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How the omicron subvariant BA.5 became a master of disguise – and what it means for the current COVID-19 surge

Face masks are still an effective way to help stop the spread of the BA.5 subvariant.

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The new BA.5 subvariant has caused a sharp rise in cases and hospitalizations throughout much of the United States. Irfan Khan/Los Angeles Times via Getty Images

The omicron subvariant known as BA.5 was first detected in South Africa in February 2022 and spread rapidly throughout the world. As of the second week of July 2022, BA.5 constituted nearly 80% of COVID-19 variants in the United States.

Soon after researchers in South Africa reported the original version of the omicron variant (B.1.1.529) on Nov. 24, 2021, many scientists – including me – speculated that if omicron’s numerous mutations made it either more transmissible or better at immune evasion than the preceding delta variant, omicron could become the dominant variant around the world.

The omicron variant did indeed become dominant early in 2022, and several sublineages, or subvariants, of omicron have since emerged: BA.1, BA.2, BA.4 and BA.5, among others. With the continued appearance of such highly transmissible variants, it is evident that SARS-CoV-2, the virus that causes COVID-19, is effectively using classic techniques that viruses use to escape the immune system. These escape strategies range from changing the shape of key proteins recognized by your immune system’s protective antibodies to camouflaging its genetic material to fool human cells into considering it a part of themselves instead of an invader to attack.

I am a virologist who studies emerging viruses and viruses that jumped from animals to humans, such as SARS-CoV-2. My research group has been tracking the transmission and evolution of SARS-CoV-2, evaluating changes in how well the omicron subvariants evade the immune system and the severity of disease they cause after infection.

The BA.5 subvariant is better able to evade the body’s immune system than previous subvariants.

How is virus transmissibility in a population measured?

The basic reproduction number, R0 – pronounced “R-naught” – measures the transmissibility of a virus in a yet-uninfected population.

Once a proportion of individuals in a population become immune due to prior infection or vaccination, epidemiologists use the term effective reproduction number, called Re or Rt, to measure the transmissibility of the virus. The Re of the omicron variant has been estimated to be 2.5 times higher than the delta variant. This increased transmissibility most likely helped omicron out-compete delta to become the dominant variant.

The larger question, then, is what is driving the evolution of omicron sublineages? The answer to that is a well-known process called natural selection. Natural selection is an evolutionary process where traits that give a species a reproductive advantage continue to be passed down to the next generation, while traits that don’t are phased out through competition. As SARS-CoV-2 continues to circulate, natural selection will favor mutations that give the virus the greatest survival advantage.

What makes omicron and its offshoots so stealthy at spreading?

Several mechanisms contribute to the increased transmissibility of SARS-CoV-2 variants. One is the ability to bind more strongly to the ACE2 receptor, a protein in the body that primarily helps regulate blood pressure but can also help SARS-CoV-2 enter cells. The more recent omicron sublineages have mutations that make them better at escaping antibody protection while retaining their ability to effectively bind to ACE2 receptors. The BA.5 sublineage can evade antibodies from both vaccination and prior infection.

Omicron sublineages BA.4 and BA.5 share several mutations with earlier omicron sublineages, but also have three unique mutations: L452R, F486V and reversion (or the lack of mutation) of R493Q. L452R and F486V in the spike protein help BA.5 escape antibodies. In addition, the L452R mutation helps the virus bind more effectively to the membrane of its host cell, a crucial feature associated with COVID-19 disease severity.

The BA.5 subvariant is responsible for two-thirds of all current COVID-19 cases in the United States.

While the other mutation in BA.5, F486V, may help the sublineage escape from certain types of antibodies, it could decrease its ability to bind to ACE2. Strikingly, BA.5 appears to compensate for decreased ACE2 binding strength through another mutation, R493Q reversion, that is thought to restore its lost affinity for ACE2. The ability to successfully escape immunity while maintaining its ability to bind to ACE2 may have potentially contributed to the rapid global spread of BA.5.

In addition to these immune-evading mutations, SARS-CoV-2 has been evolving to suppress its hosts’ - in this case, humans’ – innate immunity. Innate immunity is the body’s first line of defense against invading pathogens, comprised of antiviral proteins that help fight viruses. SARS-CoV-2 has the ability to suppress the activation of some of these key antiviral proteins, meaning it’s able to effectively get past many of the body’s defenses. This explains the spread of infections among vaccinated or previously infected people.

