Global COVID monitoring is crashing as BA.2.86 variant raises alarm

WHO's COVID-19 technical lead, Maria Van Kerkhove, looks on during a press conference at the World Health Organization's headquarters in Geneva, on December 14, 2022.
Enlarge / WHO’s COVID-19 technical lead, Maria Van Kerkhove, looks on during a press conference at the World Health Organization’s headquarters in Geneva, on December 14, 2022.

With global attention and anxiety locked onto the latest coronavirus omicron subvariant BA.2.86, health officials and experts are still mostly in the dark about how the highly mutated virus will play out.

At the start of the week, amid a flurry of headlines, researchers had only six genetic sequences of the virus in the public repository GISAID, even though the virus had already spread to at least four countries (Denmark, Israel, UK, and the US). As of the time of publication of this article on Friday, there are still only 10 sequences from five countries (Denmark, Israel, UK, US, and South Africa). According to the World Health Organization, the variant has also appeared in wastewater sampling from Thailand and Switzerland.

As Ars reported Monday, BA.2.86 gained attention for having a large number of mutations compared with BA.2, the omicron subvariant from which it descended. The number of mutations in BA.2.86’s critical spike protein is over 30, rivaling the number seen in the original omicron subvariant, BA.1, which went on to cause a tidal wave of cases and hospitalizations. BA.2.86’s spike mutations appear geared toward evading neutralizing antibody protections built up from past infections and vaccinations. But with such scant and spotty detection, it’s impossible to say whether this variant can outspread its many omicron-subvariant cousins to cause a wave of infection. It’s also still not possible to determine if it can cause more severe disease than other variants. So far, severe disease symptoms have not been reported from the 10 cases—but that is not enough data to draw any conclusions. As the Centers for Disease Control and Prevention reported in a risk assessment Wednesday, it’s “too soon to know” the impact of BA.2.86 on transmission and disease severity.

The slow trickle of data on BA.2.86 is part of a larger, dramatic plummet in COVID-19 surveillance and reporting in general. Last October, WHO’s technical lead for COVID-19, Maria Van Kerkhove, noted, “The number of sequences that the world and our expert networks are evaluating has dropped by more than 90 percent since the start of the year. That limits our ability to really track each of these [omicron subvariants].”

The genetic surveillance landscape has eroded further since then. In a press conference Friday morning, Van Kerkhnove highlighted that even basic reporting is failing. Of 234 countries and territories, WHO is now only getting case count data from 103 countries. Only 54 countries are reporting deaths, just 19 are reporting hospitalization rates, and 17 are reporting data on intensive care utilization.

“We don’t have good visibility on the impact of COVID-19 around the world,” she said.

Critical surveillance

The lack of data makes it impossible to track trends and health impacts—potentially those from new variants—and get people the care they need, let alone adequately monitor for new variants, Van Kerkhove stressed.

While uncertainty lingers over what impact BA.2.86 will have (if any), with such sparse surveillance, health officials will have less chance to catch early rises in cases, severe disease, and deaths if a worst-case-scenario variant arises.

Although countries did impressive amounts of work to set up surveillance and reporting systems during the emergency phase of the pandemic, those critical tools are precipitously declining. Yet, the virus continues to circulate in all countries, and the little data we have shows increases in hospitalizations. In the US, new hospitalization admissions per week have nearly doubled since July 1, now up to over 12,600 in the week of August 12, according to CDC data.

“It is really important that surveillance continues,” Van Kerkhove said, “and this is on the shoulders of governments right now.” Those surveillance and reporting systems need to remain.

For now, the WHO has designated BA.2.86 as a “variant under monitoring (VUM),” which in the past was a designation only given to variants that have early signals of being able to outcompete other variants circulating. With so little data on BA.2.86, that’s not the case for this omicron subvariant. However, WHO altered the definition of VUM to accommodate BA.2.86. The designation now can include a variant that “has an unusually large number of antigenic mutations but with very few sequences and/or it is not possible to estimate its relative growth advantage.”

With so many mutations and so much concern about them, there’s also been some clamoring for BA.2.86 to have its own Greek letter, marking it beyond omicron. But, according to WHO’s current system, only variants designated “variants of concern (VOC)” are given Greek letters. To attain VOC status, BA.2.86 would have to meet at least one concerning criteria: clearly cause more severe disease; change epidemiology trends in a way that could imperil health care resources; or significantly evade vaccine protection from severe disease.

