Like so many others, I’ve been watching the HBO series The Last of Us. It’s a classic zombie apocalypse drama following Joel (played by Pedro Pascal) and Ellie (Bella Ramsey) as they make their way across the former United States (now run by a fascist government called Fedra).

I’m a big fan of zombie and other post-apocalyptic fiction. And my husband had told me how good the storyline is in the video game that inspired the series, so I was prepared for interesting storytelling. What I didn’t expect was to be so intrigued by the science behind the sci-fi.
In the opening minutes of the series, two scientists on a fictional 1968 talk show discuss the microbes that give them pandemic nightmares. One says it’s fungi — not viruses or bacteria — that keep him awake. Especially worrisome, he says, are the fungi that control rather than kill their hosts. He gives the example of fungi that turns ants into living zombies, puppeteering the insects by flooding their brains with hallucinogens.

He goes on to warn that even though human body temperature keeps us fungus-free, that might not be true if the world got a little bit warmer. He predicts that as the thermostat climbs, a fungus that hijacks insects could mutate a gene allowing it to burrow into human brains and take control of our minds. Such a fungus could induce its human puppets to spread the fungus “by any means necessary,” he says. What’s worse, there are no preventatives, treatments or cures, nor any way to make them.

It’s a brief segment, but it had me hooked. It all sounded so chilling and … plausible. After all, fungi like ones that cause nail infections, yeast infections and ringworm already infect people.

So I consulted some experts on fungal infections to find out whether this could actually happen.

I’ve got good news and bad news.

First, the bad news.

Bad news: Climate change has already helped one fungus mutate to infect humans
I wanted to know if warming has spurred any fungi to mutate and become infectious. So I called Arturo Casadevall. He has been thinking about fungi and heat for a long time. He’s proposed that the need to avoid fungal infections may have provided the evolutionary pressure that drove mammals and birds to evolve warm-bloodedness (SN: 12/3/10).

Most fungal species simply can’t reproduce at human body temperature (37° Celsius, or 98.6° Fahrenheit). But as the world warms, “these strains either have to die or adapt,” says Casadevall, a microbiologist who specializes in fungal infections at Johns Hopkins Bloomberg School of Public Health. That raises the possibility that fungi that now infect insects or reptiles could evolve to grow at temperatures closer to human body temperature.

At the same time, humans’ average body temperature has been falling since the 19th century, at least in high-income countries, researchers reported in eLife in 2020. One study from the United Kingdom pegs average body temperature at 36.6° C (97.9° F). And some of us are even cooler.

Fungi’s possible adaptation to higher heat and humans’ cooling body temperature are on a collision course, Casadevall says.
He and colleagues presented evidence of one such crash. Climate change may have allowed a deadly fungus called Candida auris to acclimate to human body temperatures (SN: 7/26/19). A version of the fungus that could infect humans independently emerged on three continents from 2012 to 2015. “It’s not like someone took a plane a spread it. These things came out of nowhere simultaneously,” Casadevall says.

Some people argue that the planet hasn’t warmed enough to make fungi a problem, he says. “But you have to think about all the really hot days [that come with climate change]. Every really hot day is a selection event,” in which many fungi will die. But some of those fungi will have mutations that help them handle the heat. Those will survive. Their offspring may be able to survive future even hotter heat waves until human body temperature is no challenge.

Fungi that infect people are usually not picky about their hosts, Casadevall says. They will grow in soil or — if given an opportunity — in people, pets or in other animals. The reason fungi don’t infect people more often is that “the world is much colder than we are, and they have no need of us,” he says.

When people do get infected, the immune system usually keeps the fungi in check. But fungal infections can cause serious illness or be deadly, particularly to people with weakened immune systems (SN: 11/29/21; SN: 1/10/23).

The second episode of The Last of Us reveals that the zombie-creating fungi initially spread through people eating contaminated flour. Then, the infected people attack and bite others, spreading the fungus.

In real life, most human infections arise from breathing in spores. But Casadevall says it’s “not implausible” that people could get infected by eating spores or by being bitten.

Also bad: Fungal genes can adapt to higher heat
I also wondered exactly how a fungus could evolve in response to heat. Asiya Gusa, a fungal researcher at Duke University School of Medicine, has published one possibility.

In 2020, she and colleagues reported in the Proceedings of the National Academy of Sciences on how one fungus mutated at elevated temperature to become harder to fight.

Cryptococcus deneoformans, which already infects humans (though it’s no zombie-maker), became resistant to some antifungal drugs when grown at human body temperature. The resistance was born when mobile bits of DNA called transposons (often called jumping genes) hopped into a few genes needed for the antifungals to work.

In a follow-up study, Gusa and colleagues grew C. deneoformans at either 30° C or 37° C for 800 generations, long enough to detect multiple changes in their DNA. Fungi had no problem growing at the balmy 30° C (86° F), the temperature at which researchers typically grow fungi in the lab. But their growth slowed at the higher temperature, a sign that the fungi were under stress from the heat.

In C. deneoformans, that heat stress really got things jumping. One type of transposon accumulated a median of 12 extra copies of itself in fungi grown at body temperature. By contrast, fungi grown at 30° C tended to pick up a median of only one extra copy of the transposon. The team reported those results January 20 in PNAS. The researchers don’t yet know the effect the transposon hops might have on the fungi’s ability to infect people, cause disease or resist fungus-fighting drugs.

So yeah, the bad news is not great. Fungi are mutating in the heat and at least one species has gained the ability to infect people thanks to climate change. Other fungi that infect people are more widespread than they were in the 1950s and 1960s, also thanks to a warming world (SN: 1/4/23).

But I promised good news. And here it is.

Good news: Human brains may resist zombification
It may not be our body temperature, but our brain chemistry, that protects us from being hijacked by zombifying fungi.

I consulted Charissa de Bekker and Jui-Yu Chou, two researchers who study the Ophiocordyceps fungi that are the model for the TV show’s fungal menace. These fungi infect ants, flooding the insects with a cocktail of chemicals that steer the ants to climb plants. Once in position, the ants chomp down and the chemicals keep the jaw muscles locked in place (SN: 7/17/19).

