Why the coronavirus’s delta variant dominated 2021

2021 was a year of coronavirus variants.

Alpha and beta kicked off the year, and several worrisome variants later, omicron is closing it out. How omicron may come to define the pandemic’s future remains uncertain. But even as omicron comes on strong, one variant, which rose to global dominance midyear in a way variants like alpha and beta never did, continues to largely define the pandemic right now: delta.

Things had actually seemed to be looking up in some parts of the world in the late spring and early summer of 2021, a year and a half into the COVID-19 pandemic. In the United States, for instance, millions of people were vaccinated, cases of the disease were falling, and people were beginning to socialize and resume normal activities.

But then delta hit hard. First spotted in India in October 2020, this variant of SARS-CoV-2, the coronavirus that causes COVID-19, quickly swept around the world, supplanting other versions of the virus in 2021 (SN: 7/2/21). Delta overwhelmed health care systems, tore through unvaccinated populations and showed that even the vaccinated were vulnerable, causing some breakthrough cases.
It soon became clear why delta wreaks so much havoc. People infected with delta make more of the virus and spread it for longer than people infected with other variants, researchers reported in Clinical Infectious Diseases in August. As a result, delta infections are more contagious. Consider two scenarios in a community where no one has immunity to the coronavirus: A person infected with an earlier version of the virus — the one first identified in Wuhan, China, that set off the pandemic — might spread it to two or three others. But a person infected with delta may transmit it to five or six people.

Delta owes its success to mutations in some of its proteins. Take, for instance, a mutation called R203M in the coronavirus’s nucleocapsid, or N protein, located inside the virus. This mutation may increase the amount of viral RNA that can be made or make it easier for the N protein to do its job, packing RNA into newly assembled viral particles, researchers reported in Science in November.
Mutations similar to delta’s have appeared here and there in other variants that proved themselves capable of spreading more easily or better evading the body’s immune defenses than the original virus. That includes alpha, first spotted in the United Kingdom; beta, first characterized in South Africa; and gamma, first noted in Brazil. The recently discovered omicron variant, first described in South Africa and Botswana, also shares some of the same mutations (SN: 12/1/21).

Some of delta’s grab bag of mutations are identical to those found in other variants, while others change the same protein building block, or amino acid, in a different way or pop up in the same part of the virus. For instance, alpha and omicron also have the same mutation of the 203rd amino acid in the N protein, but it is a different amino acid change than seen in delta. And some mutations are entirely new to delta.
Scientists don’t yet know the effect that all those changes have on delta’s ability to replicate or spread to others. What’s more, delta continues to evolve, picking up additional changes over time. But studies have zeroed in on the unique constellation of mutations decorating the virus’ spike protein. It’s the knobby protein studding each coronavirus that helps the virus latch onto and invade human cells. What looks like an individual knob is in fact composed of three identical pieces that fit together, each carrying the same set of mutations.

Some of delta’s spike protein mutations may help the virus more easily break into cells, where it turns cell machinery into virus-making factories. Two of those, dubbed T478K and L452R, are advantageously located on the receptor-binding domain. This is the part of the spike protein that attaches to ACE2, a protein on the surface of host cells.

Other mutations show up in a region of the spike protein called the N-terminal domain, which is a known target of the immune system’s neutralizing antibodies. These mutations may help the virus evade those antibodies, which can stop the virus from infecting cells.

And yet two other mutations, P681R and D614G, may help prep newly made viruses to go out and conquer. Those mutations are nestled near the dividing line for two parts of the spike protein, S1 and S2. Those parts need to be split apart to allow the coronavirus to engage in the gymnastics needed to help it fuse with the membrane of its prospective human host cell.
Human cells actually aid in this process: Inside infected cells a human protein called furin nicks the spike protein between the S1 and S2 segments, opening the receptor-binding domain so it can better grab ACE2. The P681R and D614G mutations may make the spike protein easier for furin to cut. Once snipped, newly-made viruses are primed to infect other cells.

Taken together, these mutations help delta break into cells more quickly and perform several tasks better than other variants do. As a result, in 2021, delta was able to become the dominant variant in the world.

Here’s how specific delta spike protein mutations may aid in a cell take-over:

  1. Some mutations allow the spike protein to get a better grip on cells.
    The coronavirus begins its cellular break-in by latching onto a protein called ACE2 that studs the surface of many types of human cells. Three mutations may make delta grabbier than other variants.

D614G interrupts some molecular interactions in the spike protein near a hinge that controls whether the receptor binding domain is in a closed position where it is protected from antibodies, or in an open position so that it can grab ACE2. With the D614G mutation, it’s more likely that one or more of ACE2-snagging portions of the protein will be open for action.

