New coronavirus threat galvanizes scientists

New coronavirus threat galvanizes scientists. The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by the novel coronavirus 2019‐nCoV probably came from wildlife animals, more than 9720 cases of the infection, and 213 deaths. the distance between Hefei and Wuhan is 345km, only four hours drive. Most Chinese thought that china CDC(Chinese center for disease control and prevention) made wrong decision, caused public misunderstanding of disease(2019‐nCoV ) hazards and governments delayed to take actions.
Deeply think. The Relationship between Us and Wildlife Animals Means Our Future.
The 6380 km splendid Yangtze River is the largest river in China and the third longest in the world surpassed by the Nile in Africa and the Amazon in South America. There is no fish to be caught in the Yangtze River. The giant Chinese paddlefish (up to 7m in length) was found to be extinct.
Due to the impact of rotten catch, agricultural irrigation, chemical fertilizers and pesticides pollution, ponds and ditches are easily dried up and most aquatic animals of ponds and ditches are also disappeared in Jianghuai Hilly area. The traditional forest is replaced by the economic forest and landscape forest, natural growth becomes artificial management, and animals living in the traditional forest are completely disappeared, wolves and foxes have disappeared in the Jianghuai Hilly Area. The cities expand faster and faster, and the high-speed railways and highways encroach on the living space of wild animals. Wild animals are becoming sicker, rarer, more expensive and welcome.
More and more rats live in the larger and larger underground space, dark, humid and rotten food make the rats more easy to carry virus came from wildlife animals, complex electromagnetic, chemical toxic substances and noise make the virus more easily mutated.The intermediate host probably is rats.
Most of the servicers at wildlife animals market under dim lights and worst sanitation in China work for more than 70 hours a week, they are tired for a long time and have poor immunity to the virus.
The relationship between us and wildlife animals means our future brightness or darkness, the nature of minds is being changed.

Reference
1. Ewen Callaway & David Cyranoski, New China virus: Five questions scientists are asking, doi: 10.1038/d41586-020-00166-6
2. EDITORIAL, Stop the Wuhan virus, 21 January 2020, doi: 10.1038/d41586-020-00153-x
3. An Outbreak of NCIP (2019-nCoV) Infection in China — Wuhan, Hubei Province, 2019−2020, CCDC Weekly / Vol. 2 / No. 5

Jon Cohen presented a very helpful account of the current efforts of the scientific community to understand and control the current coronavirus outbreak. He ends observing that "With luck, however, the outbreak will fade by summer, and with it the urgency of having a vaccine at the ready." Our planet, however, has two hemispheres and when summer starts in one, winter starts in the other. So keep working hard on the vaccine, millions of people may need it anyway.

