News attention



27

2020

-

02

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


1. COVID-19 Alert

■ COVID-19 urgently needs specific therapeutic drugs. Although the use of plasma treatment for convalescent patients has achieved initial results, large-scale use is limited. The actual therapeutic effect in the plasma of convalescent patients is virus-specific neutralizing antibodies. The preparation of high-purity fully human neutralizing antibodies can provide safer, more efficient and large-scale applicable treatments, providing new approaches for antibody therapy, short-term prevention, and point-of-care detection. However, the preparation of neutralizing antibodies for clinical use with the strongest specificity and highest safety requires screening among a large number of candidate antibodies, which takes a long time.

In order to greatly accelerate the screening speed of clinical neutralizing antibodies, the team of Xiaoliang Xie of the Biomedical Frontier Innovation Center (BIOPIC) of Peking University proposed a method of high-throughput single-cell sequencing of B cells in the blood of convalescent patients, constructed an overall experimental protocol and jointly researched with multiple units. Since February 2, Youan Hospital has collected blood samples from 9 convalescent patients for B-cell single-cell sorting. Subsequently, the Peking University team conducted single-cell RNA library construction and sequencing analysis, and detected a total of 12,14 IgG antibody sequences in 3,1 B cells, and selected 5 IgG antibodies with the highest enrichment. These antibodies have been produced by Beijing Yiqiao Shenzhou Technology Co., Ltd. for in vitro antibody expression. Current enzyme-linked immunosorbent (ELISA) tests utilizing recombinant viral proteins have screened antibodies that specifically bind to viral surface S proteins and RBD proteins at the nM level. In vitro cell live virus binding and neutralization experiments are ongoing.

At present, the cooperative team is committed to using the screened antibodies for the treatment of neutralizing antibodies for new coronary pneumonia, and it is expected to become a safer and more targeted treatment after follow-up animal experiments and clinical verification. At the same time, clinically validated neutralizing antibodies can also be used for short-term prophylaxis, which is expected to provide short-term immune protection for medical staff and patients' families (about 3 weeks). Not only that, the strongest antibody is also being used to develop rapid and accurate viral antigen detection kits, which are expected to provide solutions for large-scale epidemic prevention and control.

There are a large number of antibodies generated by the rearrangement of the VDJ gene of B cells in recovered patients, and the specific protein sequence of the antibody must be extracted with the help of single-cell cloning or single-cell sequencing. Conventional B-cell single-cell cloning technology takes a long time, while direct single-cell VDJ sequencing of B cells takes only two days, which greatly accelerates the development of neutralizing antibodies for clinical use. The immune system of the recovered patients has selected the best neutralizing antibodies that bind specifically to the virus, and cloned and enriched the corresponding B cells. The higher the enrichment of clonal types, the greater the likelihood that their antibodies will be used clinically. The unique advantage of single-cell VDJ sequencing is that it can quickly provide clonal enrichment and corresponding antibody coding sequences.
■ On February 2, the team of academician Wang Chen of Peking Union Medical College published an online commentary article entitled "COVID-24 control in China during mass population movements at New Year" at The Lancet, which pointed out that government policies developed during the Chinese New Year holiday help reduce the spread of the virus by reducing contact and increasing physical distancing. Despite the COVID-19 pandemic, China's robust and multifaceted response may have averted a more serious scenario. As travel and work slowly resume in China, China should consider at least partial continuation of these policies to ensure that the COVID-19 outbreak is sustainably contained.

In addition, there are some lessons to be drawn from China's extended Lunar New Year holiday: first, in countries where COVID-19 may spread or similar outbreaks in the future, outbreak control "holidays" or closures (i.e., periods when non-essential workplaces and public institutions are recommended or enforced) should be introduced as front-line social distancing measures to reduce the speed of transmission; Second, governments should design outbreak control closures based on the specific epidemiological characteristics of new diseases, such as incubation periods and transmission routes; Third, the main goal of the epidemic control closure period is to prevent the spread of disease by asymptomatic infected people. Therefore, governments should maximize their impact in information and education campaigns, community screening, proactive contact tracing, and quarantine. As for COVID-19 in China, the combination of outbreak intervals and social distancing appears to prevent new infections, especially in provinces other than Hubei, where new infections are decreasing for more than 2 weeks. Despite the COVID-19 pandemic, China's robust and multifaceted response may have averted a more serious situation[1].

2. Advances in biological research on COVID-19

■ On February 2, a research team from the National Institutes of Health published the latest research results in the journal Nature Microbiology entitled "Functional assessment of cell entry and receptor usage for SARS-CoV-24 and other lineage B betacoronaviruses". The paper reports a rapid and efficient method to detect the ability of class B β coronaviruses, including novel coronaviruses [2-nCoV], to infect cells of different species using receptors. Studies have shown that the processing of host proteases is an important barrier for several lineage B viruses during the virus entering the host, and bypassing this barrier allows several lineage B viruses to enter human cells through unknown receptors. In addition, the study demonstrated how different class B β coronaviruses recombine to enter human cells, and at the same time, further confirmed that human ACE2019 is a receptor for 2-nCoV. Lack of sequence information about the virus in the early stages of a virus outbreak can hinder virus detection. The research has developed an efficient platform for large-scale monitoring of the zoonotic potential of the virus in question, which will help to better respond to the next possible outbreak of novel virus [2019].

