Showing posts sorted by relevance for query SARS. Sort by date Show all posts
Showing posts sorted by relevance for query SARS. Sort by date Show all posts

Tuesday, July 26, 2022

Study unveils first global dataset for SARS-CoV-2 infections in animals


Structured data on the virus in animals is essential to further our understanding of the COVID-19 pandemic and mitigate its spread at the human-animal interface, according to the authors of the paper published in Scientific Data


Peer-Reviewed Publication

COMPLEXITY SCIENCE HUB VIENNA

SARS-CoV-2 variants 

IMAGE: THE DIAGRAM SHOWS THE SARS-COV-2 VARIANTS IDENTIFIED IN THE DIFFERENT ANIMAL HOSTS. THE FIGURE DESCRIBES THE NUMBER OF EVENTS (ONE EVENT MAY INCLUDE ONE OR MORE CASES). view more 

CREDIT: NERPEL, A., YANG, L., SORGER, J. ET AL.

[Vienna, July 2022] In a pioneering initiative, a multidisciplinary Austrian team created the most comprehensive global dataset of SARS-CoV-2 infections in animals. Their findings were published Saturday, July 23, in the journal Scientific Data and the epidemiological information is available on a dashboard at https://vis.csh.ac.at/sars-ani/

“There was an urgent need for a global dataset on SARS-CoV-2 events in animals that can be easily imported, processed, and analyzed,” says Amélie Desvars-Larrive, the principal investigator of the study and a researcher at the Complexity Science Hub Vienna (CSH).

The initiative intends to facilitate One Health approaches on SARS-CoV-2. The idea is to create a collaborative approach that recognizes the interdependence of human, animal, and environmental health to obtain optimal health for all. 

“To tackle major threats to human health, we need integrated approaches,” points out Desvars-Larrive. “Although animals do not appear to play a significant role in the spread of COVID-19 among people currently, One Health tools that enable the integrative analysis and visualization of SARS-CoV-2 events are critical.” 

Two major animal health databases

For the past months, Desvars-Larrive and her team meticulously extracted, combined, and structured information on SARS-CoV-2 cases in animals. They included publicly available data from two major animal health databases: the Program for Monitoring Emerging Diseases (ProMED), a reporting system of the International Society for Infectious Diseases; and the World Animal Health Information System (WAHIS) of the World Organisation for Animal Health.

The unified dataset, called SARS-ANI, feeds a dashboard, which includes an overview of SARS-CoV-2 events in animals worldwide, stratified by species; clinical signs that were allegedly associated with the disease; control measures and outcomes; and a geographical overview of all events. The dashboard is linked to the live dataset available on GitHub.

Answers to current questions

The dataset can help answering some of the many questions regarding SARS-CoV-2 in animals, according to the authors. It shows, for instance, that the number of reported SARS-CoV-2 cases in animals is steadily increasing worldwide. A total of 704 events (one event can include one or more cases that are epidemiologically related) have been reported in 39 countries, across 27 animal species (as of July 25, 2022).

In addition, the team described a high diversity of SARS-CoV-2 variants in the animal hosts, especially in American mink and white-tailed deer. These variants show similarities with human variants. In terms of animal case fatality rates, they are relatively low.

An essential tool

Also, the dataset can be useful for estimating the impact of SARS-CoV-2 on pets, farm animals, wildlife, and conservation programs. In addition, scientists and policymakers can use it to develop guidelines for prevention, risk-based surveillance, and response to SARS-CoV-2.

“We believe the SARS-ANI dataset, with timely and reliable information, can assist in the development of national and international regulations and agreements aiming to reduce the risk of transmission at the human-animal interfaces,” declares Desvars-Larrive, who is also a professor in infection epidemiology at the University of Veterinary Medicine Vienna. 

The dataset – a joint effort by experts from CSH, University of Veterinary Medicine Vienna, and Wildlife Conservation Society – will be updated weekly for at least one year. “We also hope to receive new data from researchers around the world to develop it further and expand its use”, says Desvars-Larrive.

  

CAPTION

The SARS-ANI dashboard gives an easy-to-understand overview of specific aspects of SARS-CoV-2 events in animals and is publicly accessible at https://vis.csh.ac.at/sars-ani/

CREDIT

Nerpel, A., Yang, L., Sorger, J. et al.

The study SARS-ANI: a global open access dataset of reported SARS-CoV-2 events in animals by Afra Nerpel, Liuhuaying Yang, Johannes Sorger, Annemarie Käsbohrer, Chris Walzer, and Amélie Desvars-Larrive appeared in Scientific Data 9 (438) (2022). 