Unlike most fictional zombies, the ants are alive during this process. “A lot of people get the misconception that we work on undead ants,” says de Bekker, a microbiologist at Utrecht University in the Netherlands. She’s glad to see the show “stick to the story of the host being very much alive while its behaviors change.” The fungi even help preserve the ant, keeping it alive even while feeding on it. But eventually the ant dies. Then a mushroom rises from the corpse, showering spores onto the ground where other ants may become infected.

Related species of Ophiocordyceps infect various species of ants and other insects. But each fungal species is very specific to the host it infects. That’s because the fungi had to individualize the chemicals they use to control the particular species they infect. The ability to manipulate behavior comes at the cost of not being able to infect multiple species.
A fungus that specializes in infecting ants probably can’t get past humans’ immune systems, says Chou, a fungal researcher at the National Changhua University of Education in Taiwan. “Think of a key that fits into a specific lock. It is only this unique combination that will trigger the lock to open,” he says.

Even if the fungi evolved to withstand human body temperature and immune system attacks, they probably couldn’t take control of our minds, de Bekker says. “Manipulation is like a whole different ballgame. You need a ton of additional tools to get there.” It took millions of years of coevolution for the fungi to master piloting ants, after all.

While fungi do make mind-altering chemicals that can affect human behavior (LSD and psilocybin, for instance), Casadevall agrees that fungi that mind control insects probably won’t turn humans into zombies. “It’s not one of my worries,” he says.

Infected ants don’t turn into vicious, biting zombies either, de Bekker says. “If anything, we actually see the healthy ants being aggressive toward infected individuals, once they figure out that they’re infected, to basically get rid of them.” That “social immunity” helps protect the rest of the nest from infection.

Also good: Humans are innovative enough to develop treatments
The fictional scientist’s assertion that we couldn’t prevent, treat or cure these fungal infections is also a stretch.

Antifungal drugs exist and they cure many fungal infections, though some infections may persist. Some that spread to the brain may be particularly difficult to clear.Some fungi are also evolving resistance to the drugs. And a few fungal vaccines are in the works, although they may not be ready for years.

The experts I talked to say they hope the show will bring attention to real fungal diseases.

Gusa was especially glad to see fungi in the limelight. And she shares my fondness for that retro series opening in which the scientist predicts climate change could spawn mind-controlling fungi bent on infecting every person on the planet.

“I was pretty much yelling at the TV when I watched the [show’s] intro,” in an excited kind of way, she says. “This is the foundation of a lot of my grant funding … the threat of thermal adaptation of fungi.… To see it played out on the screen was something kind of fun.”

Fledgling crustaceans have eyes like the sea, a peculiarity that could help them hide from predators.

Young shrimp, crab or lobster larvae already rock nearly translucent bodies to stay out of view. But dark eye pigments essential for vision pose the risk of exposing the animals anyway.

Some see-through ocean animals rely on mirrored irises or minuscule eyes to avoid detection. Young shrimp and prawns, on the other hand, camouflage their dark pigments behind light-reflecting glass made of tiny, crystalline spheres, researchers report in the Feb. 17 Science.
Variations in the size and placement of the orbs allow the crustaceans’ eyes to shine light that precisely matches the color of the surrounding water, possibly rendering them invisible to predators on the hunt for a meal.

Technologies that mimic the nanospheres’ structure could one day inspire more efficient solar energy or bio-friendly paints, the scientists say.

“I’ve often wondered what’s going on with [these animals’] eyeshine,” says evolutionary biologist Heather Bracken-Grissom of Florida International University in Miami, who was not involved in the study. She and colleagues often collect crustaceans from the deep sea, giving them nicknames like “blue-eyed arthropod” or “green-eyed, weird-looking shrimp” because the creatures don’t resemble their adult forms. Now, she says, that eye color makes sense.

In the study, chemist Keshet Shavit and colleagues used an electron microscope to peer into the eyes of lab-raised and wild crustaceans. Inside shrimp and prawn eyes, the team found crystalline nanospheres made of isoxanthopterin, a molecule that reflects light.

The spheres are a bit like disco balls, with highly reflective surfaces pointing outward, says study coauthor Benjamin Palmer, a chemist at Ben-Gurion University of the Negev in Beer-Sheva, Israel. Each sphere is made of thin, isoxanthopterin plates that stick together to form balls that range in size from around 250 to 400 nanometers in diameter.

These balls are arranged in clusters at the base of protein-dense cones that focus light on the animal’s light-sensing nerves, and form a protective cover over the pigmented cells. But crustacean larvae can still see because there are small holes in the glass, Palmer says. “It’s basically allowing light to go down to the retina on some specific angles, but on other angles, it’s reflecting light back.”
The size and order of the spheres seem to influence the color of the reflected light, the team’s observations and computer simulations show.

“The correlation between the particle size and the eyeshine color is beyond amazing,” says Shavit, also at Ben-Gurion University. Nanosphere size appears to help the animals’ eyes match the color of their native habitat, helping the critters blend into the background.

Blue-eyed shrimp that inhabit the Gulf of Aqaba’s clear blue waters off the coast of Israel, for instance, have spheres that are approximately 250 to 325 nanometers in diameter. The 400-nanometer-wide spheres of a freshwater prawn (Macrobrachium rosenbergii) glitter yellow-green, mimicking muddy waters found in the salty estuaries where they live.
The prawn’s eyes also seem to be able to reflect different colors in different environments. Individuals exposed to sunlight for four hours in the lab had silvery yellow eyes, possibly a result of nanospheres arranged in a disorganized jumble. But individuals left in the dark overnight had green eyes. Their nanospheres are arranged in layers — though the orbs within each layer are still disorganized, Palmer says.

Such adaptable eyes could help larvae move undetected through different parts of the ocean as changing light levels alter the color of the water, Bracken-Grissom says. At night, young crustaceans migrate to shallow waters to feed and dive back down when the sun rises. “If they are in fact using it as a form of camouflage, it would be an ingenious way to camouflage themselves as they move through these different light environments.”