L452R may strengthen the interaction between ACE2 and the spike protein, making the virus more likely to infect cells. The change switches the charge on a protein building block in a key part of the spike protein from neutral to positive. So, like a magnet attracted to metal, the mutation seems to make the spike protein bind more tightly to a part of ACE2 that has a negative charge.

T478K is unique to the delta variant. It’s so far unclear what it does, but like L452R, it may also help strengthen the spike protein’s hold on ACE2.

  1. Some mutations allow delta to better fuse with the cell’s membrane, paving the way for the coronavirus to dump its genetic material into the cell.
    Once delta latches onto ACE2, a human protein called TMPRSS2 cuts away a part of the spike protein. As a result, the S1 portion of the protein is discarded, freeing up the S2 portion of the protein to twist into shape for the next step in the process: fusing to the cell. Some evidence suggests delta may be better at letting go of S1, making breaking into cells easier.

L452R may help the virus fuse with the membrane on the outside of the cell it’s trying to infect. That allows the virus to release its genetic material and begin hijacking the cell’s machinery to begin making more copies of itself.

P681R may create a stretch of basic amino acids that could help the virus fuse better with the cell membrane, helping more viruses get inside more cells.

As a result of these and other changes, delta can fuse with cells faster and can enter cells that have lower levels of ACE2 studding their surfaces than other variants can, researchers reported in Science in October.

After the virus fuses to the cell, it sets loose its RNA and turns its new lair into a virus factory: Viral RNA is copied, human ribosomes make viral proteins and the cell churns out nearly identical copies of the coronavirus. As the virus makes copies of its RNA, it can make typos. Sometimes, the genetic errors help the virus, which can give rise to variants like delta. But not all changes are good for the virus. Some genetic typos cause damage to viral proteins, meaning the viruses with those mutations can’t infect new cells. Other changes don’t have any effect on the virus at all.

  1. Some delta mutations may better prime newly made viruses to more easily infect cells.
    Before newly made viruses are released from the cell, the human protein furin snips the spike protein between S1 and S2. That lets the spike protein adopt the right shape to snag human cells and sets the protein up to allow for better membrane fusion.

Delta may be snippier than other variants.

Mutations D614G and P681R may increase the number of spike proteins cut by furin on each newly made virus, better prepping the viruses to enter other cells.

D614G makes it easier for furin to make its snips. This preliminary cut happens in a different location than the TMPRSS2 cut. The mutation may also increase the number of spike proteins on each copy of the virus.

Like D614G, P681R may also boost the number of spike proteins cut by the human cell protein furin, priming the newly made viruses to infect new cells.

  1. Some mutations may help newly released viruses evade antibodies as the viruses seek out other cells to infect.
    The immune systems of people who have recovered from an infection or those who got vaccinated make antibodies to the coronavirus. Several of delta’s mutations may help the virus evade these antibodies, which would otherwise block viral entry into other cells.

T19R, G142D, R158G and two spots — called E156del and F157del — where amino acids are missing from the protein may hide parts of the virus from antibodies, helping it slip past those immune system defenses.

T478K, the mutation unique to the delta variant, is close to the same spot as E484K, a mutation that was implicated in the antibody-evasion tactics of the beta variant.

How a warming climate may make winter tornadoes stronger

Though tornadoes can occur in any season, the United States logs the greatest number of powerful twisters in the warmer months from March to July. Devastating winter tornadoes like the one that killed at least 88 people across Kentucky and four other states beginning on December 10 are less common.

But climate change could increase tornado intensity in cooler months by many orders of magnitude beyond what was previously expected, researchers report December 13 in a poster at the American Geophysical Union’s fall meeting.

Tornadoes typically form during thunderstorms when warm, humid airstreams get trapped beneath cooler, drier winds. As the fast-moving air currents move past each other, they create rotating vortices that can transform into vertical, spinning twisters (SN: 12/14/18). Many tornadoes are short-lived, sometimes lasting mere minutes and with a width of only 100 yards, says Jeff Trapp, an atmospheric scientist at the University of Illinois at Urbana-Champaign.
Over the last 20 years, tornado patterns have shifted so that these severe weather events occur later in the season and across a broader range in the United States than before, Trapp says (SN: 10/18/18). But scientists have struggled to pin down a direct link between the twister changes and human-caused climate change.

Unlike hurricanes and other severe storm systems, tornadoes happen at such a small scale that most global climate simulations don’t include the storms, says Kevin Reed, an atmospheric scientist at Stony Brook University in New York who was not involved in the new research.