Author: Liu, Yang *, M.D.
Department of Cardiology, the Tumor Hospital of Harbin Medical University
*Address for correspondence (Liu, Yang): Department of Cardiology, The Tumor Hospital, Harbin Medical University, Haping road 150#, Nangang District, Harbin 150081, Heilongjiang Province, China. Tel: +86-451-86298000; Mobile phome: +86-13009726899; Fax: +86-451-86663760. E-mail address at: [email protected]
At present, the pneumonia outbreak in China is a public health emergency of international concern. 9692 cases were confirmed infection of novel coronavirus on the Chinese mainland as of 24:00 on Jan 30 in 2020, 213 deaths out of the 9692 cases, 102427 suspected cases under medical observation according to the report of National Health Commission of the People's Republic of China. However, susceptible population and the pathogenesis are still unclear. In some cases with existing chronic diseases as cardiovascular diseases, chronic obstructive pulmonary diseases, metabolic diseases even pulmonary carcinoma, the virus may cause more serious threat among these cases than health population, which are also key factors determining the prognosis of infected cases.
Regarding the virus pathogeny, several recent evidences point the finger of renin-angiotensin system (RAS), and the angiotension converting enzyme (ACE) II gene, which highly expressed in type II alveolar epithelial cells, was considered the gateway of virus invading into the human body. (1,2) An recent online published article entitled "Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission" described the origin of new coronavirus, and this study further revealed the interaction between spike protein and ACE II protein in human transfection. (3) To our knowledge, lung is the main organ under attack, if lung cancer patients have a high expression level of ACE II gene, they will seem more susceptible to novel coronavirus. With this question, the author screened the expression profile of ACE II gene in patients with lung adenocarcinoma and lung squamous cell carcinoma. An online TCGA database based web tool was used (Available at: http://ualcan.path.uab. edu/index.html) for sample comparison. The results manifested that among patients with lung adenocarcinoma, a higher expression level of ACE II gene was observed in primary tumor samples (n=515) than normal samples (n=59) (Median 1.334 vs 1.154, P=2.162e-08). Moreover, patients characterized the aged (61-80Yrs (n=149), 81-100Yrs (n=32) vs Normal (n=59): Median 1.589, 1.645 vs 1.154; P=2.288e-06, 9.718e-03)), race (Asian (n=8) vs Normal (n=59): Median 6.137 vs 1.154, P=4.568e-02)),stages (Stage 1(n=277), Stage 2 (n=125), Stage 3(n=85) vs Normal (n=59): Median 1.307, 1.31, 1.407 vs 1.154; P=1.813e-10, 1.256e-03, 2.484e-03)) and nodal metastasis status (N0 (n=331), N1(n=96), N2 (n=74) vs Normal (n=59)): Median1.263, 1.333, 1.53 vs 1.154; P= 1.613e-11, 4.940e-02, 2.465e-03)) appeared a higher expression level of ACE II gene. For patients with lung squamous cell carcinoma, patients characterized the aged (61-80Yrs (n=361) vs Normal (n=52): Median 1.268 vs 1.261, P=2.557e-06)), stage(stage 1 (n=243) vs Normal (n=52): Median 1.307 vs 1.261, P=1.706e-05)) and nodal metastasis status (N3 (n=5) vs Normal (n=52): Median 1.633 vs 1.261, P=4.7e-02)) presented a higher expression level of ACE II gene. These results suggest that enhanced expression of ACE II gene exists among patients with lung cancer. Although the role of ACE II protein/gene in the pathophysiological process of 2019-nCoV infection needs follow-up investigation, these previous evidences suggest that more attention should be paid to patients with lung cancer due to the possible added susceptibility. The issues should also be mentioned in the control plan of new coronavirus.
Acknowledgements: I thank the Professor Zhang, zhiren, the leader of cardio-oncology team in the Affiliated Tumor Hospital of Harbin Medical University
1. Yu Zhao, Zixian Zhao, Yujia Wang, Yueqing Zhou, Yu Ma, Wei Zuo. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv doi: https://doi.org/10.1101/2020.01. 26.919985 (2020)
2. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE II protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 203:631-617. doi: 10.1002/path.1570 (2004)
3. Xintian Xu, Ping Chen, Jingfang Wang, Jiannan Feng, Hui Zhou, Xuan Li, Wu Zhong,Pei Hao. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. SCIENCE CHINA Life Sciences, https://doi.org/10.1007/s11427-020-1637-5 (2020)

Author: Yang Liu*, M.D.
Author details
Yang Liu*, Department of Cardiology, The Tumor Hospital of Harbin Medical University, Harbin Heilongjiang Province 150001, China. E-mail addresses: [email protected]
*Address for correspondence (Yang Liu): Department of Cardiology, The Tumor Hospital, Harbin Medical University, Haping road 150#, Nangang District, Harbin 150081, Heilongjiang Province, China. Tel: +86-451-86298000; Mobile phome: +86-13009726899; Fax: +86-451-86663760. E-mail address at: [email protected]
New coronavirus outbreak in Wuhan has been focused widely. The prevention and control work is extremely severe due to lack of effective drugs. Scientists are trying to understand the pathogenesis of the virus and screen effective antiviral drugs in China. In the past few days, clinical trials of remdesivir and chloroquine with potential value for fighting 2019-nCoV were in progress. (1) These two drugs are expected to play an important role in the treatment of infected cases. Bypass these achievements, exploring the prevention and treatment of the virus from the perspective of immunology may provide us with new therapeutic approaches
Regarding the 2019-novel coronavirus, little is known about the pathogenesis of the virus. In general viral infected cases, the ability of autoimmunity constitutes the first line of defense against the virus, and it is also the core factor which determines the prognosis of infected patients. Many of the principles and experiences we have learned in the viral system are applicable to tumor immunity, because cancer is highly similar to infectious disease environment, and chronic antigen stimulation leads to T cell depletion. For example, in the case of chronic viral infection, blocking programmed death 1 (PD-1) is enough to enhance the activity of depleted T cells, allowing the virus to be eliminated. (2)The phenomenon was reported by Guihot et al in a patient treated with nivolumab for lung cancer, and a drastic decrease of the HIV reservoir was observed. (3) Conversely, it may be an important reason for the virus to evade the recognition of the host' lymphocytes if the virus expresses programmed cell death1 (PD1) and programmed cell death-Ligand 1 (PDL1) like gene fragments.
The author preliminarily screened and compared the updated 2019-nCoV encoding gene sequence, which generally updated by Wu, F et al in Shanghai Public Health Clinical Center&School of Public Health in Fudan University and Shared by global research institutions. (Available at PubMed: NC_045512.2), and immune checkpoint related encoding gene sequences of Homo sapiens. All immune checkpoint-associated gene sequences were available at PubMed: BC074984.2, HQ258151.1, BC069381.1, BC113736.1, BC113734.1, DQ286582.1, KJ893692.1, DQ836393.1, NC_000009.12 and NC_000009.11 for CD274/PDL1; NC_000002.12 and NC_000002.11 for cytotoxic T lymphocyte-associated antigen-4 (CD152/CTLA-4); NC_000002.12, NG_012110.1 and NC_000002.11 (PD1/PDCD1). Furtherly, a FASTA format of these sequences was used to construct phylogenetic trees. I found some similar gene sequences appeared in 2019-nCoV and homo PDCD1/CD274 genes at a certain frequency, and the origin of 2019-nCoV and homo immune checkpoint gene sequences are similar with a genetic similarity above fifty-five percent, as fifty-five percent for PDCD1 gene and fifty-six percent for CD274 gene respectively. Based on these clues and medical immunology theory, I infer that the functional structures similar to PD1/PDL1 may exist in the 2019-nCoV, which may be one of the reasons why the 2019-nCoV with a certain incubation period evades the host immune responses. The author introduces that immune checkpoints as PD1/PDL1 may be potential targets for fighting 2019-nCoV.
Acknowledgements: I thank the Professor Zhang, zhiren, the leader of cardio-oncology team in the Affiliated Tumor Hospital of Harbin Medical University
REFERENCES
1. Manli Wang, Ruiyuan Cao, Leike Zhang, Xinglou Yang, Jia Liu, Mingyue Xu, Zhengli Shi, Zhi hong Hu,Wu Zhong&Gengfu Xiao. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research 0,1-3 (2020) https://doi.org/10.1038/s41422-020-0282-0
2. Spencer C. Wei, Colm R. Duffy and James P. Allison. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov 8, 1-18 (2018) doi: 10.1158/2159-8290.CD-18-0367
3. Amélie Guihot, Anne-Geneviève Marcelin, Marie-Ange Massiani, Assia Samri, Cathia Soulié, Brigitte Autran, Jean-Philippe Spano., Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer. Ann Oncol 29, 517-518 (2018) doi: 10.1093/annonc/mdx696