A technical advisory group for WHO will conduct a risk assessment of BA.2.86 as data accumulates, from which they’ll determine if a designation change is warranted.

https://arstechnica.com/?p=1963498




New omicron subvariant surges to 40.5% as COVID hospitalizations rise

Revelers celebrate New Year’s Eve in Times Square on January 1, 2023, in New York City. This year's New Year's Eve returned to pre-COVID-19 pandemic numbers, with around 1 million people estimated to fill Times Square.
Enlarge / Revelers celebrate New Year’s Eve in Times Square on January 1, 2023, in New York City. This year’s New Year’s Eve returned to pre-COVID-19 pandemic numbers, with around 1 million people estimated to fill Times Square.

A new omicron coronavirus subvariant dubbed XBB.1.5 now accounts for an estimated 40.5 percent of all US COVID-19 cases amid a winter wave that is driving up hospitalizations, particularly in places where XBB.1.5 is most prevalent.

Nationwide, new reported cases are hovering around 59,000 per day, which is still relatively low compared with previous waves. But case data has become murkier over the 3-year-old pandemic, with fewer testing sites available now and the results of common at-home tests going unreported. Additionally, data reporting generally lags around end-of-year holidays, meaning case reports may jump in the coming days as backlogged data rolls in.

Hospitalizations, however, are clearly rising, with an average of around 45,000 hospitalized per day, according to data tracking by The New York Times. National hospitalization rates now rival those from the peak over this past summer driven by bygone omicron subvariants, federal data shows. Some of the areas seeing the large upticks in hospitalizations are those where the new subvariant, XBB.1.5 is most prevalent. For instance, in the Northeast (federal health region 1), XBB.1.5 has the highest regional proportion, accounting for 75 percent of cases, and hospitalizations have risen 16 percent over the prior seven days, the largest region-specific rise, according to data from the Centers for Disease Control and Prevention.

Wave factors

This does not mean XBB.1.5 is causing more severe disease than previous variants. There is a variety of reasons why hospitalizations may be increasing as a yet more transmissible subvariant takes off. That includes waning immunity and the abysmal uptake of the bivalent booster, particularly among older adults, who are most vulnerable to severe disease. Currently, only 15 percent of Americans aged 5 and over have gotten their bivalent shot, and only 37.5 percent of people aged 65 and over have been boosted. In December, the CDC quietly expanded access to the bivalent vaccine to children aged 6 months to 5 years, but just 3 percent of that population has completed a primary series.

Meanwhile, people are traveling, gathering, and spending more time indoors amid holidays and cold weather—all things that can boost transmission. Some places where XBB.1.5 has yet to take off are also seeing rises in hospitalizations. For instance, in the South (health region 4), XBB.1.5 only accounts for about 19 percent of cases, with BQ.1.1 still accounting for 41.5 percent. Hospitalizations in the region have increased by nearly 14 percent over the past week’s data.

XBB.1.5 has a clear transmission advantage over other omicron subvariants and is expected to continue spreading throughout the country. The virus is a sublineage of omicron XBB, which is a combination of two BA.2-sublineages that merged: BJ.1 (BA.2.10.1.1) and BA.2.75. XBB.1.5 has three additional notable mutations compared with the original XBB.

Though early research has suggested that XBB.1.5 is even more immune-evasive than its predecessors, data published late last month in the New England Journal of Medicine offered some good news in regard to vaccine protection. The data indicated that people boosted with the BA.5-targeting bivalent vaccine used in the US had stronger neutralizing antibody activity against XBB than those who had only received the original booster.

https://arstechnica.com/?p=1907203




Feds may expand 2nd boosters to all adults as anxiety surges over BA.5 wave

Feds may expand 2nd boosters to all adults as anxiety surges over BA.5 wave

The swift rise of omicron subvariant BA.5—with its increased immune-evading abilities and demonstrable growth advantage—has federal officials on edge. In a flurry of activity late Monday and early Tuesday, officials doubled down on pandemic measures, renewed calls for vigilance, and are considering expanding eligibility of second boosters to all adults.

In a press briefing Tuesday morning, White House COVID-19 Response Coordinator Ashish Jha outlined a battle plan against BA.5, which, as of today, is estimated to account for 65 percent of cases in the US. Jha highlighted efforts and tools to prevent another towering wave of infection as seen with the original omicron in January. The plan includes a stronger push to get Americans vaccinated and boosted, plus renewed encouragement to test, treat, mask, and improve indoor ventilation.

US COVID-19 cases are currently plateaued at a high level of around 117,000 new cases per day—but that’s likely a significant underestimate given that many Americans are testing at home and not reporting their cases. Hospitalizations and intensive care admissions, meanwhile, are rising, with 17 percent and 21 percent increases over the past two weeks, respectively, according to tracking by The New York Times. Generally, the daily average of hospitalizations has more than doubled since the end of May, with the current average nearing 38,000.

