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The SARS-CoV-2 outbreak: what we know

Open AccessPublished:March 12, 2020DOI:https://doi.org/10.1016/j.ijid.2020.03.004

      Highlights

      • The latest summary of the COVID-19 outbreak in China.
      • There might be an oral-fecal transmission of the virus.
      • Aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.

      Abstract

      There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.

      Keywords

      Introduction

      Coronaviruses (CoVs), a large family of single-stranded RNA viruses, can infect animals and also humans, causing respiratory, gastrointestinal, hepatic, and neurologic diseases [
      • Weiss SR
      • Leibowitz JL
      Coronavirus pathogenesis.
      ]. As the largest known RNA viruses, CoVs are further divided into four genera: alpha-coronavirus, beta- coronavirus, gamma-coronavirus and delta-coronavirus [
      • Yang D
      • Leibowitz JL
      The structure and functions of coronavirus genomic 3’ and 5’ ends.
      ]. To date, there have six human coronaviruses (HCoVs) been identified, including the alpha-CoVs HCoVs-NL63 and HCoVs-229E and the beta-CoVs HCoVs-OC43, HCoVs-HKU1, severe acute respiratory syndrome-CoV (SARS-CoV) [
      • Drosten C
      • Günther S
      • Preiser W
      Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome.
      ], and Middle East respiratory syndrome-CoV (MERS-CoV) [
      • Zaki AM
      • Sv Boheemen
      • Bestebroer TM
      • Osterhaus ADME
      • Fouchier RAM
      Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.
      ]. New coronaviruses appear to emerge periodically in humans, mainly due to the high prevalence and wide distribution of coronaviruses, the large genetic diversity and frequent recombination of their genomes, and the increasing of the human-animal interface activities [
      • Zhu N
      • Zhang D
      • Wang W
      • et al.
      A Novel Coronavirus from Patients with Pneumonia in China, 2019.
      ,
      • Cui J
      • Li F
      • Shi Z
      Origin and evolution of pathogenic coronaviruses.
      ].
      In late December 2019, a number of local health authorities reported clusters of patients with pneumonia of unknown cause, which were epidemiologically linked to a seafood market in Wuhan, Hubei Province, China [
      • Zhu N
      • Zhang D
      • Wang W
      • et al.
      A Novel Coronavirus from Patients with Pneumonia in China, 2019.
      ] The pathogen, a novel coronavirus (SARS-CoV-2), was identified by local hospitals using a surveillance mechanism for “pneumonia of unknown etiology” that was established in the wake of the 2003 SARS outbreak with the aim of allowing timely identification of novel pathogens [
      • Zhu N
      • Zhang D
      • Wang W
      • et al.
      A Novel Coronavirus from Patients with Pneumonia in China, 2019.
      ,
      • Li Q
      • Guan X
      • Wu P
      • et al.
      Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.
      ]. On 30 January 2020, the World Health Organization (WHO) declared that CoVID-19 is a “public-health emergency of international concern” [
      • Li X
      • Wang W
      • Zhao X
      • et al.
      Transmission dynamics and evolutionary history of 2019-nCoV.
      ]. The pandemic is escalating rapidly. We searched the associated literature in CoVID-19 to summarize the epidemiology, clinical characteristics, diagnosis and treatments and preventions of the infection of SARS-CoV-2.

      Epidemiology

       Scope of the CoVID-19 infection outbreak

      Since December 2019, multiple cases occurring unexplainable pneumonia were successively reported in some hospitals in Wuhan city with a history of exposure to a large seafood market in Wuhan city, Hubei province, China. It has been confirmed to be an acute respiratory infection caused by a novel coronavirus. So far, this disease has rapidly spread from Wuhan to China’s other areas, and 66 countries. And then, clustered cases and confirmed cases without a history of travel to Wuhan emerged as the advancing of this disease [
      • Jin Y-H
      • Cai L
      • Cheng Z-S
      • et al.
      A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).
      ]. In addition, confirmed cases without clear exposure to the seafood market of Wuhan have been spread in many foreign countries [
      • Stoecklin SB
      • Rolland P
      • Silue Y
      • Mailles A
      First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020.
      ].
      According to National Health Commission of the People`s Republic of China, as of 24:00 on March 2, 2020, a total of 80, 302 CoVID-19 cases in China have been confirmed in 31 provinces (autonomous regions and municipalities), and Xinjiang Production and Construction Crops, including Hong Kong, Macao, and Taiwan, including 2947 (3.66%) deaths. At present, there are 30, 095 confirmed cases (6, 806 severe cases), 47, 260 (58.85%) discharged cases, and 587 suspected cases were recorded. It is worth mentioning that up to now, Tibet and Qinghai provinces have no new coronavirus infected patients [

      National-Health-Commission-of-the-People’s-Republic-of-China. CoVID-19 News Update, up to February 24, 2020. Available at: http://www.nhc.gov.cn/xcs/yqtb/202002/67e6c59a84bd4f07b6ca4a4c5ffabb79.shtml.

