New Coronavirus News from 22 Feb 2022

COVID-19 Scan for Feb 22, 2022 [CIDRAP, 22 Feb 2022]

Study highlights rare BA.2 subvariant reinfections after Omicron COVID-19

Infection with the SARS-CoV-2 Omicron BA.2 subvariant shortly after an initial infection with the Omicron BA.1 subvariant—the original Omicron strain—is rare, occurring mostly in young, unvaccinated people with mild symptoms, according to a non–peer-reviewed Danish study.

In the study, published today on the medRxiv preprint server, researchers at the Statens Serum Institut in Denmark analyzed the subgenomic and genomic RNA of viruses responsible for a randomly selected group of 263 paired samples from more than 1.8 million COVID-19 patients. The study period was Nov 22, 2021, when Omicron was first identified in that country, to Feb 11, 2022. The BA.2 variant now accounts for most COVID-19 cases in Denmark.

Of the 263 virus samples, 187 COVID-19 reinfections (71%) were identified, 47 (18%) of which were BA.2 cases after initial BA.1 infections. The severity of both types of infections was similarly mild, and no patients were hospitalized.

Median patient age was 15 years, none were older than 38, 89% were unvaccinated, 6% had received two COVID-19 vaccine doses, and 4% had received one dose.

Overall, viral load was significantly lower in patients with BA.2 reinfections than during the initial infection.

"This may indicate a more superficial and transient secondary infection that could be explained by T cell-mediated immunity obtained during the first infection," the researchers wrote.

New Coronavirus News from 23 Feb 2022

COVID-19: Top news stories about the pandemic on 23 February | World Economic Forum [World Economic Forum, 23 Feb 2022]

by Joe Myers

1. How COVID-19 is affecting the globe
Confirmed cases of COVID-19 have passed 427.8 million globally, according to Johns Hopkins University. The number of confirmed deaths has now passed 5.9 million. More than 10.6 billion vaccination doses have been administered globally, according to Our World in Data.

New daily COVID-19 infections have passed 170,000 in South Korea for the first time. The country's prime minister, Kim Boo-kyum, called on people not to panic.

It comes as South Korea approves Pfizer/BioNTech's COVID-19 vaccine for use on children aged 5-11.

Beijing, China, has reported the highest number of daily local COVID-19 cases since late January.

Singapore's health ministry has reported a record 26,032 new confirmed daily COVID-19 infections. It warned that it could take a few weeks before the current transmission wave peaks and subsides.

A Danish study has found that getting infected twice with two different Omicron COVID-19 subvariants is possible, but rarely happens.

Ireland has announced that most of its remaining COVID-19 pandemic-linked restrictions will be eased from 28 February.

European Union countries have agreed to open their borders to travellers from outside the bloc who have had COVID-19 vaccines authorized by the World Health Organization, easing restrictions on those who received Indian and Chinese vaccines.

2. COVAX vaccine supply outstrips demand for the first time
COVAX, the global project to share COVID-19 vaccines, is struggling to place more than 300 million doses in the latest sign the problem with vaccinating the world is now more about demand than supply.

Most vaccines went to wealthy nations last year, with less than a third of people in low-income countries vaccinated so far, compared with more than 70% in richer nations.

However, as supply and demand have increased, poorer nations are facing challenges including gaps in cold chains, vaccine hesitancy and lack of funds to support distribution networks, public health officials told Reuters.

Low-income nations only asked for 100 million doses for distribution by the end of May - the first time in 14 allocation rounds that supply has outstripped demand, the document from the COVAX Independent Allocation of Vaccines Group said.

Asked to comment, a Gavi spokesperson said COVAX was now in a situation where there was enough current supply to meet demand but acknowledged that the roll-out of vaccines was an issue in several less-developed nations.

"We will only close the vaccine equity gap once and for all if we are able to help countries roll out vaccines rapidly and at scale," the spokesperson said.

2. BA.2 Omicron COVID-19 subvariant to remain variant of concern
The World Health Organization has advised that the BA.2 sublineage should continue to be considered a variant of concern and should remain classified as Omicron.

The organization's Technical Advisory Group on SARS-CoV-2 Virus Evolution also said that Omicron remains the dominant variant circulating globally. There are several sublineages of Omicron, of which BA.1, BA 1.1 and BA.2 are the most common, with the proportion of reported BA.2 cases increasing in recent weeks compared to BA.1. However, global circulation of all variants is reported to be falling.

Studies into differences between BA.2 and BA.1 are ongoing, the group said.

New Coronavirus News from 24 Feb 2022

As long COVID cases grow, clues emerge about who is most at risk [National Geographic, 22 Feb 2022]

BY EMILY SOHN

Tens of millions of people now have an array of lingering symptoms. Figuring out their common risk factors could help tailor treatments.

