Characteristics of published studies
Among the 65 research articles included in the analysis, more than 31 are on preprint servers, and 34 are published in peer-reviewed journals, including The Lancet and the New England Journal of Medicine. Most of the publications (n = 58, 89.23%) are in English and few (n = 7, 10.77%) are in Chinese. Around 75.86% of English language publications focus on epidemiology and causes, while 85.71% of Chinese papers focus on prevention and control (Table 1).
As shown in figure 2, academic publications are distributed across the following research domains: epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control. The largest portion of the papers (n = 25, 38.46%) are related to causes, followed by papers on epidemiology (n = 19, 29.23%), while 18.46% examined prevention and control and 13.85% reported clinical manifestations and diagnosis. Initially, there were more research articles focused on causes of the virus, yet prevention and control studies have gradually increased over time (Figure 3). The majority of the articles (n = 44, 67.69%) were published by Chinese scholars whereas 29.23% (n = 19) articles were from scholars outside of China, and few (n = 2, 3.08%) are based on international collaborative research by scholars from different countries (Table 2).
Table 1 Breakdown of 2019-nCoV research articles by language in January 2020
Research
domains
|
English literature
|
|
Chinese literature
|
|
Total
|
n
|
%
|
|
n
|
%
|
|
n
|
%
|
Epidemiology
|
19
|
32.76
|
|
0
|
0.00
|
|
19
|
29.23
|
Causes
|
25
|
43.10
|
|
0
|
0.00
|
|
25
|
38.46
|
Clinical manifestation and diagnosis
|
8
|
13.79
|
|
1
|
14.29
|
|
9
|
13.85
|
Prevention and control
|
6
|
10.34
|
|
6
|
85.71
|
|
12
|
18.46
|
Total
|
58
|
89.23
|
|
7
|
10.77
|
|
65
|
100.00
|
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).
Table 2 Breakdown of 2019-nCoV research articles by type of collaboration in January 2020
Research
domains
|
Inside
China
|
|
Outside
China
|
|
International
Collaboration
|
|
Total
|
n
|
%
|
|
n
|
%
|
|
n
|
%
|
|
n
|
%
|
Epidemiology
|
8
|
18.18
|
|
9
|
47.37
|
|
2
|
100.00
|
|
19
|
29.23
|
Causes
|
17
|
38.64
|
|
8
|
42.11
|
|
0
|
0.00
|
|
25
|
38.46
|
Clinical manifestation and diagnosis
|
8
|
18.18
|
|
1
|
5.26
|
|
0
|
0.00
|
|
9
|
13.85
|
Prevention and control
|
11
|
25.00
|
|
1
|
5.26
|
|
0
|
0.00
|
|
12
|
18.46
|
Total
|
44
|
67.69
|
|
19
|
29.23
|
|
2
|
3.08
|
|
65
|
100.00
|
Table 3 Methodological characteristics of 2019-nCoV research articles in January 2020
|
Characteristics
|
Categories
|
n
|
%
|
Study design
(n=65)
|
Cross-sectional studies
Mathematical modeling
Molecular studies
Diagnostic studies
Review
Theoretical study
|
12
29
10
2
3
9
|
18.46
44.62
15.38
3.08
4.62
13.85
|
|
|
|
|
Targets of study
(n=65)
|
Population
Patients
General population
Healthcare workers
Species (virus structure, gene sequence)
Other
|
32
22
6
4
24
9
|
49.23
33.85
9.23
6.15
36.92
13.85
|
Study related to population (n=32)
|
Sample size
|
1-10
11-50
51-100
>100
Not specified
|
11
5
3
3
10
|
34.38
15.63
9.38
9.38
31.25
|
|
|
|
|
Study setting
|
Laboratory
Hospital
Community
Hospital and community
Not specified
Questionnaire
|
2
10
0
0
20
7
|
6.25
31.25
0.00
0.00
62.50
10.77
|
|
|
|
|
Data-collection instrument*
|
Biological specimen collection
Physical examinations
Environmental sample
Hospital, medical, or exposure records
Secondary data
|
1
0
0
14
16
|
3.13
0.00
0.00
43.75
50.00
|
Quality-control activities
for data collection
|
Indicated in the article
Not specified
|
14
18
|
56.25
43.75
|
* Percentages in this section do not add up to 100% because multiple answers were possible.