Following the most severe known mass extinction in Earth’s history, vibrant marine ecosystems may have recovered within just a million years, researchers report in the Feb. 10 Science. That’s millions of years faster than previously thought. The evidence, which lies in a diverse trove of pristine fossils discovered near the city of Guiyang in South China, may represent the early foundations of today’s ocean-dwelling ecosystems.

The conventional story was that the ocean was kind of dead for millions of years after this mass extinction, says paleontologist Peter Roopnarine of the California Academy of Sciences in San Francisco, who was not involved in the research. “Well, that’s not true. The ocean [was] very much alive.”
The Great Dying, or Permian-Triassic mass extinction, occurred around 251.9 million years ago, at the end of the Permian Period, after a series of massive volcanic eruptions (SN: 12/6/18).

“The oceans warmed significantly, and there’s evidence for acidification, deoxygenation [causing widespread dead zones], as well as poisoning,” says Roopnarine. “There [were] a lot of toxic elements like sulfur entering into parts of the ocean.”

Life in the seas suffered. More than 80 percent of marine species went extinct. Some researchers have even proposed that entire trophic levels — castes in an ecosystem’s food web — may have vanished.

Figuring out how long life took to fully recover in the wake of all that loss has been challenging. In 2010, researchers studying fossils from the Luoping biota in China proposed that complex marine ecosystems fully rebounded within 10 million years. Later, other fossil finds, such as the Paris biota in the western United States and the Chaohu biota in China, led scientists to suggest that marine ecosystems reestablished themselves within just 3 million years.

Then in 2015, a serendipitous discovery narrowed the gap again. Paleontologist Xu Dai, then an undergraduate student at the China University of Geosciences in Wuhan, was studying rocks from the early Triassic during a field trip near the city of Guiyang, when he split open a piece of black shale. Within the rock, he discovered a surprisingly well-preserved fossil of what would later be identified as a primitive lobster.

The arthropod’s immaculate condition sparked a series of return trips. From 2015 to 2019, Dai, now at the University of Burgundy in Dijon, France, and his colleagues uncovered a bricolage of fossilized life: Predatory fish as long as baseball bats. Ammonoids in swirled shells. Eel-like conodonts. Early shrimps. Sponges. Bivalves. Fossilized poo.
And the prizes kept coming. Both under and within the Guiyang biota, Dai and his colleagues discovered beds of volcanic ash. An analysis of the amounts of uranium and lead in the ash revealed that the Guiyang biota contained fossils from roughly 250.7 to 250.8 million years ago (SN: 5/2/22). The dating was further supported by the types of fossils found and by an analysis of the different forms of carbon in the rocks.

Finding a potpourri of life of this age suggests that marine ecosystems rebounded quickly after the Great Dying, within just 1 million years or so, Dai says.

Alternatively, it may indicate that the extinction event failed to wipe out entire trophic levels, says paleontologist William Foster from the University of Hamburg in Germany, who was not involved in the study. “You have this really environmentally stressful world, but some former marine ecosystems survive.”

Regardless, it seems clear that these ecosystems were hardy. Due to the motion of tectonic plates, the community preserved in the Guiyang biota was located in the tropics during the early Triassic. At that time, the temperature of the sea surface was nearly 35⁰ Celsius, and past research had suggested many organisms may have migrated away to escape the heat. But, the discovery of the Guiyang biota challenges that, Foster says. Sea creatures “are tolerating it somehow, they’re adapting.”

According to Dai, the fossils may be evidence that the roots of today’s marine ecosystems took hold shortly after the Great Dying. “These groups are related to modern fish, lobsters and shrimps, their ancestors,” he says. “The oldest time we can find similar seafood to today is [in the time of] the Guiyang biota.”

But Roopnarine is skeptical. It remains to be seen exactly how the Guiyang biota connects to today’s ecosystems, he says. The fossil assemblage could represent an ephemeral collective of life rather than a stable community, he adds, pointing out that ammonoids and conodonts went extinct.

Further work will help resolve the many questions unearthed with the Guiyang biota, Dai says. He and his colleagues plan to head back into the field this summer for the first time since 2019. When asked if he’ll be keeping his eyes peeled for another lobster, he responds: “Of course.”

Tanklike armored dinosaurs probably pummeled each other — not just predators — with huge, bony knobs attached to the ends of their tails. Thanks to new fossil findings, researchers are getting a clearer understanding of how these rugged plant eaters may have used their wicked weaponry.

Many dinosaurs known as ankylosaurids sported a heavy, potentially microwave-sized tail club. This natural sledgehammer has long been considered by both scientists and artists as a defensive weapon against predators, says Victoria Arbour, a paleontologist at the Royal British Columbia Museum in Victoria, Canada.

Fossil evidence for tail clubs’ targets was largely lacking, until Arbour and her colleagues chipped more rock away from the same skeleton they used to describe a new armored dinosaur, Zuul crurivastator, in 2017 (SN: 6/12/17).

The dinosaur had five broken spikes on its sides. The team’s statistical analyses showed the damaged spikes clustered in specific regions of the body. If a large carnivorous dinosaur made these injuries, says Arbour, they’d likely be more randomly distributed and include bite and scratch marks.
Instead, the injuries are more consistent with clubbing, the researchers report December 7 in Biology Letters.

Armored dinosaurs’ tail clubs start out either absent or too tiny to mount a major defense, and they get proportionally larger with age. Similar growth patterns occur in some modern animal weaponry like antlers. It’s possible that tanklike dinosaurs sparred with each other for mates, food or territory much like male deer and giraffes do today.

And that tail could also be useful in a pinch. “Having a tail club you can swing around at the ankles of a two-legged predator is a pretty effective weapon,” says Arbour.

“Ankylosaurs are often portrayed as stupid, loner dinosaurs,” she adds. The findings “show that they probably had much more complex behaviors than we give them credit for.”

Books about the pandemic. Books about the ancient past. Books about outer space. These were a few of Science News staff’s favorite reads. If your favorite didn’t make this year’s cut, let us know what we missed at feedback@sciencenews.org.

Vagina Obscura
Rachel E. Gross
W.W. Norton & Co.
$30

For centuries, scientists (mostly males) have ignored female biology, and women’s health has suffered. But researchers are finally paying attention, as Gross explains in this fascinating tour of what little is known about female anatomy (SN: 4/9/22, p. 29).

