POST 218. December 5, 2021. CORONAVIRUS. “In some ways, Delta is the ideal variant: It’s transmissible enough to dominate more dangerous variants, and its virulence can be controlled through vaccination. In the next few weeks, we’ll find out whether Omicron will have its own silver lining—or whether it’ll be catastrophically worse.”

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“Barely a week has elapsed since scientists in Botswana and South Africa alerted the world to a fast-spreading SARS-CoV-2 variant now known as Omicron. Researchers worldwide are racing to understand the threat that the variant — now confirmed in more than 20 countries — poses to the world. Yet it might take scientists weeks to paint a more complete picture of Omicron, and to gain an understanding of its transmissibility and severity, as well as its potential to evade vaccines and cause reinfections…

Omicron’s rapid rise in South Africa is what worries researchers most, because it suggests the variant could spark explosive increases in COVID-19 cases elsewhere. On 1 December, South Africa recorded 8,561 cases, up from the 3,402 reported on 26 November and several hundred per day in mid-November, with much of the growth occurring in Gauteng Province, home to Johannesburg.

Epidemiologists measure an epidemic’s growth using R, the average number of new cases spawned by each infection. In late November, South Africa’s National Institute for Communicable Diseases (NICD) in Johannesburg determined that R was above 2 in Gauteng. That level of growth was last observed in the early days of the pandemic, Richard Lessels, an infectious-disease physician at KwaZulu-Natal University in Durban, South Africa, told a press briefing last week.

Gauteng’s R value was well below 1 in September — when Delta was the predominant variant and cases were falling — suggesting that Omicron has the potential to spread much faster and infect vastly more people than Delta, says Tom Wenseleers, an evolutionary biologist at the Catholic University of Leuven in Belgium. Based on the rise in COVID-19 cases and on sequencing data, Wenseleers estimates that Omicron can infect three to six times as many people as Delta, over the same time period. “That’s a huge advantage for the virus — but not for us,” he adds.

Researchers will be watching how Omicron spreads in other parts of South Africa and globally to get a better read on its transmissibility, says Christian Althaus, a computational epidemiologist at the University of Bern, Switzerland. Heightened surveillance in South Africa could cause researchers to overestimate Omicron’s fast growth. But if this pattern is repeated in other countries, it would be very strong evidence that Omicron has a transmission advantage, adds Althaus. “If it doesn’t happen, for example, in European countries, it means things are a bit more complex and strongly depend on the immunological landscape. So we have to wait.”

The threat of Omicron has prompted some rich countries, such as the United Kingdom, to accelerate and broaden the roll-out of COVID vaccine booster doses. But it’s not yet clear how effective these doses will be against this variant…

Early reports linked Omicron with mild disease, raising hopes that the variant might be less severe than some of its predecessors. But these reports — which are often based on anecdotes or scant scraps of data — can be misleading, cautions Müge Çevik, an infectious-disease specialist at the University of St Andrews, UK. “Everyone is trying to find some data that could guide us,” she says. “But it’s very difficult at the moment.” (A)

“Is omicron worse than delta?

Right now, it’s too early to tell. Omicron has some similar mutations in its spike protein to the delta variant, according to the Republic of South Africa’s Department of Health, as well as the alpha, gamma and beta variants — all classified as variants of concern by the WHO. This means omicron will also be very transmissible, likely enabling the virus to more easily get around someone’s antibodies, lowering the vaccine’s efficacy against symptomatic disease (as in the delta variant’s case, scientists expect the vaccines to remain protective against severe COVID-19). Scientists from South Africa also believe omicron may lead to more cases of reinfection in people who’ve already had COVID-19.

Omicron has more mutations on its spike protein than the delta variant does, but whether that means anything remains to be seen.

“What all those changes in the aggregate are going to do for the things that matter for this virus, we don’t really know yet,” Robert Garry, a virologist at Tulane University, told CNN.

At a briefing Wednesday, Fauci emphasized that within the next two or three weeks, there will be more information about omicron and its efficacy with the vaccines, monoclonal antibodies and more.” (B)

“When I’m reading about the new omicron variant, I feel like I need a medical degree. What does “immune evasion” mean, exactly? Virus neutralization assay?! Help!

