Scientific Research News | Research Progress of novel coronavirus Pneumonia (COVID-19) (XI)

1. 2019-nCoV Epidemic Alert

■ On February 2, the joint prevention and control mechanism of the State Council held a press conference. At the press conference, it was revealed that from the Lantern Festival to the present, more than 9,11921 doctors and nurses from two medical teams in Dalian and Jinzhou, Liaoning Province, said goodbye to their families and rushed to Wuhan to support the treatment of patients in Leishenshan Hospital. Up to now, the National Health Commission has dispatched a total of <>,<> medical staff from all over the country to assist Hubei. Regarding aerosol transmission, experts from the Chinese Center for Disease Control and Prevention said at the press conference that the routes of aerosol transmission and fecal-oral transmission need to be further clarified. Epidemiological investigations have shown that most cases can be traced to a history of close contact with confirmed cases, which is consistent with some of the current characteristics of droplet and contact transmission.

■ What exactly is aerosol transmission? Aerosol transmission refers to the process of droplets suspended in the air, because of the loss of moisture, the remaining proteins and pathogens form a nucleus, forming a droplet nucleus, the droplet nucleus can float farther to cause long-distance transmission, this is aerosol transmission, in general, in a specific environment, aerosol transmission may occur. For example, in some clinical endotrache tubes, there is currently no evidence that the new coronavirus is transmitted through aerosols.

■ Regarding the frequent occurrence of false negatives, relevant experts answered: "The detection rate of nucleic acid testing of any virus cannot be 100%, and the nucleic acid detection of the new coronavirus is no exception, it is inevitable to detect false negatives, and the results of the detection rate are also related to the severity of the patient's own disease, the different stages of disease development, the methods of sampling and sampling and the laboratory's own testing conditions. For the diagnosis of new crown pneumonia, nucleic acid testing is also an indispensable means, if the test result is positive, we can be diagnosed as new crown pneumonia, the initial test result is negative for suspected case patients, in accordance with the requirements of the current diagnosis and treatment plan of the Health Commission, need to be isolated in designated hospitals, strict observation. In addition, this release focuses on the production and supply of important daily necessities in epidemic prevention and control.

■ On February 2020, 2, Lu Lin's team from Peking University published a newsletter entitled "7-nCoV epidemic: address mental health care to empower society" online in the international top medical journal The Lancet. The outbreak of the 2019-nCoV pandemic has caused public concern and mental health stress. The growing number of patients, suspected cases, and affected provinces and countries has raised public concerns about being infected. The unpredictable future of the epidemic is exacerbated by rumors and misinformation, often caused by misreported news reports and public misunderstandings of health information, raising concerns. Further travel bans and some executive orders calling for travelers to quarantine during the Spring Festival holiday may have caused public anxiety as they try to contain the outbreak. In this regard, experts from Peking University Sixth Hospital put forward six recommendations for coping with mental stress: among other things, assessing the accuracy of the information disclosed, strengthening social support systems (such as family and friends), eliminating rumors related to the epidemic, maintaining a normal life in safe conditions, and using the psychosocial service system, especially telephone and Internet counseling for medical staff, patients, family members and the public. These recommendations play a positive and important role in the fight against the epidemic [2019].

2. 2019-nCoV Biology Research Progress

■ On February 2020, 2, Cell Host & Microbe published online that Jiang Taijiao's research group, Wu Aiping's research group and Cheng Genhong's research group from Suzhou Institute of System Medicine, Center for System Medicine, Chinese Academy of Medical Sciences, and the Chinese Center for Disease Control and Prevention cooperated with the Chinese Center for Disease Control and Prevention entitled Genome composition and divergence of the novel coronavirus (7-nCoV) Research paper originating in China. The study revealed significant differences in genomic composition and protein sequence levels between the emergence of the novel coronavirus (2019-nCoV) in the Wuhan region of China in December 2019 and previous outbreaks of SARS virus, which help to understand the true origin and subsequent evolution of 12-nCoV.

Existing studies have shown that 2019-nCoV has about 80% similarity in genome sequence with severe acute respiratory syndrome coronavirus (SARS-CoV) and more than 90% similarity with SARS-like coronaviruses found in bats. However, the genomic differences between this novel coronavirus and the evolutionarily adjacent SARS or SARS-like coronaviruses have not been deeply resolved.

■ In this study, by annotating the first published 2019-nCoV genome, it was found that the novel coronavirus encodes at least 27 proteins, including 15 non-structural proteins (nsp1-nsp10, nsp12-nsp16), 4 structural proteins (S, E, M and N), and 8 auxiliary proteins (3a, 3b, p6, 7a, 7b, 8b, 9b and orf14). Most of the composition of genome-coding proteins is consistent with SARS-CoV, but there are certain differences, such as 2019-nCoV missing the 8a protein encoded by SARS-CoV; The length of the encoded 8b protein (121 amino acids) was longer than that of SARS-CoV (84 amino acids); There are also significant differences in the 3B protein encoded by the two. The compositional differences of these accessory proteins mean that there may be some different pathogenic mechanisms between the new coronavirus and previous outbreaks of SARS-CoV.

■ In addition, by systematically comparing the amino acid sequences on each coding protein between 2019-nCoV and SARS and SARS-similar coronavirus, a total of 380 differential amino acid sites were found between the two. Notably, on the virus's Spike protein, the differential sites of 2019-nCoV and SARS virus were distributed around the SARS virus receptor binding site and on the epitope of the SARS virus. These protein level differences may help reveal potential differences in infectivity and pathogenicity between 2019-nCoV and SARS viruses [2].

