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New SARS-CoV-2 Variant BA.2.75 Evades All Approved Monoclonal Antibody Therapies

William A. Haseltine wrote . . . . . . . . .

Viral variation has proved to be a critical weak point in our approach to medical solutions for controlling Covid-19. Over the last two and a half years, we’ve seen successive waves of reinfection by new variants of those who’ve been previously infected, those who have been vaccinated and boosted, and those who have been infected, vaccinated, and boosted as well. Behind this unfortunate dynamic is the dramatic variation in the structure of the virus exterior, specifically the Spike protein, which plays a critical role early in infection by binding to the cell surface and forcing entry.

Antibodies that recognize this structure can block infection. However, changes in the exterior structure negate antibody collections in convalescent sera and monoclonal antibodies from binding and neutralizing the virus. A recent study by Yamasoba et al. summarizes the effectiveness of existing monoclonal antibodies against a successive set of virus variants, namely the BA.2 variant, which first emerged in late 2021 and quickly spread around the world, driving the most infectious wave of the virus to date, BA 4/5, which are the predominant strains circulating at the time of writing, and BA.2.75, a new sublineage of BA.2 which is likely more infectious and immune evasive than its predecessors, suggesting it may be the predominant variant in the coming weeks and months.

FIGURE 1: Neutralization assay was performed using pseudoviruses harboring the SARS-CoV-2 Spike … [+] YAMASOBA ET AL.

The ability of the virus to evade natural immunity from the previously infected and vaccinated is also reflected in its ability to escape a host of specific monoclonal antibodies. As is clear from Figure one, the later Omicron viruses evade monoclonal antibodies much more effectively than early strains.

Immediately, we note that five antibodies: adintrevimab, bamlanivimab, casirivimab, etesevimab, and imdevimab failed to neutralize any of the three Omicron sublineages. Casirivimab and imdevimab, as well as etesevimab and bamlanivimab, are designed to be used in tandem in an antibody cocktail, yet their combination antibodies were just as ineffective. Adintrevimab is intended for individual use, meaning its neutralization potency for the strains circulating today is nonexistent. These were among the first monoclonal antibodies developed, rationalizing why they are so ineffective against recent strains.

This leaves five individual monoclonal antibodies. Regdanvimab, sotrovimab, and tixagevimab did not neutralize the previously circulating BA.2 and the currently circulating BA.4/5. However, the three effectively neutralized the BA.2.75 pseudovirus. This suggests that if BA.2.75 became the dominant strain in the coming weeks and months, these three monoclonal antibodies could be effective treatments for those suffering from Covid due to this strain.

Of the two remaining antibodies, cilgavimab poorly neutralized BA.2 and BA.4/5 but was 24.4-fold worse against BA.2.75. Although bebtelovimab effectively neutralized BA.2 and BA.4/5, it again was much worse against BA.2.75, this time 21.2 to 25.6-fold. Despite poorly neutralizing BA.2.75 compared to BA.4/5, bebtelovimab still neutralized the strain better than any other antibody.

Even newer generations of viruses recently detected in South Africa with more extensively mutated Spike proteins, against which bebtelovimab and others may perform even more poorly.

New variants evading monoclonal antibodies should come as no surprise. After infection, the convalescent sera of a recovered patient contains many antibodies designed to inhibit the virus the host just overcame. For the virus to reinfect, it must mutate considerably to evade the convalescent antibodies. Monoclonal antibodies are effectively the same as convalescent antibodies on an individual scale. They are designed to overcome a virus by binding to specific amino acids on the Spike. If the virus mutates enough, the monoclonal antibody can no longer bind. This is how the cat and mouse game of developing antibodies and the virus mutating has continued for two and a half years.

What then can be done? The search is on for monoclonal antibodies that recognize regions of the virus that are critical to the virus lifecycle and therefore are resistant to most mutations. In other words, scientists worldwide are rushing to identify and develop antibodies with broadly neutralizing capabilities, i.e., antibodies that recognize highly conserved sequences of the Spike protein that may overcome all viral variants.

The good news is that many such antibodies have already been identified. We recently described the Cv2.1169 antibody discovered by scientists at the Pasteur Institute and will continue to detail others as data is released. Whether these antibodies recognize and neutralize the latest variants such as BA.2.75 remains an open question.

A second potential solution is to use extensive combinations of functional monoclonal antibodies. While many fail to neutralize, some retain neutralizing capability against the latest variants, and new monoclonal antibodies are constantly advancing. Combining two, three, or four antibodies into a single treatment may suppress infection. Our hope remains high for monoclonal antibodies as a short-term relief for those infected and, in the long run, as a prophylactic against infection in the first place.