In his article that "New Coronovirus threat galvanizes scientists," Joh Cohen highlighted the difficulty in obtaining accurate estimate of the number of infected people since the virus has spread at alarming rate in the past few weeks. Equally difficult is the estimate for the death toll attributed to this deadly new strain of coronovirus at the epicenter of this outbreak in Wuhan, China.

Accurate death toll calculation of the Wuhan coronavirus is critical to assessing the threat of the new disease to public health, which may help relevant authorities to take measures to contain the disease more rationally and proportionally. The current daily death toll published by the Chinese government is based on perished patients with confirmed diagnosis of the coronavirus infection by PCR tests. This approach works when the cases are few and the medical service is adequate to perform most necessary examinations. However, this model of statistics may fail significantly in the case of Wuhan, China, where the medical system is now simply overwhelmed. Individual activists attempted to balance the Chinese government statistics with anecdotal observations and reporting. Their efforts show bravery and heart breaking drama, but lacked the scientific discipline to generate meaningful data.

Here I introduce a simple formula to calculate the death toll of the coronavirus infection:

SC = SB - SA

Where SC is the daily death toll to be reported which is mostly likely related to the new disease, SB is the total number of death counted during the day, and SA is the average daily death toll in the whole year immediately before the outbreak of the disease.

The use of SC in compliment to the current model of reporting Corona virus infection related death rate avoids the bias caused by the inadequacy of diagnostic resources.

My proposed formula for counting the coronavirus death toll in Wuhan, China is as simple as doing algebra with A, B, C. It may be used to assess the risk of any novel causes of death, not necessarily associated with a particular virus or disease, in a region where a natural or man made disaster with overwhelming societal disruptions. One caveat would be that caution must be excised to eliminate any other significant cause of death that may come to play concurrently during a particular time period of interest. This new formula may also inadvertently include deaths caused by heightened psychological stress with or without the virus being actually present in the body of the patients. The novel coronavirus may simply kill with fear alone in the absence of data that inspire public confidence.

