On March 11, the World Health Organization declared the outbreak of COVID-19 a pandemic. There are now more than 2.5 million confirmed COVID-19 cases worldwide. 

But how did this all begin? What are the origins of the novel coronavirus that causes COVID-19? And what can we do to prevent the next pandemic? 

Origin of COVID-19

Coronaviruses are zoonotic, meaning they originate in animals and can eventually be transmitted between animals and people. Many experts believe that the novel coronavirus originated in horseshoe bats.

The novel coronavirus is “96% identical at a whole genome level to bat coronaviruses,” said James Holland Jones, a biological anthropologist and associate professor in Stanford’s Earth system science department.

What’s unclear is the mechanism of “spillover” — how the novel coronavirus jumps from animals to humans. Usually, but not always, zoonotic viruses spread from a reservoir host to an intermediate host, which is important for viral transmission. Intermediate hosts can provide an effective way for a virus to adapt to a novel host, which is helpful for eventual transmission into humans.

“In reservoir hosts, diseases naturally occur in the environment of the host, and usually the virus and host have naturally coexisted for a very long time,” said Nicole Nova M.S. ’20, a fourth-year Ph.D. student in the lab of assistant biology professor Erin Mordecai, studying viral transmission between animals and humans. “The host has adapted or evolved many different defense mechanisms that humans, unfortunately, haven’t developed.” 

This is a pattern Nova has noticed in the zoonotic viruses she has studied. 

“Viruses travel from wildlife to humans through an intermediate, or amplifier, host, which has close contact with humans but is evolutionarily more similar to wild animals,” she said. “Through mutations, the virus evolves into a strain that can eventually infect humans.” 

The presence of large numbers of animals in crowded places results in the possibility for viruses to spread not just between animals, but also from these intermediate hosts to humans. 

“Animal markets are virus factories,” she said.

In the case of the novel coronavirus, while the reservoir hosts are bats, the identity of the intermediate hosts is not completely clear. 

“Although it probably spread from bats to civets and then to humans, it could have been people using contaminated guano as fertilizer, people wandering into bat caves,” Jones said, “but we don’t know for sure.” 

Pangolins also could have been an intermediate host, according to Nova. 

Jones says that wet markets — marketplaces that sell meat, fish and other perishable goods — can be particularly effective vehicles for spillover of zoonotic viruses from animals to humans.

“Since bats are really good at harboring viruses, it’s a good idea to keep them out of wet markets,” he said. “The presence of exotic game such as bats is inherently dangerous, and animals with the potential for pandemic spillover should not be traded at wet markets.”

Wet markets are dangerous not only for humans, but also for endangered species, according to Nova. 

In the case of the novel coronavirus, “horseshoe bats taken to wet markets might have infected pangolins, among other animals, and then infected humans who came into close contact with infected pangolins,” Nova said. 

Other zoonotic viruses

The novel coronavirus isn’t the only zoonotic virus. The related virus SARS-CoV likely also originated in horseshoe bats and then also spread to civets in wet markets in China as part of a global outbreak in 2002, phylogenetic evidence suggests. 

“Farmers likely brought civets infected with SARS, whether dead or alive, to wet markets,” Nova said. “These civets then spread the virus to other animals in close proximity.” 

The flu virus H1N1 originally infected wild fowl such as ducks and geese before mutating and spilling over through fecal or oral transmission to domesticated animals such as pigs, which are physiologically similar enough to humans that they eventually spread it to humans as well, according to Jones. 

“Pigs provided a mixing vessel for engineering a virus that could infect humans, since pigs allow for natural selection for a more transmissible flu virus,” Nova said. 

There have been several outbreaks linked to H1N1, most notably the 1918 H1N1 flu pandemic, which killed an estimated 50 million people worldwide.

Human immunodeficiency virus (HIV) — currently classified as a “global epidemic” by the WHO — is an anthroponosis of zoonotic origin, meaning it originated in animals and spilled over to humans, but it can be transmitted from animals to humans as well as among humans. In the 1920s, a group of chimpanzees infected humans with HIV in Central Africa. 

When these chimps were hunted and eaten by people living in the area, blood-to-blood contact resulted in spillover. As hunters used blades to cut into chimps for bushmeat, they also cut their own fingers, and from these cuts, infected chimp blood entered humans, according to Jones. 

Preventing the next outbreak

Preventing zoonotic virus outbreaks is vital not only for human health, but for the health of other species, too. Viral spillover from zoonotic reservoir hosts to intermediate hosts which are endangered species, such as pangolins, has devastating consequences for the environment, according to Nova. 

Researchers advise that limiting close contact between wild animals, domestic animals and humans to prevent spillover of zoonotic viruses is essential for preventing the next outbreak. 

“We need to prevent existing zoonotic viruses from even reaching an environment where they can infect humans,” Nova said. 

“It is important not only to study diseases that have already entered the human population, but also to study diseases that are constantly adapting to new species,” she said. “We should work to understand how these diseases evolve between other non-human species in case there might be some point in the future that they could spillover to humans.” 

Bats have low levels of inflammation and strong antiviral responses that have allowed them to adapt to coronaviruses. Since bats, like humans, are mammals, we can study their robust immune responses to identify future therapeutic targets for humans.

To prevent the next pandemic, “we should follow harm reduction as a general principle, and let science guide the policies,” Jones said. 

Contact Vilina Mehta at vmehta19 ‘at’ stanford.edu.