Source : Forbes

New Coronavirus Mutant Raises Concerns in India and Beyond

Laura Ungar and Aniruddha Ghosal wrote . . . . . . . . .

The quickly changing coronavirus has spawned yet another super contagious omicron mutant that’s worrying scientists as it gains ground in India and pops up in numerous other countries, including the United States.

Scientists say the variant – called BA.2.75 – may be able to spread rapidly and get around immunity from vaccines and previous infection. It’s unclear whether it could cause more serious disease than other omicron variants, including the globally prominent BA.5.

“It’s still really early on for us to draw too many conclusions,” said Matthew Binnicker, director of clinical virology at the Mayo Clinic in Rochester, Minnesota. “But it does look like, especially in India, the rates of transmission are showing kind of that exponential increase.” Whether it will outcompete BA.5, he said, is yet to be determined.

Still, the fact that it has already been detected in many parts of the world even with lower levels of viral surveillance “is an early indication it is spreading,” said Shishi Luo, head of infectious diseases for Helix, a company that supplies viral sequencing information to the U.S. Centers for Disease Control and Prevention.

The latest mutant has been spotted in several distant states in India, and appears to be spreading faster than other variants there, said Lipi Thukral, a scientist at the Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology in New Delhi. It’s also been detected in about 10 other countries, including Australia, Germany, the United Kingdom and Canada. Two cases were recently identified on the West Coast of the U.S., and Helix identified a third U.S. case last week.

Fueling experts’ concerns are a large number of mutations separating this new variant from omicron predecessors. Some of those mutations are in areas that relate to the spike protein and could allow the virus to bind onto cells more efficiently, Binnicker said.

Another concern is that the genetic tweaks may make it easier for the virus to skirt past antibodies — protective proteins made by the body in response to a vaccine or infection from an earlier variant.

But experts say vaccines and boosters are still the best defense against severe COVID-19. In the fall it’s likely the U.S. will see updated formulations of the vaccine being developed that target more recent omicron strains.

“Some may say, ‘Well, vaccination and boosting hasn’t prevented people from getting infected.’ And, yes, that is true,” he said. “But what we have seen is that the rates of people ending up in the hospital and dying have significantly decreased. As more people have been vaccinated, boosted or naturally infected, we are starting to see the background levels of immunity worldwide creep up.”

It may take several weeks to get a sense of whether the latest omicron mutant may affect the trajectory of the pandemic. Meanwhile Dr. Gagandeep Kang, who studies viruses at India’s Christian Medical College in Vellore, said the growing concern over the variant underlines the need for more sustained efforts to track and trace viruses that combine genetic efforts with real world information about who is getting sick and how badly. “It is important that surveillance isn’t a start-stop strategy,” she said.

Luo said BA.2.75 is another reminder that the coronavirus is continually evolving – and spreading.

“We would like to return to pre-pandemic life, but we still need to be careful,” she said. “ We need to accept that we’re now living with a higher level of risk than we used to.”

Source : AP

Dominant Omicron Subvariants Better at Evading Vaccines, Antibody Treatments

The latest omicron subvariants—including the BA.4 and BA.5 forms causing new surges in infections in the United States—are even better at eluding vaccines and most antibody treatments than previous variants, finds a study by researchers at Columbia University Vagelos College of Physicians and Surgeons.

The study, led by David D. Ho, MD, director of the Aaron Diamond AIDS Research Center and the Clyde‘56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons, was published July 5 in Nature.

Subvariants BA.2.12.1, BA.4, and BA.5 are rapidly expanding worldwide, with BA.4/5 now making up more than 50% of new COVID cases in the United States. These subvariants are thought to be even more transmissible than prior omicron subvariants, owing to several new mutations in spike proteins.

“The virus is continuing to evolve, as expected, and it is not surprising that these new, more transmissible subvariants are becoming more dominant around the world,” says Ho. “Understanding how currently available vaccines and antibody treatments stand up to the new subvariants is critical to developing strategies to prevent severe disease, hospitalizations, and deaths—if not infection.”

In laboratory experiments, Ho and his team studied the ability of antibodies from individuals who received at least three doses of an mRNA vaccine, or got two shots and were then infected with omicron, to neutralize the new subvariants. (Ho’s team did not look at individuals who had not received a booster shot, because a previous study found that two doses provide little protection against infection by earlier omicron variants.)

The study revealed that while BA.2.12.1 is only modestly more resistant than BA.2 in individuals who were vaccinated and boosted, BA.4/5 was at least four times more resistant than its predecessor.