      ]. As of 11 February, a total of 1,715 medical workers had been infected, of which 5 had died, with a crude case fatality rate of 0.3%. The number of confirmed cases has surpassed SARS in 2003.
      Internationally, confirmed cases have been reported in 66 countries and 6 continents and another Diamond Princess. Outside of China, a total of 10415 cases of CoVID-19 have been reported from 66 countries, with 168 deaths. The epidemics in the Republic of Korea, Italy, Iran and Japan have been became the greatest concern of WHO [

      WHO. WHO Director-General’s opening remarks at the media briefing on COVID-19-2 March 2020. Available at: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---2-march-2020.

      ]. According to the European Centre for Disease Prevention and Control (ECDC) [

      European-Centre-for-Disease-Prevention-and-Control. Daily risk assessment on COVID-19, 2 March 2020 Available at: https://www.ecdc.europa.eu/en/current-risk-assessment-novel-coronavirus-situation.

      ], the latest daily risk assessment on COVID-19, March 2, they ECDC have now considered the risk moderate to high level. The case fatality rate of the currently reported cases in China is less than 4%, which implies that so far, this novel coronavirus does not seem to cause the high fatality rates previously observed for SARS-CoV and MERS-CoV, 10% and 37%, respectively [
      • Chaolin H
      • Yeming W
      • Xingwang L
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      ]. According to the latest data, a total of 36167 cases were reported in Hubei, China, that gives a cumulated attack rate (CAA) of 0.11% (the permanent resident population of Hubei is about 59, 170, 000). However, when compared to the influenza virus of pH1N1, which shared the same transmission route, have a 50 times higher CAA, this data showed the importance of the intense quarantine and social distancing measures the Huibei government have taken.

      Host and reservoir

      Wild animals and bats are considered as the natural reservoir hosts and play a crucial role in transmitting various viruses, including Ebola, Nipah, Coronavirus and others [
      • Cui J
      • Li F
      • Shi Z
      Origin and evolution of pathogenic coronaviruses.
      ,
      • Malik YS
      • Sircar S
      • Bhat S
      • et al.
      Emerging novel Coronavirus (2019-nCoV) - Current scenario, evolutionary perspective based on genome analysis and recent developments.
      ]. SARS-CoV-2 is the seventh member of the family coronaviruses, which is the beta-CoV with over 70% similarity in genetic sequence to SRAS-nCoV [
      • Cheng ZJ
      • Shan J.
      2019 Novel coronavirus: where we are and what we know.
      ]· Like SARS-CoV, MERS-CoV, and many other coronaviruses, SARS-CoV-2 likely originated in bats, but it requires further confirmation whether pneumonia infected by the SARS-CoV-2 is transmitted directly from bats or through an intermediate host [
      • Jin Y-H
      • Cai L
      • Cheng Z-S
      • et al.
      A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).
      ,
      • Zhou P
      • Yang XL
      • Wang XG
      • Hu B
      • Zhang L.
      A pneumonia outbreak associated with a new coronavirus of probable bat origin.
      ,
      • Perlman S
      Another Decade, Another Coronavirus.
      ].Recent research has found that the virus is 96% identical at the whole-genome level to a bat coronavirus, which means bats is the most possible host of the SARS-CoV-2 [
      • Zhou P
      • Yang XL
      • Wang XG
      • Hu B
      • Zhang L.
      A pneumonia outbreak associated with a new coronavirus of probable bat origin.
      ,
      • Perlman S
      Another Decade, Another Coronavirus.
      ]. Also, Ji and colleagues [
      • Ji W
      • Wang W
      • Zhao X
      • Zai J
      • Li X.
      Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human.
      ] demonstrated that snack as possible virus reservoir for human infection. And Zhu et al [
      • Cheng ZJ
      • Shan J.
      2019 Novel coronavirus: where we are and what we know.
      ] indicated that bats and minks maybe the two potential hosts of the novel coronavirus, while the minks may be the intermediate hosts of this virus. Subsequently, studies have shown that pangolins are potential intermediate hosts, but in general, intermediate hosts may have multiple hosts [
      • TT-Y Lam
      • MH-H Shum
      • Zhu H-C
      • et al.
      Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China.
      ]. For many viruses, one of the key steps in the emergence process is the jump from animals to humans. Thus, identifying the source of the virus will help control its spread [
      • Perlman S
      Another Decade, Another Coronavirus.
      ].

