A 62-year-old man in Germany decided to get 217 COVID-19 vaccinations over the course of 29 months —for “private reasons.” But, somewhat surprisingly, he doesn’t seem to have suffered any ill effects from the excessive immunization, particularly weaker immune responses, according to a newly published case study in The Lancet Infectious Diseases.

The case is just one person, of course, so the findings can’t be extrapolated to the general population. But, they conflict with a widely held concern among researchers that such overexposure to vaccination could lead to weaker immune responses. Some experts have raised this concern in discussions over how frequently people should get COVID-19 booster doses.

In cases of chronic exposure to a disease-causing germ, “there is an indication that certain types of immune cells, known as T-cells, then become fatigued, leading to them releasing fewer pro-inflammatory messenger substances,” according to co-lead study author Kilian Schober from the Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene. This, along with other effects, can lead to “immune tolerance” that leads to weaker responses that are less effective at fighting off a pathogen, Schober explained in a news release.

The German man’s extreme history of hypervaccination seemed like a good case to look for evidence of such tolerance and weaker responses. Schober and his colleagues learned of the man’s case through news headlines—officials had opened a fraud investigation against the man, confirming 130 vaccinations over nine months, but no criminal charges were ever filed. “We then contacted him and invited him to undergo various tests in Erlangen [a city in Bavaria],” Schober said. “He was very interested in doing so.” The man then reported an additional 87 vaccinations to the researchers, which in total included eight different vaccine formulations, including updated boosters.

The researchers were able to collect blood and saliva samples from the man during his 214th to 217th vaccine doses. They compared his immune responses to those of 29 people who had received a standard three-dose series.

Throughout the dizzying number of vaccines, the man never reported any vaccine side effects, and his clinical testing revealed no abnormalities related to hypervaccination. The researchers conducted a detailed look at his responses to the vaccines, finding that while some aspects of his protection were stronger, on the whole, his immune responses were functionally similar to those from people who had far fewer doses. Vaccine-spurred antibody levels in his blood rose after a new dose but then began declining, similar to what was seen in the controls.

His antibodies’ ability to neutralize SARS-CoV-2 appeared to be between fivefold and 11-fold higher than in controls, but the researchers noted that this was due to a higher quantity of antibodies, not more potent antibodies. Specific subsets of immune cells, namely B-cells trained against SARS-CoV-2’s spike protein and T effector cells, were elevated compared with controls. But they seemed to function normally. As another type of control, the researchers also looked at the man’s immune response to an unrelated virus, Epstein-Barr, which causes mononucleosis. They found that the unbridled immunizations did not negatively impact responses to that virus, suggesting there were no ill effects on immune responses generally.

Last, multiple types of testing indicated that the man has never been infected with SARS-CoV-2. But the researchers were cautious to note that this may be due to other precautions the man took beyond getting 217 vaccines.

“In summary, our case report shows that SARS-CoV-2 hypervaccination did not lead to adverse events and increased the quantity of spike-specific antibodies and T cells without having a strong positive or negative effect on the intrinsic quality of adaptive immune responses,” the authors concluded. “Importantly,” they added, “we do not endorse hypervaccination as a strategy to enhance adaptive immunity.”

https://arstechnica.com/?p=2008036

More than four years after SARS-CoV-2 made its global debut, the US Food and Drug Administration is still working to clear out the bogus and unproven products that flooded the market claiming to prevent, treat, and cure COVID-19.

The latest example is an alcohol-based sanitizer meant to be smeared inside the nostrils. According to its maker, the rub can protect you from becoming infected with SARS-CoV-2 and other nasty germs, like MRSA, and that protection lasts up to 12 hours after each swabbing. That all sounds great, but according to the FDA, none of it is proven. In a warning letter released Tuesday, the agency determined the sanitizer, called Nozin, is an unapproved new drug and misbranded.