In addition, the scientists tested the ability of 19 monoclonal antibody treatments to neutralize the variants and found that only one of the available antibody treatments remained highly effective against both BA.2.12.1 and BA.4/5.

“Our study suggests that as these highly transmissible subvariants continue to expand around the globe, they will lead to more breakthrough infections in people who are vaccinated and boosted with currently available mRNA vaccines,” Ho says. Though the current study suggests that the new variants may cause more infections in vaccinated individuals, the vaccines continue to provide good protection against severe disease.

“Efforts in the United States to develop new vaccine boosters aimed at BA.4/5 may improve protection against infection and severe disease,” Ho says. “In the current environment, though, we may need to look toward developing new vaccines and treatments that can anticipate ongoing evolution of the SARS-CoV-2 virus.”

Source: Columbia University Irving Medical Center

U.S. Dominant Coronavirus Mutant Contains Ghost of Pandemic Past

Laura Ungar wrote . . . . . . . . .

The coronavirus mutant that is now dominant in the United States is a member of the omicron family but scientists say it spreads faster than its omicron predecessors, is adept at escaping immunity and might possibly cause more serious disease.

Why? Because it combines properties of both omicron and delta, the nation’s dominant variant in the middle of last year.

A genetic trait that harkens back to the pandemic’s past, known as a “delta mutation,” appears to allow the virus “to escape pre-existing immunity from vaccination and prior infection, especially if you were infected in the omicron wave,” said Dr. Wesley Long, a pathologist at Houston Methodist in Texas. That’s because the original omicron strain that swept the world didn’t have the mutation.

The omicron “subvariant” gaining ground in the U.S. — known as BA.2.12.1 and responsible for 58% of U.S. COVID-19 cases last week — isn’t the only one affected by the delta mutation. The genetic change is also present in the omicron relatives that together dominate in South Africa, known as BA.4 and BA.5. Those have exactly the same mutation as delta, while BA.2.12.1 has one that’s nearly identical.

This genetic change is bad news for people who caught the original omicron and thought that made them unlikely to get COVID-19 again soon. Although most people don’t know for sure which variant caused their illness, the original omicron caused a giant wave of cases late last year and early this year.

Long said lab data suggests a prior infection with the original omicron is not very protective against reinfection with the new mutants, though the true risk of being reinfected no matter the variant is unique to every person and situation.

In a twist, however, those sickened by delta previously may have some extra armor to ward off the new mutants. A study released before it was reviewed by other scientists, by researchers at Ohio State University, found that COVID patients in intensive care with delta infections induced antibodies that were better at neutralizing the new mutants than patients who caught the original omicron.

“The omicron infection antibody does not appear to protect well against the subvariants compared to delta,” said Dr. Shan-Lu Liu, a study author who co-directs the viruses and emerging pathogens program at Ohio State.

But Liu said the level of protection a delta infection provides depends partly on how long ago someone was ill. That’s because immunity wanes over time.

People who got sick with delta shouldn’t think of themselves as invulnerable to the new subvariants, especially if they’re unvaccinated, Long said. “I wouldn’t say anyone is safe.”

One bright spot? Booster shots can provide strong protection against the new mutants, Liu said. In general, vaccines and prior infection can protect people from the worst outcomes of COVID-19. At this point, scientists say, it’s too early to know if the new mutant gaining ground in the U.S. will cause a significant uptick in new cases, hospitalizations and deaths.

Scientists are still trying to figure out how virulent these new mutants are. Long said he hasn’t seen anything that answers that question for him, but Liu said emerging data points toward more serious illness. Liu said the subvariants have properties suggesting they spread more efficiently cell-to-cell.

The virus “just hides in the cell and spreads through cell-to-cell contact,” Liu said. “That’s more scary because the virus does not come out for the antibody to work.”

Dr. Eric Topol, head of Scripps Research Translational Institute, said the new mutants certainly don’t appear less virulent than previous versions of omicron, and whether they are more virulent or not “will become clear in the months ahead.”

In the meantime, scientists expect the latest powerhouse mutants to spread quickly, since they are more transmissible than their predecessors.

Though home testing makes it tough to track all U.S. COVID cases, data from Johns Hopkins University shows that cases are averaging nearly 107,000 a day, up from about 87,000 two weeks ago. And new hospital admissions of patients with COVID-19 have been trending upwards since around mid-April, according to the Centers for Disease Control and Prevention.