SARS-CoV-2 transmission levels are considered high in about 90 percent of US counties, according to a red-soaked map from the Centers for Disease Control and Prevention. The agency recommends that everyone wear masks in public indoor settings in around 21 percent of counties, based on the agency’s gentler COVID-19 community-levels metric.

The current vaccines have proven highly effective at preventing severe disease, hospitalizations, and death. But to date, only 67 percent of Americans are fully vaccinated against the pandemic virus. Of the fully vaccinated, only 48 percent have received a booster. That means that just around 32 percent of Americans have had one booster, which is available to everyone ages 5 years and up. Additionally, people ages 50 and up or at high risk (such as immunocompromised) are currently eligible for a second booster. But only 18.7 million people have gotten that second booster. That’s about 28 percent of the people over age 50 who are fully vaccinated and boosted.

On Monday evening, The Washington Post broke the news that the Biden administration is considering expanding eligibility of second boosters to include all adults. The report cited five unnamed officials with knowledge of the matter, who said that Jha and top infectious disease expert Anthony Fauci support the idea of expanding second boosters to all adults.

In the press briefing Tuesday morning, Fauci and Jha stressed that only the Food and Drug Administration and the CDC have the ability to ultimately expand booster eligibility. The Washington Post noted that administration officials hoped to have the regulatory sign-off on the expansion within the next two weeks. The quick timeframe could keep a summer booster expansion from complicating the rollout of next-generation boosters this fall.

Boost now and later

Currently, the administration and the FDA are anticipating the rollout of next-generation, bivalent boosters this fall that would target both the ancestral strain and the BA.4/5 omicron subvariants. That rollout is expected to begin around October or November, or roughly three to four months from now. In the past, booster intervals have been around four to six months, Jha noted.

Jha and CDC Director Rochelle Walensky said repeatedly Tuesday that getting a booster now—or in two weeks or so—would not preclude getting a bivalent booster this fall. Their thinking is simply based on the time frame and anticipated interval for boosters.

“As we’ve looked at the cadence of where we’ve needed to get boosts before, it’s been four, five months,” Walensky said. “We anticipate that that’s going to be a similar cadence. We also really want to emphasize that there are many people who are high risk right now, and waiting until October/November for their boost—when, in fact, their risk is in the moment—is not a good plan,” she added. “So, we really do want to say ‘Now get your boost. We have every anticipation that the data will suggest that you will be eligible for a [bivalent] boost in the fall. We will, of course, continue to evaluate those data.”

For now, there’s no clinical data on the efficacy of a second booster in healthy people younger than 50. It’s also unclear if a fourth dose with the current vaccines—which target the ancestral strain of SARS-CoV-2—could skew immune responses to future variant-targeting boosters back toward the ancestral strain. But this has not been a significant concern for people already eligible for second boosters. Additionally, a majority of Americans have already been exposed to variants.

As such, many experts have, like Jha and Fauci, embraced the idea of expanding second booster access amid the BA.5 spike. That includes virologist and vaccine expert Peter Hotez, who is dean of the National School of Tropical Medicine at Baylor College of Medicine.

“We have already seen the benefits in 50 and older,” he told the Post. “Eventually what’s true for older people turns out to be true for younger folks—it just takes longer to reveal itself.”

https://arstechnica.com/?p=1866160




With BA.2.12.1 now dominant in US, experts eye new subvariants BA.4 and BA.5

A person holds a positive SARS-CoV-2 rapid test on February 17, 2022 in Berlin, Germany.
Enlarge / A person holds a positive SARS-CoV-2 rapid test on February 17, 2022 in Berlin, Germany.

Omicron subvariant BA.2.12.1 has overtaken BA.2 as the dominant version of the pandemic coronavirus in the US, now accounting for an estimated 59 percent of cases nationwide. But BA.2.12.1’s reign may end as quickly as it began, with yet another batch of omicron subvariants gaining ground—BA.4 and BA.5—and threatening to cause more breakthrough infections.

BA.2.12.1 has a transmission advantage over BA.2, which itself has an edge over the initial omicron subvariant, BA.1, that caused a towering surge of US cases in mid-January. BA.2 peaked in mid-April, accounting for 76 percent of US cases at its height. But then came BA.2.12.1, which is named for being the 12th lineage stemming from BA.2 and the first branch of that BA.2.12 lineage.

When BA.2 peaked in mid-April, BA.2.12.1 accounted for about 18 percent of cases. It reached about 43 percent prevalence by mid-May and has since overtaken BA.2, which currently accounts for only about 35 percent of cases. BA.2.12.1 is dominant in every region of the country, except for the Northwest, according to the Centers for Disease Control and Prevention.

But, while BA.2.12.1 continues its rise, omicron subvariants BA.4 and BA.5 are gaining ground. In mid-May, BA.4 and BA.5 collectively accounted for less than 2 percent of cases nationwide. But now, they’re accounting for at least 6 percent, according to the latest figures from the CDC.