By Feb 24 2020, the novel coronavirus (2019-nCoV) outbreak in China caused more than 74,000 people infected and 2,100 died (1). Outside China, nearly 900 infected individuals also have been reported. Coronaviruses are RNA viruses that have been in co-existence with human and many other creatures for millions of years (2). Usually, these coronaviruses are quietly parasitic in the bodies of original hosts (3). Game consumption and the 2019 novel coronavirus.), including human beings, monkeys, orangutans, cats, dogs, pigs, tigers, lions, bears etc, without causing severe harm. However, under some extreme circumstances like trans-species intimate interaction or virus mutation, the coronavirus will be transmitted from original host to human beings and become infectious and fatal in humans (4).
Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two infectious coronaviruses which had caused severe respiratory epidemics and was likely to be passed from bats through respectively masked civets and camels and then to humans (5, 6). Similarly, Current scientific findings suggested that the 2019-nCoV (also officially termed as SARS-CoV-2 by International Committee on Taxonomy of Viruses) was probably transmitted from wild animals sold in the Wuhan Huanan Seafood Market (7). It has caused wide-ranging criticism on the illegal trade of wild animals, the food taste for exotic meat, and even the wet markets as the breeding ground for the virus (8). Several questions emerged: why does game consumption still exist in modern China despite farmed animal products are already sufficient? Why do some Chinese regard wild meat as good and healthy? What are the food ethics underlying this eating habit?
Food ethics in Chinese context can be summarized as "Tian-Ren-He-Yi", literally meaning "nature-human unity." In terms of eating practice, this signifies that "nature and human body are materially shared when they meet as eaten and eating." Tian-Ren-He-Yi requires people to subordinate themselves to the laws of nature, so as to form a reciprocal relationship between nature and human. For thousands of years, Tian-Ren-He-Yi had been an integral principle for Chinese food consumption for thousands of years. As modern lifestyle continuously separate human (Ren) from the place and nature (Tian) sustaining them, the Tian-Ren-He-Yi discourse has been challenged, which further encouraged wild meat consumption. This is manifested in three aspects:
First, consuming wild meat is a sign of body-centered food ethics. The original emphasis of Tian-Ren-He-Yi is on the reciprocal relationship between nature and human but now it is mis-interpreted as a body-centered domination of nature. Game consumption demonstrated this shift: by classifying certain animal products as yang or yin substance (both are concepts in Chinese medicine that means food with warm or cold property), it turns out that all wild animals can be beneficial to human health and are at the disposal of human. Consumer of wild meat, regardless of their motivations, typically care neither about the origin nor the process of production. Few concerned people merely use this information to predict the taste and quality. Also, consumers perceive certain healing effects of wild meat, such as animal's eyes good for human's eyesight and animal's penis tonifying yang qi. Based on a crude link between animal appearance and its function, these perceptions drive human to satisfy their corporeal and imaginative needs at the expense of other creatures' lives.
Second, consuming wild meat transcend the boundary between nature and human. Traditionally, Tian-Ren-He-Yi prescribed that "we are where we eat", meaning human should acquire food ingredients from their immediate environment. The term "immediate" emphasized the boundary set by nature, which delimits what is edible and what is not in particular cultural context. Adhering to such boundary, ancient human avoided dangerous food-matter and survived in the nature. This boundary, however. has been continuously overstepped by consuming wild animals in modern era. Bats and Chinese pangolin were traditionally excluded from Chinese everyday menus, but modern technique such as farm-raising wild animals and online mukbang convince that consuming the wild meat is safe and healthy, which in turn facilitate the encroachment of the boundary. Such transgression blurs the boundary between edible and inedible, human and nature; consequently, it invites a boomerang by nature, namely the 2019 novel coronavirus.
Third, justifying wild meat consumption by traditional culture is fundamentally static and conservative. Tian-Ren-He-Yi originally requires human to adjust themselves to the environment, which implies a dynamic relation between human and nature. However, some consumers enact this principle rigidly and superficially, claiming eating wild meat a tradition inherited from their ancestors. They believe that wild meat is natural and authentic as it has been testified by their ancestors. It has not been widely realized that actually wild animals hunted from some "natural" habitats where severe pollution prevails become deadly risky. Without taking the effects of natural environmental changes into consideration, any food practices simply following prior generations are fundamentally conservative.
In addition, Since the outbreak of 2019-nCoV, numerous western media reports have attributed this simply to the wet markets (9, 10), and thus urged for abolishing all wet markets in China. Within these reports, Chinese "omnivorous" wet markets were consciously depicted as unregulated, out of order, full of exotic foodstuffs that are aesthetically and culturally unacceptable for western eaters (9). Through such depiction, these medias present an image that all Chinese wet markets are disgusting and dangerous, while without acknowledging that a variety of wet markets exist in China and most of them do not sell exotic foodstuffs. Such misrepresentations are typical orientalism stigma of China, by referring to western ideas of what is edible and what is good to eat, they implicitly prioritize western food ethics over Chinese's. To prevent coronaviruses, while it is necessary to shuttle down wet markets temporarily and ban wild animal trade, it is still no need to overturn traditional wisdom and local knowledge to embrace western approach.
What is needed is to recognize the above mis-interpretations of Chinese traditional food ethics, to take a progressive understanding of food ethics and respect the boundary between nature and human, in so doing to re-shift to a reciprocal relationship between human and nature. Only in this way can human live in harmony with other creatures in the nature.