Denver Zoo Conservation Alliance
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In the fall of 2021, as Denver was grinding through yet another phase of the COVID-19 pandemic, the SARS-CoV-2 virus quietly crossed a boundary that most people never considered: It jumped from humans and moved into big cat enclosures at the Denver Zoo.
That episode, involving Amur tigers, African lions and spotted hyenas, is the subject of a newly released study in the journal Nature Communications, led by Colorado researchers who analyzed how SARS-CoV-2, the virus that causes COVID-19, behaved after infecting animals housed in a controlled zoo environment. Drawing on months of diagnostic testing and viral genome sequencing, the research offers a detailed look at what happens when the virus crosses into non-human hosts.
The study’s authors include scientists from Colorado State University, the CSU Veterinary Diagnostic Laboratories and the Denver Zoo Conservation Alliance. One of those authors is Sue VandeWoude, a CSU veterinarian and virologist who has spent years studying how viruses move across species.
From Humans to Cats
“What this analysis allowed us to do, because of the unique samples we had, was to evaluate the changes that are occurring in the virus genome as it moves from species to species,” VandeWoude tells Westword. “It shows that when the virus does that, it has to change a little bit to be optimized to grow within a different host.”
According to the study, the outbreak was likely initiated by a single human-to-animal spillover event involving a rare Delta sublineage of SARS-CoV-2. While the mechanism of that spillover isn’t identified, the authors note that human-to-animal transmission had already been documented at other zoos earlier in the pandemic.
Clinical signs were observed first in the zoo’s Amur tigers, followed by African lions and then spotted hyenas. The tigers were housed in a separate exhibit roughly 200 meters away from the lions and hyenas and were cared for by different animal specialists, a detail the researchers highlight as part of their effort to understand how the outbreak unfolded across species.
The animals exhibited mild respiratory signs, according to the study. All of the infected animals recovered fully, says a spokesperson for the Denver Zoo..
To monitor the infections, veterinarians collected nasal swabs repeatedly over the course of the outbreak, using diagnostic PCR testing to detect viral RNA and sequencing samples to examine how the virus changed over time. The analysis found that SARS-CoV-2 did not remain genetically static once it entered these animals. The researchers documented substantial within-host viral diversity, meaning that as the virus replicated inside individual animals, it accumulated genetic changes.
COVID Affected Lions and Tigers Differently
The team examined how those changes differed between species. One mutation, detected in both lions and hyenas but not in tigers, stood out as an example of how the virus’s genetic profile diverged after crossing species boundaries. The study shows that host shifts can shape viral evolution in measurable ways.
“That is really like a mixing pot,” VandeWoude explains. “When a virus infects a new host, it either changes to adapt to replicate in that body, or it dies out because the body prevents it from doing that.”
Although likely scary in the moment, the Denver Zoo outbreak offered an unusual opportunity to observe that process, VandeWoude emphasizes.
“It was a very unusual situation to see three different species sequentially infected like this, and we really don’t know how that happened,” she says. “[The zoo was] taking significant precautions.”
The virus identified in the animals was also unusual. The Delta sublineage detected during the outbreak accounted for less than 1 percent of circulating human cases at the time, making its appearance in multiple zoo species especially notable, according to the study.
“That was interesting to us, because it wasn’t what was widely circulating in people,” VandeWoude says. “It raises questions about whether that strain was more capable of infecting other species, or whether there were environmental or physiological factors at play.”
VandeWoude points to differences in body temperature, respiratory biology and internal chemistry among species as possible pressures shaping viral adaptation. Each animal presents a slightly different internal environment that the virus must navigate in order to survive.
“The virus has to learn how to live in a slightly different soup,” she says.
The genetic data also helped the team evaluate the timing and relationships among infections across species, complementing clinical observations about when symptoms appeared in different animals.
Years after the Denver Zoo outbreak, this study documents how a virus that reshaped human life also left its mark on the animals living alongside the people, and provides new data for future vaccines.