The Song of the Cell
Siddhartha Mukherjee
Scribner
$32.50

Patient stories and conversations with scientific luminaries enliven this tale of cell biology’s past, present and future, and how advances in the field have reshaped medicine (SN: 11/5/22, p. 28).

Breathless
David Quammen
Simon & Schuster
$29.99

In this portrait of the coronavirus and the scientists who study it, Quammen investigates some of the most pressing questions about the pandemic, including whether or not the coronavirus could have accidentally escaped from a lab (SN: 9/24/22, p. 28).

Virology
Joseph Osmundson
W.W. Norton & Co.
$16.95

This wide-ranging collection of essays is a meditation on society’s complicated relationship with viruses. In pondering SARS-CoV-2, HIV and more, Osmundson calls for more equitable access to medical care (SN: 7/16/22 & 7/30/22, p. 36).

The Milky Way
Moiya McTier
Grand Central Publishing
$27

This absorbing “autobiography,” written from the perspective of the Milky Way (a very sassy Milky Way), draws on mythology and astronomy to persuade readers that our home galaxy deserves respect and admiration (SN: 9/10/22, p. 28).

A Portrait of the Scientist as a Young Woman
Lindy Elkins-Tanton
William Morrow
$29.99

In this moving memoir, Elkins-Tanton recounts her journey to becoming a planetary scientist and leader of a NASA asteroid mission. Her struggles with childhood trauma and sexism in her career lay bare the barriers that many women in science still face (SN: 8/13/22, p. 26).

An Immense World
Ed Yong
Random House
$30

So much of the world is beyond the grasp of human perception, but this safari through animal senses helps readers imagine what we’re missing (SN: 7/16/22 & 7/30/22, p. 36).

How Far the Light Reaches
Sabrina Imbler
Little, Brown, & Co.
$27

By drawing parallels between their own life and the stories of bobbit worms, octopuses, sperm whales and other deep-sea dwellers, Imbler muses on such weighty themes as adaptation, survival and sexuality.

The Last Days of the Dinosaurs
Riley Black
St. Martin’s Press
$28.99

The basic story of the downfall of nonbird dinosaurs is familiar: They were killed off by an asteroid that slammed into Earth 66 million years ago. Using the most up-to-date science, Black fleshes out this tale, painting a vivid portrait of life before and after this apocalypse (SN: 4/23/22, p. 28).

The Rise and Reign of the Mammals
Steve Brusatte
Mariner Books
$29.99

The perfect follow-up to Black’s book on how the Age of Dinosaurs ended is this sweeping history of how the Age of Mammals began. Brusatte traces the origins of the evolutionary innovations that have made mammals so successful (SN: 6/18/22, p. 28).

Origin
Jennifer Raff
Twelve
$30

Exactly how and when humans first came to the Americas is still unsettled science. But Raff gathers archaeological and genetic evidence to piece together a convincing scenario. She also points out past mistreatment of Indigenous communities by geneticists and calls on researchers to do better and foster more collaborations (SN: 2/12/22, p. 29).

Pests
Bethany Brookshire
Ecco
$28.99

So-called pests are a human invention, argues Brookshire, a former staff writer for Science News for Students (now Science News Explores). In coming face to face with rats, feral cats, pythons and even elephants, Brookshire teases out the various social factors that cause people to deem certain animals a nuisance (SN: 12/3/22, p. 26).

A parasite might be driving some wolves to lead or go solo.

Wolves in Yellowstone National Park infected with Toxoplasma gondii make more daring decisions than their uninfected counterparts, researchers report November 24 in Communications Biology. The wolves’ enhanced risk-taking means they are more likely to leave their pack, or become leaders of their own.

“Those are two decisions that can really benefit wolves, or could cause wolves to die,” says Connor Meyer, a field biologist at the University of Montana in Missoula. The findings reveal a parasite’s potent ability to influence a wolf’s social fate.

Disease is often considered important for wildlife, mostly in the context of killing its host, Meyer says. “We have evidence now that just being infected with a certain parasite — Toxoplasma — can have pretty major implications for wolf behavior.”
Single-celled T. gondii has a track record of altering animal behavior. Its most important hosts are cats, which provide a breeding ground for the parasite in their small intestine. The parasite offspring hitch a ride on feline feces. Other animals then ingest the parasite, which then manipulates its new hosts’ behavior by tweaking certain hormones, making the hosts bolder or more aggressive. Infected mice, for example, can fatally lose their fear of cats, allowing the parasite to infect more hosts once the mice are consumed (SN: 1/14/20).

In Yellowstone National Park, many wolves are also infected with T. gondii, recent research has shown. So Meyer and colleagues wondered if gray wolves (Canis lupus) in the park showed any parasite mind-bending of their own.
Wolves were reintroduced to Yellowstone in 1995. Ongoing study of the park’s packs meant that the researchers had access to about 26 years’ worth of blood samples, behavioral observations and movement data for 229 of the park’s wolves.

The team screened the wolf blood for antibodies against T. gondii parasites, which reveal an infection. The researchers also noted which wolves left their pack — usually a family unit consisting of a breeding pair and their offspring — or became a pack leader.

Both are high-stakes moves for a wolf, Meyer says.

Infected wolves were 11 times as likely as noninfected wolves to disperse from their pack, the team found, and about 46 times as likely to eventually become leaders. The findings fit in with T. gondii’s apparent ability to boost boldness across a wide range of warm-blooded life.
The study fills a crucial gap in the Toxoplasma pool of knowledge, says Ajai Vyas, a neurobiologist at Nanyang Technological University in Singapore, who was not involved with the study.

“Most of the earlier work has been done in the lab,” Vyas says. But there are limitations to that approach, especially for re-creating how animals experience the effects of the parasite in their natural environment. Such research has “become almost like studying whale swimming behavior in backyard pools; [it] does not work very well.”

Wolves’ enhanced boldness may even form a feedback loop, the team proposes. The researchers found that not only do cougars (Puma concolor) in the park carry the parasite, but wolves’ infection rates were highest when the animals’ ranges overlapped with the park’s densest aggregations of cougars. Infected wolf leaders may be more likely to bring pack members into riskier situations, including approaching cougar territories, making additional infections more likely.

