‘Goldilocks virus’: Delta vanquishes all variant rivals as scientists race to understand its tricks

People ride a tour bus with no masks in Times Square during the coronavirus disease (COVID-19) pandemic in the Manhattan borough of New York City, New York, U.S., May 14, 2021. REUTERS/Carlo Allegri

The variant battle in the United States is over. Delta won.

Since late last year, the country has been overrun by a succession of coronavirus variants, each with its own suite of mutations conferring slightly different viral traits. For much of this year, the alpha variant – officially known as B.1.1.7 and first seen in the United Kingdom – looked like the clear winner, accounting for the majority of cases by April. In second place was iota, B.1.526, first seen in New York City. A few others made the rogue’s gallery of variants: gamma, beta, epsilon.

Then came delta – B.1.617.2. It had spread rapidly in India, but in the United States, it sat there for months, doing little as the alpha advanced. As recently as May 8, delta caused only about 1% of new infections nationally.

Today, it has nearly wiped out all of its rivals. The coronavirus pandemic in America has become a delta pandemic. By the end of July, it accounted for 93.4% of new infections, according to the Centers for Disease Control and Prevention.

The speed with which it dominated the pandemic has left scientists nervous about what the virus will do next. The variant battles of 2021 are part of a longer war, one that is far from over.

Delta is sending thousands of people into hospitals every day and has knocked the Biden administration back on its heels. In a few short weeks, the delta variant changed the calculations for what it will take to end the pandemic.

Epidemiologists had hoped getting 70 or 80% of the population vaccinated, in combination with immunity from natural infections, would bring the virus under control. But a more contagious virus means the vaccination target has to be much higher, perhaps in the range of 90%.

Globally, that could take years. In the United States, the target may be impossible to reach anytime soon given the hardened vaccine resistance in a sizable fraction of the country, the fact that children under 12 remain ineligible and the persistent circulation of disinformation about vaccines and the pandemic.

With so many people unvaccinated, in the United States and around the world, the virus has abundant opportunity not only to spread and sicken large numbers of people, but to mutate further. Some scientists have expressed hope that the virus has reached peak “fitness,” but there is no evidence this is so.

“To see delta just running laps around these other strains is very concerning,” said Benjamin Neuman, a virologist with Texas A&M University. “It’s like ‘Jurassic Park’ the moment you realize the dinosaurs have all got loose again.”

Delta’s meteoric takeover of the pandemic in the United States brought a jarring, premature end to a summer of relative freedom from the global viral emergency. Just as schools and workplaces were ready to hit reset and embrace a level of normalcy, indoor mask-wearing is back in much of the country, regardless of vaccination status.

Hospitals in states with low vaccination rates are struggling to cope with a flood of patients. At the same time, vaccination rates are jumping as the reality of the pandemic and the efficacy of the vaccines overcome fear, inertia and disinformation.

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Several factors have played a role in the rise of delta:

Behavior. This is almost impossible for researchers to quantify. As infection numbers started dropping in mid-April, people began returning to crowded gyms, restaurants, ballparks, indoor theaters, dance clubs. The CDC said vaccinated people didn’t need to wear masks. Human nature took over. Only the hypervigilant refused to behave as if the pandemic hadn’t ended.

Vaccine resistance. When the United States was reporting 3 million inoculations each day, it appeared plausible that by July 4 the Biden administration would reach its goal of 70% of adults with at least one shot. But in May, the rate of vaccination slowed dramatically. As of today, more than 90 million people nationwide who could get a shot haven’t. Tens of millions of children remain ineligible because the vaccines do not have approval for those age groups yet.

The delta variant itself. The rapid ascendancy to total domination is the real-world proof that this variant is different. For virologists studying the coronavirus up close, that difference remains somewhat mysterious. Scientists are racing to understand what makes this variant so successful. They are studying it in animal models and in petri dishes, and scrutinizing the genomes of thousands of closely related lineages.

What’s most sobering to scientists is how the coronavirus keeps getting better at jumping from person to person.

The original strain that emerged in Wuhan, China, had an estimated reproductive number – an “R-naught” – of roughly 2.5. That’s the average number of new infections generated by each infected person in a population without immunity or mitigations. Any number above 1 means that outbreaks will expand and spread. But the CDC and other scientists say delta has a reproductive number greater than 5.

The result is what the United States has endured this summer: viral explosion.

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Although the greater transmissibility of delta is clear at this point, scientists are less certain about whether it has enhanced virulence – that is, whether it’s more likely to make a person severely ill. The evidence on disease severity is limited and largely anecdotal.