“I’m hopeful that we don’t see a similar increase in hospitalizations that we’ve had in prior waves,” Long said. “But with COVID, any time you have lots of people being infected, it’s just a numbers game. Some of those people are going to be severe. Some of those people are going to need hospitalization. Some of them, unfortunately, are going to pass away.”

Source : AP

South Africa in New Surge of COVID from Sub-variants of Omicron

Andrew Meldrum wrote . . . . . . . . .

South Africa is experiencing a surge of new COVID-19 cases driven by two omicron sub-variants, according to health experts.

For about three weeks the country has seen increasing numbers of new cases and somewhat higher hospitalizations, but not increases in severe cases and deaths, said Professor Marta Nunes, a researcher at Vaccine and Infectious Diseases Analytics at Chris Hani Baragwanath Hospital in Soweto.

“We’re still very early in this increase period, so I don’t want to really call it a wave,” Nunes said. “We are seeing a slight, a small increase in hospitalizations and really very few deaths.”

South Africa’s new cases have gone from an average of 300 per day in early April to about 8,000 per day this week. Nunes says the actual number of new cases is probably much higher because the symptoms are mild and many who get sick are not getting tested.

South Africa’s new surge is from two variations of omicron, BA.4 and BA.5, which appear to be very much like the original strain of omicron that was first identified in South Africa and Botswana late last year and swept around the globe.

“The majority of new cases are from these two strains. They are still omicron … but just genomically somewhat different,” said Nunes. The new versions appear to be able to infect people who have immunity from earlier COVID infections and vaccinations but they cause generally mild disease, she said. In South Africa, 45% of adults are fully vaccinated, although about 85% of the population is thought to have some immunity based on past exposure to the virus.

“It looks like the vaccines still protect against severe disease,” Nunes said.

Nunes said that the BA.4 and BA.5 strains of omicron have spread to other countries in southern Africa and a few European countries, but it is too early to tell if they will spread across the globe, as omicron did.

The increase in COVID cases is coming as South Africa is entering the Southern Hemisphere’s colder winter months and the country is seeing a rise in cases of flu.

At a COVID testing center in the Chiawelo area of Soweto, many people come in to be tested for COVID, but find out they have flu.

“Now we’re in flu season … so it’s flu versus COVID-19,” said Magdeline Matsoso, site manager at the Chiawelo vaccination center. She said people come for testing because they have COVID symptoms.

“When we do the tests, you find that the majority of them, they are negative when it comes to COVID, but they do have flu symptoms,” said Matsoso. “So they get flu treatment and then they go home because the majority is related to flu and not COVID.”

Vuyo Lumkwani was one of those who came to get tested.

“I wasn’t feeling well when I woke up this morning. I woke up with body pains, a headache, blocked (nose), feeling dizzy, so I decided to come here,” she said.

“I was terrified about my symptoms because I thought it might be COVID-19, but I told myself that I’d be OK because I have been vaccinated,” said Lumkwani. She said she was relieved to be diagnosed with flu and advised to go home with some medications and rest.

Source : AP

BA.4 and BA.5 Variants, Pandemic Fatigue, and Waning Immunity: A Toxic Mix

Kevin Kavanagh wrote . . . . . . . . .

In the beginning of the Omicron surge, the COVID-19 deniers were stating that no one died of the Omicron. At the end of the wave, the United States had more deaths than with Delta.

On Dec. 14, 2021, Infection Control Today® warned in an article entitled “Omicron’s Mild Symptoms Can’t Mask Danger It Poses” that “those who are not vaccinated or immunosuppressed are at risk for severe disease.” On Dec. 20, 2021, Reuters reported that “infections caused by the Omicron variant of the coronavirus do not appear to be less severe than infections from Delta, according to early data from the UK.” Despite the early warnings, reporting on infections being more benign with a lower-case fatality rate continued in most of the news media. This month, a definitive study from Harvard and the Massachusetts General Hospital concluded that the “Omicron variant is as deadly as previous waves after adjusting for vaccinations, demographics, and comorbidities.”

The confusion occurred because Omicron’s case-fatality rates are biased with the inclusion of a large number of vaccinated individuals. If someone concluded that the disease from Omicron was less severe, and thus, they do not need to become vaccinated and protect themselves, then they might have made a fatal error and, at the very least, increased their risk of developing long COVID-19.

For those who have not recently recovered from an infection or let their vaccination immunity wane, their chances of dying or getting long COVID-19 by undertaking a risky activity is far too high. One must remember that even with a low case fatality rate, very high infectivity can overcome the lower virulence by producing a large number of severe cases. Thus, their chances of getting sick during an event is a combination of the infectivity and virulence of the virus; and infectivity increases the chance of severe illness exponentially.