      Route of transmission

      Chan and his colleagues [
      • Fuk-Woo CJ
      • Shuofeng Y
      • Kin-Hang K
      • et al.
      A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.
      ] reported a case of five patients in a family cluster, which confirmed Person-to-person transmission of CoVID-19. Health officials have identified evidence of transmission along a chain of 4 “generations” (a person who originally contracted the virus from a nonhuman source infected someone else, who infected another individual, who then infected another individual), suggesting sustained human-to-human transmission [
      • Phelan AL
      • Rebecca Katz
      • Gostin L
      The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance.
      ,

      WHO. How does COVID-19 Spread? Available at: https://www.who.int/news-room/q-a-detail/q-a-coronaviruses.

      ]. Up to present, the main infection source was the patients who with pneumonia infected by the SARS-CoV-2. Respiratory droplet transmission is the main route of transmission, and it can also be transmitted through aerial droplets and contact [
      • Jin Y-H
      • Cai L
      • Cheng Z-S
      • et al.
      A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).
      ]. However, we also should attach importance to asymptomatic cases which may play a critical role in the transmission process [
      • Shen K
      • Yang Y
      • Wang T
      • et al.
      Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement.
      ]. Recently, new coronavirus was detected in the feces of confirmed patients in Wuhan, Shenzhen and even the first case in the United States, indicating that the virus can replicate in the digestive tract and exist, suggesting the possibility of fecal-oral transmission [
      • Holshue ML
      • DeBolt C
      • Lindquist S
      • et al.
      First Case of 2019 Novel Coronavirus in the United States.
      ], but it is not certain that eating virus-contaminated food causes infection and transmission. There were also views that viruses in feces may be re-transmitted by aerosol formation of virus-containing droplets, requiring further investigation. At present, there is no evidence for aerosol transmission of CoVID-19. WHO also believes that further evidence is needed to assess the possibility of aerosol transmission [

      WHO. How does COVID-19 Spread? Available at: https://www.who.int/news-room/q-a-detail/q-a-coronaviruses.

      ]. In addition, it has been reported that the mother was diagnosed with a new type of coronavirus pneumonia, and the newborn was positive for viral nucleic acid in pharynx swabs after 30 hours of birth [

      CCTV.COM. A 30-hour old infant in Wuhan diagnosed and mother-to-child infection suspected. Available at: http://m.news.cctv.com/2020/02/05/ARTIywVxQICUUURSIWzSzvkf200205.shtml.

      ], suggesting that the new type of coronavirus may cause neonatal infection through mother-to-child transmission, which of course needs to be confirmed by more scientific studies [
      • Zhu H
      • Wang L
      • Fang C
      • et al.
      Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia.
      ].
      WHO has published their estimation of R0 to be 2.0-2.5 using early information [
      • WHO
      Report of the WHO-China Joint Mission on Coronavirus Disease.
      ]. Li et al. [
      • Li Q
      • Guan X
      • Wu P
      • et al.
      Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.
      ] analyzed data on the first 425 confirmed cases in Wuhan and found that the R0 to be 2.2, without specifying their modelling method Jonathan Read and his colleagues [
      • Cheng ZJ
      • Shan J.
      2019 Novel coronavirus: where we are and what we know.
      ] from Lancaster University who used a deterministic Susceptible-Exposed-Infected-Recovered (SEIR) metapopulation transmission model to determine the R0 to be around 3.1. Majumder and his colleagues [
      • Maimuna M
      • MK D
      Early Transmissibility Assessment of a Novel Coronavirus in Wuhan, China (January 26, 2020).
      ] used Incidence Decay and Exponential Adjustment (IDEA) model to estimate the R0 to be 2.0-3.3 (The study did not published yet, available at SSRN). Recently, a large group of researchers from multiple institutes led by Jianhong Wu from York University [
      • Tang B
      • Wang X
      • Li Q
      • et al.
      Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions.
      ] proposed a more general deterministic SEIR compartmental model using more parameters, and arrived at a much higher R0 number of 6.47. A recent research [
      • Zhang S
      • Diao M
      • Yu W
      • Pei L
      • Lin Z
      • Chen D.
      Estimation of the reproductive number of Novel Coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: a data-driven analysis.
      ] on the Diamond Princess cruise ship outbreak, at a loosen intervention and quarantine condition, showed the R0 was 2.28, and if reduce the R0 by 25% and 50%, the estimated cumulative cases would be reduce from 1514 to 1081 and 758, also proved that intense quarantine and social distancing measures should be taken to control the outbreak.
      While Estimates from the SARS-CoV outbreak in 2003 reported an R0 of 3 [
      • Bauch CT
      • Lloyd-Smith JO
      • Coffee MP
      • Galvani AP
      Dynamically Modeling SARS and Other Newly Emerging Respiratory Illnesses Past, Present, and Future.
      ], which means SRAS-CoV-2 has a similar ability to spread as SRAS-CoV, or higher spreading ability than SRAS-CoV, so that the SARS-COV-2 outbreak caused more than 90000 cases in 66 countries all over the world in less than 2 months, that’s times of the SARS-COV outbreak [
      • Peeri NC
      • Shrestha N
      • Rahman MS
      • et al.
      The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?.
      ,
      • Wu Z
      • McGoogan JM
      Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention.
      ].