Innate immunity exerts a strong selective pressure on SARS-CoV-2. Delta and omicron, the two most recent and highly successful SARS-CoV-2 variants, share several mutations that could be key in helping the virus breach innate immunity. However, scientists do not yet fully understand what changes in BA.5 might allow it to do so.

What’s next?

BA.5 will not be the end game. As the virus continues to circulate, this evolutionary trend will likely lead to the emergence of more transmissible variants that are capable of immune escape.

While it is difficult to predict what variants will arrive next, we researchers cannot rule out the possibility that some of these variants could lead to increased disease severity and higher hospitalization rates. As the virus continues to evolve, most people will get COVID-19 multiple times despite vaccination status. This could be confusing and frustrating for some, and may contribute to vaccine hesitancy. Therefore, it is essential to recognize that vaccines protect you from severe disease and death, not necessarily from getting infected.

Research over the past two and a half years has helped scientists like me learn a lot about this new virus. However, many unanswered questions remain because the virus constantly evolves, and we are left trying to target a constantly moving goal post. While updating vaccines to match circulating variants is an option, it may not be practical in the short term because the virus evolves too quickly. Vaccines that generate antibodies against a broad range of SARS-CoV-2 variants and a cocktail of broad-ranging treatments, including monoclonal antibodies and antiviral drugs, will be critical in the fight against COVID-19.

Suresh V. Kuchipudi receives funding from the National Institutes of Health, National Science Foundation and USDA-National Institute of food and Agriculture.

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International

Memory in action: what the UK’s official COVID commemoration should look like

Memorialising a pandemic that is still underway is a challenge. Official commemoration needs to be about remembrance and preparedness.

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Whether an actual bereavement or a loss of experience, everyone has lost something to COVID. From early on in the pandemic, grassroots memorials sought to acknowledge this collective experience, including the national COVID memorial wall in London and the annual national day of reflection organised by the Marie Curie charity.

In September 2023, the UK Commission on COVID Commemoration released its final report on how a more official reckoning with the pandemic’s legacy should be shaped. It outlines ten recommendations.

The pandemic has affected people in vastly different ways. How governments, institutions and the wider public have responded has varied enormously, too. It is also still ongoing, which complicates things further.

New variants of the virus are on the rise. And nearly two million people in the UK alone continue to suffer with long COVID.

As immunologist Sheena Cruickshank put it recently, “it may feel like we should all be done with COVID-19, but sadly COVID-19 is not done with us”.

My research into memorial culture and modernism shows how the lack of a clear or coherent narrative for an event like a pandemic makes commemorating it that much harder. The official and cultural memory of the 1918 flu pandemic was subsumed into that of the first world war – and it remained largely unremembered, until COVID brought it back to public attention.

Nurses began erecting memorials early on in the first world war. Wellcome Collection Images, CC BY-NC-ND

Remembrance and preparedness

From October to December 2022, the UK Commission on Covid Commemoration held a six-week period of public consultation. It conducted surveys, garnering 5,000 responses. It also met with affected groups, including bereaved families and long-COVID sufferers, as well as groups that are sceptical about the illness and lockdown strategies.

The report is, to my mind, admirably well considered, sensitive to the difficulties of the task. It firmly establishes why memorialising all deaths that have occurred during the pandemic – COVID-related or otherwise – is necessary. This chimes with previous research that has found that COVID-related grief is particularly difficult and that public commemoration is necessary for social cohesion.

The 11 members of the commission suggest a range of commemorations, which will now be considered for implementation by the British government. These include an annual day of reflection on the first Sunday in March, a new symbol to represent the pandemic, the establishment of a commemoration trust to organise and promote these initiatives, along with a commemoration website and an online book of remembrance.

The commissioners suggest creating ten green spaces across the country, each boasting a sculpture created by local artists. They recommend preserving those grassroots initiatives already in place, including the national COVID memorial wall.

Finally, they propose various educational initiatives. These include teaching the history of the pandemic in schools and college and collating oral histories from a wide range of groups, to, as the report puts it, “serve as a historical record of this period of our time and as an educational tool for future generations”. A postdoctoral fellowship programme is suggested, too, to enable future researchers to work with policy makers on national preparedness for natural hazards.

Most of these recommendations are fairly standard commemorative gestures. The decision to create disparate pockets of remembrance across the UK rather than one large-scale memorial is expected, as there is no consensus or agreed-upon version of the pandemic.