Heirs apparent

BA.4 and BA.5 aren’t new; they were first seen causing a massive wave of infection in South Africa in mid-to-late April that peaked in mid-to-late May. BA.4 and BA.5 are often clumped together because they share the same mutations in their spike protein, though they have different mutations elsewhere in their genetic blueprints. The spike protein is the critical protein that SARS-CoV-2 uses to latch onto human cells and, as such, is the prime target of vaccine- and infection-based immune responses.

BA.4 and BA.5 have a lot of unappealing qualities that have experts wary. First, the duo has a clear transmission advantage over BA.2.12.1, according to recent analyses of head-to-head comparisons of BA.4/5 to BA.2.12.1. They are poised to overcome BA.2.12.1 in the US, potentially causing yet another wave of infections.

A recent preprint study posted by researchers in Japan reported that BA.2.12.1, BA.4, and BA.5 replicate better in human lung cells than the previous reigning subvariant, BA.2. But, BA.4 and BA.5 cause more severe disease in hamsters than both BA.2 and BA.2.12.1.

The study also found that BA.4 and BA.5 can evade neutralizing antibodies generated from BA.1 and BA.2 infections. That means that people who have recovered from previous omicron infections may not have optimal protection from BA.4 and BA.5.

Additionally, another recent preprint study by researchers at Columbia University reported that BA.4 and BA.5 are better able to thwart immune responses in vaccinated and boosted people than BA.2 and BA.2.12.1. Specifically, BA.2.12.1 was 1.8-fold more resistant to the antibodies from vaccinated and boosted people than BA.2. But, BA.4 and BA.5 were collectively 4.2-fold more resistant. “Thus,” the authors concluded, the rise of BA.4 and BA.5 “is likely to lead to more breakthrough infections in the coming months.”

https://arstechnica.com/?p=1859291




Switch to Moderna booster after Pfizer shots better against omicron in 60+

The Comirnaty (Pfizer/BioNTech) and Moderna COVID-19 vaccines.
Enlarge / The Comirnaty (Pfizer/BioNTech) and Moderna COVID-19 vaccines.

People ages 60 and older who were initially vaccinated with two Pfizer-BioNTech COVID-19 vaccine doses were better protected from the omicron coronavirus variant after being boosted with a Moderna vaccine rather than another dose of the Pfizer-BioNTech vaccine.

Those results are according to interim data from a small but randomized controlled clinical trial in Singapore and published this week in the journal Clinical Infectious Diseases.

The study—involving 98 healthy adults—can’t determine if the Moderna booster is simply superior to a Pfizer-BioNTech booster for older adults or if a mix-and-match booster strategy is inherently better. It also focused solely on antibody levels, which may or may not translate to significant differences in infection rates and other clinical differences. It also only followed people for 28 days after a booster, so it’s unclear if the Moderna booster’s edge will hold up over time.

Still, the authors of the study, led by Barnaby Young of Singapore’s National Centre for Infectious Diseases, report that the beneficial effect seen by swapping from Pfizer-BioNTech to Moderna was significant enough that they don’t expect it to vanish with more participants. It also follows other studies that have suggested that mix-and-match boosting—aka heterologous boosting—can generate slightly different antibodies and reduce the incidence of SARS-CoV-2 infections in people 60 and older.

For the new study, Young and colleagues looked at antibody levels in adults of all ages who had received two Pfizer-BioNTech COVID-19 vaccine doses between six and nine months before receiving a booster dose. The researchers excluded people from the trial if they had compromised immune systems or had evidence of prior SARS-CoV-2 infections (the presence of anti-N antibodies).

Of the 98 participants, 50 went on to get another Pfizer-BioNTech vaccine dose for their booster (homologous booster), while the remaining 48 received a Moderna booster (heterologous booster). The authors looked at their resulting antibody responses on the day of their booster, seven days later, and 28 days later. Specifically, they compared total levels of antibodies that targeted a key part of the SARS-CoV-2 spike protein, called the receptor-binding domain. They also looked at levels of neutralizing antibodies against a range of specific SARS-CoV-2 variants, from the ancestral strain to alpha, beta, delta, and omicron.

Slightly bigger boost

Overall, the heterologous-boosted group had slightly higher total antibody levels than the homologous group—about 40 percent higher on day seven and 30 percent higher on day 28, though the confidence intervals overlapped. But, when the authors broke out the groups by age, they found that the benefit was entirely from differences in the 60-and-up group. Antibody levels were equivalent among younger participants, regardless of booster type.