Unfortunately, one’s protection from an infection is not durable. The virus mutates and immune escape variants emerge. This appears to have happened in South Africa with the BA.4 and BA.5 variants. An estimated 90% of the population of South Africa has been exposed to Omicron, and they are still undergoing another surge with the new variants.

BA.4 and BA.5 are thought to be 36% more infectious than the BA.2 Variant and effectively evade immunity. The severity of the disease is not known. Initial reports from South Africa indicate that severity is similar to Omicron; however, the accuracy of reporting from South Africa, similar to Sweden, has come under fire. An article in The Lancet reported South Africa’s excess death rate to be 3.31 times higher than their COVID-19 death rate—one of the highest ratios in the world.

The immediate outlook for the United States warrants concern. Cases are up 25% in the last week with hospitalizations increasing 9%. This increase is fueled by the BA.2 variant and its more infectious offspring, BA.2.12.1. The BA.2.12.1 variant is more infectious than BA.2 and currently comprises 36% of sequenced cases in the United States (as of April 30).

The CDC has also reported the BA.4 and BA.5 variant in 14 states and is likely already in every state in the nation. Although only a few cases have been reported and these variants comprise only a small minority of sequenced cases, individuals need to react now. especially because the United States does not have the best active surveillance system for variants with “some European countries and even South Africa have better sequencing capabilities than the U.S.” Because of these risks, the CDC has restated their recommendation to wear masks on public transportation, and individuals may need to reevaluate the wisdom of holding large events such as the White House Correspondence Dinner. The latter may well be another super spreader event with staff from at least 5 news agencies testing positive for the virus.

Although many individuals measure success by the number who die of COVID-19, the ravages of long COVID-19 are deeply disturbing. The United Kingdom’s Office for National Statistics estimates that 10% to 25% of COVID-19 survivors may develop persistent symptoms. A recent study from the University of Cambridge found that “78% (of patients with long COVID-19) reported difficulty concentrating, 69% reported brain fog, 68% reported forgetfulness, and 60% reported problems finding the right word in speech.” Further, COVID-19 causes impairment similar to what occurs between the ages of 50 to 70, equivalent to losing 10 IQ points.

From Dec. 2021 to Feb. 2022, the seroprevalence in the United States from SARS-CoV-2 infections was 58%. Since that time, many more infections from Omicron have occurred. In addition, 66% of the United States citizens are currently “fully vaccinated.” Thus, almost everyone in the United States has had some exposure to SARS-CoV-2. If herd immunity can be achieved, then the United States should have achieved it. If another surge occurs, unfortunately, those numbers may be the status quo.

With new variants emerging, cases rising and a more complete understanding of the dangers of long COVID-19, one can make a strong case for resuming public health measures intended to control spread and infections from this disease. Unfortunately, even in the face of waning immunity, few individuals in the United States are currently wearing masks, and many are continuing to engage in risky behavior. This may well be a toxic mix, and healthcare facilities, and infection preventionists need to prepare for another possible surge in cases.

Source : Infection Control Today

New Coronavirus Variants Emerge: BA.4, BA.5 Likely Reinfecting Omicron Survivors

Rong-gong Lin II and Luke Money wrote . . . . . . . . .

A pair of new Omicron subvariants has emerged, raising the possibility that survivors of earlier Omicron strains can get reinfected.

BA.4 and BA.5 have gained increasing attention in South Africa as weekly coronavirus cases tripled in the last two weeks, according to data from Johns Hopkins University.

“It really came out of the blue over the weekend. We were already settling down with BA.2.12.1, and then BA.4 and BA.5?” said Dr. Peter Chin-Hong, an infectious diseases expert at UC San Francisco. “It just seems like the latest chapter of a never-ending saga.”

The rapid growth of BA.4 and BA.5 in South Africa has implications for a potential future surge in California and the U.S. Until now, scientists had been reassured that people who survived the first Omicron variant over the winter, BA.1, were unlikely to be reinfected by the even more infectious subvariant BA.2, which is now dominant nationwide.

But the surge in cases in South Africa of BA.4 and BA.5 follows an earlier Omicron wave. An estimated 90% of South Africa’s population has immunity to the earlier Omicron variants either due to surviving a natural infection or through vaccination.

“If 90% of people are immune already, and they’re seeing a surge in cases, it means that this particular dynamic duo [BA.4 and BA.5] are causing more reinfections — even in people who already had Omicron,” Chin-Hong said.