While ethyl alcohol is used in common topical antiseptics, like hand sanitizers, the FDA does not generally consider it safe for inside the nostrils—and the agency is unaware of any high-quality clinical data showing that Nozin is safe, let alone effective. The FDA also noted that, for general over-the-counter topical antiseptics, calling out specific pathogens it can fight off—like SARS-CoV-2 and MRSA—is not allowed under agency rules without further FDA review. Making claims about protection duration is also not allowed.

The FDA’s warning letter is nothing to sneeze at; the letter threatens seizure and injunction for failing to adequately respond.

Nozin’s maker, Maryland-based Global Life Technologies Corp., did not immediately respond to a request for comment from Ars. On its website, the company touts its product’s effectiveness with a link to a published study from 2014, indicating that use of Nozin lowered the colonization levels of S. aureus and other bacteria in the noses of 20 healthy health care workers. The study did not address protection from infection or carriage of any viruses. The company also lists unpublished studies indicating that the product can kill bacteria in laboratory conditions, does not irritate skin, and lowered bacterial growth in the noses of 30 people over a 12-hour period.

This is far from the first dubious, nasal-based COVID product the FDA has called out. There was the Corona-cure nasal spray of 2020, and the Halodine and NanoBio Protect nasal antiseptics of 2021. That year, the Federal Trade Commission sued a company called Xlear over allegedly false claims that its nasal spray can prevent and treat COVID-19. At least two more nasal spray makers received FDA warning letters in 2022.

To date, the FDA has not approved any nasal sprays to prevent or treat COVID-19, and the scant data on their efficacy remains inconclusive. But there are still plenty of such products for sale online. Most, like Nozin, claim to work by killing bacteria and viruses directly. One product, a nitric oxide nasal spray called Sanotize, is currently in a Phase III clinical trial to test whether it can prevent SARS-CoV-2 infections. Others claim to work by coating the nasal passage with the gelling agent iota-carrageenan to provide a barrier to viral entry. A pilot clinical trial of 400 health care workers in Argentina published in 2021 found that the use of an iota-carrageenan nasal spray led to a 4 percent absolute risk reduction in SARS-CoV-2 infection.

https://arstechnica.com/?p=2003503

It’s summer 2021. You rent a house in the countryside with a bunch of friends for someone’s birthday. The weather’s gorgeous that weekend, so mostly you’re all outside—pool, firepit, hammock, etc.—but you do all sleep in the same house. And then on Tuesday, you get an alert on your phone that you’ve been exposed to SARS-CoV-2, the virus that causes COVID-19. How likely are you to now have it?

To answer that question, a group of statisticians, data scientists, computer scientists, and epidemiologists in the UK analyzed 7 million people who were notified that they were exposed to COVID-19 by the NHS COVID-19 app in England and Wales between April 2021 and February 2022. They wanted to know if—and how—these app notifications correlated to actual disease transmission. Analyses like this can help ensure that an app designed for the next pathogen could retain efficacy while minimizing social and economic burdens. And it can tell us more about the dynamics of SARS-CoV-2 transmission.

Over 20 million quarantine requests

The NHS COVID-19 app was active on 13 to 18 million smartphones per day in 2021. It used Bluetooth signals to estimate the proximity between those smartphones while maintaining privacy and then alerted people who spent 15 minutes or more at a distance of 2 meters or less from a confirmed case. This led to over 20 million such alerts, each of which came with a request to quarantine—quite a burden.

The researchers found that the app did, in fact, accurately translate the duration and proximity of a COVID-19 exposure to a relevant epidemiological risk score. The app assessed a contact’s risk by multiplying the length of contact, the proximity of contact, and the infectiousness of the index case as determined by how long it had been since the index case started showing symptoms or tested positive.