Among those 60 and older, there were 24 homologous-boosted participants and 23 heterologous-boosted participants. At seven days after the booster, the heterologous-boosted participants had two-fold higher antibody levels than the homologous group and 60 percent higher levels at 28 days.

Older heterologous-boosted participants also had higher levels of neutralizing antibodies against all of the SARS-CoV-2 variants tested—with the largest difference seen against omicron, which is notorious for thwarting vaccine-derived immune responses. At seven days, the level of neutralizing antibody inhibition was 89 percent in the heterologous-boosted group compared with 64 percent in the homologous-boosted group. At 28 days, the spread was 84 percent in the heterologous-boosted group to 73 percent in the homologous-boosted group.

Overall, Young and co-authors concluded: “For the vulnerable older age group in particular, a heterologous booster COVID-19 vaccine regimen induces a higher anti-spike antibody titer and a stronger neutralizing antibody response against the highly infectious Omicron variant (~20 percent higher neutralization) than a homologous booster regimen.”

The trial is still ongoing, so the authors will continue to add participants and data. They intend to reassess antibody responses in all participants at six months and 12 months after the booster. They will add people to the study who initially received Moderna vaccines to see if switching to the Pfizer-BioNTech vaccine for the booster offers a similar benefit.

https://arstechnica.com/?p=1854282




Unvaccinated North Korea reports omicron outbreak, raising fears of new variants

People watch a television broadcast showing a file image of North Korean leader Kim Jong Un during a military parade at the Seoul Railway Station on May 4, 2022 in Seoul, South Korea.
Enlarge / People watch a television broadcast showing a file image of North Korean leader Kim Jong Un during a military parade at the Seoul Railway Station on May 4, 2022 in Seoul, South Korea.

North Korea instituted a nationwide lockdown Thursday after reporting an omicron coronavirus variant outbreak in its capital, Pyongyang. The report marks the first time during the pandemic that the secretive, authoritarian country has acknowledged coronavirus cases within its borders, though outside experts have doubted the country’s previous claims of zero infections.

Acknowledging omicron cases in Pyongyang raises questions over whether the admission is a sign of deteriorating public health conditions and/or a signal that the country is willing to accept pandemic aid, including vaccines.

So far, North Korea’s government has rejected offers of COVID-19 vaccine supplies from the United Nation’s global vaccination effort, COVAX, and China’s domestically produced vaccines. North Korea is one of the few countries that has not run a public vaccination effort, and its 26 million people are believed to be largely unvaccinated.

The lack of widespread immune protection from vaccination or prior infection, combined with an ongoing food crisis and an overall weak health care system, makes an outbreak of the ultra-transmissible omicron variant particularly worrying. The effects of a mushrooming outbreak could not only be devastating for North Korea’s people, but some experts have worried that it could also become a breeding ground for new, more dangerous variants.

For now, details are scant on the current outbreak. North Korea state media reported that unidentified people showing signs of fever were tested on Sunday, and results indicated they were infected with the BA.2 omicron subvariant. The report did not say how many people had tested positive but declared a “most serious national emergency,” according to The Washington Post.

The state media showed images of leader Kim Jong Un wearing a mask, along with other masked officials, according to the Associated Press. Kim ordered “all the cities and counties to thoroughly lock themselves down” to prevent spreading omicron. Factory and farm workers were told to work in isolation, according to The New York Times.

Kim reportedly advised North Koreans to remain vigilant and united as a nation to fight the spread of disease. “An enemy worse than the malicious virus is unscientific fear and a lack of faith and will,” he said.

But, the country’s situation is generating fear among experts on the outside, particularly because if omicron runs rampant in North Korea, it could give rise to new variants there. Kee Park, a global health expert at Harvard Medical School who has worked on health care projects in North Korea, expressed concern to The Washington Post, calling on the international community to come to North Korea’s aid. “It is in everyone’s interest to help North Korea in responding to the breach. No one wants another variant.”

https://arstechnica.com/?p=1854072




Omicron is trouncing the argument for “natural immunity” to COVID

A 13-year-old celebrates getting the Pfizer-BioNTech COVID-19 vaccine in Hartford, Connecticut, on May 13, 2021.
Enlarge / A 13-year-old celebrates getting the Pfizer-BioNTech COVID-19 vaccine in Hartford, Connecticut, on May 13, 2021.

So-called “natural immunity” against COVID-19 has always been a dodgy argument for avoiding vaccination during the pandemic. But amid omicron, natural immunity is clearly rubbish.

Unvaccinated people who recover from an omicron coronavirus variant infection are left with paltry levels of neutralizing antibodies against omicron. They also have almost no neutralizing antibodies against any of five other coronavirus variants, including delta. People who were vaccinated before getting an omicron infection, however, have strong protection against all five variants, and they have some of the highest levels of neutralizing antibodies against omicron.