The feedback-loop idea is “very fascinating,” but more research is needed to confirm it, says Greg Milne, an epidemiologist at the Royal Veterinary College in London, who was not involved with the study. Such research may involve determining if infected wolves are more likely to migrate into an area with more cougars.

“I think people are just starting to really appreciate that personality differences in animals are a major consideration in behavior,” says study coauthor Kira Cassidy, a wildlife biologist at the Yellowstone Wolf Project in Bozeman, Mont. “Now we add a parasite-impacting behavior to the list.”

Next, the team is interested in examining the long-term consequences of a T. gondii infection, and whether infected wolves make better leaders or dispersers than uninfected wolves.

It’s also not known how infection impacts survival and reproduction rates, Cassidy says. “Infection may very well be detrimental in some ways and advantageous in others.”

As we head into our third pandemic winter, most people are all too familiar with the signs of COVID-19. The disease wears many different faces and can show up as chills, cough, difficulty breathing or other troublesome jumbles of symptoms. But sometimes, this illness can look positively peculiar.

On rare occasions, SARS-CoV-2 rears its head in body parts not typically touched by respiratory viruses. From head to COVID toe, doctors have seen a bevy of bizarre cases. Patchy tongues, puffy digits, hair loss — such issues can be worrisome for patients, says Peter Chin-Hong, an infectious diseases physician at the University of California, San Francisco.

But the outlook doesn’t have to be. That’s because such symptoms can end up going away on their own, says Chin-Hong, who has treated hundreds of people with COVID-19.

No one knows exactly how often COVID tongue, COVID toe, COVID eye or other rare conditions occur — and it’s not always clear that COVID-19 is the actual culprit. Still, the sheer scale of coronavirus infections means that SARS-CoV-2 has had many chances to show its stuff (SN: 9/8/22). The United States is now closing in on 98 million confirmed cases. Such a staggering case count means that “statistically speaking, you’re going to find people with more and more weird things,” Chin-Hong says.
Doctors rely on medical case reports for leads on potential treatments and hints about how long symptoms may last. Even just knowing that someone else has had splotchy mouth sores or tender toes can be helpful, Chin-Hong says. That lets him tell his patients, “You’re not the only one,” he says. “That means a lot to a lot of people.”

Internal medicine doctor Saira Chaughtai published one such study in October in the Journal of Medical Case Reports after one of her primary care patients came in with a symptom Chaughtai had never seen. Ten days after testing positive for COVID-19, the patient’s tongue began to swell, eventually erupting in white-ringed lesions.

Certain spots looked “denuded,” says Chaughtai, of Hackensack Meridian Health in Neptune, N.J. It was as if some of the tongue’s surface bumps had been sandpapered away. The patient wasn’t someone doctors would typically consider vulnerable, either. She was 30 years old, fit and healthy.

“I was like, ‘Oh my god, COVID can do anything,’” Chaughtai remembers thinking.
Oral sores can look different among patients. Chin-Hong has seen people with tongues coated white, as if they’d chewed a mouthful of tortilla chips. For Chaughtai’s patient, COVID tongue felt sensitive and irritated, with flare-ups that burned. Chaughtai wasn’t sure how to treat it.

She searched the scientific literature and prescribed an assortment of mouthwashes, which helped. But six months in, the patient’s tongue hadn’t fully healed. So Chaughtai got creative. She teamed up with a sports medicine doctor, who beamed low-level laser light at the patient’s tongue. He had previously used this photobiomodulation therapy to treat muscle injuries.

Laser light therapy makes blood vessels dilate, enhancing blood flow to treated areas, which could promote healing, Chaughtai says. It seemed to work for her patient. The tongue lesions began to heal and flare-ups subsided. The woman still occasionally feels some tongue sensitivity when stressed, but never as bad as her initial outbreak.

The effects of COVID toe
About 1,300 kilometers west, a podiatrist in Crown Point, Ind., also dilated a patient’s blood vessels to treat a curious coronavirus condition: COVID toe. After infection with SARS-CoV-2, patients’ fingers and toes can plump up, sometimes painfully, and turn pink or reddish purple.

“We were seeing cases of these lesions that look like chilblains, which is something you get when you’re exposed to cold weather,” says Michael Nirenberg of Friendly Foot Care. But his patients hadn’t been in the cold — they’d been exposed to the coronavirus.

Nirenberg has seen as many as 40 people with the symptom, which he’s found tends to clear up in a month or two. But one of his patients, a 59-year-old man, just couldn’t kick COVID toe. It ultimately lingered for nearly 670 days — the longest documented case Nirenberg has seen. “The term we used was long COVID toe,” he says. Nirenberg and colleagues reported the case this spring in the Journal of Cutaneous Pathology.
Nirenberg prescribed daily application of a nitroglycerin ointment to boost blood flow to the toes. That may have helped, Nirenberg says, “but I don’t know if time also did the trick.” After 22 months, the condition may have finally resolved on its own.

The number of COVID toes Nirenberg encounters these days has gone down, but he’s still seeing people come in with the condition. And though Chaughtai has not treated another case of COVID tongue, a man recently e-mailed her saying that he had suffered from a similar affliction for two years.

UCSF’s Chin-Hong says he thinks it’s important for people to know that COVID-19 can cause such a variety of symptoms (SN: 11/11/22). “We can’t really predict who’s going to get what,” he says. But in his experience, strange symptoms have tended to crop up more often in people who haven’t been vaccinated.

Such symptoms may not be as serious as COVID-affected hearts or lungs, but they can certainly look scary, Chin-Hong says. “If this is a reason why some people might get vaccinated,” he says, “I think that would be great.”

If you saw Carlos Argüelles-Delgado’s childhood bedroom — the whiteboard for working out problems, the math textbooks they asked for as birthday gifts — you’d likely not be surprised that this kid would grow up to push the boundaries of modern physics.

For years, physicists have known that the most successful theory to describe what the universe is made of, called the standard model, is broken. By prying at one of the biggest cracks in the framework — neutrinos — Argüelles aims to discover what’s next for the field.