      Clinical manifestations

      A wide range of clinical manifestations are seen in patients with SARS-CoV-2 from mild, moderate, to severe and rapidly progressive and fulminant disease. And most of the patients with SARS-CoV-2 were normal and mild, and their mortality was lower than SARS-CoV and MERS-CoV.

      Incubation Period

      In recent publications, the mean incubation period of CoVID-19 was a little bit different. Wang et al, with 138 cases, reported that the median durations from first symptoms to dyspnea, hospital admission, and Acute severe respiratory syndrome (ARDS) were 5 days (range, 1-10), 7 days (range, 4-8), and 8 days (range, 6-12), respectively [
      • Wang D
      • Hu B
      • Hu C
      • et al.
      Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
      ]. And Li et al, with 425 confirmed cases, instructed that the mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9) [
      • Li Q
      • Guan X
      • Wu P
      • et al.
      Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.
      ]. While Guan et al [
      • Guan WJ
      • Ni ZY
      • Hu Y
      • et al.
      Clinical Characteristics of Coronavirus Disease 2019 in China.
      ], with 1099 patients, reported that the estimated mean incubation period of SARS-CoV-2 infection was 3.0 days (range, 0 to 24.0), which was shorter than the two researches above (3.0 days vs 5 days and 5.2 days ). The median incubation period of CoVID-19 ARD was 3.0 days and it had a relatively lower fatality rate than SARS and MERS [
      • Wang D
      • Hu B
      • Hu C
      • et al.
      Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
      ]. While the estimated mean incubation period of SARS-CoV infection was 4.6 days (95% CI, 3.8–5.8 days) [
      • Chiu WK
      • Cheung PC
      • Ng KL
      • et al.
      Severe acute respiratory syndrome in children: experience in a regional hospital in Hong Kong.
      ] and 95% of illness onset occurred within 10 days [
      • DC A.
      • GA C.
      • LG M.
      • et al.
      Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong.
      ]. The mean time from symptom onset to hospitalization was between 2 and 8 days, but was shorter toward the later phase of the epidemic. The mean time from symptom onset to need for invasive mechanical ventilation (IMV) and to death was 11 and 23.7 days, respectively [
      • Leung GM
      • Hedley AJ
      • Ho L-M
      • Chau P.
      The Epidemiology of Severe Acute Respiratory Syndrome in the 2003 Hong Kong Epidemic: An Analysis of All 1755 Patients.
      ].

      Symptoms

      Symptom of CoVID-19 are non-specific and the disease presentation can range from no symptoms (asymptomatic) to severe pneumonia and death A study of 41 patients [
      • Chaolin H
      • Yeming W
      • Xingwang L
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      ] who were initially diagnosed with the outbreak (the diagnosis date was up to 2 January) found that the most common symptoms were fever (98%), cough (76%), myalgia or fatigue (44%), and atypical symptoms included sputum (28%), headache (8%), hemoptysis (5%) and diarrhea (3%). About half of the patients had dyspnea (the median from onset to dyspnea was 8 days). Lymphocytopenia was observed in 63% of patients. All patients had pneumonia. Complications included acute respiratory distress syndrome (29%), acute heart injury (12%), and secondary infections (10%); 32% of patients require to be treated in the ICU. An analysis of 1099 confirmed cases (up to 29 January) conducted by NanShan Zhong’s team [
      • Weijie G
      • Zhengyi N
      • Yu H
      • et al.
      Clinical characteristics of 2019 novel coronavirus infection in China.
      ], found that the most common symptoms were fever (87.9%) and cough (67.7%), diarrhea (3.7%) and vomiting (5.0%). 25.2% of the patients had at least one underlying disease (such as hypertension, chronic obstructive pulmonary disease). Lymphocytopenia was observed in 82.1% of patients. On admission, 50% of the patients presented ground-glass shadow on chest CT. A retrospective study [
      • Wang D
      • Hu B
      • Hu C
      • et al.
      Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
      ] of 138 hospitalized patients from January 1 to 28 found that patients receiving treatment in the ICU were older, more likely to have underlying diseases, and more likely to have dyspnea, and the median length of stay was 10 days [
      • Wang D
      • Hu B
      • Hu C
      • et al.
      Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
      ]. Recent studies indicate that patients≥60 years of age are at higher risk than children who might be less likely to become infected or, if so, may show milder symptoms or even asymptomatic infection [
      • Li Q
      • Guan X
      • Wu P
      • et al.
      Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.
      ]. Epidemiology Working Group for NCIP Epidemic Response of the Chinese Center for Disease Control and Prevention [
      • Epidemiology Working Group for NCIP Epidemic Response CCfDCaP
      The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China.
      ], with a total of 72314 patients, reported that there were 44672 (61.8%) confirmed cases, and 889 asymptomatic cases (1.2%) among the total number of the patients. Among confirmed cases, most were aged 30-79 years (86.6%), and considered mild/mild pneumonia (80.9%).