That’s all according to a new study surveying neutralizing antibody profiles in people who have all recovered from an omicron infection, with or without pre-existing immunity. The study was published Wednesday in The New England Journal of Medicine by a team of Austrian researchers. The researchers were led by virologist Janine Kimpel of the Medical University of Innsbruck.

Overall, the findings highlight that omicron is “an extremely potent immune-escape variant that shows little cross-reactivity with the earlier variants,” the authors conclude. As such, unvaccinated people who recovered from an omicron infection might not have protection from other variants. “For full protection, vaccination is warranted,” they conclude.

The findings and conclusion are likely to rekindle discussion on the importance of “natural immunity,” which is immune protection following an infection rather than vaccination.

People who oppose getting COVID-19 shots argue that their prior infections gave them equal—if not superior—immunity to the pandemic coronavirus compared with vaccination. However, experts repeatedly noted that, while past infection can offer protection, it is not always strong and can vary widely. Some people who recover from COVID-19 have weak defenses, particularly if they had mild infections. Vaccination, meanwhile, offers relatively consistent and high-level protection. Moreover, so-called hybrid immunity—getting vaccinated after an infection—offers some of the highest levels of protection.

Variants and vaccines

Still, the omicron wave has been the pandemic’s golden age of confirmation bias for those who oppose vaccines. The ultratransmissible coronavirus variant is perceived as milder than earlier versions, and it can thwart defenses from vaccines, leading to more breakthrough infections. To some, this conflagration makes vaccines appear both less necessary and less useful.

But omicron is not a mild virus. According to data from the Centers for Disease Control and Prevention, nearly 146,000 people in the US have died of COVID-19 since January 1, when the omicron surge was well underway. By the end of January, the country saw a record high for hospitalizations, with a seven-day average of nearly 160,000 per day.

And vaccines have clearly been effective. People ages 12 and up who were vaccinated and boosted amid the omicron wave were 3.5 times less likely to test positive for COVID-19 and 21 times less likely to die of COVID-19.

The new study led by Kimpel adds further evidence for the usefulness of vaccines and their clear advantage over natural immunity. The researchers looked at neutralizing antibody levels in four groups of people who had recently recovered from an omicron infection: 15 vaccinated people; 18 unvaccinated people; 11 vaccinated people who had previously been infected (with wildtype, alpha, or delta variants); and 15 unvaccinated people who had been previously infected. The researchers looked at each person’s neutralizing antibody levels against six variants: wildtype, alpha, beta, gamma, delta, and omicron.

Neutralization Capacity of Serum Samples Obtained from Patients Who Recovered from Infection with the Omicron BA.1 Variant.
Enlarge / Neutralization Capacity of Serum Samples Obtained from Patients Who Recovered from Infection with the Omicron BA.1 Variant.

The unvaccinated people fared the worst, producing a mean 50 percent neutralizing antibody titer of just 79.5 against omicron. The mean titer against omicron in vaccinated people was 680. Unvaccinated people also had low-to-negligible levels of neutralizing antibodies against the other five variants.

People who were in either the vaccinated group or the vaccinated-and-previously-infected group had the highest levels of protection against all six variants. People who were unvaccinated but had immunity from an infection prior to omicron had higher and broader protection than the unvaccinated group. However, antibody levels were more variable and lower overall than those seen in the vaccinated groups.

The study has limitations, such as the small group sizes. However, the data demonstrates that omicron infections do not provide broad immunity against coronavirus variants. It also bolsters earlier findings that past coronavirus infections don’t provide the same consistent and high levels of protection as vaccination.

https://arstechnica.com/?p=1843383




Delta-omicron recombinant virus no reason for panic, health experts say

Transmission electron micrograph of a SARS-CoV-2 virus particle isolated from a patient sample and cultivated in cell culture.
Enlarge / Transmission electron micrograph of a SARS-CoV-2 virus particle isolated from a patient sample and cultivated in cell culture.

Researchers in France have reported the first compelling genetic evidence of a recombinant SARS-CoV-2 virus that contains elements of both the omicron coronavirus variant and the delta variant. However, health experts at the World Health Organization and elsewhere have been quick to note that such a recombinant virus is expected to arise and, so far, there’s no reason to be worried about the hybrid.

The delta-omicron recombinant—a combination of the delta AY.4 subvariant’s backbone and the omicron BA.1 subvariant’s spike protein—has been circulating at very low levels since at least early January 2022 in France. Researchers have also reported a smattering of cases in Denmark, Germany, and the Netherlands. So far, epidemiology data on the recombinant’s spread does not raise any red flags, and the variant does not appear to cause more severe disease, according to WHO technical lead Maria Van Kerkhove, who addressed the variant in a press briefing this week. However, researchers are in the process of conducting more studies on the recombinant and will be monitoring it closely, as the organization does with other new variants, she noted.