To see how climate change may affect tornadoes, Trapp and colleagues started with atmospheric measurements of two historical tornadoes and simulated how those storm systems might play out in a warmer future.

The first historical tornado took place in the cool season on February 10, 2013, near Hattiesburg, Miss., and the second occurred in the warm season on May 20, 2013, in Moore, Okla. The researchers used a global warming simulation to predict how the twisters’ wind speeds, width and intensity could change in a series of alternative climate scenarios.

Both twisters would likely become more intense in futures affected by climate change, the team found. But the simulated winter storm was more than eightfold as powerful as its historical counterpart, in part due to a predicted 15 percent increase in wind speeds. Climate change is expected to increase the availability of warm, humid air systems during cooler months, providing an important ingredient for violent tempests.

“This is exactly what we saw on Friday night,” Trapp says. The unseasonably warm weather in the Midwest on the evening of December 10 and in the early morning of December 11 probably contributed to the devastation of the tornado that traveled hundreds of miles from Arkansas to Kentucky, he speculates.

Simulating how historical tornados could intensify in future climate scenarios is a “clever way” to address the knowledge gap around the effects of climate change on these severe weather systems, says Daniel Chavas, an atmospheric scientist at Purdue University in West Lafayette, Ind., who was not involved in the new research.

But Chavas notes that this research is only one piece of a larger puzzle as researchers investigate how tornados might impact communities in the future.

One drawback of this type of simulation is it often requires direct measurements from a historical event, Reed says. That limits its prediction power to re-creating documented tornadoes rather than broadly forecasting shifts in large-scale weather systems.

Though the team based its predictions on only two previous tornados, Trapp says he hopes that adding more historical twisters to the analysis could provide more data for policy makers as well as residents of communities that may have to bear the force of intensifying tornadoes.

Why it matters that health agencies finally said the coronavirus is airborne

This year, health experts around the world revised their views about how the coronavirus spreads. Aerosol scientists, virologists and other researchers had determined in 2020 that the virus spreads through the air, but it took until 2021 for prominent public health agencies to acknowledge the fact. The admission could have wide-ranging consequences for everything from public health recommendations and building codes to marching band practices (SN: 8/14/21, p. 24).

For decades, doctors and many researchers have thought that respiratory viruses such as cold and flu viruses spread mainly by people touching surfaces contaminated by mucus droplets and then touching their faces. That’s why, in the early days of the pandemic, disinfectant wipes flew off store shelves.

Surface-to-face transfer is still a probable route of infection for some cold-causing viruses, such as respiratory syncytial virus, or RSV. But it turns out that the coronavirus spreads mainly through fine aerosol particles that may hang in the air for hours, particularly indoors.

People spread such aerosols when coughing or sneezing, but also when talking, singing, shouting and even quietly breathing, allowing infected people to spread the disease even before they know they’re sick. Some evidence suggests that the coronavirus may be evolving to spread more easily through the air (SN: 9/25/21, p. 6).

It took collecting reams of data and more than 200 scientists pushing the World Health Organization and other public health agencies to acknowledge airborne spread of the coronavirus. In April 2021, both the WHO and U.S. Centers for Disease Control and Prevention updated their recommendations to note that airborne spread is a major route of infection (SN Online: 5/18/21).

That recognition was vital to public understanding of why wearing well-fitting masks is necessary in public indoor places (SN: 3/13/21, p. 14; SN Online: 7/27/21). Masking, social distancing and other measures to guard against the coronavirus are also credited with nearly wiping out flu last winter (SN Online: 2/2/21). Experts fear a resurgence of cold and flu this winter if those measures aren’t continued (SN Online: 8/12/21).

Knowledge that COVID-19 is an airborne disease has led to such measures as rearranging seating in orchestras (SN Online: 6/23/21) and updating recommendations for proper ventilation and filtration in buildings. Some scientists and activists have also suggested that the safety of indoor air should be regulated to reduce the spread of diseases, much like safety standards for food and drinking water.

A custom brain implant lifted a woman’s severe depression

A personalized brain implant eased the crushing symptoms of a woman’s severe depression, allowing her to once again see the beauty of the world. “It’s like my lens on the world changed,” said Sarah, the research volunteer who requested to be identified by her first name only.

The technology, described October 4 in Nature Medicine, brings researchers closer to understanding how to detect and change brain activity in ultraprecise ways (SN: 2/10/19).

The device was bespoke; it was built specifically for Sarah’s brain. The details of the new system may not work as a treatment for many other people, says Alik Widge, a psychiatrist and neural engineer at the University of Minnesota in Minneapolis. Still, the research is “a really significant piece of work,” he says, because it points out a way to study how brain activity goes awry in depression.