We get it: COVID-19 news happens fast, and those of us without a medical degree can feel a little lost. So we turned to three COVID-wise experts — Dr. Jill Weatherhead, assistant professor of adult and pediatric infectious diseases at Baylor College of Medicine; Dr. Greg Poland, professor of medicine and infectious diseases at the Mayo Clinic in Rochester, Minn.; and Matthew Binnicker, Ph.D., vice chair of practice in the Department of Laboratory Medicine and Pathology at the Mayo Clinic — to help us translate some of the terms you’re likely to run across.

So let’s start with a quote from Weatherhead:

“The omicron variant has over 50 genetic mutations in the viral genome. Many of these mutations are found in the spike protein region,” Weatherhead says. “Some of the individual mutations suggest that the omicron variant may be more transmissible or evade immune responses. Despite the association of these mutations with transmissibility and immune evasion, the clinical impact of omicron remains unknown because of the phenomenon of epistasis.”

If you didn’t quite catch all of that, here’s a guide to help.

Mutation: A mutation is a change in a virus’s genetic code. Mutations are a normal part of viral replication. Viruses make copies of themselves as they spread within a human. Mutations happen when a mistake is made during copying. In rare instances, mutations change the behavior of the virus. Most of the time, they don’t.

Variant: In essence, a variant is a version of the virus with a slightly different genetic sequence because of the appearance of mutations. Many mutations quickly disappear as the virus spreads. But sometimes, mutations stick around and get passed down to future generations of the virus. Over time, the virus can accumulate a unique set of mutations that make it distinct from other versions of the virus. These distinct versions are called variants.

Variant of concern (VOC): The World Health Organization and the Centers for Disease Control and Prevention monitor variants and alert the public to variants of concern that could pose added risk because of “increased transmissibility, increased severity of disease or decreased effectiveness of public health interventions [diagnostic tests, preventive measures like vaccines or therapeutic measures like monoclonal antibodies],” Weatherhead explains.

Transmissibility: The ability of a virus to spread from infected people to others. The delta variant is more transmissible than previous variants because of mutations on its spike protein, which make it better at attaching to and infecting cells. There is concern that omicron could be even more transmissible than the highly transmissible delta variant, but we don’t know yet whether that is the case.

Immune evasion: After an infection or a vaccine, your body produces antibodies that can detect and kill the virus upon a subsequent exposure. Sometimes a virus can mutate in a way that helps it evade or escape detection by those antibodies. That’s what scientists call “immune evasion.” There’s preliminary evidence that omicron could be much better at immune evasion than the delta variant or any other variant before it because of the specific mutations on its spike protein.

Outcompete: In sports, if you outcompete other athletes by getting to the finish line first or scoring more points, you’re No. 1. In the world of viruses, winning is more akin to the reality show Survivor; viruses can evolve to infect more people — or to infect them faster — than previous variants and become No. 1. “It’s basically survival of the fittest,” Binnicker explains. “Delta showed us it was king of the hill. We’ll have to see over the next two to four weeks if omicron is better at transmitting than delta.” If it is, it will likely push delta out of many regions of the world and could become the dominate variant.

Epistasis: The Greek roots of this word mean “standing upon.” So what does that have to do with viruses? Well, in genetics, the term describes how mutations depend on each other. The way an individual mutation makes a virus behave often depends on what other mutations are present. That’s why scientists can’t look at a single mutation and know exactly how it will change a virus — mutations need to be assessed together. Think of it as cheerleaders standing on each other: Any movement by one of them often affects the entire formation.

Virus neutralization assay (VNA): OK, let’s take this apart. An assay is a test. Neutralization is a term familiar to those who love science fiction. If you neutralize an attack from an alien ship, you’ve won! In the world of viruses, we want to know if antibodies can stop — or neutralize — a virus particle. And the way to find out is a VNA: a lab test that measures the capability and magnitude of a human’s antibodies to stop infection. This test can be used to determine how well one part of the immune system is working to prevent or clear an infection. Scientists can use it to estimate how well a vaccine may work.

