Friday, March 27, 2020

Wuhan Outbreak (Feb-21): Where Is Patient Zero?

                          (Staff article from the BBC FUTURES on 21 February 2020.)

As the cases of coronavirus increase in China and around the world, the hunt is on to identify "patient zero". But can singling out one person as causing an outbreak do more harm than good? Chinese authorities and experts are at odds about the origin of the ongoing coronavirus outbreak. More specifically, who is "patient zero" for the outbreak.

Also known as an index case, patient zero is a term used to describe the first human infected by a viral or bacterial disease in an outbreak. Advances in genetic analysis now make it possible to trace back the lineage of a virus through those it has infected. Combined with epidemiological studies, scientists can pinpoint individuals who may have been the first people to start spreading the disease and so trigger the outbreak.

Identifying who these people are can help address crucial questions about how, when and why it started. These can then help to prevent more people from getting infected now or in future outbreaks. Do we know who patient zero is in the Covid-19 coronavirus outbreak that started in China? The short answer is – no.

Chinese authorities originally reported that the first coronavirus case was on 31 December and many of the first cases of the pneumonia-like infection were immediately connected to a seafood and animal market in Wuhan, in the Hubei province.

This region is the epicentre of the outbreak, with almost 82% of the 75,000-plus cases registered so far in China and globally are from here, according to statistics complied by Johns Hopkins University. (Read more about the global fight against coronavirus.)

However, a study, by Chinese researchers published in the Lancet medical journal, claimed the first person to be diagnosed with Covid-19, was on 1 December 2019 (a lot of earlier) and that person had "no contact" with the Huanan Seafood Wholesale Market.

Wu Wenjuan, a senior doctor at Wuhan's Jinyintan Hospital and one of the authors of the study, told the BBC Chinese Service that the patient was an elderly man who suffered from Alzheimer's disease. "He (the patient) lived four or five buses away from the seafood market, and because he was sick he basically didn't go out,” Wu Wenjuan said.

She also said that three other people developed symptoms in the following days – two of whom had no exposure to Huanan either. However, the researchers also found that 27 people of a sample of 41 patients admitted to hospital in the early stages of the outbreak "had been exposed to the market".

The hypothesis that the outbreak started at the market and could have been transmitted from a living animal to a human host before spreading human-to-human is still considered the most likely, according to the World Health Organization (WHO).

(Blogger's notes: Some Chinese I know used to joke that one can't even fart in Communist China without local Party bosses knowing it. Is it believable that the Chinese Communist Party still does not know who and where the patient zero of the Wuhan Virus Outbreak is? Rumours and innuendos are the natural weapons of the oppressed to counter the blatant concealment and outright lies of the oppressive ruling class.)
Following research paper is written by two Chinese scientists and published in mid February. But they later withdrew, under pressure from Chinese Communist Party, from the publication.

The Possible Origins of 2019-nCoV Coronavirus

The possible origins of 2019-nCoV coronavirus by Botao Xiao1,2* and Lei Xiao3: 

1 Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China  
2 School of Physics, Huazhong University of Science and Technology, Wuhan 430074, China
3 Tian You Hospital, Wuhan University of Science and Technology, Wuhan 430064, China 
* Corresponding author: Tel / Fax: 86-20-3938-0631             

The 2019-nCoV coronavirus has caused an epidemic of 28,060 laboratory-confirmed infections in human including 564 deaths in China by February 6, 2020. Two descriptions of  the  virus published  on  Nature  this week  indicated that  the  genome  sequences  from patients were  96%  or 89% identical to the  Bat  CoV ZC45 coronavirus originally found in Rhinolophus affinis 1,2.

It was critical to study where the pathogen came  from and how it passed onto human. An article published on The Lancet reported that 41 people in Wuhan were found  to have the acute respiratory syndrome and 27 of them  had  contact  with  Huanan  Seafood Market 3.

The 2019-nCoV was found in 33 out of 585 samples collected in the market after the outbreak. The market was suspicious to be  the origin of the epidemic, and  was  shut down according to the rule of quarantine the source during an epidemic.  

The bats carrying  CoV  ZC45  were originally  found  in Yunnan or Zhejiang province, both of  which were more than 900 kilometers away  from  the seafood market. Bats were normally found to live in caves and trees. But the seafood market is in a densely-populated district of Wuhan, a metropolitan of ~15 million people. The probability was very low for the bats to fly to the market.