The SARS-ANI dashboard gives an easy-to-understand overview of specific aspects of SARS-CoV-2 events in animals and is publicly accessible at https://vis.csh.ac.at/sars-ani/


About CSH 

The mission of Complexity Science Hub Vienna is to host, educate, and inspire complex systems scientists dedicated to making sense of Big Data to boost science and society. Scientists at the Hub develop methods for the scientific, quantitative, and predictive understanding of complex systems.

The CSH is a joint initiative of AIT Austrian Institute of Technology, Central European University CEU, Danube University Krems, Graz University of Technology, IIASA, Medical University of Vienna, TU Wien, VetMedUni Vienna, Vienna University of Economics and Business, and Austrian Economic Chambers (WKO). 

https://www.csh.ac.at

 

Sunday, April 05, 2020

Clues to COVID-19 coronavirus's vulnerability emerge from an antibody against SARS

Clues to COVID-19 coronavirus's vulnerability emerge from an antibody against SARS
Antibody CR3022 bound to the receptor binding domain of SARS2-CoV-2. Credit: Meng Yuan and Nicholas Wu
An antibody recovered from a survivor of the SARS epidemic in the early 2000s has revealed a potential vulnerability of the new coronavirus at the root of COVID-19, according to a study from scientists at Scripps Research.
The study, published today in Science, is the first to map a human antibody's interaction with the new  at near-atomic-scale resolution. Although the antibody was produced in response to an infection of SARS (severe acute respiratory syndrome), which is caused by the SARS-CoV , it cross-reacts with the new coronavirus, SARS-CoV-2.
The structural mapping revealed a nearly identical site on both coronaviruses to which the antibody binds, suggesting a functionally important and vulnerable site for this family of coronaviruses.
"The knowledge of conserved sites like this can aid in structure-based design of vaccines and therapeutics against SARS-CoV-2, and these would also protect against other coronaviruses—including those that may emerge in the future," says the study's senior author Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research.
SARS-CoV, which causes SARS, originated in horseshoe bats, but jumped to humans in South China in 2002, eventually infecting more than 8,000 people and killing almost 800 before it was quelled by lockdowns, quarantines and other measures.
SARS-CoV-2, a closely related coronavirus that causes COVID-19, first emerged in the Chinese city of Wuhan in late 2019. Much more infectious than its viral cousin, it has led to a pandemic, causing far more cases of illness and fatalities than SARS. The development of a vaccine or even an effective treatment could significantly ameliorate the crisis.
The Wilson lab is known for its pioneering structural studies of  bound to viruses including HIV and influenza. These studies have been used to inform designs of vaccines and antibody drugs, as well as other therapeutics. Along with hundreds of other labs around the world, Wilson's team is now focused on SARS-CoV-2.
"Our ultimate goal here is to obtain structural information on antibodies and their binding sites, and use that to guide SARS-CoV-2 vaccine design, just as our lab has done with influenza and HIV," says the study's co-first author Nicholas Wu, Ph.D., a postdoctoral research associate in the Wilson lab.
The new study centers on an anti-SARS-CoV antibody called CR3022 that was originally isolated in 2006 by the pharmaceutical company Crucell Holland B.V. in the Netherlands. A report from Chinese scientists earlier this year indicated that CR3022 cross-reacts against SARS-CoV-2. Wilson's team used their structural mapping expertise to determine how the antibody binds to SARS-CoV-2.
A key finding is that the antibody's binding site is highly similar between the two coronaviruses—differing by just four protein building blocks called amino-acids. That high degree of similarity implies that the site has an important function that would be lost if it mutated significantly.
Yet, the site's function remains mysterious. The Scripps Research analysis found that the antibody binding site is relatively remote from the part of the virus that grabs hold of cell-surface protein receptors in preparation for penetrating cells in our lungs. That suggests that, at least for SARS-CoV, CR3002 neutralizes the virus's ability to infect cells in some indirect way.
Adding to the mystery is the finding that the antibody binding site on these viruses is not normally accessible to antibodies.
"We found that this region is usually hidden inside the virus, and only exposed when that part of the virus changes its structure, as it would in natural infection," says co-first author Meng Yuan, Ph.D., also a research associate in the Wilson lab.
Despite the slightness of difference between the two coronaviruses, the antibody binds much less tightly to SARS-CoV-2 than it does to the SARS virus, and cannot neutralize SARS-CoV-2 in lab dish tests as it does SARS-CoV.
Still, the findings suggest that the binding site for this antibody on SARS-CoV-2 is a site of vulnerability, and that antibodies binding it more tightly would plausibly succeed in neutralizing the virus. Such neutralizing antibodies, if developed into therapies, could be used to treat COVID-19 patients and to provide temporary protection from the virus to uninfected individuals, for example healthcare workers.
The fact that this binding site is highly conserved between SARS-CoV and SARS-CoV-2 also hints that there may be antibodies, still to be discovered, that can effectively neutralize both viruses—and perhaps in the same way, can neutralize future emergent coronaviruses before they can cause pandemics.
Labs at Scripps Research and throughout the world are currently seeking antibodies, via blood donations, from people who have recovered from COVID-19 for further studies along these lines.How the novel coronavirus binds to human cells

