COVID-19 Series: The Emergence of SARS-CoV-2

In our first story, we look at the role wet markets, wildlife trafficking, and pangolins have played an important in the emergence of SARS-CoV-2.

A review published in the December 2019 issue of the journal Infectious Disease Clinics of North America concluded: “The SARS epidemic demonstrated that novel highly pathogenic viruses crossing the animal-human barrier remain a major threat to global health security.” Little did the authors know that by the date of publication, just such a virus was brewing. “[I]t will not be surprising if new coronaviruses emerge in the near future,” read another review a few months before. “[I]t is highly likely that future SARS- or MERS-like coronavirus outbreaks will originate from bats, and there is an increased probability that this will occur in China.” These warnings are not new, dating back more than a decade. “The presence of a large reservoir of SARS-like coronaviruses in… bats, together with the culture of eating exotic mammals in southern China, is a time bomb.” A time bomb that just went off.

Now I hope you can understand how Dr. Li’s “7 SARS cases confirmed …” forewarning was so ominous. That’s why I did the last video about SARS, because it gives some context. It wasn’t the SARS coronavirus he found, though (the cause of SARS, severe acute respiratory syndrome), but instead a virus that would come to be known as SARS coronavirus 2 (SARS-CoV-2), the cause of COVID-19, short for coronavirus disease 2019. Before it became known as SARS-CoV-2, though, it was just the “Wuhan seafood market pneumonia virus.”

According to the director of the Chinese CDC, ground zero for the COVID-19 pandemic was the Hua’nan Market in Wuhan, China, where most of the first human cases could be traced back. Described as the largest wholesale seafood market in Central China, the Hua’nan Market reportedly also sold 75 species of wild animals. If you want to see what that part of the market looked like, you can go to bit.ly/HuananMarket, but I’m not going to show the photos because some may find them disturbing.

Although there are fish coronaviruses, 90 percent of the samples that turned up positive for the virus were found in the section of the half-million square-foot seafood market where those photos were taken—the part that trafficked in exotic animals sold for food.

The fact that the genetic sequences of the viruses obtained from some of the early human victims were 99.9 percent identical, despite the rapid mutation rate of coronaviruses, suggests the current pandemic originated within a very short period from a single source. Although there have been documented reports of the original SARS coronavirus escaping from laboratories, the fact that the COVID-19 coronavirus was optimized for binding to human cells in a novel way suggests that the new pandemic we now face was not made in some laboratory but rather natural means, though to lock in the necessary mutations the “animal host would probably have to have a high population density.”

The new coronavirus appears to share a common ancestor with the original SARS virus, for which it is about 80 percent identical, but it’s more than 95 percent identical with a coronavirus found in a bat in 2013. The current thinking is that the COVID-19 virus originated in bats, but then jumped to humans only after passing through an intermediate host. The pandemic emerged in winter, after all, when most bat species in Wuhan are hibernating, and no bats were reportedly found at the Hua’nan Market. There were labs in the proximity of the market where bat viruses might have escaped, but the virus was found in environmental samples taken directly from the market. Unfortunately, the market was closed and cleared before the animals themselves were tested, complicating the forensic search for the source. In the case of SARS, the intermediate host between bats and human-to-human transmission was the civet; in MERS it was camels. What was the intermediate host for COVID-19? The leading candidate for the stepping-stone civet of the current outbreak is the pangolin.

Also known as scaly anteaters, pangolins look like a cross between a sloth and a pinecone. But between the demand for their meat as a delicacy and their scales for use in traditional Chinese medicine, pangolins are the most trafficked mammal in the world.

Coronaviruses from two separate batches of diseased pangolins being smuggled into China were found to be about 90 percent identical with the COVID-19 virus. Not only is the pangolin the only other mammal found to be infected with SARS-CoV-2-like viruses, but the critical receptor-binding region of the pangolin coronavirus spike protein is virtually identical to the human strain. Work is still underway, but whichever the animal was, that one meal, that one medicine, may have ended up costing humanity a few trillion dollars and a few million lives.

Given the role exotic animal trafficking appears to have played in the current global health crisis, some in the international scientific community have called for a ban on the sale of wild animals and a closure of live animal markets. Even infectious disease experts within Wuhan started calling for “completely eradicating wildlife trading.”