Stephen Brierre, chief of critical care at Baton Rouge General in Louisiana, said the onset of respiratory failure requiring ventilation seems to be more rapid: “This is observational and anecdotal at this point: They get sicker quicker.”

Emily Tull, a nurse practitioner in the covid unit at Willis-Knighton Medical Center in Shreveport, La., said she is encountering more renal failure, more liver damage and more blood clots in patients since delta took over. More patients are unable to get off ventilators, she said.

Under normal circumstances, one nurse manages two patients in intensive care. In recent weeks, Tull said, “these patients are so sick they’re requiring one-on-one care.”

Patients are younger compared with earlier in the pandemic, perhaps because fewer young people are vaccinated. Tull said health care workers are “having to make the decision of, do we start dialysis on a healthy 25-year-old?”

In Alabama, where about 43% of adults are fully vaccinated and virtually all 67 counties are reporting high levels of community transmission, health officials are seeing inpatient data supporting that “delta may be more harmful,” according to Jeanne Marrazzo, director of the infectious-diseases division at the University of Alabama at Birmingham School of Medicine.

At the 1,200-bed UAB hospital, patients hospitalized for covid-19 are younger, the patients who have died are younger, and there appears to be greater use of a last-resort treatment, called ECMO, that can mechanically substitute for badly damaged lungs. The heavy use of ECMO “connotes truly serious systemic illness,” Marrazzo wrote in an email.

An internal CDC document, first disclosed late last month by The Washington Post, cited several studies from other countries showing that infections with delta are more likely to result in hospitalization. The document concluded that greater disease severity is “likely” with delta – one reason the authors said the agency needed to “acknowledge the war has changed.”

CDC Director Rochelle Walensky said Thursday that such research is preliminary. She noted that the delta variant spread rapidly in a time when mitigation efforts such as masking and social distancing had been relaxed. That has led to many more people being exposed and made it difficult for researchers to disentangle the severity of the virus from important changes in how people are exposed to it.

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At the CDC, the war has indeed changed. The agency has often acted at the pace of an academic institution. It can be glacial in putting out new guidance. Delta forced it to accelerate its normal process when evidence emerged that vaccinated people with breakthrough infections are spreading the virus. The agency changed its masking guidance without initially publishing the data that incited the change.

A “full-court press” to understand the delta is underway at the agency and will continue “until we break this surge,” said one official, who spoke on the condition of anonymity because he wasn’t authorized to speak publicly on the matter.

Vaccinations remain key. All three vaccines with emergency use authorization in the United States are highly effective at preventing severe illness or death from delta or other variants. Vaccinated people rarely need hospitalization for covid-19, the disease caused by the virus. Delta is spreading fastest in areas with low vaccination rates. Vaccination lowers the risk of infection eightfold and the risk of hospitalization or death 25-fold, according to the CDC.

But vaccinated people are getting sick, too. Delta appears to be slightly more capable than some other variants at causing breakthrough infections, which are usually mild to moderate cases that do not require hospitalization.

The rising number of breakthrough infections isn’t surprising: As the number of vaccinated people increases, and delta swarms the nation, it’s inevitable that the virus will sometimes sneak past the enormously robust shield of protection afforded by vaccines.

The recent Provincetown, Mass., outbreak that drew national attention illustrates the point. The people who flocked to the tourist town at the tip of Cape Cod were overwhelmingly vaccinated. Hundreds of people became infected, three-fourths of them with breakthrough cases. But the vaccines kept them from becoming severely ill: Only four people with breakthrough infections were hospitalized. What alarmed the CDC were tests showing that vaccinated people with delta infections had viral loads similar to those among unvaccinated people. That suggested vaccinated people could spread the virus.

There is limited data on how common breakthrough cases are. The CDC has published only its tally of breakthrough hospitalizations and deaths, not infections. Vaccinated people who have mild symptoms of covid-19 may think they have a summer cold and never get tested.

Walensky and Surgeon General Vivek Murthy have said in recent weeks that 97% of people hospitalized with covid-19 were unvaccinated. A document posted Monday by the White House stated, “Virtually all U.S. Hospitalizations and Deaths are Among Unvaccinated People.” The document cited that in Ohio, 99.5% of deaths and 98.8% of hospitalizations were among the unvaccinated.

But officials have relied on older data that does not capture the current impact of the delta, Walensky acknowledged Thursday when questioned at a White House covid-19 task force briefing.

The Ohio health department, contacted by The Post, confirmed the numbers for the state but noted that the data covers Jan. 1 to July 21. Walensky said she had been relying on data from January to June. The use of figures from early in the year skews the picture by including a large number of people sickened and killed by the virus before vaccinations were widely available.