There was an increasing probability of reported infection as the app’s risk score increased: more contacts whom the app deemed were at a high transmission risk did go on to test positive for COVID-19 within the following two weeks than those who were notified but had lower risk levels. (That’s positive tests that were reported by using the app. Some of the high-risk people probably did not test at all, did not report their test results, or did not report them within the allotted time. So this is an underestimation of the correlation between notification of risk and infection.)

More exposure = higher risk

When the researchers separated the factors contributing to the risk of an exposure, they found that duration was the most important indicator. Household exposures accounted for 6 percent of all contacts but 41 percent of transmissions.

One caveat: The app didn’t record any contextual variables that are known to impact transmission risk, like if people live in an urban or rural area, was the meeting indoors or outdoors, was it during the week or over the weekend, was anyone vaccinated, etc. Including such data could make risk assessment more accurate.

Based on their work, the researchers suggest that an “Amber Alert” stage could have been introduced to the app, in which people deemed to have an interim degree of risk would be guided to get a PCR test rather than immediately jumping to quarantine. Including this intermediate Amber Alert population could have significantly reduced the socioeconomic costs of contact tracing while retaining its epidemiological impact or could have increased its effectiveness for a similar cost. Performing analyses like this early on in the next pandemic to determine how it is transmitted might minimize illness and strain on society.

Nature, 2023.  DOI:  10.1038/s41586-023-06952-2

https://arstechnica.com/?p=1992331

With every new infection, the pandemic coronavirus gets new chances to mutate and adapt, creating opportunities for the virus to evolve new variants that are better at dodging our immune systems and making us sicker.

Anti-viral drugs, such as Paxlovid and remdesivir, aim to halt this incessant evolution in individual patients—shortening illnesses, snuffing out opportunities for mutation, and reducing transmission. But one antiviral appears to be backfiring—allowing SARS-CoV-2 more opportunities to mutate.

According to a new peer-reviewed study in the journal Nature, the anti-viral drug dubbed molnupiravir is linked to specific SARS-CoV-2 mutation signatures that happened to spring up in 2022 when the drug was introduced.

The study’s authors—led by researchers at the Francis Crick Institute in London and the University of Cambridge—scanned through more than 15 million SARS-CoV-2 genome sequences found in global databases. They picked out unique mutation signatures that closely linked to signatures seen in viruses from patients known to have been treated with molnupiravir. These suspected molnupiravir-linked mutation signatures also matched those seen in viruses examined in a clinical trial of molnupiravir. Overall, the signatures appeared in older people, who are most likely to have been treated with an antiviral, and people in countries where molnupiravir has often been used.

Beyond simply finding molnupiravir-linked mutations, the researchers noted concerning features of them. The researchers found evidence that some of the molnupiravir-linked mutations were under positive selection—that is, they increased in frequency, suggesting that they were advantageous to the virus in some way. They also noted that some viruses with molnupiravir-linked mutations were passed on from person to person in clusters, which suggested onward transmission of these drug-induced mutations.

The findings indicate that “molnupiravir results in new mutations, increasing the genetic diversity in the surviving viral population,” Theo Sanderson, lead author and postdoctoral researcher at the Francis Crick Institute, said in a statement.

For now, there is no evidence that molnupiravir has contributed to the development of any of the most significant SARS-CoV-2 variants, such as omicron. And the clusters of transmission seen in the data are small. Still, Sanderson says the study’s finding is important for weighing the risks and benefits of molnupiravir, highlighting the “possibility of persistent antiviral-induced mutations.”

https://arstechnica.com/?p=1971307

Americans will again have an opportunity to receive free at-home COVID-19 rapid tests from the US government, with orders beginning next Monday, September 25, the Biden administration announced Wednesday.

Households will be eligible to receive four free rapid tests that will “detect the currently circulating COVID-19 variant,” the Department of Health and Human Services said in an announcement. The tests, available next week via COVIDTests.gov and expected to start shipping on October 2, are meant to help Americans detect COVID-19 and keep from spreading it for the rest of the year—especially during holiday gatherings.