Only a small number of cases of BA.4 and BA.5 have been documented in California. In April, one case of BA.5 was documented, and in March, one case of BA.4 was confirmed, according to the California Department of Public Health.

The Omicron subvariant BA.2 remains California’s dominant variant, accounting for 88% of nearly 3,600 analyzed cases in April, while the ascendant BA.2.12.1 and its relative, BA.2.12, accounted for 9% of cases.

BA.2.12.1 is estimated to be 25% more transmissible than BA.2.

Earlier in the pandemic, “it seemed like every few months we heard about a potential new variant of concern,” said Los Angeles County Public Health Director Barbara Ferrer.

But more recently, she said Tuesday, “within weeks of one variant of concern dominating, there are reports from other parts of the country or other parts of the world of other either subtypes or different strains, and this has been especially true with Omicron.”

“When folks ask why public health remains cautious, it is because every time there’s a new variant that is more infectious or potentially more infectious, that means it can spread more easily,” Ferrer said. “You have to be super careful about those that are most vulnerable in our communities. And here in L.A. County, that’s millions of people. It’s not a tiny number.”

Will BA.4 and BA.5 lead to another wave in the U.S.?

Some health experts say South Africa’s BA.4/BA.5 wave could repeat in the U.S. — but probably not immediately.

South Africa will begin its winter next month, while summer is coming for the U.S.

But will South Africa’s experience be a prelude to a surge in late summer or autumn in the U.S., as Americans’ immunity from a natural Omicron infection or their last vaccination weakens? Maybe, but “we don’t know,” Chin-Hong said.

Current data do not suggest that BA.4 and BA.5 cause people to get sicker than the earlier Omicron variants. But BA.4 and BA.5 do appear to be more transmissible, Chin-Hong said, and have a better shot at evading existing immunity, given the surge in South Africa.

People who are unvaccinated and haven’t been previously exposed to the coronavirus will have a higher chance of not doing well if infected, Chin-Hong said.

The emergence of BA.4 and BA.5 means “that Omicron is still very much alive and well, and seeking ways in which it can evolve to be even more transmissible,” said Dr. Robert Kim-Farley, epidemiologist and infectious diseases expert with the UCLA Fielding School of Public Health.

Fortunately, the available data so far have not suggested the coronavirus is evolving to give infected people a higher chance of hospitalization or death.

Still, people should be aware of where the pandemic is heading in their own communities, Kim-Farley said. When transmission is high — as it is in L.A. County — it’s time to be more vigilant about wearing masks in indoor crowded places, he said.

And people who are at higher risk for severe illness and death from COVID-19 may want to avoid risky situations entirely, Kim-Farley said.

“We’re in a better place, so we can remain hopeful, but we shouldn’t lose all of our caution,” Ferrer said. “We can remain hopeful because lots of people have a lot of protection. Lots of people are fully boosted. Lots of people are vaccinated. Lots of people were recently infected and have some natural immunity — not sure how durable that is and how long it will last, but it certainly will offer some protection.”

But, she continued, “it is time for people to go get boosted. Go get your first doses of the vaccine if you haven’t yet been vaccinated. And be careful, particularly if you’re around others who are higher risk or you’re at higher risk yourself.”

Chin-Hong said it’s important for people to know ways to reduce risk. Besides getting up to date on vaccinations and booster shots and wearing a mask in indoor public settings, people also can reduce risk by learning where to get Paxlovid, an anti-COVID pill that can reduce the risk of hospitalization by 90%.

For the immunocompromised, Evusheld is available to prevent COVID-19 among people who haven’t been exposed to the coronavirus and either have a weakened immune system because of a medical condition or cannot get vaccinated for medical reasons.

Kim-Farley said it’s likely there will be increased cases during the summer in California. “However, I’m optimistic that we will not see these translate into high levels of hospitalizations or deaths, just due to the fact that the variants that are emerging appear to be more transmissible but less causing of severe disease and death.”

The more worrisome wild card would be a totally new variant more likely to cause severe illness and death, and against which vaccinations and natural immunity would be less effective.

“The important take-home message for everyone is, still, to be vaccinated, and, if eligible, boosted because these are life-saving vaccines,” Kim-Farley said.

Source : Los Angeles Times

New Omicron Subvariant Causing COVID-19 Spike in South Africa

A new Omicron subvariant called BA.4 appears to be driving a sharp rise in COVID-19 cases in South Africa, health experts say.

The number of daily cases reported by the country has shot up from just a few hundred a few weeks ago to just over 6,000, and the rate of positive tests has jumped from 4% in mid-April to 19% as of Thursday, according to the Associated Press.