Coronaviruses are known to recombine, and researchers fully expected that such recombinant SARS-CoV-2 viruses would crop up from time to time. Generally, recombination can happen when two variants infect one person at the same time and invade the same cells. In this scenario, the cellular machinery that viruses hijack to make clones of themselves can sometimes abruptly switch from translating the genetic code of one of the variants to the code of the other, resulting in a mosaic virus.

Viral merger

It’s particularly unsurprising that a recombinant of delta and omicron popped up, given that omicron gained global dominance while delta transmission was still very high in many places. That situation provided the two highly transmissible viruses plenty of opportunities to cross paths. Additionally, it’s easier for researchers to identify delta-omicron hybrids. Genetic monitoring has ramped up significantly amid the pandemic, making detection more efficient. And the two variants are relatively distinct from each other, making delta-omicron recombinants far easier to pick out than recombinants of past variants, which had more in common with each other. All of those factors make it more likely that there will be reports of delta-omicron recombinants.

Still, detecting when recombination happens can be tricky. Some genetic-sequencing efforts can easily appear to detect recombinant viruses if there’s a co-infection without recombination or if there’s contamination in laboratory procedures. Some form of contamination was suspected to be the case in a report from January of a recombinant SARS-CoV-2 virus detected by researchers at the University of Cyprus. But in the case of the virus detected in France, researchers are more confident that it’s truly a recombinant virus because the quality of sequence data is better and researchers were able to grow the recombinant virus in laboratory cell cultures.

While confirmation of a delta-omicron recombinant may sound alarming, virologists have pointed out that recombination isn’t like creating a super-variant progeny that contains only the most dangerous aspects of its menacing parent variants. Like most mutations, most recombination isn’t advantageous to the virus. And so far, there’s no indication that the delta-omicron recombinant identified will take off and become the next globally dominant variant.

However, the possibility for dangerous recombinants is yet another reason to remain vigilant amid the pandemic virus to try to keep transmission low. The lower the transmission, the fewer opportunities there are for variants to emerge and recombine. That means we should be sticking with proven methods to reduce transmission, namely staying up to date on vaccination and taking health precautions like mask-wearing and physical distancing when the risk of transmission is high.

https://arstechnica.com/?p=1840515




Omicron subvariant BA.2 continues global rise as experts assess mixed data

Omicron subvariant BA.2 continues global rise as experts assess mixed data

A sub-lineage of the omicron coronavirus variant, dubbed BA.2, continues to increase steadily around the globe as scientists and health officials are still working to understand the risk it poses to public health.

So far, the overall data has been a mix. Some recent laboratory and animal data have suggested that BA.2 can cause more severe disease than the original omicron variant, BA.1. But, so far, that finding isn’t bearing out in real-world data. Countries where BA.2 is dominant are not seeing higher rates of severe disease. And, many places seeing BA.2 increasing are also seeing cases decline, along with hospitalizations.

While animal experiments have hinted that BA.2 interacts differently to some immune responses than the original omicron variant, so far real-world vaccine data finds two doses and booster doses are just as effective—if not slightly more effective—against BA.2 than BA.1.

There is one thing that everyone agrees on, however: BA.2 is a little more transmissible than BA.1, which was already considered ultratransmissible. Studies have consistently found that BA.2 has a growth advantage, and current estimates peg BA.2’s transmission as about 30 percent to 40 percent higher than BA.1’s. That explains how BA.2 is now chipping away at BA.1’s global domination.

BA.2 now accounts for at least 21 percent of all sequenced omicron cases worldwide. It has overtaken BA.1 as the dominant virus in at least 10 countries, including Bangladesh, China, Denmark, India, Nepal, Pakistan, and the Philippines. Where it rises, it rises quickly. In South Africa, for instance, BA.2 jumped from 27 percent on February 4 to 86 percent by February 11. In the United Kingdom, BA.2 prevalence jumped six-fold from January 17 to January 31. And in the US, it has more than tripled from 1.2 percent in the week ending on January 29 to its most recent prevalence estimate of 3.9 percent as of February 12.

Mostly good news

But those rises haven’t been accompanied by concerning upticks in severe disease and hospitalizations, as noted in a recent epidemiological report by the World Health Organization. In Denmark, where BA.2 is quickly nearing 100 percent of all infections, researchers have seen no difference in hospitalizations among people infected with BA.2 compared with BA.1. The analysis accounted for sex, age, vaccination status, time period, region, comorbidity, and previous SARS-CoV-2 infection. In South Africa, where BA.2 is also dominant, hospital admissions continue to decline. And likewise, in Nepal, though BA.2 cases have risen in February, cases still continue to fall from late January, and use of intensive care and mechanical ventilation is also on the decline.