Hybrid immunity: Scientists say a person has “hybrid immunity” if the person was infected with SARS-CoV-2 and then, at least six months later, received a COVID-19 vaccine. This scenario triggers high levels of antibodies and strong protection against variants. Some scientists have called it “super-immunity.”

Spike protein: You’ve probably seen more than enough pictures of the SARS-CoV-2 virus. The spike protein creates the bumps on the virus particle. It’s a critical region of the virus for several reasons. Spike proteins bind to human cells and help the virus gain entry inside cells. And these spike proteins are the target of many critical antibodies. A major way the immune system detects the virus is by its spike proteins.

Preventive measures: OK, this isn’t a hard one to figure out. And for now, the fact remains that not enough is known to take much action to forestall infections besides getting vaccinated and boosted and following the prevention strategies of masking and physical distancing that we’ve relied on throughout the coronavirus pandemic.” (C)

“How the Omicron Variant Got So Many Scary Mutations So Quickly

Mutations develop spontaneously as a virus replicates and spreads, but scientists are now trying to understand how so many mutations arose in Omicron in such a seemingly short space of time.

“The question is how this [rapid evolution] occurred, where it occurred, and which were the conditions that fueled [it],” says Gonzalo Bello, a virologist at the Oswaldo Cruz Institute in Rio de Janeiro. Bello was part of the team that tracked the rise of the Gamma variant in Brazil in November 2020, which fueled outbreaks in that country. With Gamma, “we realized that mutations did not appear in a single step in a single individual,” Bello explains. Instead, some mutations occurred in certain individuals but not in others. The rise of Gamma “was a process that occurred in a population of individuals, not in a single [person],” he says.

One possibility for how a heavily mutated variant, such as Omicron, could have arisen is that the virus began circulating and mutating in an isolated group of people, where it would have had an opportunity to change dramatically compared with variants outside of that bubble. It could then have gotten introduced, with its numerous mutations, into the larger population, where it was able to travel into different groups and countries, Bello says.

Alternatively, the virus may have mutated significantly in a single individual before finding a new host. “This could happen in an immune-suppressed person,” such as someone with HIV, Anna-Lise Williamson, chair in vaccinology at the University of Cape Town, and Ed Rybicki, director of the university’s biopharming research unit, wrote in response to e-mailed questions. South Africa has the world’s largest HIV epidemic, with more than seven million people infected with the virus. Neighboring countries also have widespread HIV infections. This has led some scientists to hypothesize that Omicron arose in Southern Africa because it was first identified there, but older cases have since been identified in European countries and the U.S…

To fully understand where Omicron arose, it helps to determine the earliest human patient or community in which it spread. But it is difficult to identify the patient zero for a variant, says Akiko Iwasaki, a professor of immunobiology and molecular, cellular and developmental biology at Yale University. “That is because [virus] surveillance efforts only capture a fraction of infected people,” she says. As more people are tested, and their viral genomes are sequenced, it may be possible to pinpoint a general geographic area and an approximate time when the virus mutated into Omicron, Iwasaki says.

For Michael Head, a senior research fellow in global health at the University of Southampton in the U.K., Omicron is a wake-up call about vaccine inequity and the need for greater access. According to Oxford University’s Our World in Data platform, as of November 30, about eight billion vaccinations had been administered globally, and only 6 percent of people in low-income countries had received at least one dose. African countries have administered more than 235 million vaccines, according to the African Centers for Disease Control and Prevention, but the continent’s population exceeds 1.2 billion people.

“The main variants that have caused concern so far—in terms of Alpha to Delta, basically—have emerged from uncontrolled outbreaks in unvaccinated populations,” Head says. “That’s where COVID thrives best and that’s where the virus has the greater chance to mutate. If [the vaccine] can keep outbreaks under control, you reduce those opportunities.”

The World Health Organization’s Director-General Tedros Adhanom Ghebreyesus echoed these sentiments on November 28: “The Omicron variant reflects the threat of prolonged vaccine injustice,” he wrote in a tweet. “The longer we take to deliver #VaccinEquity, the more we allow the #COVID19 virus to circulate, mutate and become potentially more dangerous.”” (D)

“As the world waits for studies that give a clear picture of the Omicron variant, early clinical data emerging from South Africa hint at a virus that may cause less severe cases of Covid-19.

