Monday, March 2, 2020

Not easy to investigate the earliest origin of SARS-CoV-2

Reporter : Shen Hui, Economic Daily
Ref : https://news.sina.com.cn/w/2020-02-29/doc-iimxxstf5398964.shtml
Translation, editing : Gan Yung Chyan
                                 / KUCINTA SETIA

Image : Courtesy of Sina.

As the disease COVID-19 (covid, in short) swept the world, a video "Taiwan programme traced the source of virus SARS-CoV-2 (covi, in short) to  the United States" went viral. In the programme, the main basis for the guests to determine the source of covi in the United States is a paper recently published by the Chinese Academy of Sciences Xishuangbanna Tropical Botanical Garden, South China Agricultural University, and the Beijing Brain Center on the ChinaXiv paper preprint website.

This paper, co-authored by Yu Wenbin and others from Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, collected genomic data of 93 novel coronavirus samples covering 12 countries on four continents (as of 12 February), and found that these 93 virus samples contained 58 haplotypes.

The reporter specially invited Zhao Xumao, a researcher at Lanzhou University focusing on climate change ecology and conservation biology research, to interpret the relevant information in this paper.

One important reason why the Taiwan TV programme traced the source of covi to the United States is that a haplotype H38 virus sample was found in the United States.

What is a haplotype? 

Zhao Xumao made an analogy,

"Just as a company can work effectively when multiple departments with different responsibilities cooperate with each other, the characteristics of the virus are also determined by many genes, and a single gene cannot function. These haplotypes are like separate departments. In short, haplotypes are combinations of genes that determine the same trait.

Moreover, in the paper, the haplotype evolution relationship shows that the haplotypes H13 and H38 are relatively "old" haplotypes, through an intermediate carrier-mv1 (may be an ancestral haplotype, or it may be from an intermediate host or "Patient Zero") is associated with bat coronavirus RaTG13, and haplotype H1 is derived from haplotype H3.

According to this haplotype evolution relationship, if we simply sort out, we can get the following two sets of schematic diagrams:

Mv1 → H13 → H3 → H1

Mv1 → H38 → H3 → H1

Covi is like a family business. The beginning was haplotype mv1. 38H38 and H13 are the first generation founders of the virus, we can call them grandpa haplotypes;

After H3 is the second generation of the virus, we can call it the parental haplotype;

3 H3, the grandson H1, is the third generation of the virus. It is this grandson H1 that made the virus unprecedentedly powerful.

H1 has derived great-grandchildren H56 and mv2 as the fourth generation head.

According to normal logic, the haplotype of the grandpa is the origin of the virus. However, the research team of the paper found that the patients who were associated with the Huanan Seafood Market had sample haplotypes of their grandchildren H1 and their descendants (that is, haplotypes H2, H8-H12), and the only Wuhan sample Haplotype H3, also known as the parental haplotype H3, has nothing to do with the seafood market.

According to this, combined with the patient's onset time record and population expansion time, the research team inferred that covid in the seafood market was introduced from other places and spread rapidly outside the market. In other words, the paper argues that Huanan Seafood Market is not the source of the virus."


Is the source of the virus and disease in the United States?

The study is not over yet. The research team traced the virus samples of two "old" haplotypes, that is, the grandpa haplotypes H13 and H38, and found that they were patients from Shenzhen (the first case in Guangdong) and one patient from Washington State (first case in the United States). Among them, the patient in the United States has the haplotype H38 virus sample mentioned in the Taiwan program.

Since the haplotypes of grandparents were found in Shenzhen and the United States, does this mean that Shenzhen and the United States are the birthplaces of covi?

Things are not as simple as imagined. Regarding the determination of the source of the virus, Zhang Wenhong, the leader of the Shanghai Covid Medical Treatment Expert Group and the director of the Department of Infectious Diseases, Huashan Hospital affiliated to Fudan University, said in an interview with relevant media:

"1. When did the virus first appear? Where did the disease first appear?

2. To find its position on the evolutionary tree, the evolution of the following genes is based on the front."

Zhao Xumao further analyzed,

"While tracking the infection time and activity trajectory of grandpa and haplotype H13 and H38 patients, the research team found that the travel records of the two patients showed that they should have been infected during the activity in Wuhan from the end of December 2019 to the beginning of January 2020. In other words, the research team believes that the two grandpa haplotypes H13 and H38 came from Wuhan.