More information: Meng Yuan et al. A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV, (2020). DOI: 10.1101/2020.03.13.991570

Wednesday, May 07, 2025

SCIENCE SAYS NO LAB LEAK

Bat virus evolution suggests wildlife trade sparked COVID-19 virus emergence in humans


Study finds that SARS-CoV-2 arrived in Wuhan, China too quickly for its bat hosts to have carried it there — a dispersal pattern consistent with that of SARS-CoV-1, which caused the 2002 SARS outbreak




University of California - San Diego

Composite COVID Image, UC San Diego Health Sciences 

image: 

Horseshoe bats are the primary host for the ancestor of the viruses that caused both the 2002 SARS outbreak and the COVID-19 pandemic, but a new study suggests that the wildlife trade transported the virus to the places where they first emerged in humans.

view more 

Credit: Composite image: COVID-19, Greater horseshoe bats, Raffaele Maiorano, CC0 1.0 via iNaturalist; SARS-CoV-2 virus, NAIAD, CC-BY-2.0; palm civet, Rejoice Gassah, CC BY 4.0 via iNaturalist





The ancestor of the virus that causes COVID-19 left its point of origin in Western China or Northern Laos just several years before the disease first emerged in humans up to 2,700 kilometers away in Central China, according to a new study by University of California San Diego School of Medicine researchers and their colleagues. That’s not enough time for the evolving virus to have been carried there via the natural dispersal of its primary host, the horseshoe bat. This has led the researchers to conclude that it instead hitched a ride there with other animals via the wildlife trade, consistent with what happened during the SARS outbreak in 2002. The study was published in Cell on May 7, 2025.

Horseshoe bats are the main hosts of sarbecoviruses. These viruses don’t harm the bats, but are thought to have made the leap to humans through “zoonotic spillover” events. Sarbecoviruses gave rise to severe acute respiratory syndrome-related coronaviruses including SARS-CoV-1, the strain that caused the SARS pandemic of 2002-2004, and SARS-CoV-2, the strain that resulted in the COVID-19 pandemic. How they got to the places where these events occurred and whether animals besides bats were involved has been a matter of ongoing debate, however.

To clarify these questions, the researchers analyzed the family tree of both viral strains using genome sequence data available online, mapping their evolutionary history across Asia before they emerged in humans. However, the picture was blurred by the fact that these RNA viruses undergo a large amount of recombination inside their bat hosts, exchanging genetic material.

“When two different viruses infect the same bat, sometimes what comes out of that bat is an amalgam of different pieces of both viruses,” said co-senior author Joel Wertheim, Ph.D., a professor of medicine at UC San Diego School of Medicine’s Division of Infectious Diseases and Global Public Health. “Recombination complicates our understanding of the evolution of these viruses because it results in different parts of the genome having different evolutionary histories.”

The researchers avoided that problem by identifying all of the non-recombining regions of the viral genomes and using those to recreate the evolutionary history of the viruses instead.

The study found that sarbecoviruses related to SARS-CoV-1 and SARS-CoV-2 have circulated around Western China and Southeast Asia for millennia. During this time, they moved around the landscape at similar rates as their horseshoe bat hosts. 

“Horseshoe bats have an estimated foraging area of around 2-3 km and a dispersal capacity similar to the diffusion velocity we estimated for the sarbecoviruses related to SARS-CoV-2,” said co-senior author Simon Dellicour, Ph.D., head of the Spatial Epidemiology Lab at Université Libre de Bruxelles and visiting professor at KU Leuven.

In contrast, the analysis also revealed that the most recent sarbecovirus ancestors of both SARS-CoV-1 and SARS-CoV-2 left their points of origin less than 10 years before they were first reported to infect humans — more than a thousand kilometers away.

“We show that the original SARS-CoV-1 was circulating in Western China — just one to two years before the emergence of SARS in Guangdong Province, South Central China, and SARS-CoV-2 in Western China or Northern Laos — just five to seven years before the emergence of COVID-19 in Wuhan,” said Jonathan E. Pekar, Ph.D., a 2023 graduate of the Bioinformatics and Systems Biology program at UC San Diego School of Medicine, now a  postdoctoral researcher at the University of Edinburgh. 