The South African Medical Research Council posted a report Saturday of the early experiences at several hospitals in Gauteng Province, where Omicron was first spotted in the country. Strikingly, most hospitalized patients who tested positive for Covid did not need supplemental oxygen. Few developed Covid pneumonia, few required high-level care, and fewer still were admitted to intensive care.

Experts caution against reading too much into these early reports, which are based on small numbers of patients. They suggest it will take time for the true profile of the Omicron variant to come into focus. But several note that while early discussions about previous variants of concern have hinged on trying to figure out whether they caused more severe disease, with Omicron the questions relate to whether it is associated with milder infections.

The report included an analysis of 42 Covid patients in the hospital on Dec. 2 which showed that most were actually hospitalized for other medical reasons; their infections were only detected because hospitals are testing all incoming patients for Covid. Many did not have respiratory symptoms. And the average length of hospital stay was 2.8 days, far shorter than the average of 8.5 days recorded in the region over the past 18 months, the report said.

“The relatively low number of Covid-19 pneumonia hospitalizations in the general, high care and ICU wards constitutes a very different picture compared to the beginning of previous waves,” said the report, authored by Fareed Abdullah, director of the SAMRC’s office of AIDS and TB research.

Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy, told STAT he has “really been impressed by the relative lack of severe illness” seen with Omicron so far. “We’re just not seeing the number of patients that have been seen in previous surges who are seriously ill, even this soon into the surge.”

Amesh Adalja, an expert on emerging infectious disease and pandemic preparedness at Johns Hopkins University’s Center for Health Security, said more data are needed but the early indications are “very intriguing.”

“It’s part of a trend of anecdotal reports that we’re hearing that the clinical spectrum seems to be more mild, especially in vaccinated people,” he said.

It appears that the Omicron variant may be more transmissible than past variants of the virus, potentially even the highly transmissible Delta variant. But it was only identified within the past couple of weeks and still makes up only a tiny fraction of  cases worldwide, so drawing conclusions at this point is a risky business…

Osterholm and others said it will be important, too, to watch how Omicron fares in places where the Delta variant is currently causing high levels of illness, as is the case in many parts of the United States and Europe presently.

And Peter Hotez, dean of Baylor College of Medicine’s national school of tropical medicine, said we’ll have to see what kind of illness Omicron triggers in other places before drawing conclusions.

“Potentially it means that the severity of illness is less with Omicron,” he acknowledged. “But I think we have to be very cautious about making any definitive statement. Right now, it’s an interesting anecdote as much as anything else. And we’ll see as Omicron accelerates in the United States whether if falls along a similar pattern.”” (E)

“The omicron coronavirus variant likely acquired at least one of its mutations by picking up a snippet of genetic material from another virus, potentially one that causes the common cold.

This genetic sequence does not appear in any earlier versions of the coronavirus.

By inserting this particular snippet into itself, omicron might be making itself look “more human,” which would help it evade attack by the human immune system, said Venky Soundararajan of Cambridge, Massachusetts-based data analytics firm nference.

The omicron variant of the virus that causes Covid-19 likely acquired at least one of its mutations by picking up a snippet of genetic material from another virus – possibly one that causes the common cold – present in the same infected cells, according to researchers.

This genetic sequence does not appear in any earlier versions of the coronavirus, called SARS-CoV-2, but is ubiquitous in many other viruses including those that cause the common cold, and also in the human genome, researchers said.

By inserting this particular snippet into itself, omicron might be making itself look “more human,” which would help it evade attack by the human immune system, said Venky Soundararajan of Cambridge, Massachusetts-based data analytics firm nference, who led the study posted on Thursday on the website OSF Preprints.