Neutrinos are mysterious even for subatomic particles. They’re hard to study because they barely interact with matter, and what scientists do know about them is baffling — like the fact that neutrinos have mass when the standard model predicts they shouldn’t. “That’s why I like neutrinos,” Argüelles says. “They misbehave.”

Many scientists think this confusing behavior is a sign that neutrinos are affected by undiscovered particles. In that case, demystifying neutrinos could open a new window on the universe. The question is: Who are these hidden partners, and how can scientists find them?
Standout research
To search for answers, Argüelles often relies on data from the IceCube Neutrino Observatory in Antarctica. IceCube’s thousands of buried detectors spot neutrinos from the faint flashes of light they leave after interacting with ice.

For their Ph.D., Argüelles combed through these signals to look for “sterile” neutrinos. If this breed of neutrinos exists, they would interact with matter even less than normal neutrinos do. Sterile neutrinos could explain several troubling problems with the standard model, like why neutrinos have mass and why antimatter is rarer than matter. Sterile neutrinos are also a candidate for dark matter, the unidentified substance that outweighs normal matter in the universe.

The search made for a huge project, but Argüelles finished it in about half of the time typical for U.S. Ph.D.s in the physical sciences. And though they found no signs of the would-be particle, Argüelles ruled out some ideas about what it could be like.
“It was an amazing performance,” says neutrino physicist Francis Halzen, who advised Argüelles’ Ph.D. work at the University of Wisconsin–Madison and is IceCube’s head scientist. “It was a piece of art.”

Argüelles also looks for other possible hidden particles, like WIMPs, a hypothetical particle that could be a form of dark matter. And Argüelles isn’t afraid to pursue research farther from their specialty. Though no expert in quantum computers, for example, Argüelles was the first to use a quantum computer to simulate how neutrinos can change from one type to another. That could one day help scientists better understand neutrino-rich events like supernova explosions.

“I just hate when people tell me I cannot do something,” Argüelles says.

Halzen describes Argüelles as fearless, the kind of scientist who is never afraid to ask questions. “I don’t think they have any regard for their reputation, ever,” he says.
Backstory
Argüelles’ attitude toward research is, in part, forged by past struggles to overcome hardship and discrimination.

“There are worse things in life than not being able to solve a problem,” they say.

Growing up in Peru meant building a life on shifting ground. The economy was unstable, and at times Argüelles’ family struggled to make ends meet.

Though Argüelles’ parents were supportive and saw knowledge as a safe investment, they at first rejected Argüelles’ desire to study physics. Argüelles, wiping a tear from their eye, recalls their father saying, “You’re just going to die of hunger.” Soon Argüelles’ parents did embrace the career choice.

Argüelles says Peru, when they were growing up, was also an “extremely negative environment” for LGBTQ+ people. “I’m a gay man,” they say, “and it was very, very, very difficult.”

Same-sex marriages are not recognized in Peru. Hate crimes and discrimination based on sexual orientation were only prohibited in 2017, by a presidential decree that the country’s Congress tried but failed to overturn.

When Argüelles left Peru in 2012 to pursue their Ph.D., they found that studying physics in the United States wasn’t without obstacles. Almost nobody high up in the field looked like them. They struggled under the weight of expectations and felt that voicing their anxieties would get them branded as weak. But with help from mentors, Argüelles persevered.

Now, as an assistant professor at Harvard, Argüelles sees their students — particularly women and Hispanics — facing the same challenges. Argüelles is passionate about supporting them.

“It’s about not giving up, right?” Argüelles says. “I still go through some of these things myself. But I’ll survive it.”

Visitors to the village of Drumnadrochit, on the western shore of Scotland’s murky Loch Ness, come to see the nearby ruins of Urquhart Castle or to chance a glimpse of the elusive Loch Ness Monster. But growing up in Drumnadrochit, planetary scientist Robin Wordsworth says it was the unobscured view of the cosmos that seized his attention. “There are incredibly clear skies up there,” he says.

Today, Wordsworth lives on the other side of the Atlantic. He’s a researcher and professor at Harvard University. But his gaze is still set on the solar system and beyond. From studying how rocky planets may occasionally become encased in glaciers to exploring the sizes of alien raindrops or the details of how humans might one day settle Mars, Wordsworth’s scientific explorations vary widely. His research group tends to “do a lot of different things at once,” he says. “If I was to summarize it in a sentence, it would be to understand what drives habitability on planets through time.”

Standout research
Wordsworth defines a planet’s habitability as its ability to support life. The idea that life could survive elsewhere in the cosmos has always fascinated Wordsworth, a science fiction fan. Apart from Earth, astronomers have discovered roughly 20 potentially habitable worlds in the universe. With data collected by ground-based observatories, satellites and rovers, he uses supercomputers to construct simulations of planets and the evolution of their climates. Climate is a big focus because it determines whether a planet’s surface can harbor liquid water — a necessity for all known forms of life.
Wordsworth’s most notable research reconstructs the climate of early Mars. Martian river valleys and other geologic clues suggest that abundant liquid water once flowed across the Red Planet, and the early Martian climate has thus become a hot topic for scientists seeking signs of alien life. But for decades, the best researchers could do was build one-dimensional models that struggled to replicate key atmospheric components, such as clouds.

In 2013 while at the Laboratory of Dynamic Meteorology in Paris, Wordsworth and colleagues presented a 3-D model of the early Martian climate, with clouds and an atmosphere containing large amounts of carbon dioxide. Those are key components for studying how the early Martian atmosphere may have reflected and trapped heat, says astrobiologist James Kasting of Penn State.

Wordsworth was the one who figured out how to incorporate clouds into the model, thanks to his strong programming skills, handle over mathematics and determination, Kasting says. “He’s been publishing the best climate calculations for early Mars. There’s really nobody else who is in his lane.”
What’s next
Wordsworth’s otherworldly reconstructions may help us better understand whether life might have emerged on Mars or elsewhere. Another strand of his research could help humans one day settle the Red Planet.

