It’s been 20 years since West Nile virus cleared the skies of crows and magpies and, courtesy of Culex tarsalis mosquitoes, infected thousands of people in Colorado, killing 66.

As we enter the months in which birds flock and mosquitoes multiply, Lisa Montez has a message to share: West Nile never went away, and if you’re among the unlucky few, it can do lasting damage.

How do you know if you have West Nile virus? What are the symptoms?

Montez, who lives in Windsor, came down with West Nile in July 2022. That she was diagnosed put her in the minority: Roughly 80% of those infected show no symptoms at all, or symptoms are mild enough that the person doesn’t know they’re sick. Most of the 20% who get sick and deal with symptoms that can include fatigue, fever, headaches, joint pain, rashes, and stomach issues recover within a couple of weeks. But about 1% of all cases become neuroinvasive.

Dr. Daniel Pastula, chief of neuroinfectious disease and global neurology at the University of Colorado School of Medicine and Colorado School Public Health, places those neuroinvasive cases into three categories. West Nile meningitis involves the membranes around the brain and spinal cord. West Nile encephalitis involves the brain itself. And West Nile acute flaccid paralysis involves the gray matter of the spinal cord or peripheral nerves

The precise mechanisms differ, and they’re still not well understood. But, Pastula says, some combination of damage done by the replicating West Nile viruses and the immune system’s efforts to clear those viruses out can kill neurons that can’t regenerate as most other bodily cells can.

In other words, the damage can be permanent.

Severe cases can strike older people and those who are immunocompromised. Young mom was not a typical patient.

Some people are at greater risk for West Nile virus than others: those older than 60, those who are immunocompromised, those who are fighting cancer, those with diabetes, and those with kidney disease among them. None apply to Lisa Montez.

She is 31. She was, until last July, a software developer pulling 50-hour weeks while helping run a household with husband Abel and being an active mom to daughter Aria, 5. She was an avid hiker.

Nearly a year later, Montez has dialed back to a simpler job and works only part-time. She lacks the energy to hike. Her trouble focusing has sapped the enjoyment from her knitting and pleasure reading. For months on end, she couldn’t drive, and the reasons why shed light on what West Nile has done to her cognitive functioning.

“I just couldn’t use my brain to multitask and do all of the things that you need to do to drive safely, like check your speed limit and check other cars around you,” Montez says. “If another car in front of me stopped abruptly, I couldn’t really do all of the fast processing I need to do to react in time.”

Her husband has taken over much of the cooking, cleaning and child care. He, or local in-laws, drive her to appointments.

Aria is coming to terms with her mom’s curious limitations.

“She just could not understand why, all of a sudden, Mommy can’t play with me. Mommy has to lay down,” Montez says. “So she’s really kind of understood, you know, ‘If Mommy needs to rest, let Mommy rest.’”

Montez’s balance has also been affected. Aria sometimes holds her mom’s hand in a parking lot and walks her into the store, “because she thinks she’s helping,” Montez says.

With no vaccine or cure yet, how can you deal with West Nile virus?

Twenty-four years after the first North American West Nile case was diagnosed in New York, there’s only so much modern medicine can do for neuroinvasive cases. There are neither vaccines to prevent nor antivirals to treat the infection yet. Pastula says that by the time someone presents with neuroinvasive West Nile disease, much of the damage may have already been done.

But that’s not to say nothing can be done. Those who have had West Nile and feel they’re experiencing cognitive symptoms should seek what’s called supportive care and rehabilitation, Pastula says. To that end, Montez has seen physicians and therapists at UCHealth Greeley Medical Center, UCHealth Medical Center of the Rockies, and UCHealth University of Colorado Hospital on the Anschutz Medical Campus. Her medical team consists of a primary care physician, a neurologist, an infectious disease specialist, a clinical audiologist, a psychiatrist, and specialists in vestibular rehabilitation (to help with balance issues) as well as occupational therapy.

Physical therapy, speech therapy, and sleep therapy can come into play also, Pastula adds. The brain may not be able to significantly regenerate lost neurons, but it can adapt in many cases, he says.

“It’s important to come up with a multidisciplinary rehabilitation plan to gradually push the nervous system to try to adapt to various physical or cognitive loads,” he says. “It’s important for people who have West Nile neuroinvasive disease to do rehabilitation to maximize the recovery they can get.”

The earlier one receives such care, the better, he says. But starting weeks or months can also sometimes bring benefits.

“There is hope for recovery – whether complete or partial – through rehabilitation,” Pastula says.

Montez’s progress is a case in point: She recently started driving again.

Scientists working to better understand West Nile and to develop vaccines

Meanwhile, scientists continue to work the West Nile problem. Vaccine development has been slow, but there has been progress, and the endemic nature of the virus and the personal and health-care-related costs merit more resources be dedicated to vaccine development, experts argue. In the meantime, scientists are focusing on understanding the still-foggy mechanisms of neuroinvasive West Nile. Some of that work his happening on the Anschutz Medical Campus.

CU School of Medicine postdoctoral research fellow Jennifer Berger, PhD, is working under the guidance of CU School of Medicine Immunology and Microbiology Department Chair Leslie Berg, PhD, on understanding how the virus infects the central nervous system. The key question their work is addressing, Berg says, is whether and how much damage the immune system’s T-cells are doing to neurons and other cells as they clear out the infection.

“For certain viral infections, a lot of the bad symptoms come not from the virus, but from the immune response,” Berg says.

Using a weakened strain of a West Nile-type virus called Venezuelan equine encephalitis virus, Berger is observing in mice how a first wave of T-cells rushes into the infected brain before the immune system has had a chance to produce many West Nile-specific T-cells.

“We’re very interested in trying to understand things like, ‘What told them to go there?’ ‘How did they know to go there?’ ‘What kind of cells are they?’ ‘Are they helpful or harmful?’” Berg says. “Based on the data so far, it looks like they’re helpful.”

There’s much more scientific work to be done, she says.

“That’s the goal of most basic science – you try to figure out the basic mechanisms of how things work, and that will help you decide where to put your energy in developing therapeutics,” she says.

How can you prevent West Nile virus?

In the meantime, protecting yourself from mosquito bites can help prevent West Nile infection in the first place. That means taking seriously combinations of bug spray, long sleeves and pants, and avoiding being outside at dusk and dawn. We’ve heard this all before, but take it from Montez – and Pastula, who has spent time studying infectious diseases in some of the world’s mosquito-born-disease hotspots – avoiding getting bitten is worth the trouble.

Whether this spring’s heavy precipitation across much of Colorado will translate into a bad West Nile year remains to be seen. Pastula says seasonal severity depends on some still-nebulous combination of temperature, rainfall, mosquitoes, bird migration, bird immunity, and human activity. Last year was worse than recent ones, with 132 neuroinvasive cases and 20 deaths.

Montez, one of those 132, says being aware of – and avoiding – mosquitoes is the way to go.

“Mosquitoes are just a part of summer. You never think about West Nile or dengue or anything like that – until it happens to you,” she says. “It has cost people their careers and their lives, and children are growing up not being able to be kids because of this. I just I really hope that we can do something to either prevent it or help people that get it in the future.”