      Diagnosis

       Clinical Diagnosis

      The SARS-CoV-2 infected cases have symptoms like fever, fatigue, dry cough, dyspnea etc., with or without nasal congestion, runny nose or other upper respiratory symptoms [
      • Weiss SR
      • Leibowitz JL
      Coronavirus pathogenesis.
      ,
      • Holshue ML
      • DeBolt C
      • Lindquist S
      • et al.
      First Case of 2019 Novel Coronavirus in the United States.
      ]. Despite the atypical symptoms were reported, Guan et al. [
      • Weijie G
      • Zhengyi N
      • Yu H
      • et al.
      Clinical characteristics of 2019 novel coronavirus infection in China.
      ] pointed out that fever is still the typical symptom of SARS-CoV-2 infection.
      • a)
        Physical examination
      Patients with mild symptoms may not be present positive signs. Patients in severe condition may have shortness of breath, moist rales in lungs, weakened breath sounds, dullness in percussion, and increased or decreased tactile speech tremor, etc.
      • b)
        CT imaging examination
      The imaging finding vary with the patient`s age, immunity status, disease stage at the time of scanning, underlying diseases, and drug interventions.
      Chest X-ray examination In the early stage of pneumonia cases, chest images show multiple small patchy shadows and interstitial changes [
      • Chaolin H
      • Yeming W
      • Xingwang L
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      ], remarkable in the lung periphery [
      • Fuk-Woo CJ
      • Shuofeng Y
      • Kin-Hang K
      • et al.
      A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.
      ]. Severe cases can further develop to bilateral multiple ground-glass opacity, infiltrating shadows, and pulmonary consolidation, with infrequent pleural effusion. While Chest CT scan Pulmonary lesions are shown more clearly by CT than X-ray examination, including ground-glass opacity and segmental consolidation in bilateral lungs, especially in the lung periphery. In children with severe infection, multiple lobar lesions may be present in both lungs. A study of CT scans of 21 patients with SARS-CoV-2 infection showed that three (21%) with normal CT scans, 12 (57%) with ground-glass opacity only, and six (29%) with ground-glass opacity and consolidation at presentation [
      • Chung M
      • Bernheim A
      • Mei X
      • Zhang N.
      CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV).
      ] Another study of 41 patients with confirmed SARS-CoV-2 infection was reported to have bilateral lung involvement on chest radiographs [
      • Chaolin H
      • Yeming W
      • Xingwang L
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      ]. Overall, the imaging findings reported for CoVID-19 are similar to those reported with SARS [
      • Nicolaou S
      • Al-Nakshabandi NA
      • Müller NL
      SARS: Imaging of Severe Acute Respiratory Syndrome.
      ,
      • Ooi GC
      • Khong PL
      • Khong PL
      • Yiu WC
      • Zhou LJ.
      Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients.
      ] and MERS [
      • Das KM
      • Lee EY
      • Jawder SEA
      • Enani MA
      Acute Middle East Respiratory Syndrome Coronavirus: Temporal Lung Changes Observed on the Chest Radiographs of 55 Patients.
      ,
      • DK M.
      • LE Y.
      • EM A.
      • et al.
      CT Correlation With Outcomes in 15 Patients With Acute Middle East Respiratory Syndrome Coronavirus.
      ], not surprising as the responsible viruses are also coronaviruses.