“At this point, our focus is getting through the holidays and making sure folks can take a test if they’re going to see Grandma for Thanksgiving,” Dawn O’Connell, assistant secretary for preparedness and response at the HHS, told the Associated Press.

But, beyond the upcoming gatherings and respiratory virus season, the HHS also noted that the free tests will “include clear instructions on how to verify extended expiration dates.”

The tests will be released from the Strategic National Stockpile; their distribution marks the fifth time the government has provided free tests to American households. So far, the US has provided over 755 million to households, with an additional 500 million going to long-term care facilities, low-income senior housing, uninsured individuals, and underserved communities.

The reopening of COVIDTests.gov is coupled with an announcement of a $600 million total investment in 12 domestic COVID-19 test manufacturers. The investment deals require the companies to maintain rapid test manufacturing capacity in the event of future surges. It also stipulates that the government will get about 200 million rapid tests in the near future to replenish the stockpile.

“These critical investments will strengthen our nation’s production levels of domestic at-home COVID-19 rapid tests and help mitigate the spread of the virus,” HHS Secretary Xavier Becerra said in the announcement.

While officials look to mitigate a potential COVID-19 this winter, transmission is increasing due to a late summer wave that hasn’t yet declined. The absolute numbers of hospitalizations and deaths are low compared with previous waves, but trends are still on an incline, as they have been for weeks, according to data from the Centers for Disease Control and Prevention.

The announcement of more free tests also comes amid the fall COVID-19 vaccination campaign, now underway with the recently updated vaccines targeting the omicron subvariant XBB.1.5. Unlike the free tests, this is the first round of vaccines that are not paid for and distributed by the government. And the rollout has been bumpy so far. There have been numerous reports of pharmacies canceling vaccination appointments because they’ve run out of doses. Many people have run into billing problems, with insurance plans being slow to update their billing codes to include the new vaccine, leaving customers to see $200 bills for shots that are required to be covered at no out-of-pocket expense.

The snags are expected to get ironed out in the coming days, and Moderna and Pfizer have reported that they believe they have enough supply. According to recent polling, more than half of US adults say they will definitely or probably get the new shot this fall.

https://arstechnica.com/?p=1970322

The Food and Drug Administration greenlit two updated COVID-19 vaccine booster shots Monday—a day before advisors for the Centers for Disease Control and Prevention are scheduled to meet and vote on recommendations for use of the updated vaccines.

The two shots are the 2023-2024 formulations of mRNA vaccines from Moderna and Pfizer-BioNTech, both of which target the recent omicron subvariant XBB.1.5. The FDA granted full approval of both Pfizer-BioNTech’s updated vaccine (Comirnaty) and Moderna’s updated vaccine (Spikevax) for use in those ages 12 years and up. The agency issued emergency use authorizations for both updated vaccines for use in children ages 6 months to 11 years.

If CDC and its advisors sign off on use of the vaccines Tuesday—which is likely—the shots could become fully available at local pharmacies and doctor’s offices in the coming days. While the FDA timed today’s actions to boost the population ahead of an anticipated winter wave of infection, the regulatory clearance come amid a mild increase of COVID-19 transmission that began in late summer.

“Vaccination remains critical to public health and continued protection against serious consequences of COVID-19, including hospitalization and death,” Peter Marks, the FDA’s top vaccine regulator, said in a press announcement. “The public can be assured that these updated vaccines have met the agency’s rigorous scientific standards for safety, effectiveness, and manufacturing quality. We very much encourage those who are eligible to consider getting vaccinated.”

In its announcement, the FDA said it determined that preliminary data on the shots found they can spur neutralizing antibody responses against currently circulating variants—including EG.5 and the highly mutated BA.2.86—that are “of a similar magnitude” to the neutralizing antibody responses seen in prior COVID-19 formulas targeting prior variants. Safety data also continues to be favorable. Thus, “the benefit-risk profile is favorable” for everyone ages 6 months and up to get the updated vaccine, the FDA said.

