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Frontiers of Medicine

  • Cover Illustration

    2020, Vol.14  No.2

    Back to the spring of 2020. Sakura garden of East Lake, Wuhan, 2019. (Courtesy of Mr. Zhenyin Chen. See pages 113‒116 by Guangbiao Zhou et al. for more information.)

    Table of Contents

, Volume 14 Issue 2

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EDITORIAL
Back to the spring of 2020: facts and hope of COVID-19 outbreak
Guangbiao Zhou, Saijuan Chen, Zhu Chen
Front. Med.. 2020, 14 (2): 113-116.  https://doi.org/10.1007/s11684-020-0758-9
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REVIEW
Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies
Guangbiao Zhou, Saijuan Chen, Zhu Chen
Front. Med.. 2020, 14 (2): 117-125.  https://doi.org/10.1007/s11684-020-0773-x
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Since the outbreak of the COVID-19 pandemic in early December 2019, 81 174 confirmed cases and 3242 deaths have been reported in China as of March 19, 2020. The Chinese people and government have contributed huge efforts to combat this disease, resulting in significant improvement of the situation, with 58 new cases (34 were imported cases) and 11 new deaths reported on March 19, 2020. However, as of March 19, 2020, the COVID-19 pandemic continues to develop in 167 countries/territories outside of China, and 128 665 confirmed cases and 5536 deaths have been reported, with 16 498 new cases and 817 new deaths occurring in last 24 hours. Therefore, the world should work together to fight against this pandemic. Here, we review the recent advances in COVID-19, including the insights in the virus, the responses of the host cells, the cytokine release syndrome, and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm. By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis, we believe that the community can efficiently develop effective vaccines and drugs, and the mankind will eventually win this battle against this pandemic.

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Coronavirus disease 2019 (COVID-19): a clinical update
Min Zhou, Xinxin Zhang, Jieming Qu
Front. Med.. 2020, 14 (2): 126-135.  https://doi.org/10.1007/s11684-020-0767-8
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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials.

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Molecular network-based intervention brings us closer to ending the HIV pandemic
Xiaoxu Han, Bin Zhao, Minghui An, Ping Zhong, Hong Shang
Front. Med.. 2020, 14 (2): 136-148.  https://doi.org/10.1007/s11684-020-0756-y
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Precise identification of HIV transmission among populations is a key step in public health responses. However, the HIV transmission network is usually difficult to determine. HIV molecular networks can be determined by phylogenetic approach, genetic distance-based approach, and a combination of both approaches. These approaches are increasingly used to identify transmission networks among populations, reconstruct the history of HIV spread, monitor the dynamics of HIV transmission, guide targeted intervention on key subpopulations, and assess the effects of interventions. Simulation and retrospective studies have demonstrated that these molecular network-based interventions are more cost-effective than random or traditional interventions. However, we still need to address several challenges to improve the practice of molecular network-guided targeting interventions to finally end the HIV epidemic. The data remain limited or difficult to obtain, and more automatic real-time tools are required. In addition, molecular and social networks must be combined, and technical parameters and ethnic issues warrant further studies.

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Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in hemagglutinin globular head
Yulu Wang, Dan Hu, Yanling Wu, Tianlei Ying
Front. Med.. 2020, 14 (2): 149-159.  https://doi.org/10.1007/s11684-020-0764-y
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Influenza causes seasonal outbreaks yearly and unpredictable pandemics with high morbidity and mortality rates. Despite significant efforts to address influenza, it remains a major threat to human public health. This issue is partially due to the lack of antiviral drugs with potent antiviral activity and broad reactivity against all influenza virus strains and the rapid emergence of drug-resistant variants. Moreover, designing a universal influenza vaccine that is sufficiently immunogenic to induce universal antibodies is difficult. Some novel epitopes hidden in the hemagglutinin (HA) trimeric interface have been discovered recently, and a number of antibodies targeting these epitopes have been found to be capable of neutralizing a broad range of influenza isolates. These findings may have important implications for the development of universal influenza vaccines and antiviral drugs. In this review, we focused on the antibodies targeting these newly discovered epitopes in the HA domain of the influenza virus to promote the development of universal anti-influenza antibodies or vaccines and extend the discovery to other viruses with similar conformational changes in envelope proteins.

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Development of oncolytic virotherapy: from genetic modification to combination therapy
Qiaoshuai Lan, Shuai Xia, Qian Wang, Wei Xu, Haiyan Huang, Shibo Jiang, Lu Lu
Front. Med.. 2020, 14 (2): 160-184.  https://doi.org/10.1007/s11684-020-0750-4
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Oncolytic virotherapy (OVT) is a novel form of immunotherapy using natural or genetically modified viruses to selectively replicate in and kill malignant cells. Many genetically modified oncolytic viruses (OVs) with enhanced tumor targeting, antitumor efficacy, and safety have been generated, and some of which have been assessed in clinical trials. Combining OVT with other immunotherapies can remarkably enhance the antitumor efficacy. In this work, we review the use of wild-type viruses in OVT and the strategies for OV genetic modification. We also review and discuss the combinations of OVT with other immunotherapies.