The researchers calculated that given the distances that SARS-CoV-1 and SARS-CoV-2 would have had to cover so quickly, it is highly improbable that they could have been carried there via bat dispersal. Much more likely: they were transported there accidentally by wild animal traders via intermediate hosts.

In fact, previous studies have suggested that SARS-CoV-1 was likely carried from Yunnan Province in Western China to Guangdong Province by infected palm civets or raccoon dogs — animals commonly traded for their fur and meat. However, the current study provides the strongest evidence to date that SARS-CoV-2 made it to humans in a similar manner.

“The viruses most closely related to the original SARS coronavirus were found in palm civets and raccoon dogs in southern China, hundreds of miles from the bat populations that were their original source,” said co-senior author Michael Worobey, Ph.D., professor and head of the Department of Ecology and Evolutionary Biology at The University of Arizona. For more than two decades the scientific community has concluded that the live-wildlife trade was how those hundreds of miles were covered. We’re seeing exactly the same pattern with SARS-CoV-2.”

The findings dispute a widely circulated idea that SARS-CoV-1 emerged naturally, but SARS-CoV2 was the result of a lab leak.

“At the outset of the COVID-19 pandemic, there was a concern that the distance between Wuhan and the bat virus reservoir was too extreme for a zoonotic origin,” Wertheim said. “This paper shows that it isn't unusual and is, in fact, extremely similar to the emergence of SARS-CoV-1 in 2002.”

Zoonotic spillover events are on the rise worldwide due to an increase in human-animal interactions via the wildlife trade, as well as urbanization and habitat destruction. The researchers believe that by continuing to sample wild bat populations for sarbecoviruses, it may be possible to discover where the next coronavirus pandemic will come from. What’s more, understanding the evolutionary history of these viruses and other pathogens can help us prepare for and control future disease outbreaks.

Additional co-authors on the study include: Jennifer L. Havens and Yu Wang at UC San Diego; Tetyana I. Vasylyeva at UC San Diego and University of California Irvine; Andrew Rambaut at University of Edinburgh; Spyros Lytras at University of Tokyo and University of Glasgow; Joseph Hughes and David L. Robertson at University of Glasgow; Mahan Ghafari and Aris Katzourakis at University of Oxford; Andrew F. Magee and Marc A. Suchard at University of California Los Angeles; Edyth Parker at The Scripps Research Institute and Redeemer’s University; Xiang Ji at Tulane University; Alice C. Hughes at University of Hong Kong and China Biodiversity Green Development Foundation; and Philippe Lemey at KU Leuven.

The study was funded, in part, by the National Institutes of Health (grants R01 AI135992, R01 AI153044, R01 AI162611, U19 AI135995, and T15LM011271), Fonds National de la Recherche Scientifique (grant F.4515.22), the Research Foundation - Flanders (grant G098321N, G0D5117N and G051322N), the European Union Horizon 2020 project MOOD (grant agreement 874850), and the European Union Horizon 2020 research and innovation programme (grant agreement 725422).

Disclosures: Wertheim has received ongoing funding from the CDC through contracts or agreements to his institution unrelated to this research. Wertheim, Pekar, and Worobey have received consulting fees and/or provided compensated expert testimony on SARS-CoV-2 and the COVID-19 pandemic.