On January 26, 2020, the Chinese government responded, announcing a total ban on the trade and sale of wild animal meat, reportedly shutting down or quarantining almost twenty thousand wildlife farms across seven Chinese provinces, though the ban is only set to be temporary. After the SARS outbreak in 2003, Chinese officials enacted a similar ban on the trade of civet cats, but within months the ban was lifted, and the animals were back on the menu.

Much of the wildlife trade was already illegal in China in the first place, with flaunted bans dating back more than a decade. The Chinese pangolin, for example, is officially considered a critically endangered species.

That’s part of the draw, though, as a serving of “extra rare” meat may project prestige and wealth. A thriving black market already exists, and it could potentially be driven further underground by government action. “The ultimate solution,” wrote a group of Chinese scientists, “lies in changing people’s minds about what is delicious, trendy, prestigious, or healthy to eat.” Having spent the bulk of my professional life trying to get people to eat more healthfully to prevent chronic disease, I can certainly relate.

Even in the unlikely event the current ban was to be made permanent and was enforced effectively, there remains a glaring loophole: The ban exempts the use of wild animals for traditional Chinese medicine. So, while it’s currently illegal to eat pangolin meat, it’s not illegal to eat other pangolin parts. How ironic that the pandemic appears to have arisen in a market selling remedies purported to promote immunity and longevity. Pangolin blood is said to “promote…circulation.”

For only about $30 a pound, anyone can go online and buy Chinese bat feces to treat their eye disorders. While the drying of excrement would presumably inactivate coronavirus, the trade and handling of live and recently killed bats for use in traditional remedies could infect people directly, or certainly introduce opportunities for cross-infection with susceptible hosts.

Now it is easy for xenophobic Westerners to condemn cultures consuming rhino horns, tiger bones, and pangolin scales, or 21^st century manifestations such as mukbangs (livestreaming broadcasts of people eating bat soup and the like). But, as I discuss in my new book How to Survive a Pandemic (all proceeds I receive for which are donated to charity), the last pandemic, the 2009 H1N1 swine flu virus, arose not from some backwater wet market in Asia, but rather was largely made-in-the-USA from industrial pig operations in the United States. So, for the emergence of SARS-CoV-3, we may need look no further than our own plates.

In our next story – we look at how the next coronavirus pandemic may come from pigs not pangolins.

Before I take a deep dive into COVID-19, I wanted to touch on some of the new coronaviruses emerging in livestock. As we’ve seen, COVID-19 is only one of many coronavirus diseases to jump from bats in the 21st century to cause deadly outbreaks. There was SARS in 2002, MERS in 2012, and then SADS in 2016. A new disease killing up to 90 percent of young piglets, SADS, Swine Acute Diarrhea Syndrome, devastated industrial pig farms in the same region in China where SARS had broken out. SADS was traced to a coronavirus discovered in a bat cave in the vicinity. So, one could say coronaviruses can infect pigs, right off the bat.

The combination of deforestation and intensive pork production, with millions of pigs encroaching on bat habitat, may have facilitated the coronavirus spillover from bats to pigs.

Then there is Porcine Epidemic Diarrhea, another presumed bat-to-pig coronavirus. In 2010, a highly virulent strain emerged in China that caused massive outbreaks when it hit the United States and spread coast-to-coast a few years later, killing millions of pigs—approximately 10 percent of the entire U.S. herd.

Then there’s porcine-delta coronavirus, the third new pig coronavirus to emerge from China in the last decade, rapidly spreading once it reached U.S. shores in 2014. This pattern of emergence and outbreaks of new coronaviruses in livestock appears to be accelerating, facilitated by intensive confinement practices resulting in thousands of animals being housed together in a closed environment.

The pattern of new human coronavirus outbreaks also appears to be accelerating, but currently, none of these emerging pig coronaviruses appears able to infect humans. Nevertheless, continued monitoring of these pig coronaviruses is necessary for not just pig health but public health, because coronaviruses are known for their high rates of mutation and their recombination––the process by which viruses swap parts of their genetic code to better adapt to their hosts or find new ones. The fact that many livestock coronaviruses cause persistent, epidemic infections increases the likelihood that a coronavirus mutant could arise with what’s called an “extended host range,” meaning the potential to invite humanity to the party.