According to municipal reports and the testimonies of 31 residents and 28 visitors, the bat was never a food source in the city, and no bat was traded in the market. There was possible natural recombination or intermediate host of the coronavirus, yet little proof has been reported.   Was there  any  other  possible  pathway? 

We  screened the  area  around the  seafood market and identified two laboratories conducting research on bat coronavirus. Within ~280 meters  from  the  market,  there  was  the  Wuhan  Center  for  Disease  Control  &  Prevention (WHCDC) (Figure  from Baidu and Google maps). 

WHCDC hosted animals in laboratories for research purpose, one of which was specialized in pathogens collection and identification 4-6.  In  one  of  their  studies,  155  bats  including  Rhinolophus affinis were  captured  in  Hubei province, and other 450 bats were captured in Zhejiang province 4. The expert in  collection was noted in the Author Contributions (JHT).

Moreover, he was broadcasted for collecting viruses on nation-wide newspapers and websites in 2017 and 2019 7,8. He described that he was once  attacked  by  bats and  the blood of  a  bat  shot on  his skin.  He  knew  the extreme danger of the infection so he quarantined himself for 14 days 7.

In another accident, he quarantined himself again because bats peed on him. He was once thrilled for capturing a bat carrying a live tick 8.   Surgery was performed on the caged animals and the tissue samples were collected for DNA and RNA extraction and sequencing 4, 5. The tissue samples and contaminated trashes were  source  of  pathogens.

They  were  only  ~280  meters  from  the  seafood  market.  The WHCDC was also adjacent to the Union Hospital where the first group of doctors  were infected during this  epidemic. It is plausible  that the virus leaked around and some of them contaminated the  initial  patients  in  this  epidemic,  though  solid  proofs are needed in future study.  

The second laboratory was ~12 kilometers from the seafood market and belonged to Wuhan Institute of Virology, Chinese Academy of Sciences 1, 9, 10. This laboratory reported that the Chinese horseshoe bats were natural reservoirs for the severe acute respiratory syndrome coronavirus (SARS-CoV) which caused the 2002-3 pandemic 9.

The principle investigator participated in a project which generated a chimeric virus using the SARS-CoV reverse genetics system, and reported the potential for human emergence 10. A direct speculation was that SARS-CoV or its derivative might leak from the laboratory.

In summary, somebody was entangled with the evolution of 2019-nCoV coronavirus. In addition to origins of natural recombination and intermediate host, the killer coronavirus probably originated from a laboratory in Wuhan. Safety level may need to be reinforced in high  risk  biohazardous  laboratories. Regulations  may  be  taken  to  relocate  these laboratories far away from city center and other densely populated places.  

Contributors BX designed the comment and performed literature search. All authors performed data acquisition and analysis, collected documents, draw the figure, and wrote the papers.  
Acknowledgements This work is supported by the National Natural Science Foundation of China (11772133, 11372116).  
Declaration of interests: All authors declare no competing interests. 


1.  Zhou  P,  Yang  X-L,  Wang  X-G,  et  al.  A  pneumonia  outbreak  associated  with  a  new coronavirus of probable bat origin. Nature 2020.
2.  Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020.
3.  Huang  C,  Wang  Y,  Li  X,  et  al.  Clinical  features  of  patients  infected  with  2019  novel coronavirus  in  Wuhan,  China.  The Lancet  2019. 5.
4.  Guo WP, Lin XD, Wang W, et al. Phylogeny and origins of hantaviruses harbored by bats, insectivores, and rodents. PLoS pathogens 2013; 9(2): e1003159.
5.  Lu M, Tian JH, Yu B, Guo WP, Holmes EC, Zhang YZ. Extensive diversity of rickettsiales bacteria in ticks from Wuhan, China. Ticks and tick-borne diseases 2017; 8(4): 574-80.
6.  Shi M, Lin XD, Chen X, et al. The evolutionary history of vertebrate RNA viruses. Nature 2018; 556(7700): 197-202.
7.  Tao P. Expert in Wuhan collected ten thousands animals: capture bats in mountain at night. Changjiang Times 2017.
8.  Li QX, Zhanyao. Playing with elephant dung, fishing for sea bottom mud: the work that will change China's future. thepaper 2019.
9.  Ge XY, Li JL, Yang XL, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 2013; 503(7477): 535-8. 10.  Menachery  VD,  Yount  BL,  Jr.,  Debbink  K, et  al. A  SARS-like  cluster of  circulating  bat coronaviruses shows potential for human emergence. Nature medicine 2015; 21(12): 1508-13.