# # #

Friday, March 20, 2020

New coronavirus stable for hours on surfaces: study


New coronavirus stable for hours on surfaces
This scanning electron microscope image shows SARS-CoV-2 (yellow)--also known as 2019-nCoV, the virus that causes COVID-19--isolated from a patient in the U.S., emerging from the surface of cells (blue/pink) cultured in the lab. Credit: NIAID RML
The virus that causes coronavirus disease 2019 (COVID-19) is stable for several hours to days in aerosols and on surfaces, according to a new study from National Institutes of Health, CDC, UCLA and Princeton University scientists The New England Journal of Medicine. The scientists found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard and up to two to three days on plastic and stainless steel. The results provide key information about the stability of SARS-CoV-2, which causes COVID-19 disease, and suggests that people may acquire the virus through the air and after touching contaminated objects. The study information was widely shared during the past two weeks after the researchers placed the contents on a preprint server to quickly share their data with colleagues.
The NIH scientists, from the National Institute of Allergy and Infectious Diseases' Montana facility at Rocky Mountain Laboratories, compared how the environment affects SARS-CoV-2 and SARS-CoV-1, which causes SARS. SARS-CoV-1, like its successor now circulating across the globe, emerged from China and infected more than 8,000 people in 2002 and 2003. SARS-CoV-1 was eradicated by intensive contact tracing and case isolation measures and no cases have been detected since 2004. SARS-CoV-1 is the human coronavirus most closely related to SARS-CoV-2. In the stability study the two viruses behaved similarly, which unfortunately fails to explain why COVID-19 has become a much larger outbreak.
The NIH study attempted to mimic  being deposited from an infected person onto everyday surfaces in a household or , such as through coughing or touching objects. The scientists then investigated how long the virus remained infectious on these surfaces.
The scientists highlighted additional observations from their study:
  • If the viability of the two coronaviruses is similar, why is SARS-CoV-2 resulting in more cases? Emerging evidence suggests that people infected with SARS-CoV-2 might be spreading virus without recognizing, or prior to recognizing, symptoms. This would make disease control measures that were effective against SARS-CoV-1 less effective against its successor.
  • In contrast to SARS-CoV-1, most secondary cases of virus transmission of SARS-CoV-2 appear to be occurring in community settings rather than healthcare settings. However, healthcare settings are also vulnerable to the introduction and spread of SARS-CoV-2, and the stability of SARS-CoV-2 in aerosols and on surfaces likely contributes to transmission of the virus in healthcare settings.
The findings affirm the guidance from public health professionals to use precautions similar to those for influenza and other respiratory viruses to prevent the spread of SARS-CoV-2:
  • Avoid close contact with people who are sick.
  • Avoid touching your eyes, nose, and mouth.
  • Stay home when you are sick.
  • Cover your cough or sneeze with a tissue, then throw the tissue in the trash.
  • Clean and disinfect frequently touched objects and surfaces using a regular household cleaning spray or wipe.
Tests show new coronavirus lives on some surfaces for up to three days

More information: Neeltje van Doremalen et al, Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1, New England Journal of Medicine (2020). DOI: 10.1056/NEJMc2004973

Tuesday, May 12, 2020

A close relative of SARS-CoV-2 found in bats offers more evidence it evolved naturally

CELL PRESS
There is ongoing debate among policymakers and the general public about where SARS-CoV-2, the virus that causes COVID-19, came from. While researchers consider bats the most likely natural hosts for SARS-CoV-2, the origins of the virus are still unclear. On May 10 in the journal Current Biology, researchers describe a recently identified bat coronavirus that is SARS-CoV-2's closest relative in some regions of the genome and which contains insertions of amino acids at the junction of the S1 and S2 subunits of the virus's spike protein in a manner similar to SAR-CoV-2. While it's not a direct evolutionary precursor of SARS-CoV-2, this new virus, RmYN02, suggests that these types of seemingly unusual insertion events can occur naturally in coronavirus evolution, the researchers say.
"Since the discovery of SARS-CoV-2 there have been a number of unfounded suggestions that the virus has a laboratory origin," says senior author Weifeng Shi, director and professor at the Institute of Pathogen Biology at Shandong First Medical University in China. "In particular, it has been proposed the S1/S2 insertion is highly unusual and perhaps indicative of laboratory manipulation. Our paper shows very clearly that these events occur naturally in wildlife. This provides strong evidence against SARS-CoV-2 being a laboratory escape."
The researchers identified RmYN02 from an analysis of 227 bat samples collected in Yunnan province, China, between May and October of 2019. "Since the discovery that bats were the reservoir of SARS coronavirus in 2005, there has been great interest in bats as reservoir species for infectious diseases, particularly as they carry a very high diversity of RNA viruses, including coronaviruses," Shi says. RNA from the samples was sent for metagenomic next-generation sequencing in early January 2020, soon after the discovery of SARS-CoV-2.
Across the whole genome, the closest relative to SARS-CoV-2 is another virus, called RaTG13, which was previously identified from bats in Yunnan province. But RmYN02, the virus newly discovered here, is even more closely related to SARS-CoV-2 in some parts of the genome, including in the longest encoding section of the genome called 1ab, where they share 97.2% of their RNA. The researchers note that RmYN02 does not closely resemble SAR-CoV-2 in the region of the genome that encodes the key receptor binding domain that binds to the human ACE2 receptor that SARS-CoV-2 uses to infect host cells. This means it's not likely to infect human cells.
The key similarity between SARS-CoV-2 and RmYN02, is the finding that RmYN02 also contains amino acid insertions at the point where the two subunits of its spike protein meet. SARS-CoV-2 is characterized by a four-amino-acid insertion at the junction of S1 and S2; this insertion is unique to the virus and has been present in all SARS-CoV-2 sequenced so far. The insertions in RmYN02 are not the same as those in SARS-CoV-2, which indicates that they occurred through independent insertion events. But a similar insertion event happening in a virus identified in bats strongly suggests that these kinds of insertions are of natural origin. "Our findings suggest that these insertion events that initially appeared to be very unusual can, in fact, occur naturally in animal betacoronaviruses," Shi says.
"Our work sheds more light on the evolutionary ancestry of SARS-CoV-2," he adds. "Neither RaTG13 nor RmYN02 is the direct ancestor of SARS-CoV-2, because there is still an evolutionary gap between these viruses. But our study strongly suggests that sampling of more wildlife species will reveal viruses that are even more closely related to SARS-CoV-2 and perhaps even its direct ancestors, which will tell us a great deal about how this virus emerged in humans."
###
This work was supported by the Academic Promotion Programme of Shandong First Medical University, the Strategic Priority Research Programme of the Chinese Academy of Sciences, the Chinese National Natural Science Foundation, the National Major Project for Control and Prevention of Infectious Disease in China, the High-End Foreign Experts Program of Yunnan Province, the Taishan Scholars Programme of Shandong Province, the NSFC Outstanding Young Scholars, Youth Innovation Promotion Association of CAS, and an ARC Australian Laureate Fellowship.
Current Biology, Zhou et al.: "A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein" https://www.cell.com/current-biology/fulltext/S0960-9822(20)30662-X
Current Biology (@CurrentBiology), published by Cell Press, is a bimonthly journal that features papers across all areas of biology. Current Biology strives to foster communication across fields of biology, both by publishing important findings of general interest and through highly accessible front matter for non-specialists. Visit: http://www.cell.com/current-biology. To receive Cell Press media alerts, contact press@cell.com.