      Laboratory Diagnosis

      It mainly should be distinguished from other known viral virus of pneumonia, such as influenza viruses, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, SARS-CoV, etc.; and also, from mycoplasma pneumonia, chlamydia pneumonia, and bacterial pneumonia. In addition, it should be distinguished from non-infectious diseases, such as vasculitis, dermatomyositis, and organizing pneumonia [
      • Jin Y-H
      • Cai L
      • Cheng Z-S
      • et al.
      A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).
      ]. So, laboratory diagnosis is necessary. Identification of CoVID-19 mainly includes virus isolation and viral nucleic acid detection. According to the traditional Koch`s postulates, virus isolation is the “gold standard” for virus diagnosis in the laboratory [
      • Yu F
      • Du L
      • Ojcius DM
      • Pan C
      • Jiang S.
      Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China.
      ] A variety of specimens (such as swabs, nasal swabs, nasopharynx or trachea extracts, sputum or lung tissue, blood and feces) should be retained for testing in timely manner, which gives a higher rate of positive detection of lower respiratory tract specimens [
      • Yu F
      • Du L
      • Ojcius DM
      • Pan C
      • Jiang S.
      Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China.
      ].
      Viral nucleic acids can also be used for early diagnosis, which is the most important thing. So, we should detect SARS-CoV-2 nucleic acid: accurate RNA detection of SARS-CoV-2 is with diagnostic value [
      • Yu F
      • Du L
      • Ojcius DM
      • Pan C
      • Jiang S.
      Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China.
      ]. The full gene sequence of SARS-CoV-2 has now been obtained and samples can be collected from the upper respiratory tract (oropharyngeal and nasopharyngeal) and lower respiratory tract (endotracheal aspirate, expectorated sputum, or bronchoalveolar lavage) of patients suspected SARS-CoV-2 infection for diagnosis by real time RT-PCR method [
      • Corman VM
      • Olfert LandtKaiser M
      • Kaiser M
      • et al.
      Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR.
      ] Also, in the early stage of the disease, the total number of leukocytes decreased or keeps normal, with decreased lymphocyte count or increased or normal monocytes also indicated the diagnosis of CoVID-19 [
      • Jin Y-H
      • Cai L
      • Cheng Z-S
      • et al.
      A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).
      ].

      Treatments and Preventions

      At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the CoVID-19 outbreak. WHO has announced that a vaccine for SARS-CoV-2 should be available in 18 months, but achieving this will require funding and public interest to be maintained even if the threat level falls [
      • Diseases TLI.
      Challenges of coronavirus disease 2019.
      ]. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients [
      • Zumla A
      • Hui DS
      • Azhar EI
      • Memish ZA
      • Maeurer M.
      Reducing mortality from 2019-nCoV: host-directed therapies should be an option.
      ].
      The general strategies include bed rest and supportive treatment, including antiviral therapy [
      • Arabi YM
      • Alothman A
      • Balkhy HH
      • et al.
      Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial.
      ], antibioics application, immunomodulating therapy [
      • Arabi YM
      • Mandourah Y
      • Al-Hameed F
      • Sindi AA
      • Mekhlafi GAA
      Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome.
      ], organ function support, respiratory support, bronchoalveolar lavage (BAL), blood purification and extracorporeal membrane oxygenation (ECMO) [
      • Wang T
      • Wang W
      • Wang Y
      • et al.
      Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.
      ].
      Novel coronavirus infection is a new communicable disease with an emergent outbreak that affects all populations [
      • Burki T.
      Outbreak of coronavirus disease 2019.
      ]. SARS-CoV-2 infection has been classified as category B infectious disease legally but managed as category A infectious disease by Chinese government. It is paramount to implement infection control practices by infection source controlling, transmission route blocking, and susceptible population protection. The unprecedented flurry of activity by WHO and other global public health bodies has mainly focused on preventing transmission, infection control measures, and screening of travelers [
      • Zumla A
      • Hui DS
      • Azhar EI
      • Memish ZA
      • Maeurer M.
      Reducing mortality from 2019-nCoV: host-directed therapies should be an option.
      ].

      Conclusions

      How easily the virus is transmitted between persons, and how it affects individual persons and potentially vulnerable population subgroups, such as the elderly or those with chronic health conditions? What is the source of the virus? And how can it spread around the world in such a short time? At the moment, we know relatively little about CoVID-19, except that it is a highly pathogenic human pathogen, possibly a zoonotic agent. Now that a pandemic has occurred, it is critical that countries around the world take steps to stop transmission and save lives. In addition, we should actively study its origin, tropism, and pathogenesis with the aim of providing some guidance in dealing with this rapidly spreading epidemic. Challenges remain in several key areas, including the recent cases of people who have tested positive for the virus. Can these cured patients be transmitted to others? All these suggest that we should develop more detailed criteria for the prevention and control of the virus, and more stringent criteria for discharge of patients after treatment.

      Contributors

      All authors contributed to the conception of the Review. Di Wu, Tiantian Wu and Qun Liu contributed the literature search, data traction and data synthesis, created the tables, and wrote the manuscript. All authors contributed to the interpretation of the data and revision of the manuscript.

      Funding

      This work was supported by the National Natural Science Foundation of China Grants (81803325), Medical Science and Technology Project of Guangzhou (20191A011064), Guangdong Medical Science and Technology Research Project (A2019379).

      Ethical Approval

      None.

      Conflicts of interests

      We declare no conflicts interests.