Increases in coronavirus spread have also been detected in wastewater surveillance.

Despite the surge in cases, there has been only a slight bump in COVID-19 hospitalizations and no increase in deaths, stressed Salim Abdool Karim, a public health expert at the University of KwaZulu-Natal who previously advised the South Africa government on its COVID-19 response.

It appears the BA.4 subvariant is quickly pushing aside the original Omicron variant and other versions of the coronavirus, but “it’s too early to tell whether BA.4 is going to cause a fully-fledged wave,” Abdool Karim said, the AP reported.

There is one concerning trend involving the new subvariant, however: Children infected with it are the first to be ending up in hospitals, echoing what happened during the first Omicron surge, said Helen Rees, executive director of the Reproductive Health and HIV Institute at the University of Witwatersrand in Johannesburg.

The original Omicron variant first appeared in November in South Africa and Botswana before spreading worldwide.

BA.4 appears more transmissible than both the original Omicron variant and an Omicron subvariant called BA.2, experts say. However, the World Health Organization recently said that BA.4 doesn’t seem to cause more severe illness than other versions of the coronavirus, the AP reported.

BA.4 has been detected in other countries, but it’s not clear whether “it’s going to become a globally dominant variant,” Abdool Karim said.

The new Omicron subvariant isn’t yet an issue in the United States, where the Omicron subvariant BA.2 is the dominant strain, and a descendant called BA.2.12.1 that’s believed to spread faster than previous versions of the coronavirus is becoming more common, the AP reported.

Last week, BA.2.12.1 caused about 29% of COVID-19 cases in the United States, according to the U.S. Centers for Disease Control and Prevention.

Source: HealthDay

Survival Of The Fittest: The Rise Of BA.2.12.1

William A. Haseltine wrote . . . . . . . . .

Contrary to the popular belief that Covid infections are receding universally, recent reports show that several countries are in the midst of accelerating Covid rates. This draws cause for concern with the Summer fast approaching. Recall that Summer 2021 was dominated by Delta variant infections. This Summer may be in for something similar. The current increase is almost certainly due to new members of the Omicron family of viruses.

Current estimates suggest that BA.2 variants have replication rates at least 30% greater than BA.1 variants. Two variants, BA.4 and BA.5 in Europe, were recently identified as strains to monitor by the World Health Organization. Figure two illustrates how rapidly descendants of Omicron have diversified and established themselves not only in the United States, but around the world.

One such subvariant is already causing significant case numbers in the American Northeast. In the GISAID SARS-CoV-2 database, BA.2.12.1 is attributed to roughly 2,000 sequenced infections, which suggests that the actual number of BA.2.12.1 cases is at least in the tens of thousands. A recent analysis by the CDC suggests that BA.2.12.1 comprises at least 19% of new cases while BA.2 lineages overall comprise over 90%.

As its lineage name suggests, BA.2.12.1 is a descendant of the BA.2 virus. BA.2 was the main driver of the winter wave of Omicron infections that peaked in the United States on January 14th, 2022, when the daily average was over 800,000 new infections. Part of BA.2’s viral fitness was its remarkably high transmissibility, and another was its expert evasion of the immune system, including antibodies developed from previous infections and vaccinations.

The BA.2 virus’s viral fitness is attributed to its wealth of mutations within and external to the Spike protein. The BA.2 genome contains 53 amino acid mutations, 29 of which are in the Spike protein, far outnumbering the Spike mutations of previous variants of concern and interest.

One mutation lies in the receptor-binding domain. This is a substitution of lysine for glutamine at position 452 (L452Q). This mutation is notable for two reasons. First, L452Q has been previously identified in several variants of concern, like Lambda, Delta, Delta plus, and Epsilon. Second, unlike many mutations where we must only speculate on their impact on viral fitness, L452Q was studied and found to increase escape immunity, allowing the virus to attach more strongly to human cells and avoid neutralizing antibodies.

The second mutation is more mysterious. It is a substitution from serine to leucine at position 704 (S704L). Unlike L452Q, S704L is a relatively rare mutation by way of major variants, and its exact impact on the virus is unstudied. Based on its position in the S2 region of the Spike protein, we can speculate that the mutation may affect either viral fusion or furin cleavage efficiency, but further study would be welcome.

We can say with near certainty that BA.2.12.1 is at least as transmissible and immune evasive as BA.2. It is unlikely that the two Spike mutations would decrease either of these facets of the virus strain. However, due to the wealth of BA.2 cases in previous months, the BA.2.12.1 virus may be impeded by antibodies developed from infections during that wave, which could explain why cases are low relative to the Omicron wave.