Monday, April 03, 2023

Scientists Fear ‘Catastrophic’ COVID Combination With Another Virus

David Axe
Sun, April 2, 2023 

Photo Illustration by Elizabeth Brockway/The Daily Beast

The SARS-CoV-2 virus is highly contagious but the current dominant strains are not very lethal. Its much rarer cousin in the betacoronavirus family of pathogens, MERS-CoV, is highly lethal but not very contagious. Now imagine a blend of the two—a respiratory virus with the most dangerous qualities of both. Contagious and lethal.

It’s a real risk, according to a new study from China. And it’s a strong argument for a new, more widely effective vaccine.

Different viruses from the closely related families can combine through a process called “recombination” and produce hybrids called “recombinants.” This recombination requires the viruses to share an infection mechanism. For the first time, a team of scientists in China has identified the mechanism by which SARS and MERS could combine—by entering human cells via colocated receptors. Basically, the cells’ entry points for external molecules.

If a single person ever catches SARS and MERS at the same time through neighboring receptors and the two viruses combine, we could have a whole new pandemic on our hands—one that could be far worse than the current COVID-19 pandemic.

The recombination risk is one driver of a global effort to develop new vaccines that could prevent, or reduce the severity of, infection by a variety of SARS viruses, MERS, and any hybrid of them. A universal vaccine for a whole family of viruses.

Good news: Universal vaccines are in development. Bad news: They’re still a long way from large-scale human trials—and an even longer way from regulatory approval and widespread availability. Years, perhaps.

A team led by Qiao Wang, a virologist at the Shanghai Institute of Infectious Disease and Biosecurity, part of Fudan University in Shanghai, highlighted the SARS-MERS recombination risk in a peer-reviewed study that first appeared in the journal Signal Transduction and Targeted Therapy on March 15.

SARS-CoV-2 tends to favor a receptor called ACE2, while MERS-CoV tends to favor the DPP4 receptor, Wang and their coauthors explained. Our cells tend to have one or the other, not both. In the very unlikely chance someone catches both SARS and MERS at the same time, the viruses should stay safely in their separate cells.

But Wang and company identified a few cell types, in the lungs and intestines, that have both ACE2 and DPP4 receptors, thus “providing an opportunity for coinfection by both SARS-CoV-2 and MERS-CoV.” Wang and a teammate did not respond to a request for comment.

This hypothetical coinfection—SARS-CoV-2 and MERS-CoV mixing and mutating in the same cells—“may result in the emergence of recombined [betacoronavirus],” Wang and their coauthors wrote. Call it “SARS-CoV-3” or “MERS-CoV-2.”

Either way, this new virus “may bear high SARS-CoV-2-like transmissibility along with a high MERS-CoV-like case-fatality rate, which would have catastrophic repercussions,” Wang and their teammates wrote.


Did AI Just Help Us Discover a Universal COVID Vaccine?