Research domains
Epidemiology
On 29 December 2019, the first four cases of an acute respiratory syndrome of unknown etiology among people linked to a seafood market (“wet market”) were reported in Wuhan city, Hubei province, China [2]. Research is underway to understand more about transmissibility, severity, and other features associated with 2019-nCoV [3]. It appeared most of the early cases had contact history with the original seafood market [2, 12-14]. Soon, the secondary source of infection was found to be human-to-human transmission among close contacts. There was an increase of infected people with no history of exposure to wildlife or visiting Wuhan, and multiple cases of infection were detected among medical professionals [2, 14-17]. The 2019-nCoV infection occurs through exposure to the virus, and both the immunosuppressed and normal population appear susceptible. Some studies have reported an age distribution of adult patients between 25 and 89 years old. Most adult patients are between 35 and 55 years old. There are fewer identified cases among children and infants [14, 18]. A study on early transmission dynamics of the virus reports the median age of patients to be 59 years, ranging from 15 to 89 years, with the majority (59%) being male [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].
The 2019-nCoV has been found to have higher levels of transmissibility and pandemic risk than the SARS-CoV as the effective reproductive number (R) of 2019-nCoV (2.9) is estimated to be higher than the reported effective reproduction number (R) of SARS (1.77) at the early stage [15]. The average incubation duration of 2019-nCoV were estimated to be 4.8±2.6, ranging from 2-11 days [15] and 5.2 days (95% Confidence interval, 4.1 to 7) [2]. The latest guidelines from Chinese health authorities mentioned an average incubation duration of 7 days, ranging from 2-14 days [19].
In China, 11791 cases were confirmed and 17988 were suspected cases in 34 provinces as of 24:00, January 31, 2020 (Figure 4) [20]. The studies mentioned a relatively quick spread of the 2019-nCoV, and also reported the spread to several other countries after its outbreak in China; there were 213 deaths reported globally on January 31, 2020 [21]. Confirmed cases were reported in the following 19 countries outside of China: Australia (9), Canada (3), Cambodia (1), France (6), Finland (1), Germany (5), India (1), Italy (2), Japan (14), Nepal (1), Malaysia (8), Philippines (1), Republic of Korea (11), Singapore (13), Sri Lanka (1), Thailand (14), United States of America (6), United Arab Emirates (4) and Vietnam (5) (Figure 5) [21].
Causes
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]. Other than 2019-nCoV, there are six known coronaviruses in human: HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU,1 and MERS-CoV [2, 19, 23, 24]. Coronavirus has caused two large scale pandemics in the last two decades: SARS [25] and MERS [12, 26].
To detect the infection source of 2019-nCoV, the China CDC researchers collected 585 environmental samples from the Huanan Seafood Market in Wuhan, Hubei Province, China on January 1 and January 12, 2020. They detected 33 samples containing 2019-nCoV and 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 S-protein supported strong interaction with human ACE2 molecules despite its sequence diversity with SARS-CoV [12, 30].
Transmission pattern
Many domestic and wild animals, including camels, cattle, cats, and bats, may serve as hosts for coronaviruses [19]. It is considered that, generally, animal coronaviruses do not spread among human beings [3]. However, there are exceptions, such as SARS and MERS, which are mainly spread though close contact with infected people via respiratory droplets from cough or sneezing. With regard to 2019-nCoV, early patients were reported to have some link to the Huanan Seafood Market in Wuhan, China, suggesting that these early infections were due to animal-to-person transmission. Soon, more cases were reported among medical staff and others with no history of exposure to that market or visiting Wuhan, which was taken as an indication for human-to-human transmission [2, 4, 15-17].
The latest guidelines from Chinese health authorities [19, 31], described three main transmission routes for the 2019-nCoV: 1) direct transmission, 2) aerosol transmission, 3) contact transmission. Direct transmission are reported to occur when respiratory droplets (as produced when an infected person coughs or sneezes) are ingested or inhaled by individuals nearby in close proximity; Aerosol transmission may occur when respiratory droplets mix into the air, forming aerosols and causing infection when inhaled into the lungs; and Contact transmission may occur when a subject touches a surface or object contaminated with the virus. According to the literature, individuals could be infected when they subsequently touch their mouth, nose, or, possibly, eyes [19, 31]. In addition to 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]. Under this policy, medical institutes can adopt isolation treatment and observation protocols to prevent and control the spread of the 2019-nCoV. On January 22, 2020, the National Health Commission published national guidelines for the prevention and control of 2019-nCoV for medical institutes to prevent the nosocomial infection [34]. On January 28, 2020, the National Health Commission issued protocols for rapid prevention and control measures in order to effectively contain the spread of epidemic through a "big isolation and big 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]. Airborne precautions and other protective measures have been discussed and proposed for prevention. Infection preventive and control (IPC) measures that may reduce the risk of exposure include the following: use of face masks; covering coughs and sneezes with tissues (or flexed elbow) that are then safely disposed of; regular hand washing with soap or disinfection with hand sanitizer containing at least 60% alcohol (if soap and water is not available); avoidance of contact with infected people and keeping the distance as much as possible; and the refrain from touching eyes, nose, and mouth with unwashed hands [3].
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. Regarding infected patients with 2019-nCoV, it has been recommended to apply appropriate symptomatic treatment and supportive care [3, 16].