Together, that data is comforting given a recent pre-print study suggesting that BA.2 appears to be more pathogenic than BA.1—at least in lab and animal experiments. The study, led by researchers at the University of Tokyo, found that BA.2 could bind to human cells better than BA.1 and replicated to higher levels in lung and nasal cells. In experiments with hamsters, the researchers also found that BA.2 caused more severe lung disease than BA.1. Work with hamsters and mice also suggested that BA.2 could thwart immune responses generated to BA.1. But this finding didn’t hold up statistically when the researchers pitted BA.2 against antibody samples from three unvaccinated people who had recovered from BA.1. The rodent data also conflicts with the real-world data from Denmark, referenced above.

Vaccine-effectiveness data from the UK and Denmark offer yet more comfort. A recent report released by the UK Health Security Agency found that current vaccines are just as effective—if not slightly more effective—against BA.2 than BA.1. Specifically, 25 weeks after a second dose, vaccines were 10 percent effective against symptomatic COVID-19 from BA.1 but were 18 percent effective against BA.2. Protection against symptomatic infection from BA.1 increased to 69 percent two weeks after a booster, but protection increased to 74 percent against BA.2. Preliminary data from Denmark, noted in the WHO report, found that vaccinated people with breakthrough BA.2 infections were less likely to spread the infection to household contacts than vaccinated people infected with BA.1

Overall, the WHO concluded that this “suggests that vaccination is at least equally effective in preventing acquisition of BA.2 and could be more effective in preventing transmission of BA.2 compared to BA.1.”

https://arstechnica.com/?p=1835390




Vaccine makers announce slowdowns for omicron-specific booster

Rows of small glass vials.
Enlarge / Vials of undiluted Pfizer COVID-19 vaccine.

Vaccine makers are pushing back when omicron-specific COVID-19 vaccines could be ready for use. The shots were initially expected in March.

Delays in the vaccines’ development come as cases of omicron have been dropping rapidly, and several animal studies have suggested the variant-specific formulations will not offer an advantage over the current vaccines.

BioNTech CEO Uğur Şahin on Wednesday said that his company’s omicron-specific vaccine had been delayed by several weeks due to unexpectedly slow data gathering, according to Reuters. BioNTech and its COVID-19 vaccine partner, Pfizer, had announced last month that they had begun a clinical trial with the omicron-specific shot.

Meanwhile, Moderna CEO Stéphane Bancel said Wednesday that Moderna’s omicron-specific shot could now be ready by August, according to a separate Reuters report. Bancel did not provide an explanation for the slower timeline but said that the company was aiming to have the booster ready for the autumn, when he thinks more people will need a booster dose.

The slowdowns come as global cases decline and the US, in particular, is seeing a precipitous drop. US cases have fallen 68 percent in the last two weeks. Although hospitalizations and deaths are still high, those numbers are trending downward as well.

The declines have many experts and officials cautiously optimistic that the worst of the pandemic is behind us. With so many people leaving the omicron wave with protection from past infection and/or vaccination, many experts hope that omicron will be the last big COVID-19 surge.

Future boosters

Still, other experts are more wary, noting that new variants can still arise, immunity can wane over time, and seasonal upticks are not out of the question.

“If the wave ends, that does not mean it can’t begin again,” BioNTech’s Sahin said Wednesday. He noted that BioNTech is prepared to continue developing variant-specific vaccines as needed.

Moderna’s Bancel was also convinced that the pandemic isn’t over. “We believe a booster will be needed,” he said. “I don’t know yet if it is going to be the existing vaccine, omicron-only, or bivalent—[meaning] omicron and existing vaccine, two mRNA [vaccines] in one dose.”

Omicron’s dramatic rise last November and December raised immediate concern that an omicron-specific vaccine would be necessary. As the variant swept the globe, scientists were struck by the large suite of mutations it carried as well as its clear ability to thwart immune defenses built up by previous infection and current vaccines. However, data on the real-world effectiveness of vaccines made clear that three doses of current mRNA vaccines could largely restore high levels of protection from omicron, particularly from severe disease, hospitalization, and death.

At the same time, animal studies have cast doubt on whether omicron-specific vaccines, which are designed to match critical mutations in the variant, will provide better protection. In a small primate study released earlier this month, the omicron-specific booster did not offer significantly better protection from omicron than a current vaccine. The study only involved eight monkeys, but the findings were consistent with several other studies in mice, which all suggest that a single variant-specific booster will not offer slam-dunk protection against a new variant.

https://arstechnica.com/?p=1835112