Walensky said Thursday that her agency plans to update the breakthrough data.

The uncertainty about breakthrough infections “is disconcerting, and I think the reality is it’s humbling as a medical community,” said William Morice, chair of the department of laboratory medicine and pathology at the Mayo Clinic.

“Even with the whole world being focused on covid, we still don’t truly understand the intricacies of the virus and its interplay with the immune system,” he said.

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A Colorado county, perched on the western slopes of the Rocky Mountains, tells the story of delta’s swift spread.

In early May, five cases of the delta variant were reported in Mesa County. The extent of the threat was still emerging, but public health officials urged residents to get vaccinated. They noted that only 36% of people eligible for a shot had been fully vaccinated. A week later, the county announced the first pediatric death from covid-19 – a child infected with delta and too young for a vaccine.

In late June, the Country Jam music festival opened. Public health officials sent a bus to administer vaccines on-site, and used signs and messages on the Jumbotron to warn concertgoers about delta.

By early August, there were nearly 900 known cases of infection caused by the delta variant. Vaccines remained the best protection against severe illness, but about half of known cases were in fully vaccinated people.

The national numbers are similarly vertical. The seven-day rolling average of cases used by The Post showed about 13,000 new cases a day July 1. On Friday, that figure topped 100,000, and there is no sign of the curve flattening. Deaths are rising sharply as well: The daily average jumped from 209 on July 6 to 489 on Friday, a month later.

Because the delta variant replicates so well when it gets inside human cells, the infectious dose may be lower. Infected people may also begin shedding the virus sooner and in greater quantities. It’s a numbers game, and delta has numbers on its side. Rapid replication of the virus has probably shortened the period between a person getting infected and becoming infectious, to perhaps two or three days rather than five or six.

The flip side is that the delta surge is expected to peak faster. A more contagious virus finds susceptible people quickly and burns through that “fuel” faster. This may explain why the United Kingdom and India have both experienced surprisingly swift drop in cases after recent delta surges.

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Human beings have never before seen viral evolution in such vivid scientific detail. Genomic sequencing technologies developed in recent years allow scientists to witness the evolution of a pandemic virus in real time, as one lineage evolves into another.

Scientists say the delta variant’s mutations look, at first glance, unremarkable compared with the mutations in variants it has outcompeted. It lacks some of the immunity-evading mutations seen in gamma and beta, for example.

But one mutation, P681R, may play an outsized role in boosting delta. The coronavirus requires two steps to get into the cell, akin to putting a key into a lock and turning it to open the door. Most of the mutations identified in the other “variants of concern” seem to improve the key’s fit to the lock, said Vineet Menachery, a scientist who studies coronaviruses at the University of Texas Medical Branch in Galveston. The P681R mutation seems to improve how the key is turned, making it better at getting into cells.

Most laboratory research has focused on the spike protein the virus uses to enter cells. But delta has mutations that affect other regions – and little is known about what they do.

Nevan Krogan, a senior investigator at the Gladstone Institute of Data Science and Biosciences, found this year that the highly contagious alpha variant may have derived some of its advantage from being able to suppress a person’s innate immune response. That’s the first line of defense again an infection. He and colleagues are exploring whether something similar helps delta.

“When these variants started, everybody was talking ‘spike, spike, spike,’ ” Krogan said. “Obviously, spike is involved in this, getting virus into cells more effectively . . . there’s other mutations that are somehow suppressing the immune response.”

Menachery said he regularly debates with people in his laboratory and other scientists about the evolutionary potential of the virus. He describes this coronavirus as a “Goldilocks virus” – many things have to be just right for it to remain successful. A mutation that helps the virus enter a cell, for example, might come with an Achilles’ heel, making it less stable.

That leaves the open question of whether delta is the fittest – that is, the worst – version of the virus, or whether it could acquire some new mutations that make it even more formidable.

“Nobody knows what tricks the virus has left,” said Jeremy Luban, a virologist at the University of Massachusetts Medical School. “It’s possible we’ve seen all of its chess moves, or its poker tricks, but it’s got a very big complicated genome and it probably still has some space to explore.”

Like everyone else, scientists are wondering when SARS-CoV-2’s contagiousness will peak.

“Delta surprised me,” said Trevor Bedford, an expert on viral evolution at the Fred Hutchinson Cancer Research Center. “This doesn’t happen with an influenza pandemic. It doesn’t happen with Ebola. It doesn’t happen with most other things.”

He knows it can’t keep evolving to become more transmissible forever. Eventually, the virus will hit a ceiling, he said.

“But it’s not exactly clear what that is.”



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