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RESEARCH ARTICLE
Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection
Xin Zou, Ke Chen, Jiawei Zou, Peiyi Han, Jie Hao, Zeguang Han
Front. Med.. 2020, 14 (2): 185-192.  https://doi.org/10.1007/s11684-020-0754-0
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It has been known that, the novel coronavirus, 2019-nCoV, which is considered similar to SARS-CoV, invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.

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Clinical characteristics of 19 neonates born to mothers with COVID-19
Wei Liu, Jing Wang, Wenbin Li, Zhaoxian Zhou, Siying Liu, Zhihui Rong
Front. Med.. 2020, 14 (2): 193-198.  https://doi.org/10.1007/s11684-020-0772-y
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The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2 infected mothers and increase the current knowledge on the perinatal consequences of COVID-19. Nineteen neonates were admitted to Tongji Hospital from January 31 to February 29, 2020. Their mothers were clinically diagnosed or laboratory-confirmed with COVID-19. We prospectively collected and analyzed data of mothers and infants. There are 19 neonates included in the research. Among them, 10 mothers were confirmed COVID-19 by positive SARS-CoV-2 RT-PCR in throat swab, and 9 mothers were clinically diagnosed with COVID-19. Delivery occurred in an isolation room and neonates were immediately separated from the mothers and isolated for at least 14 days. No fetal distress was found. Gestational age of the neonates was 38.6±1.5 weeks, and average birth weight was 3293±425 g. SARS-CoV-2 RT-PCR in throat swab, urine, and feces of all neonates were negative. SARS-CoV-2 RT-PCR in breast milk and amniotic fluid was negative too. None of the neonates developed clinical, radiologic, hematologic, or biochemical evidence of COVID-19. No vertical transmission of SARS-CoV-2 and no perinatal complications in the third trimester were found in our study. The delivery should occur in isolation and neonates should be separated from the infected mothers and care givers.

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Phase- and epidemic region-adjusted estimation of the number of coronavirus disease 2019 cases in China
Ruijie Chang, Huwen Wang, Shuxian Zhang, Zezhou Wang, Yinqiao Dong, Lhakpa Tsamlag, Xiaoyue Yu, Chen Xu, Yuelin Yu, Rusi Long, Ning-Ning Liu, Qiao Chu, Ying Wang, Gang Xu, Tian Shen, Suping Wang, Xiaobei Deng, Jinyan Huang, Xinxin Zhang, Hui Wang, Yong Cai
Front. Med.. 2020, 14 (2): 199-209.  https://doi.org/10.1007/s11684-020-0768-7
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The outbreak of the coronavirus disease 2019 in China was first reported in Wuhan in December 2019 and gradually spread to other areas in China. After implementation of prevention and control measures, the estimation of the epidemic trend is needed. A phase- and region-adjusted SEIR model was applied for modeling and predicting the number of cases in Wuhan, Hubei Province and regions outside Hubei Province in China. The estimated number of infections could reach its peak in late February 2020 in Wuhan and Hubei Province, which is 55 303–84 520 and 83 944–129 312, respectively, while the epidemic peaks in regions outside Hubei Province in China could appear on February 13, 2020 with the estimated 13 035–19 108 cases. According to the estimation, the outbreak would abate in March and April all over China. Current estimation provided evidence for planned work resumption under stringent prevention and control in China to further support the fight against the epidemic. Nevertheless, there is still possibility of the second outbreak brought by the work resumption and population migration, especially from Hubei Province and high intensity cities outside Hubei Province. Strict prevention and control measures still need to be considered in the regions with high intensity of epidemic and densely-populated cities.

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CASE REPORT
Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19
Li Ni, Ling Zhou, Min Zhou, Jianping Zhao, Dao Wen Wang
Front. Med.. 2020, 14 (2): 210-214.  https://doi.org/10.1007/s11684-020-0757-x
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In December 2019, an outbreak of novel coronavirus (2019-nCoV) occurred in Wuhan, Hubei Province, China. By February 14, 2020, it has led to 66 492 confirmed patients in China and high mortality up to ~2.96% (1123/37 914) in Wuhan. Here we report the first family case of coronavirus disease 2019 (COVID-19) confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid (SHL). This report describes the identification, diagnosis, clinical course, and management of three cases from a family, suggests the expected therapeutic effects of SHL on COVID-19, and warrants further clinical trials.

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COMMENTARY
COVID-19 containment: China provides important lessons for global response
Shuxian Zhang, Zezhou Wang, Ruijie Chang, Huwen Wang, Chen Xu, Xiaoyue Yu, Lhakpa Tsamlag, Yinqiao Dong, Hui Wang, Yong Cai
Front. Med.. 2020, 14 (2): 215-219.  https://doi.org/10.1007/s11684-020-0766-9
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The world must act fast to contain wider international spread of the epidemic of COVID-19 now. The unprecedented public health efforts in China have contained the spread of this new virus. Measures taken in China are currently proven to reduce human-to-human transmission successfully. We summarized the effective intervention and prevention measures in the fields of public health response, clinical management, and research development in China, which may provide vital lessons for the global response. It is really important to take collaborative actions now to save more lives from the pandemic of COVID-19.