This could mean the virus transmits more easily, while only causing mild or asymptomatic disease. Scientists do not yet know whether omicron is more infectious than other variants, whether it causes more severe disease or whether it will overtake Delta as the most prevalent variant. It may take several weeks to get answers to these questions.” (F)

“The arrival of the newest coronavirus variant, first identified in Botswana and South Africa and now present in the United States, might be bad news, or it might be terrible news—or maybe it’s just a temporary distraction from Delta. Ultimately, Omicron’s effect on the course of the pandemic will be determined by three factors: its transmissibility; the degree to which it evades our existing immune defenses; and its virulence, or the severity of the disease that it causes. If Omicron turns out to jump between hosts with ease, blow past our neutralizing antibodies, and cause unusually dangerous complications, we’ll all be in deep trouble. But it could also turn out to do a lot of other things, with more subtle implications. If Omicron ends up being super contagious, for example, but mild in its symptoms, that might even be a good thing—a perfect variant, just in time for Christmas…

If Omicron continues to show signs of being milder than Delta, that’s good news, of course. But if it also turns out to spread more quickly than Delta, that could be great news. When two variants are circulating, the one that infects more people more quickly will tend to dominate, said Samuel Scarpino, of the Rockefeller Foundation’s Pandemic Prevention Institute. That variant could win out either because it replicates more quickly in its human hosts and spreads more efficiently between them—that is, it’s more transmissible—or because it more deftly evades the immunity we already have….

Omicron could, of course, turn out to be pretty much anything. Maybe it’s somewhat more transmissible than Delta, but no more virulent; that, Kirk Sell said, could send us back to stricter masking and social-distancing programs for a while. Or else it might be less transmissible than Delta, and no better at slipping past our immune barriers, in which case “it’s going to be a blip on the horizon” regardless of how virulent it is, according to Halloran. If that happens, we’ll effectively be back where we were two weeks ago: stuck with Delta and waiting for the next shoe to drop.

There are worse fates. “In some ways, Delta is the ideal variant,” Scarpino said: It’s transmissible enough to dominate more dangerous variants, and its virulence can be controlled through vaccination. In the next few weeks, we’ll find out whether Omicron will have its own silver lining—or whether it’ll be catastrophically worse.” (G)

“On Thursday night, New York Governor Kathy Hochul announced that five cases of the new variant had been confirmed in the state. One of the cases involves a 67-year-old woman from Suffolk county “with some vaccination history” who had recently been in South Africa. The patient reported mild symptoms after testing negative upon her return on November 25. She tested positive on November 30. Two more cases were confirmed in Queens, in addition to one in Brooklyn, and a “suspected traveler case” in “one of the five boroughs,” according to public-health officials. The vaccination status and potential exposure of the four New York City cases were unknown…

Here are some things to know about New York and the Omicron variant:

This could be the fourth variant to hit the city in 2021

New York City has already weathered rising caseloads from three coronavirus variants this year. First there was a homegrown variant, called B.1.526 or Iota, which spread rapidly from January to March. That was followed this spring by the highly transmissible Alpha variant, first identified in Britain. Then by summer came the even more highly transmissible Delta variant, which caused a small wave of infections and then subsided in October before rising again in November.

Each new variant provoked worry. But so far, the coronavirus has been diminishing as a threat, after the devastating first wave last year. The long second wave that stretched from the autumn of 2020 to this spring saw far fewer infections and deaths than the first, even as several strains of Covid-19 spread.

The pattern of diminishing waves is different than what has been seen in much of the country and owes something to New York City’s relatively high rate of vaccination — about 77 percent of residents of all ages have received at least one shot.

There are other factors: Considerable levels of natural immunity from the devastation of the first wave in spring 2020. A willingness to wear masks. Widely available testing and a robust public health apparatus.

“I think we are potentially more prepared than most,” said Dr. Bernard Camins, an infectious diseases specialist and medical director of infection prevention for the Mount Sinai Health System. “The question is whether at this point people are more fatigued from all those mitigation strategies, and they may not listen.”

Mayor Bill de Blasio says that a mask mandate could prove a distraction from the city’s main goal: getting vaccines and booster shots into more people.

What happens next turns mainly on the variant

Initial reports suggest this variant might be especially contagious. But little is known about Omicron’s virulence, or what protection existing coronavirus vaccines offer.