To trigger a pandemic, the virus would first have to spread to the lungs. Most coronaviruses in bats and livestock, to date, have been intestinal infections. The exception is Infectious Bronchitis Virus (IBV) in chickens, which was actually the first coronavirus ever discovered back in 1931. And it was to become the major cause of respiratory infections in the nine billion chickens raised for meat in the United States every year. But it is prevalent in all countries with industrial poultry production, with infection rates often approaching 100 percent. Currently, the only way IBV has been shown to cause disease in mammals, though, is by being directly injected into the brain.

But with so many different coronaviruses circulating among so many different species, it is considered likely not a matter of if, but when the next recombinant coronavirus will emerge and explode into the human population. Already, the spikes of the newly discovered porcine deltacoronavirus in pigs that has posed such a serious threat to the pork industry can attach to receptors found not only in pig intestines, but also in the respiratory tract of humans. This broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility. We already know porcine deltacoronaviruses can infect both human and chicken cells in a petri dish, and we know they can infect chickens themselves (just like there’s a bovine coronavirus in calves that can infect turkeys—these coronaviruses jump around). And once they do, even more concerning is that porcine deltacoronavirus, once it jumps to chickens, can then spread rapidly from chicken to chicken.

In fact, this new paper, published in February 2020 in the CDC’s Emerging Infectious Diseases journal, concluded that given the susceptibility of human cells to infection, porcine deltacoronavirus should be investigated for its pandemic health risk to humans.

The SADS coronavirus can also infect human cells in a petri dish and infect mice in a laboratory. In fact, a team of researchers concluded in the upcoming December 2020 issue of the Journal of Virology that given “the ability of SADS-coronavirus to grow efficiently in human cell lines, we should not underestimate the risk that this bat-origin coronavirus may ‘jump’ from pigs to humans.”

Bottom line: pigs, not just pangolins, may act as the mixing vessels for the generation of new coronaviruses with pandemic potential.

Coronaviruses are increasingly emerging and circulating among livestock populations around the world. The more new coronaviruses we have mixing in more and more animals, the greater the likelihood that strains with pandemic potential may emerge. While global pangolin populations are in drastic decline, we produce and slaughter more than a billion pigs each year (about half in China alone), raising the specter that the next pandemic may arise from domestic rather than wild animals—an event that may actually have already happened. The last coronavirus pandemic may have been caused by livestock. Wait, the last coronavirus pandemic? Hear me out.

Coronaviruses are the second most common cause of the common cold. So far, we’ve discovered four human cold coronaviruses, so that makes seven coronaviruses in all that can cause human disease: the six listed here, plus COVID-19. We suspect we got SARS from civets, MERS from camels, and the COVID-19 virus, perhaps, from pangolins. Where did we get the four common cold coronaviruses?

The origin of two of the four mild coronaviruses remains a mystery, but one—called human coronavirus 229E—has been traced back to camels, and the other—called OC43—to cattle or pigs. Well, if the jump by the common cold from camels to humans foreshadowed the deadly MERS species jump that went on to kill one in three people, might the coronavirus jump from livestock to humans portend a deadly human outbreak as well? It may already have.

So-called molecular clock analyses dating the emergence of human coronavirus OC43 suggest that the bovine coronavirus, now causing so-called shipping fever in cattle, jumped to humans around the year 1890. Cows to humans in 1890. That’s interesting timing. There was a pandemic in 1890. While the 1890 pandemic was presumed to be influenza, the timing of the emergence of human coronavirus OC43 has led some to conjecture that it instead may have been a SARS-like or COVID-19-like interspecies transmission of a coronavirus. Maybe it was just a coincidence, though? Well it’s not just the timing. There seemed to be a lot of neurological symptoms during that pandemic, and that’s relatively unusual for influenza, and more characteristic of the coronavirus. But the most compelling data to me is the fact that there was this highly infectious respiratory disease raging in cattle, and in the years leading up to the pandemic—1870 to 1890—there were massive culling operations to eradicate the disease, devastating cattle herds the world over, ample opportunity for lots of respiratory secretion exposure.

Now we may never know what caused the 1890 pandemic, but we can take steps to prevent the next one. And that’s a subject I dive deep into in my new book How to Survive a Pandemic (all proceeds I receive are donated to charity). Yes, I go into how to best protect yourself and your family, your community from COVID-19, but I also address pandemic prevention. The best way to survive a pandemic is not to have one in the first place.