      References

        • Weiss SR
        • Leibowitz JL
        Coronavirus pathogenesis.
        Adv Virus Res. 2011; 81: 85-164
        • Yang D
        • Leibowitz JL
        The structure and functions of coronavirus genomic 3’ and 5’ ends.
        Virus Res. 2015; 206: 120-133
        • Drosten C
        • Günther S
        • Preiser W
        Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome.
        N Engl J Med. 2020; 348: 1967-1976
        • Zaki AM
        • Sv Boheemen
        • Bestebroer TM
        • Osterhaus ADME
        • Fouchier RAM
        Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.
        N Engl J Med. 2012; 367: 1814-1820
        • Zhu N
        • Zhang D
        • Wang W
        • et al.
        A Novel Coronavirus from Patients with Pneumonia in China, 2019.
        N Engl J Med. 2020; : 727-733
        • Cui J
        • Li F
        • Shi Z
        Origin and evolution of pathogenic coronaviruses.
        Nat Rev Microbiol. 2019; 17: 181-192
        • Li Q
        • Guan X
        • Wu P
        • et al.
        Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.
        N Engl J Med. 2020; (Epub ahead of print)
        • Li X
        • Wang W
        • Zhao X
        • et al.
        Transmission dynamics and evolutionary history of 2019-nCoV.
        J Med Virol. 2020; (Epub ahead of print)
        • Jin Y-H
        • Cai L
        • Cheng Z-S
        • et al.
        A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).
        Mil Med Res. 2020; 7: 4
        • Stoecklin SB
        • Rolland P
        • Silue Y
        • Mailles A
        First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020.
        Euro Surveill. 2020; 252000094
      1. National-Health-Commission-of-the-People’s-Republic-of-China. CoVID-19 News Update, up to February 24, 2020. Available at: http://www.nhc.gov.cn/xcs/yqtb/202002/67e6c59a84bd4f07b6ca4a4c5ffabb79.shtml.

      2. WHO. WHO Director-General’s opening remarks at the media briefing on COVID-19-2 March 2020. Available at: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---2-march-2020.

      3. European-Centre-for-Disease-Prevention-and-Control. Daily risk assessment on COVID-19, 2 March 2020 Available at: https://www.ecdc.europa.eu/en/current-risk-assessment-novel-coronavirus-situation.

        • Chaolin H
        • Yeming W
        • Xingwang L
        • et al.
        Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
        The Lancet. 2020; 395: 497-506
        • Malik YS
        • Sircar S
        • Bhat S
        • et al.
        Emerging novel Coronavirus (2019-nCoV) - Current scenario, evolutionary perspective based on genome analysis and recent developments.
        Vet Q. 2020; (Epub ahead of print)
        • Cheng ZJ
        • Shan J.
        2019 Novel coronavirus: where we are and what we know.
        Infection. 2020; (Epub ahead of print)
        • Zhou P
        • Yang XL
        • Wang XG
        • Hu B
        • Zhang L.
        A pneumonia outbreak associated with a new coronavirus of probable bat origin.
        Nature. 2020; (Epub ahead of print)
        • Perlman S
        Another Decade, Another Coronavirus.
        N Engl J Med. 2020; 382: 760-762
        • Ji W
        • Wang W
        • Zhao X
        • Zai J
        • Li X.
        Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human.
        J Med Virol. 2020; 92: 433-440
        • TT-Y Lam
        • MH-H Shum
        • Zhu H-C
        • et al.
        Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China.
        bioRxiv preprint. 2020; (epub)
        • Fuk-Woo CJ
        • Shuofeng Y
        • Kin-Hang K
        • et al.
        A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.
        The Lancet. 2020; : 514-523
        • Phelan AL
        • Rebecca Katz
        • Gostin L
        The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance.
        JAMA. 2020; (Epub ahead of print)
      4. WHO. How does COVID-19 Spread? Available at: https://www.who.int/news-room/q-a-detail/q-a-coronaviruses.

        • Shen K
        • Yang Y
        • Wang T
        • et al.
        Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement.
        World J Pediatr. 2020; (Epub ahead of print)
        • Holshue ML
        • DeBolt C
        • Lindquist S
        • et al.
        First Case of 2019 Novel Coronavirus in the United States.
        N Engl J Med. 2020; (Epub ahead of print)
      5. CCTV.COM. A 30-hour old infant in Wuhan diagnosed and mother-to-child infection suspected. Available at: http://m.news.cctv.com/2020/02/05/ARTIywVxQICUUURSIWzSzvkf200205.shtml.