“We do expect the vaccines to retain some degree of effectiveness, but precisely how much will take a few weeks to clarify,” Dr. Chokshi said on Monday. “We’re counseling, you know, a bit of patience as the science sorts itself out.”

But Dr. Denis Nash, an epidemiology professor at CUNY School of Public Health, warns that “if this is more transmissible than Delta or more virulent, or more evasive of the immune protection that the vaccine provides,” then the city “could be susceptible to a surge.”

Amid these unknowns, Mayor Bill de Blasio had some blunt advice: Get vaccinated, or get a booster shot, and “get those masks back on now,” he said on Monday. Fewer than 20 percent of adult residents have gotten their booster shot.

In particular, he urged parents to get their children vaccinated. Just 17 percent of 5- to 11-year-olds have received a first dose since they became eligible a month ago. “It’s time,” he said.

Since Nov. 1, daily case counts have risen more than 75 percent, reaching 1,500 newly identified cases a day last week. The rise, driven by the Delta variant, has been steepest in Queens, a borough with vaccination rates well above the citywide average.

The increase, epidemiologists say, is likely caused by the changing of the seasons, with colder weather pushing people indoors and prompting them to close windows, raising the risk of transmission. Cold, drier air may also benefit the coronavirus by helping viral particles to survive and linger in the air for longer.

Holiday travel and gatherings could also accelerate transmission.

One disease model from a team at New York University Grossman School of Medicine, which predated Omicron, predicted about 10 deaths a day from Delta in the weeks ahead, according to a member of the team, Dr. Ronald Scott Braithwaite, a professor at N.Y.U. and an adviser to the city. At an earlier point this year, during the height of last winter’s wave, there were as many as 98 Covid-19 deaths in a single day.

In New York City, the Delta variant is expected to drive only a minor surge in cases. But it is creating a potentially dire situation in Western New York, where last week, the number of coronavirus patients admitted to hospitals on a single day — 120 on Nov. 26 — was the highest in the region since the start of the pandemic.

Surveillance and testing systems are strong

As new forms of the virus began to emerge across the globe early this year, New York City began cobbling together its own surveillance system. Turning to universities, hospitals and other laboratories, the city set out to analyze at least 10 percent of coronavirus cases in New York for mutations.

When the coronavirus reached New York early last year, New York’s officials, including then-Gov. Andrew M. Cuomo and Mr. de Blasio, were slow to act.

Citing this history, a reporter asked Mr. de Blasio on Monday why he was merely recommending mask wearing, rather than imposing interventions like a mask mandate until more about Omicron was understood.

Mr. de Blasio said that he worried that a mask mandate would prove a distraction from the city’s main goal: getting vaccines and booster shots into more people.

“What we do not want to do is mix messages about what’s the thing that actually has the most profound impact,” Mr. de Blasio said. “The thing that we need to do with urgency is get people vaccinated.”

Dr. Jay Varma, an epidemiologist who has helped guide New York City’s pandemic response as a mayoral adviser, says that like Delta, Omicron could take months to spread widely in New York, giving the city time to nudge more residents to get vaccinations or boosters, and convince more companies to impose vaccine requirements.

Nearly 89 percent of adults in New York City have gotten at least one dose — six percentage points higher than the national average. In recent months, the city raised the vaccination rate through mandates for municipal employees and by imposing restrictions on people who are not vaccinated.

Yet the rate is uneven. Though the gap has shrunk, Black residents are less likely to be vaccinated than other groups, particularly among younger people; just 57 percent of Black New Yorkers between 18 and 44 have gotten at least one dose of a vaccine. And children younger than 5 still remain ineligible for vaccination.

Public health experts also worry that nursing homes are underprotected.

As of last week, only 51.4 percent of the nearly 92,000 nursing home residents statewide had received a booster shot, according to the state Department of Health. Across the city, there are more than 30 nursing homes where fewer than 25 percent of residents have received booster shots. 

“I find it highly, highly distressing,” said Dr. Nash, the epidemiology professor. “I’m afraid it will be a travesty with a lot of avoidable deaths.” (H)


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