In a statement Monday, Moderna CEO Stéphane Bancel thanked the FDA for its timely review and called updated vaccines “critical to protecting the population” as the virus evolves. Pfizer’s CEO Albert Bourla, meanwhile, highlighted that COVID-19 cases are already climbing.

“We expect this season’s vaccine to be available in the coming days, pending recommendation from public health authorities, so people can ask their doctor about receiving their COVID-19 vaccine during the same appointment as their annual flu shot, saving time now and helping to prevent severe disease later when respiratory viruses are at their peak,” Bourla said in a statement.

Booster price

In the early years of the pandemic, the FDA moved to establish this annual update of COVID-19 vaccines, with boosters rolling out in the fall alongside flu shots ahead of anticipated winter waves. This was despite many experts expressing concern that COVID-19 has not necessarily established seasonality. Nevertheless, the FDA has charged forward with the plan, and this will be the third fall booster rollout. But, it will be the first in which the government is not paying for the shots.

This year, COVID-19 vaccines moved from government distribution to the commercial market, and Pfizer and Moderna hiked the prices of their vaccines significantly—raising them by around 400 percent. In recent vaccination rounds, the government spent around $26 to $30 for doses of the mRNA vaccines. But on the commercial market, the vaccines cost $110 to $130. The hikes have drawn intense criticism for price gouging, especially against Moderna, which developed its vaccine in partnership with federal scientists and with the help of $1.7 billion in federal grant money.

Assuming the CDC recommends the updated vaccines, most insured Americans will continue to have the vaccine available with no out-of-pocket costs. The federal government has also provided a “Bridge Access Program” to provide the vaccine freely to uninsured people through December 2024.

Still, the widely panned price hikes are not likely to help improve vaccination coverage. To date, only 17 percent of the US population (and 43 percent of the people age 65 and older) have gotten the updated booster released in the fall of 2022.

Who should get boosted

There’s also room for debate about who should receive this year’s booster dose. Experts generally agree that the elderly and people with compromised immune systems should have access to the boosters. But some experts say it’s less clear—or at least less critical—whether younger, healthy people should get the shot. The vaccines primarily provide strong protection against severe disease and death, for which young, healthy people generally have lower risk. Protection against infection and mild disease, meanwhile, is weaker and short-lived, on the order of weeks to a few months.

Thus, the benefits of vaccination for the young, healthy crowd are lower. But, some experts argue that boosters for all can help reduce transmission to the most vulnerable. Although young, healthy people have lower risks than other groups, they are not wholly immune from severe disease and complications like long COVID. Boosting can help protect against those outcomes, even if they’re less likely.

Tomorrow’s meeting

Discussion of who should get the vaccine will likely come up in tomorrow’s advisory meeting—a meeting of the CDC’s Advisory Committee on Immunization Practices (ACIP)—which is the committee that sets such things as age recommendations for immunizations.

The ACIP will also discuss a vaccine left out of today’s FDA’s actions: Novavax, a non-mRNA, protein-based COVID-19 vaccine. Novavax also developed an XBB.1.5-targeting updated vaccine for ages 12 and up. The company said in an announcement Monday that it is ready to roll out its updated shot, pending FDA authorization and CDC sign-off, but that it is “currently responding to the FDA’s requests to facilitate final review, and timing is ultimately at the discretion of the FDA.”

https://arstechnica.com/?p=1967187

Concern over the highly evolved omicron subvariant BA.2.86 is easing as the first batch of preliminary studies on the virus suggests it may not be as immune evasive or dangerous as its numerous mutations suggest.

But the good news is tempered by the latest COVID-19 data, which shows increasing rates of hospitalizations, emergency department visits, and deaths—all driven by the current gang of circulating omicron subvariants, led in the US by EG.5, FL.1.5.1 and XBB.1.16.6. No single variant is dominant globally, though EG.5 is on the rise.