Today, most of Mars’ surface is too cold to sustain liquid water, and the planet’s thin atmosphere offers little protection from the sun’s intense ultraviolet radiation. These conditions make it inhospitable to would-be Martian settlers. But in a 2019 study, Wordsworth and colleagues proposed that sheets of insulating silica aerogel deployed over ice-covered areas might make survival possible.

In lab tests, layers of aerogel just centimeters thick filtered out 60 percent of UVA and UVB radiation and almost all of the more dangerous UVC rays, while permitting enough light through for photosynthesis. What’s more, the shields warmed the air underneath by more than 50 degrees Celsius, which could make liquid water and growing crops possible. Looking ahead, Wordsworth plans to investigate how settlers on Mars might use bioplastics or other renewable materials to become self-sustaining.

And far beyond the Red Planet, the exoplanets await. “The James Webb Space Telescope has just begun to collect new exoplanet data,” Wordsworth says. Observations of their atmospheres will help researchers test ideas about how these distant planets and their climates evolve, he says. “It’s just an incredibly exciting time.”

Belinda Hankins first grappled with COVID-19 in the spring of 2020. She had a fever, chills and trouble breathing, but the real clincher was her loss of smell. Hankins remembers opening a canister of Tony Chachere’s creole seasoning, lowering her nose to take a whiff, and not smelling a thing. “That stuff usually clears the kitchen,” she says.

Her second infection, two years later, was worse. After 12 long weeks of endless fatigue and aching joints, her doctor suggested she seek treatment for long COVID. The lingering, sometimes full-body condition can plague people for months or years after a COVID-19 infection (SN Online: 7/29/22).

In late August, I joined Hankins, age 64, in a small exam room for her first in-person consultation at the Johns Hopkins Post-Acute COVID-19 Team clinic. Wearing a navy dress and a blue surgical mask, Hankins is sitting in a chair across from physician Alba Azola. As they discuss Hankins’ symptoms, doctor and patient face each other, Azola occasionally swiveling her stool to tap notes into a computer.

Hankins’ symptoms are extensive. Brain fog, fatigue and pain top the list. She’s depressed. Sleep doesn’t feel restful. She has trouble focusing, is often light-headed and regularly loses her balance. Even walking to the clinic from the parking lot left her winded and in pain. “I’m extremely exhausted,” she says. “I have not felt good in a long time.” Hankins, pauses, wiping away a tear. “I wasn’t like this before.”
Hankins, a retired digital media consultant, used to be an avid skier and a cyclist. She loved to travel and dance and was planning to learn how to play golf. She’s not sure what the future holds, though she tells me she still has faith she can be active again.

Treating people with long COVID can be complicated – especially for Hankins and those who have other medical conditions. She has pulmonary hypertension, fibromyalgia and the connective tissue disease scleroderma. It’s tricky to tease out which symptoms come from the viral infection. Azola’s approach is to listen, ask questions and listen some more. Then, she’ll zero in on a patient’s most pressing concerns. Her goal: manage their symptoms. “How can we make their quality of life better?” she asks.
System overload
On the afternoon of Hankins’ visit, it’s a warm summer day in Baltimore, blue skies laden with fleecy clouds. Inside the labyrinthine halls of Johns Hopkins Bayview Medical Center, the vibe is not quite as sunny: bright lights, shiny floors, people in line and people in scrubs. Everyone I see is masked.

Azola meets me in the waiting area, walking briskly and wearing bright red glasses. Before the pandemic, Azola, a rehabilitation physician, treated patients recovering from strokes, spinal cord injuries and other disorders. Most mornings, she still works with these patients. But for the past two years, her afternoons have been booked with people laid low by COVID-19.

She’s squeezed me in to talk about the Johns Hopkins PACT clinic, which opened in April 2020, around the time when the world hit one million confirmed cases. “To be honest, we didn’t know what to expect,” Azola says. Back then, most of the clinic’s patients were recovering from COVID-19 after a stay in the hospital’s intensive care unit. Now, at least half of their patients never got sick enough with COVID-19 to be hospitalized – yet still had symptoms they couldn’t shake. In a single week, Azola and her colleagues may get 30 referrals. “It’s constant,” she says, “more than we can provide service to.”

As those referrals pile up, patient wait times can stretch. The PACT clinic expanded last summer, and now has more than a dozen people on staff, including therapists, physicians and other specialists. They try to keep the wait to around two months, Azola says, but sometimes it takes up to four months for a patient to be seen.
The demand here and at clinics across the country isn’t likely to let up. As of mid-November, the United States has reported nearly 97.9 million cases of COVID-19. Though long COVID numbers can be hard to pin down, nearly half of people infected with SARS-CoV-2 hadn’t fully recovered six to 18 months after their infection, according to a large Scottish study published in Nature Communications on October 12. A more conservative estimate from the United States suggests that more than 18 million U.S. adults could have long COVID.

“We are in the middle of a mass disabling event,” says Talya Fleming, a physician at the JFK Johnson Rehabilitation Institute in Edison, N.J.

Scattershot solutions
In the United States, some 400 clinics have popped up from coast-to-coast to care for the growing wave of long COVID patients.

Although the American Academy of Physical Medicine and Rehabilitation has published some guidance, no gold-standard therapies exist and there are no formal criteria for long COVID clinic performance. The Academy brought together more than 40 post-COVID clinics, including the Hopkins PACT clinic, to share experiences and discuss best practices for long COVID treatment. “We’re kind of guiding each other,” Azola says. Other clinics in the United States are more-or-less forging their own paths.

Today, Azola and colleagues are focusing on their patients’ symptoms, a strategy other long COVID doctors and clinics are using too. “There is no one, singular long COVID experience,” says pulmonologist Lekshmi Santhosh. So doctors really need to take a “customized, symptom-directed approach.”

Santhosh founded the OPTIMAL clinic at the University of California, San Francisco to provide follow-up care for people who had COVID-19. Since 2020, she’s seen hundreds of patients, who can wait weeks to months for an appointment, like they do at Hopkins. One main question Santhosh hears from patients is: “When am I going to get better?” That’s hard to answer, she admits.
Scientists can’t yet predict how or when a patient will recover, and they don’t know why long COVID strikes some people and spares others. Right now, there are no obvious rules. “If you are young, you can get long COVID. If you have no pre-existing health conditions, you can get long COVID. If you’ve had COVID before, you still can get long COVID,” Fleming says. The list goes on.