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China’s local governments are combating COVID-19 with unprecedented responses ---- from a Wenzhou governance perspective
Fanghua Gong, Yong Xiong, Jian Xiao, Li Lin, Xiaodong Liu, Dezhong Wang, Xiaokun Li
Front. Med.. 2020, 14 (2): 220-224.  https://doi.org/10.1007/s11684-020-0755-z
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The COVID-19 caused by a novel strain of coronavirus has been spreading rapidly since its occurrence in December 2019. It is highly communicable through human-to-human transmission. China has been making unprecedented efforts in treating the confirmed cases, identifying and isolating their close contacts and suspected cases to control the source of infection and cut the route of transmission. China’s devotion in handling this epidemic has effectively and efficiently curbed communication domestically and across the border. Representative measures adopted by Wenzhou, the worst hit city out of Hubei Province, are examined to elucidate those massive undertakings with the aim of enhancing international understanding and building global rapport in fighting this evolving epidemic situation.

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2019 novel coronavirus outbreak: a quiz or final exam?
Jiuyang Xu, Yijun Chen, Hao Chen, Bin Cao
Front. Med.. 2020, 14 (2): 225-228.  https://doi.org/10.1007/s11684-020-0753-1
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The 2019 novel coronavirus (2019-nCoV) is an emerging pathogen and is threatening the global health. Strikingly, more than 28 000 cases and 550 deaths have been reported within two months from disease emergence. Armed with experience from previous epidemics in the last two decades, clinicians, scientists, officials, and citizens in China are all contributing to the prevention of further 2019-nCoV transmission. Efficient preliminary work has enabled us to understand the basic characteristics of 2019-nCoV, but there are still many unanswered questions. It is too early now to judge our performance in this outbreak. Continuous and strengthened efforts should be made not only during the epidemic, but also afterwards in order to prepare for any incoming challenges.

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Protecting healthcare personnel from 2019-nCoV infection risks: lessons and suggestions
Zhiruo Zhang, Shelan Liu, Mi Xiang, Shijian Li, Dahai Zhao, Chaolin Huang, Saijuan Chen
Front. Med.. 2020, 14 (2): 229-231.  https://doi.org/10.1007/s11684-020-0765-x
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The outbreak of a novel coronavirus disease (COVID-19, caused by the 2019-nCoV infection) in December 2019 is one of the most severe public health emergencies since the founding of People’s Republic of China in 1949. Healthcare personnel (HCP) nationwide are facing heavy workloads and high risk of infection, especially those who care for patients in Hubei Province. Sadly, as of February 20, 2020, over two thousand COVID-19 cases are confirmed among HCP from 476 hospitals nationwide, with nearly 90% of them from Hubei Province. Based on literature search and interviews with some HCP working at Wuhan, capital city of Hubei, we have summarized some of the effective measures taken to reduce infection among HCP, and also made suggestions for improving occupational safety during an infectious disease outbreak. The experience and lessons learned should be a valuable asset for international health community to contain the ongoing COVID-19 epidemic around the world.

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CONSENSUS
Organ function support in patients with coronavirus disease 2019: Tongji experience
Yong Li, Fan He, Ning Zhou, Jia Wei, Zeyang Ding, Luyun Wang, Peng Chen, Shuiming Guo, Binhao Zhang, Xiaoning Wan, Wei Zhu, on behalf of Multidisciplinary Team for COVID-19, Optical Valley Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Front. Med.. 2020, 14 (2): 232-248.  https://doi.org/10.1007/s11684-020-0774-9
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Coronavirus disease 2019 (COVID-19) is a highly contagious disease and a serious threat to human health. COVID-19 can cause multiple organ dysfunction, such as respiratory and circulatory failure, liver and kidney injury, disseminated intravascular coagulation, and thromboembolism, and even death. The World Health Organization reports that the mortality rate of severe-type COVID-19 is over 50%. Currently, the number of severe cases worldwide has increased rapidly, but the experience in the treatment of infected patients is still limited. Given the lack of specific antiviral drugs, multi-organ function support treatment is important for patients with COVID-19. To improve the cure rate and reduce the mortality of patients with severe- and critical-type COVID-19, this paper summarizes the experience of organ function support in patients with severe- and critical-type COVID-19 in Optical Valley Branch of Tongji Hospital, Wuhan, China. This paper systematically summarizes the procedures of functional support therapies for multiple organs and systems, including respiratory, circulatory, renal, hepatic, and hematological systems, among patients with severe- and critical-type COVID-19. This paper provides a clinical reference and a new strategy for the optimal treatment of COVID-19 worldwide.

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PERSPECTIVE
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