In the US, hospitalizations are up nearly 16 percent since last week, and deaths have risen almost 18 percent in that time. Test positivity is also on a steep incline, according to the latest Centers for Disease Control and Prevention data.

Although the COVID-19 numbers are still low relative to other waves of infection, surveillance systems and testing have plummeted to worrying levels, meaning the true burden of the disease is likely underestimated. And the current wave is hitting ahead of fall booster availability, raising concern for those most vulnerable to the virus.

“One of [the World Health Organization’s] biggest concerns is the low level of at-risk people who have received a dose of COVID-19 vaccine recently,” WHO Director-General Tedros Adhanom Ghebreyesus said in a press briefing Wednesday. “Our message is not to wait to get an additional dose if it is recommended for you.”

According to reporting by NBC News, the US Food and Drug Administration could sign off on fall booster doses as early as this Friday, though the timeline could slide into early next week. The CDC is expected to sign off on the shots quickly after that.

Data so far suggests that those fall boosters—designed to target XBB.1.5—are effective against the current leading variants, namely EG.5 and FL.1.5.1. In a press release Wednesday, Moderna said that its booster is also effective against BA.2.86. According to preliminary clinical trial data, the vaccine generated an 8.7-fold increase in neutralizing antibodies against BA.2.86.

Experts are still unsure of how BA.2.86 will play out—whether it will take over, fizzle out, or further evolve into a nightmare variant. The remarkably large number of mutations it has now and its seemingly abrupt international spread raised alarm last month. But in the weeks since, the mutated omicron subvariant remains a rare find. As of the time of publishing, researchers from only 12 countries had reported just 64 BA.2.86 genome sequences out of the thousands of SARS-CoV-2 sequences submitted from around the globe each week. Meanwhile, about 30 percent of the sequences submitted recently are EG.5, Maria Van Kerkhove, WHO’s COVID-19 technical lead, said Wednesday.

BA.2.86 “is not outcompeting any of the variants of interest right now or other variants that are in circulation, and this is what we’re looking out for,” Van Kerkhove said.

The latest data

Three new studies out in the last few days—all pre-prints that have not been peer-reviewed—may help explain why the subvariant has stayed mostly on the sidelines. Collectively, the studies suggest BA.2.86 may not be as good at infecting human cells as the other currently circulating subvariants, and its mutations are not enough to overcome the high levels of immunity built up from past infections and vaccinations. While the preliminary data is heartening, researchers caution that BA.2.86 can continue to evolve, and—with our severely diminished COVID monitoring systems—we may have dodged a bullet.

One of the pre-print studies, from researchers in China, found that BA.2.86 was not as efficient at infecting cells in the lab compared with other circulating omicron subvariants, namely XBB.1.5 and EG.5. “In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution,” the researchers concluded. But, they cautioned: “Close attention should be paid to monitoring additional mutations that could improve BA.2.86’s infectivity.”

A pre-print study from researchers in Sweden, meanwhile, looked at how well serum from blood donors could neutralize BA.2.86 compared with XBB.1.5 and BA.2, the omicron subvariant from which BA.2.86 descended. Though they saw dips in neutralizing levels against BA.2.86 compared to the other variants, they weren’t as severe as originally feared. In one analysis looking at the most recent serum samples—taken while XBB variants were circulating—neutralizing antibody levels against BA.2.86 were slightly lower but still pretty strong compared with levels seen against XBB.1.5. The modest drops against BA.2.86 paled in comparison to the extreme immune evasion seen when the original omicron subvariant arose in the background of the delta subvariant, leading to a massive wave of infection at the start of 2022.