In addition, Taiwan shows that the US virus contains 5 haplotype groups, so the show concluded that the United States is the origin of the virus. This shows that the United States has more ways to infect the virus, such as Wuhan, Australia, Shenzhen, etc." Zhao Xumao analyzed.

However, based on this paper, we cannot draw conclusions about the origin of covi in the United States.

According to genomic analysis, the origin of covi is not in the seafood market. Where the source is still needed to be followed up by relevant researchers, but according to the current relevant research, it should still be in Wuhan." 

In this case, why is there no “grandfather” haplotype detected in the existing Wuhan sample?

Xumao replied, "The research team believes that this may be because the existing samples were mainly collected from several designated hospitals, and the sample collection time was limited to 24 December 2019 and 5 January 2020."

According to Zhao Xumao, covi samples in Wuhan were collected late. As the virus evolves, its haplotypes continue to grow and its diversity continues to grow.  He analyzed, "Because the collection time is late in Wuhan, the haplotypes of the grandparents are likely to be replaced by the haplotypes of the parents and grandchildren."

In fact, regarding the limitations of this study, the author of the paper Yu Wenbin also stated in an interview that there is a shortcoming in this study. Among the 93 samples, the Wuhan sample is mainly early. If there are more samples collected and sequenced in Wuhan, more evidence may be found in traceability, such as the H13 and H38 haplotypes, which may help find the source of the virus.

Xumao analyzed, "The virus is constantly updated. According to the research report in this article, patients with the H38 haplotype in the United States have a history of travel during Wuhan and are inseparable from the Wuhan area. And the number of confirmed cases of the virus in the United States is relatively small. The virus spread is relatively slow, so the virus update is also slow, so it is not surprising to find the haplotypes of the grandpa. The most critical problem is that the sample size is too small and there are only 93 virus samples, and the sample collection time is late. The most important factor in the results." 

In view of this, the research team proposed that if these two haplotypes can be detected in early patients in other hospitals in Wuhan, it will be very helpful to find the source of the virus.

Why is Wuhan a major epicenter, while Guangdong, where grandpa haplotypes appeared earlier, is not? 

Zhao Xumao further analyzed, "First, the amount of virus that fell to Guangdong was relatively small. Second, relatively strict response measures were taken after local detection. In contrast, in Wuhan, the virus population is large, and more severe measures have not been taken in a timely and effective manner, which has led to more and more people being infected."

Did 12,000 people in the United States that died from influenza in 2019 actually died from covid?

In addition to this thesis of the Chinese Academy of Sciences, another basis for the guests on the Taiwan show to trace the source of covi to the United States is a piece of news about "12,000 deaths in the United States flu, many of which may have died from covid".

In this regard, Zhao Xumao believes that this kind of speculation without data basis is not credible. He said that although the clinical symptoms of covid and influenza are somewhat similar, both are RNA viruses. But these are two different viruses that are not related and that the flu and covid are detected differently.

"Humans have a long history of dealing with influenza viruses. The detection of influenza is far more mature than that of covid. Only a simple rapid nucleic acid amplification test for influenza can be used to judge it. Therefore, the possibility of misjudgment is unlikely. 

In fact, just on 28 February 2020, WHO experts said that the source of covi could not be determined at this time. Kokhov, technical director of the WHO health emergency project, said that there is still much work to be done to identify intermediate host animals that cause human infection with covid. There is no exact answer but active research is underway.

StayGate's Notes:
- Economic Daily is one of the major China Communist newspapers in Chinese.
- Zhao Xumao is a researcher of the State Key Laboratory of Grassland Agro-Ecosystem / Institute of Innovation Ecology, Lanzhou University. His research works can be found at ResearchGate, https://www.researchgate.net/scientific-contributions/2133309260_Xumao_Zhao.

Ref : China researchers : Wuhan Huanan Seafood Market is not the origin of COVID-19
https://staygate.blogspot.com/2020/02/china-researchers-wuhan-huanan-seafood.html

Xishuangbanna Tropical Botanical Garden traces the evolution and spread of SARS-CoV-2 based on genome-wide data
https://staygate.blogspot.com/2020/02/xishuangbanna-tropical-botanical-garden.html

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