The choice of green spaces is usefully open-ended in terms of meaning. The memorial sculptures destined for each will, doubtless, be similarly open-ended, in keeping with the minimalist, abstract and predominantly secular tendencies in modern contemporary memorials in the UK.

The report also proposes council funding for local commemorative spaces in existing parks or green spaces, not unlike the many community-led first world war memorials.

The COVID symbol the commission suggests is a zinnia flower. Associated with remembrance, this floral design has similarities to the poppy which has long symbolised the first world war.

Large-scale commemorative gestures have already been seen in other nations. Most notably, Joe Biden’s first act as US president was, during his inaugural address, to lead a moment of silence to remember the then 400,000 Americans lost to the pandemic.

By contrast, the UK public has felt left down by its government’s response. The news, that former prime minister Boris Johnson reportedly said, in autumn 2020, that he would rather see “bodies pile high” than impose a third lockdown on the UK, has left a bitter taste.

Johnson’s subsequent clandestine evening trip, in April 2021, to the COVID memorial wall, as well as public scandals such as Partygate, have further angered the public. Bereaved family groups such as COVID-19 Bereaved Families for Justice are understandably anxious to see that their loved ones are remembered officially as names and not as numbers.

The commission is eager to distinguish itself from the contentious COVID-19 Inquiry. This report is a useful corrective to the inadequacies of the British government in commemorating the pandemic to date.

Some may wonder if it is too early to commemorate a pandemic that isn’t yet over. After 1914, nurses began to create memorials as soon as the first deaths happened. The British government established the Imperial War Museum in 1917, while the war was still ongoing. I have shown how necessary these commemorative gestures were. They ensured that the dead were not forgotten.

Whether the government will now do is yet to be seen. In its insistence both on remembrance and on preparedness – for the next pandemic that, experts agree, will happen – this report is a good first step.

Alice Kelly received a British Academy Rising Star Engagement Award from 2017-19 for a seminar series entitled "Cultures and Commemorations of War."

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Only 2% Of Americans Have Received New COVID Vaccine: CDC

Only 2% Of Americans Have Received New COVID Vaccine: CDC

Authored by Jack Phillips via The Epoch Times,

About 2 percent of all Americans…

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Only 2% Of Americans Have Received New COVID Vaccine: CDC

Authored by Jack Phillips via The Epoch Times,

About 2 percent of all Americans have received the updated COVID-19 booster shot after it was authorized and recommended by federal health officials several weeks ago, according to updated data provided by the Department of Health and Human Services (HHS).

More than 7 million Americans have taken the updated shot, which is authorized for people aged 6 months and older, said an HHS spokesman. That's approximately 2 percent of all Americans.

“COVID-19 vaccine distribution, which has shifted to the private market, is a lot different than it was last year when the government was distributing them," said a spokesperson for HHS about the vaccination data. It added that the agency is "directly with manufacturers and distributors to ensure that the vaccines are getting to" various locations.

The statement added that 91 percent of Americans aged 12 years and older "can access the vaccine within 5 miles of where they live," adding that 14 million updated boosters for COVID-19 have been shipped to pharmacies and other locations. The vaccine was approved about a month ago by the Food and Drug Administration (FDA) before it was recommended by the U.S. Centers for Disease Control and Prevention (CDC) shortly thereafter.

It came as some people reported that it's difficult to find doses of the new vaccines at local pharmacies and doctors. Jen Kates, a senior vice president at the Kaiser Family Foundation, said on X in September that her vaccine appointment was canceled due to a lack of supply.

The 7 million figure is up since Oct. 6 when Dr. Mandy Cohen, director of the CDC, told reporters that 4 million had received the new vaccines.

The HHS said Thursday that the latest updated vaccinate rate is about the same as the initial bivalent booster shot when it was rolled out in 2022. However, demand for the 2022 booster vaccine was similarly low, according to CDC data.

Data has shown that about 17 percent of the U.S. population got that previous updated shot, or around 56.5 million people.

The updated vaccines were meant to target the COVID-19 XBB.1.5 variant, which was spreading across the United States when companies like Moderna and Pfizer came up with the new version.

Observational data for the bivalent vaccines, or the previous versions, found weak initial effectiveness that quickly waned.

CDC officials made unsupported claims during the briefing, part of a trend for the agency. “These vaccines will prevent severe disease for COVID-19,” Dr. Demetre Daskalakis, director of the CDC’s National Center for Immunization and Respiratory Disease, told reporters. There’s no evidence that’s true.