The third preprint study, led by researchers in Boston, came to a similar conclusion as the Swedish study. The US-based group looked at neutralizing antibody responses from 66 people (44 who got a bivalent booster last year and 22 people who hadn’t gotten boosted.) Across the board, neutralizing antibody levels against BA.2.86 were significantly lower than those to BA.2, but “were comparable or slightly higher” than those seen against a slew of other circulating omicron subvariants, namely XBB.1.5, XBB.1.16, EG.5, EG.5.1, and FL.1.5.1.

In a post on X, Ben Murrell, senior author of the Swedish study and a researcher at the Karolinska Institute, concluded from their data that “[O]ur antibodies do not appear to be completely powerless against [BA.2.86].” But, he offered a word of caution moving forward: “The fact, however, that another Omicron-like emergence event has occurred, with that long unobserved branch [of evolution] and subsequent spread, should warn us against giving up our genomic surveillance infrastructure.”

https://arstechnica.com/?p=1966041

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

A remarkably mutated coronavirus variant classified as BA.2.86 seized scientists’ attention last week as it popped up in four countries, including the US.

So far, the overall risk posed by the new subvariant is unclear. It’s possible it could lead to a new wave of infection; it’s also possible (perhaps most likely) it could fizzle out completely. Scientists simply don’t have enough information to know. But, what is very clear is that the current precipitous decline in coronavirus variant monitoring is extremely risky.

In a single week, BA.2.86 was detected in four different countries, but there are only six genetic sequences of the variant overall—three from Denmark, and one each from Israel, the UK, and the US (Michigan). The six detections suggest established international distribution and swift spread. It’s likely that more cases will be identified. But, with such scant data, little else can be said of the variant’s transmission or possible distribution.

Altered adversary

What grabbed quick attention is BA.2.86’s large number of mutations, particularly in the genetic code for its critical spike protein—the protein the virus uses to latch onto and enter human cells. BA.2.86 has 34 mutations in its spike gene relative to BA.2, the omicron sublineage from which it descended. This number of spike mutations between BA.2.86 and BA.2 is chillingly similar to the number of mutations seen between the original omicron (BA.1) and the ancestral Wuhan strain. The evolutionary jump from Wuhan to BA.1 caused a towering peak of COVID-19 cases and hospitalizations in early 2022. But, experts are skeptical that BA.2.86 could produce a rivaling wave, given the extensive levels of immunity in the population from both repeat vaccinations and infections.

In preliminary examinations of BA.2.86’s mutations, viral genetics experts say it looks adapted to escape neutralizing antibodies—even those spurred or boosted by exposure to a currently circulating omicron sublineage, XBB.1.5. Many of the spike mutations seen in the new variant are linked to antibody escape, according to an analysis by Jesse Bloom, a viral evolutionary biologist at the Fred Hutchinson Cancer Center in Seattle. Bloom’s analysis suggests that BA.2.86’s overall mutations give it at least as much antibody-escaping abilities as XBB.1.5, relative to BA.2. And BA.2.86’s mutations give it the ability to escape some antibodies against XBB.1.5, which is the variant targeted by the upcoming fall booster vaccines. Of course, neutralizing antibodies are not the totality of immune responses; there are non-neutralizing antibodies as well as cell-based protections that can work to prevent severe disease.

So far, it’s unknown whether BA.2.86 can cause more severe disease than existing variants, though the tiny bit of data so far suggests that it does not. Denmark’s Statens Serum Institute, which has identified three of the world’s six cases, said on X last week that “there is no indication that the new variant causes severe illness.” It also noted that the patients were not immunocompromised and did not have epidemiological links between them. In fact, all six cases are unrelated to each other. In a report by the UK Health Security Agency on Friday, officials also reported that the UK case had no recent travel history, suggesting domestic transmission.

Perhaps the biggest question left unanswered about BA.2.86 is how well it will spread relative to other variants in circulation, namely XBB.1.5, EG.5, FL.1.5.1, and others. For BA.2.86 to cause its own wave, it must couple its antibody-escaping abilities with changes that make it more easily transmissible than other variants. So far, there’s simply not enough data to know if this is the case or not.