3. Epidemiological studies of COVID-19

On February 2, Wu Zunyou of the Chinese Center for Disease Control and Prevention and others published an online report entitled "Characteristics of and Important Lessons From the Coronavirus Disease 24 (COVID-2019) Outbreak in" online in The Journal of the American Medical Association China" opinion review article. The clinical characteristics of 19,72314 patients with new coronary pneumonia in China and the current epidemic prevention and anti-epidemic measures are summarized, aiming to look forward to measures to further interrupt the spread of the epidemic and provide experience reference for countries that are also caught in the disaster of new crown pneumonia.

1. Epidemiological characteristics of 72314,1 new coronary pneumonia cases, 2% were asymptomatic infections, fatality rate was 3.2%:
the total mortality rate of new coronary pneumonia was 3.9%, which was age-related. There were no deaths among infants aged 70 years and younger, with a mortality rate of 79.8% for adults aged 0-80 years and 14.8% for 10 years and older. Deaths are concentrated in critical cases, and mild cases do not die. The mortality rate of patients with new coronary pneumonia with underlying medical conditions was increased, with 5.7% in patients with cardiovascular disease, 3.6% in diabetes, 3.6% in chronic respiratory diseases, 0.5% in hypertension and 6.<>% in cancer. In the early stage, the infected population base was mainly accumulated through zoonotic transmission in the Huanan Seafood Market, and in the later stage, large-scale rapid outbreaks were mainly achieved through human-to-human transmission.

2. COVID-19 vs. SARS and MERS:

The outbreak of the new crown pneumonia is similar to the two previous human coronavirus infection events, SARS and MERS. The origin of the three is similar, starting from the zoonotic development of the coronavirus; The symptoms are similar, all manifested as fever and cough, and the blessing of advanced age and underlying diseases makes patients more likely to develop pneumonia with a poor prognosis; Diagnosis is similar, with a throat swab to confirm viral infection, but clinical diagnosis usually relies on exposure history, symptoms, and lung imaging.
In terms of severity, although SARS and MERS mortality rates were higher (SARS: 8096 infections, 774 deaths; MERS: At present, it has not been effectively controlled, there have been 2494 infections and 858 deaths), but the total number of deaths due to more people being infected has exceeded SARS and MERS.

3. Measures taken in response to the coronavirus outbreak:

In the case of clarifying that there are no effective drugs and vaccines for the new crown virus, the most traditional and simple public health strategies are used to implement isolation and epidemic prevention measures from all dimensions of individuals, families, communities, provinces and cities [3].

■ On February 2, Yu Hongjie of Fudan University and others conducted an epidemiological analysis of 23,8579 new coronary pneumonia cases outside Hubei Province in the medical preprint journal medRxiv. A feature of this work is that the development of the epidemic is divided into two phases, the first before January 1 and the second between January 27 and February 1, according to changes in diagnostic criteria, the implementation of relevant epidemic prevention policies, and changes in population vigilance and living habits. It mainly has the following characteristics:

1. The median age of these cases is 44 years, with an increase in the proportion of younger cases (less than 18 years) and older cases (more than 64 years) as the outbreak progresses; 2. Shortened length of time from symptomatic to visit and hospital stay for patients in the second stage;

3. The average incubation period of new coronary pneumonia is 5.2 days (95% confidence interval 1.8-12.4 days), and the interval between cases is 5.1 days (here refers to the time interval between the onset of two cases with infection and infection; 95% confidence interval 1.3-11.6 days);
4. After the end of January, transmission slowed in most areas. Combined with the change in the number of cases and the interval between cases, it was inferred from Bayesian that the regeneration index Rt fell below 1 at the end of January in most areas, although there were large differences between regions.

From the above data, it can be seen that the interval between new coronary pneumonia cases is less than the incubation period, which also suggests that there is a possibility of incubation infection of new coronary pneumonia [4].

■ Zhou Hua's team from the Department of Respiratory Medicine of the First Affiliated Hospital of Zhejiang University published an article in the preprint journal Preprint, showing the diagnosis and treatment process of three patients with mild new coronavirus infection with a history of travel to Wuhan, and found that the swab nucleic acid of two of them continued to be positive after the throat swab nucleic acid test turned negative. One case lasted for 5 days and the other exceeded 14 days. This suggests that in some patients, after clearance of respiratory virus, it is still possible to excrete the virus through the digestive tract and serve as a source of transmission. The existence of fecal-oral transmission was demonstrated during the SARS outbreak, where the virus can enter the sewer system through feces to form aerosols that spread within the corridors, causing great public safety risks. In this study, two patients tested positive for swabs after the nasopharyngeal swab test turned negative, with a delay of up to 2 weeks. Therefore, close monitoring of viral nucleic acid in the feces or swabs of patients infected with Covid-2 should be used as an important indicator of treatment and observation. In addition, proper handling of stool specimens is imperative [19].

 

Bibliography:

[1] Chen S, Yang J, Yang W, Wang C, Bärnighausen T. COVID-19 control in China during mass population movements at New Year. The Lancet.

[2] Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiology 2020.

[3] 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.

[4] Zhang J, Litvinova M, Wang W, et al. Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study. medRxiv 2020:2020.02.21.20026328.

[5] Yilin HU LS, Zheming XU, Jianying ZHOU, Hua ZHOU. SARS-CoV-2 May Persist in Digestive Tract Longer than Respiratory Tract. Preprint 2020;2020020354.

 

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

Edit | Bao la