How bad could it be? The most contagious forms of SARS-CoV-2, the XBB subvariants—a.k.a., “Kraken”—is by far the most transmissible respiratory virus anyone has ever observed. It’s not for no reason that XBB subvariants quickly outcompeted rival subvariants in order to become globally dominant in just a few weeks early this year.

But Kraken is less severe—that is, less likely to kill—than earlier forms of SARS-CoV-2. Vaccines and natural immunity help a lot, but there are also signs that the novel-coronavirus is slowly evolving toward higher transmissibility but lower severity. At its worst in 2021, COVID killed nearly 5 percent of infected persons in the worst-hit countries such as Peru and Mexico. Today, the global fatality rate is around 0.9 percent.

MERS, by contrast, spreads much more slowly. It mostly affects camels. When it infects people, it’s usually when those people are in close contact with the animals. Human-to-human transmission is extremely rare. “Only a few such transmissions have been found among family members living in the same household,” the World Health Organization noted.

In 27 small outbreaks since 2012, fewer than 900 people have died of MERS. Compare that to the 6.9 million people who have died of SARS-CoV-2 since late 2019. The problem, with MERS, is that those 900 or so deaths represent a third of infections. That is to say, MERS is at least six times more lethal, on a case-by-case basis, than SARS was at its worst.

So if a SARS-MERS recombinant inherited the former’s transmissibility and the latter’s lethality, it could quickly kill millions. That’s why Wang and their coauthors are, in their own words, “calling for the development of pan-CoV vaccine.”

Don’t panic. Epidemiologists who weren’t involved in Wang and company’s study didn’t necessarily agree with the Chinese authors’ sense of possible imminent doom. “The lifecycle of a virus is delicate and recombination between different viruses is typically uncommon,” Lihong Liu, a Columbia University COVID researcher, told The Daily Beast. “We have not seen any recombination between SARS-CoV-2 and MERS during the COVID-19 pandemic, despite the millions of SARS-CoV-2 infections worldwide. Therefore, it is expected that such an event is unlikely to occur in the future.”

Michael Letko, a Washington State University virologist, told The Daily Beast that Wang’s team is actually half-right. Yes, there’s huge risk from a possible recombinant. But not necessarily a SARS-MERS recombinant. It’s more likely the novel-coronavirus will recombine with a Russian bat virus called Khosta-2, Letko said.

Khosta-2 is even more closely related to SARS-CoV-2 than MERS is, Letko pointed out. Not only is Khosta-2 fond of the same ACE2 receptor that the novel coronavirus prefers, the two viruses also replicate roughly the same way. “The machinery the viruses use to copy their genetic material can get confused, leading to mixing and matching of the genomes,” Letko said of SARS-CoV-2 and Khosta-2. That raises the recombination risk.
Prevention plan

JANUARY 2020 CHINA RELEASED THIS GENETIC CODE FOR COVID

But exactly which cousin virus might combine with SARS-CoV-2 is beside the point. Barton Haynes, an immunologist with Duke’s Human Vaccine Institute, told The Daily Beast. There are dozens of betacoronaviruses. We should develop a vaccine that works against all of them. “If a vaccine could do all this, then one would also likely be able to protect against any … recombinant virus, as well,” Haynes said. SARS-MERS. SARS-Khosta-2. MERS-Khosta-2. Whatever.

There are around two dozen pan-coronavirus vaccine projects underway all over the world. Haynes and his colleagues at Duke have been working on one since 2020—and it could be among the first to produce a deployable vaccine. Animal testing and small-scale human trials are already underway. But if history is any guide, it could be years before the Duke vaccine or any other pan-CoV jab is ready for widespread deployment.

The wait is worth it, Haynes said. “The current goal of pan-coronavirus vaccines that are currently being tested in monkeys and humans is to make vaccines that both prevent infection by any new COVID variant that might arise, to make vaccines that will prevent any new CoV-2-like CoV outbreak that may arise from bats or other animals as well to protect against any MERS-like virus that may arise.”

That should cover all the bases, at least when it comes to betacoronaviruses including SARS-CoV-2, MERS-CoV and Khosta-2. If our luck holds and we dodge a dangerous SARS recombinant for a few more years, we just might have a universal vaccine—Duke’s or another—that could prevent mass death in the event that hybrid finally appears.

Of course, that “universal” vaccine wouldn’t be truly universal. It wouldn’t save us from RSV, monkeypox, polio or—perhaps most worryingly—bird flu. For those viruses, we need totally different jabs.





Wednesday, August 03, 2022

Are cattle at risk of SARS-CoV-2 infection?