At UCSF, Santhosh says she’s seen it all. Long COVID can affect a 75-year-old patient who was hospitalized for COVID-19, or a 35-year-old marathoner whose stubborn symptoms developed after just a mild infection. One patient can be hit with a hailstorm of health conditions, another patient, just a few.

“I’ve heard some weird things,” Azola says. She remembers one patient who felt as if a phone were vibrating deep inside their bones. Another described a sensation of heaviness, like their legs were made of lead.

Long COVID’s scattershot symptoms currently require a smorgasbord of solutions. For headaches, a doctor might prescribe a combo of pain relievers. For shortness of breath, an inhaler to open the airways could help. For brain fog, patients might visit a therapist who can help them with word-finding issues. Such symptom management is necessary, Azola says, because “we don’t have strong, randomized controlled trials to support the use of specific medications or treatments,” she says.

Developing effective therapies has been “frustratingly slow,” Santhosh says. Scientists are still trying to understand what’s happening in the body that spurs long COVID and lets symptoms simmer away unchecked. “The underlying biology is unclear,” she says. That makes it “unclear exactly what treatments might work.”

Long COVID’s biological underpinnings are a hot topic among researchers today, says Mike VanElzakker, a neuroscientist at Harvard Medical School and Massachusetts General Hospital, and part of the Long COVID Research Initiative, a group working to study and treat the condition. Scientists have scads of hypotheses for what causes long COVID symptoms, including lungs scarred by SARS-CoV-2 or the reawakening of some other, long-slumbering virus. One idea posits that COVID-19 might sabotage the immune system, inviting other microbes to do harm. Another idea pins long COVID on caches of coronavirus hiding within the body’s tissues.

“It really does matter what’s causing these problems,” VanElzakker says. If doctors knew what’s driving a patient’s symptoms, they might be able to offer personalized treatments aimed at the illness’s root.

Filling the void
On Facebook pages and websites around the internet, purported long COVID treatment options abound.

Vitamins, supplements, alternative medicines: general internist Aileen Chang in Washington, D.C. used to hear all the time from long COVID patients about therapies they’ve tried. In the fall of 2020, Chang and colleagues started the George Washington Medical Faculty Associates COVID-19 Recovery Clinic, which later closed its doors due to a staffing shortage. She recalls patients who flew to different countries to have their blood filtered and others who took “every sort of supplement you can imagine,” she says. “They’re looking for solutions.”

Without clear data on what long COVID treatments work, opportunists have stepped in to fill the void. Some unproven treatments may be scams with serious side effects; they can also drain patients financially. “They’re spending all this money on things they think will make them better,” Chang says, “but the truth is… we don’t know.”

What scientists do know is that potential long COVID treatments are still in their early days. There’s some evidence that getting a COVID-19 vaccine can improve long COVID patients’ symptoms, though this idea is still controversial, researchers reported in November in eClinicalMedicine. And repeated sessions of breathing 100 percent oxygen in a hyperbaric chamber might relieve fatigue and brain fog, small studies of patients have suggested.
Last year, the U.S. National Institutes of Health launched a massive research project on the long-term effects of COVID-19. Called the RECOVER Initiative, the project aims to uncover why some people get long COVID and to identify underlying causes. As of November 11, RECOVER has enrolled 10,645 of an estimated 17,680 adults needed.

It’s a great initiative, Santhosh says, but it got rolling relatively late – well after long COVID had already upended many people’s lives. “We need… a lot more funding and a lot more therapeutic trials,” she says. Santhosh is hopeful that, in the coming months and years, doctors will have solid answers on what treatments actually work. “There are a lot of tantalizing biological leads,” she says. Though she knows that this timeframe can feel agonizingly long to patients and clinicians.
Real life
In the meantime, Santhosh, Azola and other physicians are borrowing strategies that help for other disorders – like myalgic encephalomyelitis/chronic fatigue syndrome. Many of the symptoms of that still-mysterious illness overlap with those of long COVID, a symmetry that could bring answers for both disorders, scientists suggest September 8 in Science.

One common approach isn’t a treatment like pills or surgery, it’s more of a shift in behavior: Don’t overdo it, Santhosh says. “We talk to our long COVID patients about this all the time, about the need to rest, to pace yourself and how to gently bring back your aerobic fitness.”

Long COVID patients with fatigue can be tempted to try and push through, to keep speeding through life as they had before their diagnosis. But that doesn’t seem to work for people with chronic fatigue, and “for some long COVID patients, it can actually make things worse,” she’s found.

Azola has similar advice for Hankins. About a half hour into the appointment, Azola slides away from the computer desk, and turns toward her patient. “This is the part where people want to punch me in the face,” she tells Hankins, pushing her glasses up onto her head. “We don’t have a magic wand that makes [you] feel better.”

Instead, Hankins will need to check her body’s battery every day, conserve energy where she can, and build in opportunities to recover. Little tricks, like sitting in a chair while showering or prepping food, can help patients save enough juice to make it through the day. Azola hopes to get Hankins off the “corona coaster,” where patients can feel relatively good one day, and the next day, crash. Having energy levels constantly crater can erode a patient’s ability to live their lives, she says.
For the next 20 minutes, doctor and patient talk about how Hankins’ life has changed and what her next steps will be. In a week, she’ll meet with a neuropsychologist who will help her cope with her new reality; Azola also refers Hankins to a pain specialist.

The two women have spent about an hour together – a near-eternity for a medical appointment. For Azola, it’s time well spent. “The most important thing is to listen to patients and keep an open mind,” she says.

When I speak with Hankins nearly three weeks later, she’s still feeling hopeful. She’s met with the neuropsychologist, and will continue to receive follow-up care. For Hankins, a care plan that factors in all of her conditions, including long COVID, may one day let her feel like herself again.

For now, she’s hoping that sharing her story will help others struggling with the illness. When she tells people she has long COVID, she says, “some of them don’t even think it’s real.”