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

1. COVID-19 Alert

■ On March 3, at a press conference held by the joint prevention and control mechanism of the State Council, Mi Feng, spokesperson of the National Health Commission and deputy director of the Department of Publicity, said: The daily new confirmed cases and new suspected cases in the country have remained in double digits for five consecutive days, except for Wuhan, there are 11 new local confirmed cases in the past five days, the epidemic situation has remained at a low level overall, and the prevention and control situation has continued to improve. However, the number of confirmed cases in Hubei and Wuhan is still large, the task of epidemic prevention and control is still arduous and heavy, and the rapid development of the epidemic abroad has brought uncertainty.

■ On March 3, the World Health Organization (WHO) announced that the epidemic of the new coronavirus can be described as "Pandemic". This means that the World Health Organization officially recognizes that the new coronavirus has entered a global pandemic state.

■ On March 3, the National Institute of Health Research, a subsidiary of the Korea Disease Management Headquarters, said on the same day that it had successfully synthesized a protein for recognizing antibodies to the new coronavirus. According to the National Health Research Institute of Korea, the protein can be used to extract neutralizing antibody-producing cells (B cells) from the blood of patients in the recovery stage, which helps form new coronavirus antibodies and is an indispensable part of the development of new coronavirus drug treatments. According to reports, the National Institute of Health of Korea will finalize the method of neutralization test after extracting multiple new coronavirus nucleoprotein antigens, and then evaluate the efficacy of the therapeutic agent. The institute has previously laid the foundation for the research and development of new coronavirus vaccines and preparations by developing therapeutic antibodies, exploring vaccine candidates, conducting clinical epidemiology, serum research, and expanding the scope of drug use, and jointly carried out research with academia and enterprises.

■ On March 3, the journal Nature published a news report titled "Labs rush to study coronavirus in transgenic animals — some are in short supply" that the number of new coronavirus infections worldwide has exceeded 9,11, and there is no sign that the epidemic is receding. Researchers are using animals to study COVID-19, such as monkeys, mice, and even ferrets, hoping to answer key questions about COVID-19 and accelerate the development of drugs and vaccines that can be pushed into clinical trials. At present, there are some results: the Chinese team has reported preliminary findings in monkeys and mice infected with the human ACE2 gene. And S. S. Smith, a virologist at the Australian Animal Health Laboratory. A team led by S. Vasan also had preliminary results, finding that ferrets are susceptible to the novel coronavirus. Researchers are currently studying routes of infection to later test potential vaccines. Ferrets are a common animal model for influenza and other respiratory illnesses because their lung physiology is similar to that of humans, and the researchers hope ferrets can mimic how COVID-19 is in the human body, such as how it spreads.

But no animal model is perfect. To find a better model that mimics severe infection in humans, researchers need to look at different animals and change other experimental factors, such as the way the virus enters the body. Monkeys and humans have similar immune systems, and they are useful for testing how the human body responds to viruses. Thomas Friedrich, a virologist at the University of Wisconsin-Madison, said there are signs that a person's autoimmune response may exacerbate certain illnesses, such as flu and SARS. Monkeys can help researchers determine if this is true for COVID-19. At the same time, many researchers trying to understand COVID-19 have set their sights on mice, the backbone of animal research, which they want to use to test drugs and vaccines and investigate the nature of the infection. The mice grown in Jackson's lab are called "human ACE2 (hACE2) mice" and were developed for the 2002-2003 SARS outbreak, and the causative virus of SARS is related to the new coronavirus. These animal models can help reveal how infections occur and help develop drugs and vaccines, but some animals are in short supply.

■ On March 3, Nature's daily briefing mentioned that a protein on the surface of the novel coronavirus may explain why it easily infects human cells. Coronaviruses use "spike protein" to infect cells. A handful of genetic and structural analyses have shown that the spike protein of the novel coronavirus is activated by an enzyme in a variety of human tissues, including the lung, liver and small intestine, meaning the virus has the potential to attack multiple organs and can explain some of the symptoms of infection. Other studies have shown that the spike protein binds to a specific receptor on human cells, known as angiotensin-converting enzyme (ACE9). Both results, while detected early, hint at potential treatments for the virus. (See:
■ On March 1, JAMA commented that in the early stages of the pandemic, COVID-3's ability to spread exceeded the testing capacity of the United States. The CDC's test differs in some ways from the one developed simultaneously by the Robert Koch Institute in Germany and adopted by the World Health Organization (WHO). However, as soon as the kit arrived, laboratories in many states experienced difficulties verifying the results; Some test results were found invalid because negative controls were invalid, and the root cause of these problems is still under investigation. Diagnostic testing is essential to effectively respond to the novel coronavirus. As the U.S. begins to make up for its initial missteps, new evidence should guide both policy and practice. The public health and medical professions should recognize the need for policy changes to adapt to changing circumstances, and should acknowledge that testing is also a double-edged sword. (See:

2. Progress in COVID-19 biology research

■ On March 3, SSRN released a research paper by the teams of Chen Yu, Lan Ke and Zhou Yu of the State Key Laboratory of Virology of Wuhan University, entitled "Transcriptomic Characteristics of Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells in COVID-9 Patients". The COVID-19 outbreak and epidemic that continues to spread in China and 75 other countries and regions poses a significant threat to public health. Limited understanding of the host immune response to this disease hampers efforts to effectively identify supportive therapies and treatments. To characterize the transcriptional signature of the host's inflammatory response to novel coronavirus infection, the joint team performed transcriptome sequencing on RNA extracted from bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cell (PBMC) samples from COVID-19 patients.

