WIV: Prevention of New Disease X and Investigation of the Origin of COVID-19

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WIV: Prevention of New Disease X and Investigation of the Origin of COVID-19

Wuhan Institute of Virology (WIV) Shi Zhengli Team: Prevention of New Disease X and Investigation of the Origin of COVID-19

Since the beginning of the 21st century, Severe Acute Respiratory Syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) have posed significant threats to global public health.

On April 2, 2024, the team led by Shi Zhengli from the Wuhan Institute of Virology, Chinese Academy of Sciences, published a review article in the journal Frontiers of Medicine titled “Emergence of SARS and COVID-19 and preparedness for the next emerging disease X.” The article reviews the origins of SARS and COVID-19, discusses the potential ancestors of SARS-CoV-2, the discovery of SARS-CoV-2-like viruses in wildlife, and how to prepare for future novel coronavirus outbreaks.

WIV: Prevention of New Disease X and Investigation of the Origin of COVID-19

Emergence of SARS and COVID-19 In the past 50 years, the frequency and number of Emerging Infectious Diseases (EIDs) have rapidly increased globally, with over 70% being zoonotic diseases. SARS-CoV and SARS-CoV-2 are two of the three EID events caused by coronaviruses in the past 20 years.

SARS-CoV appeared in late November 2002 in Guangdong Province, China, and spread to 29 countries and regions in the following three months. COVID-19, on the other hand, is the most serious EID in the past 100 years, affecting not only public health but also global economy, human behavior, culture, and politics.

Animal Origin of SARS-CoV After the SARS outbreak, epidemiological data showed that most early cases had direct or indirect contact with wildlife. Scientists collected samples from wildlife markets and farms, finding that SARS-CoV had been circulating in market animals for some time and had infected some animal traders before the SARS outbreak.

However, it was not until 8 years later that scientists found the closest ancestor of SARS-CoV in the Rhinolophus species in Yunnan Province.

Outbreak and Early Spread of COVID-19 in Wuhan The outbreak of COVID-19 was initially discovered at the Huanan Seafood Wholesale Market in Wuhan, China, at the end of December 2019. Many cases in the weeks before the outbreak were associated with this market, including vendors and dealers. However, retrospective studies have shown that the number of early cases associated with other markets was similar to that of the Huanan market.

It is worth noting that the earliest reported case with an onset date of December 8 had no connection to the Huanan market. Additionally, 44.6% of cases with onset in December had no history of market exposure.

Potential Transmission Chain of SARS-CoV-2 The genomic characteristics of SARS-CoV-2 suggest a close relationship with coronaviruses from Rhinolophus bats. However, unlike SARS-CoV, the direct human infection source of SARS-CoV-2 is still unclear. Extensive testing of SARS-CoV-2 in environmental and animal product samples collected from the market was conducted after its closure.

Out of more than 400 animal-related samples, including frozen farmed wildlife carcasses from the market and items in warehouses, none tested positive for SARS-CoV-2 RNA.

Detection of SARS-CoV-2 in Cold Chain Products SARS-CoV-2 can survive and remain infectious on the surface of frozen food (such as meat) and its outer packaging under cold chain transportation conditions for a long time. Several sporadic recurrences of COVID-19 from April to October 2020 in several cities in China, including Beijing, Dalian, and Qingdao, were likely due to exposure to imported frozen food and food packaging contaminated with SARS-CoV-2.

Detection of Archived Samples Outside China Before the SARS-CoV-2 Outbreak Although Wuhan was where COVID-19 was first observed and reported, different studies have also described evidence of SARS-CoV-2 appearing earlier outside China.

SARS-CoV-2 RNA was found in sewage samples collected in March 2019 in Spain and November 2019 in Brazil; SARS-CoV-2 reactivity was detected in a skin biopsy sample from an Italian woman collected in November 2019 using in situ hybridization; seroprevalence studies in France and Italy showed a high prevalence of neutralizing antibodies against SARS-CoV-2 before December 2019.

Animals Susceptible to SARS-CoV-2 As concerns about the host range of SARS-CoV-2 increase, especially considering reported reverse zoonotic events, i.e., transmission from humans to animals.

The first report of natural infection of animals by SARS-CoV-2 appeared in Hong Kong, showing that 2 out of 15 dogs from COVID-19 confirmed owners tested positive for SARS-CoV-2 PCR. Subsequent reports also showed similar cases of infected dogs.

Animals Sensitive to SARS-CoV-2 Detected by in Vitro Receptor Usage Analysis In addition to natural and experimental infections with SARS-CoV-2, protein-protein interaction analysis and pseudovirus entry assays have also been used to predict the host range of SARS-CoV-2.

Results are consistent with the observations above, showing that SARS-CoV-2 can infect a wide range of animals, including primates, lagomorphs, carnivores, perissodactyls, squamates, and artiodactyls.