Still, experts like Bloom are not alarmed. “The most likely scenario is this variant is less transmissible than current dominant variants, and so never spreads widely. This is the fate of most new SARS-CoV-2 variants,” he wrote in his analysis.

But even if BA.2.86 does what Bloom sees as mostly likely—fade away to an esoteric evolutionary anomaly—it should still raise alarm over the current state of our virus monitoring, as experts at the World Health Organization have repeatedly warned about.

Data decline

Part of the reason there is so little data on BA.2.86 is that there is relatively little data on circulating variants in general. In early 2022, at the height of pandemic genomic surveillance, scientists worldwide submitted nearly 100,000 coronavirus genetic sequences per week to the public genomic database (GISAID). In the past month, however, weekly GISAID submissions have averaged around just 5,000.

In the US, the Centers for Disease Control and Prevention has likewise seen a perilous drop in monitoring. In early 2022, the agency collected data from nearly 100,000 COVID-19 tests per week. Now, amid a summer wave with test positivity on the rise again, the test volume is just 40,000. And the agency only has enough genomic surveillance data to estimate variant prevalence for three of the country’s 10 health regions.

In October of last year, as experts were wary of a winter wave of COVID-19, Maria Van Kerkhove, WHO’s technical lead for COVID-19, warned in a press briefing that the surveillance landscape had “changed drastically.”

“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],” she said at the time.

But things have only gotten worse since then. In October 2022, for instance, scientists submitted over 20,000 coronavirus sequences per week to GISAID, compared with the current average of around 5,000.

“We need to ensure that sequencing continues. The virus is evolving,” Van Kerkhove said in a press briefing on August 9, addressing concerns about the previous variant making headlines, EG.5, which WHO had then classified as a “variant of interest.” Last week, WHO classified BA.2.86 as a “variant under monitoring.”

“The virus is circulating in every country and EG.5 is one of the latest variants of interest that we’re classifying. This will continue and this is what we have to prepare for,” she added. Currently, no single variant is dominant anywhere, and the virus is circulating essentially unchecked.

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Moderna’s updated COVID-19 vaccine provided a “significant boost” in people’s neutralizing antibody levels against the latest omicron SARS-CoV-2 subvariants circulating in the US, that is, EG.5 and FL.1.5.1, according to a press release from the company.

The updated booster shot is expected to be authorized and rolled out in the coming weeks.

Moderna, which was reporting its takeaway from preliminary clinical trial data, did not release additional details of the study, including the number of trial participants or the relative increase of neutralizing antibody levels. But the announcement aimed to ease concerns about whether the fall booster will adequately match this season’s variants.

“These new results, which show that our updated COVID-19 vaccine generates a robust immune response against the rapidly spreading EG.5 and FL.1.5.1 strains and reflects our updated vaccine’s ability to address emerging COVID-19 threats,” Moderna President Stephen Hoge said in the press release.

The shots were designed against the previously reigning omicron subvariant, XBB.1.5. In June, an advisory panel for the Food and Drug Administration determined that a shot aimed at an XBB variant, particularly XBB.1.5, was the best choice for the 2023-2024 season.

Both EG.5 and FL.1.5.1 are in the XBB family, with EG.5 related to XBB.1.9.2 and FL.1.5.1 related to XBB.1.9.1. (Some of these subvariants have been given unofficial, mythological nicknames by a scientist on social media. Ars will only use the established Pango Lineage classification system endorsed by the World Health Organization and other major health organizations to describe variant lineages.)

According to the latest data from the Centers for Disease Control and Prevention, EG.5 is estimated to account for roughly 21 percent of circulating SARS-CoV-2 viruses, while FL.1.5.1 accounts for around 13 percent.

Pfizer also said that its XBB.1.5-targeted booster also spurred neutralizing antibodies against EG.5 in a mouse study, according to a report from Reuters.

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