The results of the paper reveal the different host inflammatory cytokine profiles of patients infected with the novel coronavirus and the association between the onset of COVID-19 and the overrelease of cytokines such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. The timely release of these data can help researchers more accurately determine the inflammatory factors of macrophage and PBMC expression changes in the alveoli of COVID-19 patients, and this transcriptome dataset will provide support for clinical guidance of anti-inflammatory drugs and in-depth study of the molecular mechanism of host response. In addition, the dataset related to the paper has been uploaded to the website of the National Genomics Data Center with the serial number PRJCA002326 [1].

3. COVID-19 epidemiological studies

■ On March 3, the research team of the State Key Laboratory of Virology of Wuhan University published a research article entitled "Aerodynamic Characteristics and RNA Concentration of SARS-CoV-10 Aerosol in Wuhan Hospitals during COVID-2 Outbreak" on the preprint website bioRxiv. In a short period of time, multiple air sampling was completed for more than 19 representative monitoring points such as the intensive and general wards of Wuhan University People's Hospital, the wards and toilets of Wuchang Fangcang Hospital, residential communities and supermarkets, and the viral load and aerodynamic characteristics of the novel coronavirus at each sampling point were quantitatively analyzed through the high-sensitivity digital PCR technology developed by the laboratory. The results of this paper are the first to obtain environmental aerosol viral load data during the outbreak in Wuhan, and its results reveal:

1. The general safety of the public environment. Under the current situation of full protection and strict restrictions on the movement of personnel and vehicles in Wuhan, the number of virus copies per unit volume of air at each sampling point is extremely small or zero, and the virus copies contained in these aerosols may only be viral nucleic acid and not infectious, so under the premise of public attention to personal hygiene protection, environmental aerosols are likely not to cause disease transmission.

2. Indoor air ventilation and sanitize play an important role in preventing aerosol transmission. It is recommended to maintain and strengthen air circulation and sanitize measures in key areas for prevention and control such as hospital wards and public areas with a large flow of people such as supermarkets.

3. It is necessary to focus on preventing and controlling the formation of aerosols in hospital patients' toilets. Pay attention to strengthening the tightness of the toilet or toilet; Give priority to the use of flush toilets with lids, close the lid and flush; Avoid backwater, leakage, etc. in the sewers.

4. In a hospital environment, the formation of viruses and airborne dust particles after settling on the surface or ground may be one of the causes of aerosol formation. Measures such as paying attention to cleaning sanitize, reducing indoor dust, avoiding long-term accumulation of garbage, and keeping the ground dry and hygienic will effectively avoid the generation of aerosols caused by dust [2].

■ On March 2020, 3, researchers from Hokkaido University and other institutions published an article entitled "Ascertainment rate of novel coronavirus disease (COVID-10) in Japan" on the preprint platform medRxiv, which systematically reviewed the scientific literature and synthesized key data on the clinical features of COVID-19 from the initial outbreak to the pandemic.

The authors analyzed epidemiological data on confirmed COVID-2020 cases in Japan as of February 2, 28, and estimated the number of severe and non-severe cases. The authors note that the identification rate for non-severe cases is estimated at 19.0 (44% confidence interval, CI: 95.0, 37.0), suggesting that the actual number of non-severe cases is more than twice the number reported. Severe cases are twice as likely to be diagnosed and reported as others, but the adjusted total number of cases is approximately twice as high as the observed count, given that reported cases are typically predominantly non-severe cases [50].

■ On March 3, researchers from the School of Computer Science of South China Normal University published a paper "Prediction of COVID-10 Spreading Profiles in South Korea, Italy and Iran by Data-Driven Coding" on the preprint platform medRxiv. Based on collected COVID-19 transmission data from 367 cities in China and SEIR model parameters for each city, the study screened suitable datasets to predict the future development of epidemics in a specific population by comparing early outbreak data and complete historical data in that population. The results show that the peak of infection in South Korea, Italy, and Iran will occur before the end of March, with the proportion of infections in the population below 19.3%, 0.01%, and 0.05%, respectively[0].



[1] Xiong Y, Liu Y, Cao L, et al. Transcriptomic Characteristics of Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells in COVID-19 Patients. Available at SSRN 3549993 2020.
[2] Liu Y, Ning Z, Chen Y, et al. Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak. bioRxiv 2020:2020.03.08.982637.
[3] Omori R, Mizumoto K, Nishiura H. Ascertainment rate of novel coronavirus disease (COVID-19) in Japan. medRxiv 2020:2020.03.09.20033183.
[4] Zhan C, Tse CK, Lai Z, Hao T, Su J. Prediction of COVID-19 Spreading Profiles in South Korea, Italy and Iran by Data-Driven Coding. medRxiv 2020:2020.03.08.20032847.


Feed | Pingshan Biomedical R&D and Transformation Center, Scientific Research Department

Source | Virology, Nature Research, Lilac Garden, The Paper

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