Researchers at the University of California, San Francisco implanted temporary thin wire electrodes into Sarah’s brain. The 36-year-old woman had suffered from severe depression for years. These electrodes allowed researchers to monitor the brain activity that corresponded to Sarah’s depression symptoms — a pattern that the researchers could use as a biomarker, a signpost of trouble to come. In Sarah’s case, a particular sign emerged: a fast brain wave called a gamma wave in her amygdala, a brain structure known to be involved in emotions.
With this biomarker in hand, the researchers then figured out where to stimulate the brain to interrupt Sarah’s distressing symptoms. A region called the ventral capsule/ventral striatum, or VC/VS, seemed to be the key. That’s not surprising; previous research suggests the region is involved with feeling good and other emotions. When researchers applied tiny jolts of electrical current to this region, Sarah’s mood improved. “We could learn the road map of Sarah’s brain in a way that we could really improve her depression symptoms,” Katherine Scangos of UCSF said in a Sept. 30 news briefing.

During this mapping phase of the experiment, Sarah felt joy when the right spot was stimulated. “I laughed out loud,” she said in the briefing. “This was the first time I had spontaneously laughed and smiled where it wasn’t faked or forced in five years.”

Surgeons then implanted a more permanent device into Sarah’s brain last June. Scientists programmed the device to detect when gamma signals were high in Sarah’s amygdala, and respond with a tiny jolt to her VC/VS. This happened about 300 times a day. The stimulation was calibrated so Sarah didn’t feel any zaps, but she said they left her feeling a little more energetic.

The research paper describes Sarah’s improvements as the technology did its work in her head over two months; it’s unclear how long the benefits might last, though she’s now had the device implanted for over a year. “As time has gone on, it’s been this virtuous cycle, a spiral upwards,” Sarah said. “Everything has gotten easier and easier and easier.”

The approach used by the UCSF researchers required a lot of sophisticated imaging and machine learning technology. That complexity may prevent it from being a wider treatment, cautions Helen Mayberg, a neurologist at Icahn School of Medicine at Mount Sinai in New York City.

Still, the results — which add to a variety of ways to detect and change problematic brain activity — contain valuable information about how depression takes hold of a brain, and how brain stimulation can change that, says Mayberg, whose research has helped build and refine the field of deep brain stimulation for mood disorders. “What we all want to know is, ‘How does this work?’”

Methods of getting results from real-world experiments win 2021 economics Nobel

Some of the most insightful — and now most celebrated — studies of such major social issues as minimum wages and immigration have seized on naturally occurring events. Pioneering efforts by three economists to study the effects of real-life economic events that mimic controlled laboratory investigations have won the Nobel Memorial Prize in Economic Sciences.

David Card of the University of California, Berkeley will receive half of the prize of 10 million Swedish kronor (or half of about $1.14 million). The other half will be split by Joshua Angrist of MIT and Guido Imbens of Stanford University. The Royal Swedish Academy of Sciences announced the prize October 11.

Research by the Nobel Prize winners was instrumental in the development during the 1990s of what are known as natural experiments. These investigations rely on naturally occurring differences between groups or populations that either do or don’t experience specific conditions. In this way, social scientists can study, say, how differences in income affect physical health or how immigration influences employment rates.

Natural experiments are especially important because investigators of key social questions, such as whether pollution slows children’s mental development or whether strong public institutions promote economic growth, often can’t assign people at random to treatment and control conditions. It would be unethical, impractical or both.
“The Nobel winners developed techniques that replicate the idea of truly scientific experiments like you would use to test a vaccine, except [the experiments] occurred in the real world,” says economist Phillip Levine of Wellesley College in Massachusetts. These methods “were at the forefront of a ‘credibility revolution’ in economics” that made the field relevant and understandable to the public, he adds. Levine was a Princeton University graduate student with Angrist, and Card was his thesis adviser.

Natural experiments in economics are related to another influential line of research that examines ways to counteract poverty’s harmful effects using field experiments, work that won the 2019 economics Nobel (SN: 10/14/19).

In a key 1994 paper, Card and the late Princeton economist Alan Krueger challenged conventional wisdom in economics that increases in the minimum wage reduce employment. Card and Krueger surveyed fast-food restaurants in New Jersey and a neighboring section of eastern Pennsylvania before and after a minimum wage hike that was instituted only in the Garden State. Full-time employment slightly increased in New Jersey following wage increases, while it declined in Pennsylvania where wages stayed the same.
Further research addressed the complexities of how the minimum wage interacts with employment rates, but it was clear after Card and Krueger’s report that a simple cause-and-effect relationship didn’t exist.