In a recent research letter published in Emerging Infectious Diseases, researchers evaluated antibodies targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cattle from farms in Germany.

Study: Antibodies against SARS-CoV-2 Suggestive of Single Events of Spillover to Cattle, Germany. Image Credit: William Edge/Shutterstock
Study: Antibodies against SARS-CoV-2 
Suggestive of Single Events of Spillover to Cattle, Germany
Image Credit: William Edge/Shutterstock

Background

Since SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19) in humans, was initially discovered in late 2019, it has spread incredibly quickly globally. This massive worldwide pandemic has claimed more than 6.3 million human lives in roughly 2.5 years of virus circulation. 

SARS-CoV-2 infection in humans increases the possibility of animal transmission. With a particular focus on discovering vulnerable species and prospective reservoirs or intermediate hosts, various researchers evaluated the involvement of wildlife and livestock species at the human-animal interface since the COVID-19 pandemic's inception. 

According to prior reports, several animal species, including nonhuman primates, canids, felids, mustelids, white-tailed deer, and numerous Cricetidae rodent species, were susceptible to SARS-CoV-2 infection in experimental conditions, whereas swine or poultry were not. Following experimental SARS-CoV-2 inoculation, domestic ruminants like sheep, cattle, or goats had poor susceptibility; very few animals could contract the infection without animal-to-animal spread.

Furthermore, in only one to two days, cattle tested SARS-CoV-2-positive by reverse transcription polymerase chain reaction (rt-PCR) following experimental infection. Thus, serologic screening may be more valuable for detecting priorly infected animals and determining the spillover infection rates in the field.

About the study

In the present research, the scientists serologically examined 1,000 samples of cattle gathered in Germany at the end of 2021 to determine the COVID-19 risk to cattle. 

In detail, the team evaluated 1,000 plasma or serum samples obtained from cattle at 83 farms in four German federal states (Lower Saxony, Bavaria, Thuringia, and Saxony-Anhalt). They noted that no permissions were required to obtain these specimens because they were surplus material from standard diagnostic submissions made by the accountable veterinarians in the framework of the health surveillance of the specific cattle farm.

Sampling took place in the 2021 autumn and the early winter of 2021 to 2022, when a massive surge of SARS-CoV-2 infections attributed to the Delta variant of concern (VOC) occurred among humans. The researchers investigated two to 20 randomly chosen plasma or serum samples per farm. They sampled farm 31 twice, and the owner of the animals was quarantined in the interim.

A multispecies enzyme-linked immunosorbent assay (ELISA) based on the SARS-CoV-2 receptor-binding domain (RBD) was used to evaluate all samples from cattle. The authors analyzed an extra 100 randomly procured cattle control samples from 2016 in Germany.

Results

The study results showed that 11 cattle from nine farms were positive for the SARS-CoV-2 RBD ELISA among the 2021 cattle samples; one of these animals, from farm 31, was sampled after the quarantine of the owner. An indirect immunofluorescence test using Vero cells infected with the SARS-CoV-2 2019 nCoV Muc-IMB-1 strain as the antigen matrix confirmed positive results of ELISA for all but one sample from farm 8. Besides, titers varied from 1:8 to 1:512, with farm 31's seropositive animal having the highest titer.

The assessment of RBD-ELISA-positive 11 samples utilizing a surrogate virus neutralization test (sVNT) enabled the identification of SARS-CoV-2 neutralizing antibodies. The analysis was accomplished by simulating the interplay between the receptor protein of the host cell membrane, i.e., angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2. Moreover, four cattle from farms 74, 47, 31, and 11 had positive sVNT results.

Conclusions

According to the study findings, 11 cattle samples from Germany were positive for SARS-CoV-2 antibodies, implying that cattle may occasionally become virus-infected and seroconvert through exposure to COVID-19-infected keepers. Yet, the team found no additional evidence of intraspecies viral spread in the field, in line with the former experimental infection assessments.

However, the authors noted that future monitoring initiatives should include cattle farms, particularly given that another CoV (i.e., BCoV) was quite common across cattle, and a BCoV infection did not shield against contracting SARS-CoV-2 according to a prior study. Further, animal hosts' vulnerability to the Omicron VOC was unknown. Furthermore, recombination events between the two viruses could result from double infections in a single animal, a process seen with other CoVs.

The limited susceptibility of cattle to SARS-CoV-2 makes emergence extremely unlikely, but a potential chimera among SARS-CoV-2 and BCoV could pose an extra concern. The study stated that ruminants should be considered in outbreak studies and warranted routine testings to prevent the spread of novel SARS-CoV-2 variants across the livestock population.

Journal reference: