty information on the 2019-nCoV itself and its prevention. The key messages of the guideline include: the causes of 2019-nCoV, how to choose and wear face masks, proper hand washing habits, preventive measures at different locations (e.g., at home, on public transportation, and in public space), disinfection methods, and medical observation at home [43]. In addition to scientific knowledge on ways to handle the 2019-nCoV outbreak, the guideline also suggests ways to eliminate panic among the general population [43]. To date, no specific antiviral treatment has been confirmed to be effective.

Supplementary Files
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