        • Zhu H
        • Wang L
        • Fang C
        • et al.
        Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia.
        Translational Pediatrics. 2020; 9: 51-60
        • WHO
        Report of the WHO-China Joint Mission on Coronavirus Disease.
        (COVID-19). Available at:
        • Maimuna M
        • MK D
        Early Transmissibility Assessment of a Novel Coronavirus in Wuhan, China (January 26, 2020).
        2020https://doi.org/10.2139/ssrn.3524675 (SSRN)
        • Tang B
        • Wang X
        • Li Q
        • et al.
        Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions.
        J Clin Med. 2020; 9: 1-13
        • Zhang S
        • Diao M
        • Yu W
        • Pei L
        • Lin Z
        • Chen D.
        Estimation of the reproductive number of Novel Coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: a data-driven analysis.
        Int J Infect Dis. 2020;
        • Bauch CT
        • Lloyd-Smith JO
        • Coffee MP
        • Galvani AP
        Dynamically Modeling SARS and Other Newly Emerging Respiratory Illnesses Past, Present, and Future.
        Epidemiology. 2005; 16: 791-801
        • Peeri NC
        • Shrestha N
        • Rahman MS
        • et al.
        The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?.
        Int J Epidemiol. 2020;
        • Wu Z
        • McGoogan JM
        Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention.
        JAMA. 2020; (Epub ahead of print)
        • Wang D
        • Hu B
        • Hu C
        • et al.
        Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
        JAMA. 2020; (Epub ahead of print)
        • Guan WJ
        • Ni ZY
        • Hu Y
        • et al.
        Clinical Characteristics of Coronavirus Disease 2019 in China.
        N Engl J Med. 2020;
        • Chiu WK
        • Cheung PC
        • Ng KL
        • et al.
        Severe acute respiratory syndrome in children: experience in a regional hospital in Hong Kong.
        Pediatr Crit Care Med. 2003; 4: 279-283
        • DC A.
        • GA C.
        • LG M.
        • et al.
        Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong.
        The Lancet. 2003; 361: 1761-1766
        • Leung GM
        • Hedley AJ
        • Ho L-M
        • Chau P.
        The Epidemiology of Severe Acute Respiratory Syndrome in the 2003 Hong Kong Epidemic: An Analysis of All 1755 Patients.
        Ann Intern Med. 2004; 141: 662-673
        • Weijie G
        • Zhengyi N
        • Yu H
        • et al.
        Clinical characteristics of 2019 novel coronavirus infection in China.
        medRxiv preprint. 2020;
        • Epidemiology Working Group for NCIP Epidemic Response CCfDCaP
        The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China.
        Chinese Journal of Epidemiology. 2020; 41: 145-151
        • Chung M
        • Bernheim A
        • Mei X
        • Zhang N.
        CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV).
        Radiology. 2020; 4 (Epub ahead of print)
        • Nicolaou S
        • Al-Nakshabandi NA
        • Müller NL
        SARS: Imaging of Severe Acute Respiratory Syndrome.
        AJR Am J Roentgenol. 2003; 180: 1247-1249
        • Ooi GC
        • Khong PL
        • Khong PL
        • Yiu WC
        • Zhou LJ.
        Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients.
        Radiology. 2004; 230: 836-844
        • Das KM
        • Lee EY
        • Jawder SEA
        • Enani MA
        Acute Middle East Respiratory Syndrome Coronavirus: Temporal Lung Changes Observed on the Chest Radiographs of 55 Patients.
        AJR Am J Roentgenol. 2015; 205 (W267-74)
        • DK M.
        • LE Y.
        • EM A.
        • et al.
        CT Correlation With Outcomes in 15 Patients With Acute Middle East Respiratory Syndrome Coronavirus.
        American Journal of Roentgenology. 2015; 204: 736-742
        • Yu F
        • Du L
        • Ojcius DM
        • Pan C
        • Jiang S.
        Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China.
        Microbes Infect. 2020; (S1286-4579:30025-3)
        • Corman VM
        • Olfert LandtKaiser M
        • Kaiser M
        • et al.
        Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR.
        Euro Surveill. 2020; 25: 1-8
        • Diseases TLI.
        Challenges of coronavirus disease 2019.
        The Lancet Infectious Diseases. 2020; S1473-3099:30072-4
        • Zumla A
        • Hui DS
        • Azhar EI
        • Memish ZA
        • Maeurer M.
        Reducing mortality from 2019-nCoV: host-directed therapies should be an option.
        The Lancet. 2020; 395: e35-e36
        • Arabi YM
        • Alothman A
        • Balkhy HH
        • et al.
        Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial.
        Trials. 2018; 19: 81
        • Arabi YM
        • Mandourah Y
        • Al-Hameed F
        • Sindi AA
        • Mekhlafi GAA
        Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome.
        Am J Respir Crit Care Med. 2020; 197: 757-767
        • Wang T
        • Wang W
        • Wang Y
        • et al.
        Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.
        World J Pediatr. 2020; (Epub ahead of print)
        • Burki T.
        Outbreak of coronavirus disease 2019.
        The Lancet Infectious Diseases. 2020; S1473-3099:30076-1