Detection of SARS-CoV-2-Like Viruses in Wildlife Since early 2020, the search for ancestors of SARS-CoV-2 has led to the discovery of an increasing number of SARS-CoV-2-like coronaviruses in various Rhinolophus species in China and Southeast Asian countries, including Thailand, Cambodia, and Laos.

These bat coronaviruses share a genomic sequence identity with SARS-CoV-2 of mostly over 91%.

Hypotheses on the Emergence of SARS-CoV-2 Although we still cannot clearly depict how SARS-CoV-2 emerged, hypotheses can be made based on what we know. The close relationship of SARS-CoV-2 with its most recent ancestors in bat hosts represents decades of evolution, suggesting a lack of a more direct ancestor in unknown intermediate hosts.

The ancestor of SARS-CoV-2 may have spilled over to intermediate hosts first, spread in the populations of these hosts, acquired mutations that made it more adapted to humans, evolved into a precursor of a pandemic virus, and then spread to humans.

SARSr-CoVs Can Utilize Human ACE2 in Wildlife and Have Potential Spillover Risk The binding of the virus to the cell surface receptor is the initial and critical step for successful infection and interspecies transmission. SARSr-CoVs exhibit high diversity in the spike protein responsible for receptor binding and virus entry. They can be divided into two main groups based on comparison with the spike protein RBD of SARS-CoV.

Strategies for Preparedness for the Next Disease X Caused by SARSr-CoVs As SARSr-CoVs can utilize human and animal ACE2, indicating potential public health risks, it is necessary to prepare in advance for the prevention and control of future EIDs caused by these viruses. Given the uncertainty of mutation emergence and the appearance of future novel coronaviruses, efforts should be strengthened to develop universal diagnostic methods, pan-vaccines, and broad-spectrum antiviral drugs.

In conclusion, the origin and evolution of SARS-CoV-2 are complex processes involving various wildlife and human activities. To address future potential novel coronavirus outbreaks, we need to strengthen monitoring, research, and prevention measures. Through interdisciplinary and international cooperation, we can better understand the transmission pathways of these viruses and take measures to reduce their impact on human society.

Was COVID virus leaked from the lab of Wuhan Institute of Virology?

The origins of COVID-19 are still under investigation, and whether it leaked from the Wuhan Institute of Virology (WIV) is one theory that has not been proven. Here’s a breakdown of the situation:

Lab Leak Theory: This theory suggests the virus accidentally escaped from the WIV, where Shi Zhengli’s team studies coronaviruses. However, there’s no evidence that the WIV had the virus before the pandemic or that a leak occurred.
Arguments Against Lab Leak: Critics of the theory point out that such leaks are rare, and there’s no evidence of lax safety protocols at the WIV. Additionally, similar viruses haven’t been found in the lab’s collection.
Zoonotic Spillover Considered More Likely: Most scientists believe the virus jumped from animals to humans, possibly through an intermediary animal sold at a wet market. This aligns with past outbreaks like SARS.

Here are some resources for further reading:

Wikipedia article on the COVID-19 lab leak theory: COVID-19 lab leak theory: [Wikipedia COVID-19 lab leak theory]
Science Magazine article featuring Shi Zhengli’s response to the lab leak theory: Trump ‘owes us an apology’: [Trump owes us an apology Chinese scientist at the center of COVID 19 origin theories speaks out]

News about COVID-19 lab leak from the Wuhan Institute of Virology (WIV)

There have been reports about a possible COVID-19 lab leak from the Wuhan Institute of Virology (WIV). Here’s a breakdown:

US Intelligence Report: In 2023, the US Department of Energy concluded with “low confidence” that the virus likely originated from a Wuhan lab. This is based on new, classified intelligence, but details haven’t been made public [National Geographic article about the report can be found by searching “Did COVID-19 come from a Chinese lab? Why a new U.S. report is renewing questions”].
WHO Investigation: The World Health Organization (WHO) investigated the origins of COVID-19 in 2021. While they didn’t rule out a lab leak entirely, their initial report concluded it was most likely a zoonotic spillover (from animals to humans). However, some scientists criticized the WHO investigation for limited access in China [Nature article about the WHO investigation can be found by searching for “The COVID lab-leak hypothesis: what scientists do and don’t know”].
Political Debate: The lab leak theory has become politicized, with some calling for a more thorough investigation into the WIV. Others argue there’s no concrete evidence and focus on the zoonotic origin theory.

It’s important to note that currently, there’s no definitive proof for the lab leak theory. More investigation is needed to determine the exact origins of COVID-19.

WIV: Prevention of New Disease X and Investigation of the Origin of COVID-19

Reference: Hu, B., Guo, H., Si, H.et al. Emergence of SARS and COVID-19 and preparedness for the next emerging disease X. Front. Med. 18, 1–18 (2024). https://doi.org/10.1007/s11684-024-1066-6

(source:internet, reference only)

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