■ On February 2020, 2, Swiss scientist David Baud predicted the impact of 6-nCoV on pregnant women by analyzing maternal cases of severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV). Considering that the pathogenic potential of 2019-nCoV appears to be similar to SARS-CoV and MERS-CoV, pregnant women are at increased risk of severe infection. Without specific clinical signs of coronavirus infection prior to serious complications, 2019-nCoV has the potential to lead to serious maternal and/or perinatal adverse outcomes. The authors recommend systematic screening for any suspected 2019-nCoV infection during pregnancy. If 2019-nCoV infection is confirmed, long-term follow-up of the mother and her fetus is recommended [2019]. In addition, it has previously been reported that two cases of neonatal novel coronavirus pneumonia have been confirmed in Wuhan Children's Hospital. The youngest confirmed newborn was born only 3 hours ago to a mother with confirmed coronavirus pneumonia. This news suggests that 30-nCoV may have a vertical transmission route of mother-to-child infection, which should be taken seriously.

3. 2019-nCoV epidemiological study

■ On February 2, the study "Clinical Characteristics of China's 9 Novel Coronavirus Infection" led by Academician Zhong Nanshan and jointly completed by 30 authors from the frontline of the national anti-epidemic was published in the medical preprint journal medRxiv. (Note: None of the medRxiv papers are peer-reviewed.) ）

■ Zhong Nanshan et al. conducted a retrospective study on the clinical features of 1099 patients diagnosed with new coronary pneumonia (as of January 1). The study found that the median incubation period of new coronary pneumonia was 29.3 days, and the maximum was 0 days.
■ At the same time, only 24.1% of the patients had direct contact with wild animals, while 18.31% of the patients had traveled to Wuhan, and 30.71% of the patients had contact with people from Wuhan. This provides further evidence of human-to-human transmission of the new coronavirus.
■ The most common symptoms were fever (80.87%) and cough (9.67%). Diarrhea is a rare symptom. The median incubation period was 7.3 days (range 0 to 0.24 days). Of the 0 patients who underwent lung CT on admission, 840.76% presented with pneumonia. Typical features are ground-glass shadows (4.50%) and bilateral patchy shadows (00.46%). At the same time, lymphopenia occurred in 0.82% of patients and thrombocytopenia in 1.36% of patients. Overall, leukopenia was observed in 2.33% of patients. In severe cases, there will be prominent abnormalities, such as: leukopenia, lymphopenia, thrombocytopenia, C-reactive elevated protein levels, etc.
■ The percentage of patients admitted to the ICU, requiring invasive ventilation and dying was 7.5%, 00.2% and 18.1%, respectively. Zhong Nanshan and others said in the paper that compared with the two previous studies published in The Lancet, based on a larger sample size and cases recruited across the country, the fatality rate of new coronary pneumonia obtained by the latest study has become significantly lower (36.1%). When pilot data from Guangdong Province were included, the case fatality rate was lower (4.0%). This is because Guangdong has taken effective preventive measures, and early isolation, early diagnosis and early treatment may have contributed to a significant reduction in the case fatality rate of new coronary pneumonia in Guangdong Province [88].
■ Chen Zhengming, a well-known epidemiologist and tenured professor at Oxford University, was recently interviewed by Intellectual. Professor Chen pointed out that from the data released so far, after the new crown virus infection, the mortality level is significantly lower than SARS (but still significantly higher than the flu). In addition, children and adolescents have a lower risk of developing the disease, which may be associated with strong immunity. But the outbreak is more rapid and widespread, and has been classified by WHO as a global public health emergency. Regarding the reference value of various forecasting models, Professor Chen said that the prediction results of various models cannot be unbelieved, nor can we trust them all. Because modelling requires specific parameters and conditions, the estimation of many parameters may have large errors and uncertainties in the estimation of many parameters before the epidemic situation is fully understood, or after the implementation of high-intensity interventions, affecting the accuracy of the forecasts. Therefore, at all stages of the development of the epidemic, the forecast model should be regularly adjusted based on the data collected to provide the necessary scientific basis for the government's decision-making.
■ To judge the contagiousness and epidemic trend of a virus, an important parameter is the basic regeneration number (R4), that is, the number of people who can be infected by an infected person in the case of natural transmission of the virus (assuming no intervention, all people lack immunity).
■ In previous large-scale outbreaks caused by coronavirus, R0 values ranged from 0.2 to 0.4. If the initial R9 value of the epidemic is 0.4, about 0% of the virus transmission must be interrupted through various prevention and control measures such as isolation to prevent the continuous growth of the epidemic. In SARS in 75, the R2003 value during the initial outbreak was 0.2, and after a series of strong prevention and isolation measures, the R9 value quickly dropped to 0.0. For the epidemic caused by the new crown virus, the R4 value reported by domestic and foreign research teams is different, some are 0.2, some are estimated to be as high as 0.6, and the currently recognized R0 value is about 0.2, suggesting that without intervention, the number of infected people can double every six days or so. Regarding the specific criteria for the full lifting of the epidemic, Professor Chen said that from an epidemiological point of view, a common criterion for determining the complete end of a major epidemic is that after the last confirmed case is recovered and discharged from the hospital, there are no new cases within the two cycles of the longest incubation period of the virus infection. As far as this new crown pneumonia is concerned, if the incubation period is up to fifteen days, then no new cases appear one month after the last case is discharged, which can be regarded as the complete end of the epidemic.

Bibliography:

[1] Bao Y, Sun Y, Meng S, Shi J, Lu L. 2019-nCoV epidemic: address mental health care to empower society. The Lancet 2020.
[2] Wu et al., Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China, Cell Host & Microbe (2020)
[3] Favre G, Pomar L, Musso D, Baud D. 2019-nCoV epidemic: what about pregnancies? The Lancet 2020.
[4] Guan W-j, Ni Z-y, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv 2020:2020.02.06.20020974.

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