Card also conducted a natural experiment indicating that a huge influx of Cuban refugees to Miami in 1980 did not result in reduced wages and employment for Miami residents with low education levels. That work led Card and others to further explore how new immigration influences the economic standing of native-born citizens and earlier immigrants.

Angrist and Imbens expanded on such work by devising steps to determine under what conditions a natural experiment, such as being given an opportunity to leave school at age 16, affects later outcomes, such as annual income. For instance, the researchers’ method estimated the effect on later income of an additional year of education, which they put at about 9 percent lower for each year lost after age 16, but only for people who chose to leave school early. The estimate excluded earnings histories of individuals who had planned to go to college all along because those people never considered leaving school early.
Card, Angrist and Imbens “have promoted a type of scholarly investigation that is of practical use outside academic journals,” says economist Melissa Kearney of the University of Maryland in College Park, who has studied and worked with both Card and Angrist. The Nobel Prize winners’ research equipped social scientists with “tools to credibly draw causal conclusions about empirical relationships.”

A new map shows where carbon needs to stay in nature to avoid climate disaster

Over decades, centuries and millennia, the steady skyward climb of redwoods, the tangled march of mangroves along tropical coasts and the slow submersion of carbon-rich soil in peatlands has locked away billions of tons of carbon.

If these natural vaults get busted open, through deforestation or dredging of swamplands, it would take centuries before those redwoods or mangroves could grow back to their former fullness and reclaim all that carbon. Such carbon is “irrecoverable” on the timescale — decades, not centuries — needed to avoid the worst impacts of climate change, and keeping it locked away is crucial.

Now, through a new mapping project, scientists have estimated how much irrecoverable carbon resides in peatlands, mangroves, forests and elsewhere around the globe — and which areas need protection.

The new estimate puts the total amount of irrecoverable carbon at 139 gigatons, researchers report November 18 in Nature Sustainability. That’s equivalent to about 15 years of human carbon dioxide emissions at current levels. And if all that carbon were released, it’s almost certainly enough to push the planet past 1.5 degrees Celsius of warming above preindustrial levels.
“This is the carbon we must protect to avert climate catastrophe,” says Monica Noon, an environmental data scientist at Conservation International in Arlington, Va. Current efforts to keep global warming below the ambitious target of 1.5 degrees C require that we reach net-zero emissions by 2050, and that carbon stored in nature stays put (SN:12/17/18). But agriculture and other development pressures threaten some of these carbon stores.

To map this at-risk carbon, Noon and her colleagues combined satellite data with estimates of how much total carbon is stored in ecosystems vulnerable to human incursion. The researchers excluded areas like permafrost, which stores lots of carbon but isn’t likely to be developed (although it’s thawing due to warming), as well as tree plantations, which have already been altered (SN: 9/25/19). The researchers then calculated how much carbon would get released from land conversions, such as clearing a forest for farmland.

That land might store varying amounts of carbon, depending on whether it becomes a palm oil plantation or a parking lot. To simplify, the researchers assumed cleared land was left alone, with saplings free to grow where giants once stood. That allowed the researchers to estimate how long it might take for the released carbon to be reintegrated into the land. Much of that carbon would remain in the air by 2050, the team reports, as many of these ecosystems take centuries to return to their former glory, rendering it irrecoverable on a timescale that matters for addressing climate change.
Releasing that 139 gigatons of irrecoverable carbon could have irrevocable consequences. For comparison, the United Nations’ Intergovernmental Panel on Climate Change estimates that humans can emit only 109 more gigatons of carbon to have a two-thirds chance of keeping global warming below 1.5 degrees C. “These are the places we absolutely have to protect,” Noon says.

Approximately half of this irrecoverable carbon sits on just 3.3 percent of Earth’s total land area, equivalent to roughly the area of India and Mexico combined. Key areas are in the Amazon, the Pacific Northwest, and the tropical forests and mangroves of Borneo. “The fact that it’s so concentrated means we can protect it,” Noon says.

Roughly half of irrecoverable carbon already falls within existing protected areas or lands managed by Indigenous peoples. Adding an additional 8 million square kilometers of protected area, which is only about 5.4 percent of the planet’s land surface, would bring 75 percent of this carbon under some form of protection, Noon says.

“It’s really important to have spatially explicit maps of where these irrecoverable carbon stocks are,” says Kate Dooley, a geographer at the University of Melbourne in Australia who wasn’t involved in the study. “It’s a small percentage globally, but it’s still a lot of land.” Many of these dense stores are in places at high risk of development, she says.

“It’s so hard to stop this drive of deforestation,” she says, but these maps will help focus the efforts of governments, civil society groups and academics on the places that matter most for the climate.