The only clinical study data for the new shots is from a study Moderna ran that included injecting 50 humans with the company’s updated formation. The result was a higher level of neutralizing antibodies. Officials believe antibodies protect against COVID-19.

Moderna did not provide any clinical efficacy estimates for infection, severe disease, or death. Pfizer said it was running a trial but has not reported any results.

Novavax’s vaccine was authorized later without any new trial data, as CDC officials have said they recommend that shot. Unlike the Moderna and Pfizer vaccines, Novavax doesn't use mRNA technology and is protein-based.

Hospitalizations Down

Despite the recent push for the latest vaccines, data provided by the CDC shows that hospitalizations for COVID-19 have been down for about three consecutive weeks.

For the ending Sept. 30, the hospitalization rate is down by 6 percent, while emergency department visits are down by 14.5 percent and COVID-19 cases are down 1.2 percent, the figures show. Deaths are up 3.8 percent, although health officials have previously said that deaths generally lag behind hospitalizations and case numbers.

In July, COVID-19 hospitalizations had been increasing for several consecutive weeks. CDC historical data suggest that deaths have been relatively low compared with previous years.

But with the release of the Sept. 30 data, hospitalizations have dropped for multiple consecutive weeks.

Dr. Shira Doron, chief infection control officer for Tufts Medicine, told ABC News that that the recent “upswing is not a surge; it’s not even a wave.”

The doctor added: “What we’re seeing is a very gradual and small upward trajectory of cases and hospitalizations, without deaths really going along, which is great news.”

The CDC on Oct. 6 released a report that attempted to push older Americans to get the newest vaccines by saying that COVID-19 is still a "public health threat," namely for people aged 65 and older. The majority of hospitalizations, it said, is occurring among that older demographic, according to the paper.

In the meantime, a handful of hospitals in California, New York state, Massachusetts, and New Jersey have re-implemented mandatory masking—at least for staff.

Several Northern California counties issued a mask mandate for all health care staff starting next month and ending in late April 2024. They include Contra Costa, Sonoma, Alameda, and San Mateo counties. Officials in the Southern California county of San Luis Obispo also issued a vaccine-or-mask mandate earlier this month.

Tyler Durden Mon, 10/16/2023 - 12:20

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Spread & Containment

Worsening Treasury Liquidity Keeping Fixed-Income Vol Elevated

Worsening Treasury Liquidity Keeping Fixed-Income Vol Elevated

Authored by Simon White, Bloomberg macro strategist,

Poor liquidity in the…

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Worsening Treasury Liquidity Keeping Fixed-Income Vol Elevated

Authored by Simon White, Bloomberg macro strategist,

Poor liquidity in the Treasury market is contributing to a rise in implied and realized fixed-income volatility. A re-increase in inflation volatility means this dynamic is likely to persist.

Despite being one of the deepest markets in the world, the market for Treasuries has seen liquidity deteriorate in the years since the pandemic. On several measures – bid/offer spread, order-book depth, price impact of a trade – the Treasury market has shown marked signs of a decline in liquidity in recent years.

Bloomberg’s US Treasury Liquidity Index measures liquidity by comparing where yields are to where they “should” be based off a fitted curve. The greater the average of the yield errors across the curve, the worse liquidity is likely to be.

As the chart below shows, the Liquidity Index infers liquidity has markedly weakened over the last two years, and after showing an improvement over the last six months, it has started to worsen again.

Fixed-income volatility, using the MOVE index, intuitively rises and falls as liquidity worsens and improves respectively.

Bond volatility has been notably higher in this cycle than other assets’ volatility, such as equities and FX. Indeed, the recent rise in the MOVE index, i.e. implied volatility, has taken it to a level above realized volatility it has rarely exceeded in the last 30-plus years.

The immediate catalyst for the rise in bond volatility has been the Federal Reserve’s rate-hiking cycle. But this was itself triggered by the rise in inflation. It is the inherent increase in uncertainty that goes with elevated inflation that is the ultimate source of rising volatility.

Higher inflation volatility goes hand in hand with higher market volatility, especially in rates and fixed-income markets. Inflation is very likely to be persistent, and soon to begin re-accelerating. Inflation volatility has moderated somewhat from its recent highs, but is picking up again.

As long as inflation volatility remains elevated, bond vol will remain likewise. This is even more so the case as the yield curve continues to rise, with steeper curves an inherent source of yield volatility.

Tyler Durden Mon, 10/16/2023 - 08:45

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