However, it is critical to remain vigilant in our surveillance of these subvariants. Recent reports from Hong Kong note that Omicron BA.2 subvariants deliver a similar fatality risk to those infected relative to earlier strains of SARS-CoV-2. This is contrary to many assumptions that Omicron is less severe than previous strains. Additionally, there are indications that Omicron is as dangerous in terms of long-term complications in children as the Delta variant of last summer.

We also note the growing danger of long Covid. As many as 30-50% of Omicron recoverees describe at least some lingering issue post-infection. This is independent of vaccination status and severity of their given infection—the rate increases for those hospitalized.

A new wave of Omicron with BA.2.12.1 or another variant yet to be identified could be as catastrophic as the wave from December to February. At the time of writing, over 1 million people died in the U.S. due to Covid-related complications. We should make every effort to keep that number from continuing to increase. One such avenue is to continue surveilling new variants to inform public health measures and aid the development of Covid-19 treatments.

Source : Forbes

Omicron BA.2 Variant Takes Over. What’s Known About It?

Laura Ungar wrote . . . . . . . . .

In the latest battle of the coronavirus mutants, an extra-contagious version of omicron has taken over the world.

The coronavirus version known as BA.2 is now dominant in at least 68 countries, including the United States.

The World Health Organization says it makes up about 94% of sequenced omicron cases submitted to an international coronavirus database in the most recent week. And the Centers for Disease Control and Prevention says it was responsible for 72% of new U.S. infections last week.

Dr. Wesley Long, a pathologist at Houston Methodist in Texas, said he’s seen BA.2 quickly become dominant in his medical system. At the end of last week, the variant was responsible for more than three-quarters of cases in Houston Methodist hospitals. Less than two weeks earlier, 1% to 3% of cases were caused by BA.2.

“It’s not terribly surprising because it is more contagious” than the original omicron, Long said.

As the variant advances, scientists are learning more about it. But they still don’t know exactly how it will affect the trajectory of the pandemic.


BA.2 has lots of mutations. It’s been dubbed “stealth omicron” because it lacks a genetic quirk of the original omicron that allowed health officials to rapidly differentiate it from the delta variant using a certain PCR test.

One reason BA.2 has gained ground, scientists say, is that it’s about 30% more contagious than the original omicron. In rare cases, research shows it can sicken people even if they’ve already had an omicron infection — although it doesn’t seem to cause more severe disease.

Vaccines appear equally effective against both types of omicron. For both, vaccination plus a booster offers strong protection against severe illness and death.


Coronavirus cases rose in parts of Europe and Asia when BA.2 became dominant, and some scientists are concerned that the variant could also push up cases across the U.S.

Besides being more contagious, it’s spreading at a time when governments are relaxing restrictions designed to control COVID-19. Also, people are taking off their masks and getting back to activities such as traveling, eating indoors at restaurants and attending crowded events.

At this point, overall coronavirus cases in the U.S. are still on the decline. But there have been upticks in some places, including New York, Arizona and Illinois. Health officials have also noted that case counts are getting more unreliable because of the wide availability of home tests and the fact some people are no longer getting tested.

“We’re entering a phase where increasing cases or waves may be very regional and it may depend a lot on vaccination levels in the community — and not just vaccination levels but timing of the vaccinations,” Long said. “How long ago were they? Did people get boosters? Because we know the immunity to the vaccine wanes a little bit over time.”

Long said he feels “very certain” that cases will eventually go back up in the U.S., whether that’s because of BA.2 or some future variant. “If it’s BA.2,” he said, “it may be more of a wave or a speed bump than a surge.”

For now, COVID-19 hospitalizations and deaths are still trending down nationally.


As the coronavirus continues to evolve, the WHO is tracking other mutants, including hybrids known as “recombinants.”

These include combinations of delta and omicron and hybrids of BA.2 and the original omicron, also known as BA.1.

One recombinant that health authorities are tracking closely is a BA.1-BA.2 hybrid called XE, which was first detected in the United Kingdom in January. About 600 cases have been reported, and scientists believe it may be about 10% more contagious than BA.2.


The advice from experts remains the same: Take precautions to avoid getting COVID-19.

“The virus is still out there circulating,” Long said. “Vaccination is still your best defense.”

Get the shots if you haven’t already, he said, and get the second booster if you’re eligible because you are 50 or older or have a compromised immune system.

“If cases start going up in your community, think about assessing your risk level,” Long said. “If you stopped masking and stopped worrying about distancing and things … that’s the time to reinstitute those protective measures.”

Source : AP