Eliana Uku wasn’t too worried when she got sick from COVID-19 in March 2020. She was 26 and healthy, she exercised most days, and at first her symptoms were mild. Even with a low fever, cough, fatigue, and mild headache, she kept working in her job as a corporate strategist in New York City. Three weeks after her first symptoms appeared she felt well enough to resume running.

But her cough persisted, and after a month or so, new symptoms appeared, such as memory lapses and sensitivity to sound. Everything was painfully loud, including the sound of her boyfriend washing dishes, leading the couple to switch to paper plates. She would forget words, and her mind would go blank at work meetings. By May she had insomnia, restless legs, and severe nausea. Her heart rate would skyrocket into the 160s after standing for a few minutes, even though she used to be a marathon-runner with a resting heart rate in the high 40s.

Scared and confused, Uku went to the emergency room in May 2020, where a doctor told her that some patients were reporting lingering or even new COVID-19 symptoms—a condition now called long COVID. Now, nearly two years after she first got sick with SARS-CoV-2, Uku still can’t work, and she has had to defer admission to Stanford Business School.

With scientific studies ongoing and a definition in flux, long COVID continues to confuse and frustrate patients and healthcare providers. But estimates of the number of people who suffer from long COVID range from 10 percent to more than 50 percent of all confirmed cases, making it imperative for researchers to understand its causes and effects.

In one important step forward, scientists are now sleuthing out biological risk factors that make some people more susceptible to this condition. In a recent paper, researchers completed the most comprehensive analysis to date of predictors of long COVID, discovering a set of specific conditions that were associated with lingering symptoms.

Figuring out how these factors influence an individual’s COVID-19 trajectory could alert people—either before they get sick or early on in the infection—that they are vulnerable to developing long COVID, says Jim Heath, president of the Institute for Systems Biology, a research nonprofit in Seattle and one of dozens of co-authors on the new paper.

The new study, while thorough, is not the only attempt to identify biological vulnerabilities of long COVID, says Anna Ssentongo, an infectious disease epidemiologist at Penn State College of Medicine in Hershey, Pennsylvania, who was not on the study team. But it’s not the only attempt to identify biological vulnerabilities, she notes. Other studies have zeroed in on genetic factors and even changes in the microbiome as possible risk factors for long COVID.

Eventually, research into these risk factors could lead to personalized treatments for long COVID, says Avindra Nath, the clinical director of the National Institute of Neurological Disorders and Stroke, part of the U.S. National Institutes of Health. It could also reduce the rates of long COVID, he adds, and help legitimize the complaints of people who developed an illness that doesn’t have an obvious test or even a clear definition.

Huge spectrum of symptoms
Uku encountered much skepticism when she started seeking medical care for her post-COVID-19 problems. Friends and family members doubted her symptoms were real. Doctors prescribed antidepressants and told her boyfriend her illness was probably psychosomatic.

“Patients who have long COVID go to the doctor, and they say they’ve got brain fog, or they can't sleep or they're tired all the time, and the doctor just tells them to get some rest or something. And people find that incredibly frustrating. They know something's wrong with them,” says Heath. “As soon as you can begin to define a condition like that, that's the first step toward treating it.”

But not everyone was surprised that Uku and people like her were showing up at hospitals and clinics.

Before the pandemic began, Ssentongo was a graduate student looking at long-term illnesses that follow various viral, bacterial, and parasitical infections. Researchers have seen that dementia that can follow HIV infections, she says, and lifelong epilepsy can develop after a severe case of malaria.

When Ssentengo heard about long COVID—known medically as post-acute sequelae of COVID-19, or PASC—she shifted gears and began exploring how common it was. In a review of 57 studies that included more than 250,000 people, she and colleagues reported in October 2021 that 54 percent of people who survived COVID-19 had at least one lingering symptom six months after either diagnosis or discharge from the hospital. In the mostly unvaccinated population included in the review, nearly 80 percent of people had been hospitalized, but rates of long COVID were the same after both mild and severe cases.

Those numbers are still a work in progress. Other studies have found higher rates of long COVID in people with more serious disease. Among people with mild infections who were not hospitalized or in the ICU, Nath says, long COVID rates are closer to 10 percent.

What makes this condition difficult to study and quantify is that long COVID has become a catch-all term for a wide diversity of experiences. In the research Ssentengo reviewed, symptoms ranged from mild to life-threatening. The list of possible issues included memory problems, trouble concentrating, difficulty breathing, joint pain, skin rashes, sleep problems, and symptoms that worsen with exercise. Some problems seem the direct result of viral infection, Ssentengo’s team wrote in the paper, while others may originate from post-traumatic stress and other mental health consequences of the original COVID-19 illness.

That huge spectrum of long COVID symptoms suggests that many processes in the body can trigger the condition, Ssentengo says, and that risk factors for each route will also differ.
“There is no one clear set of symptoms, and there are likely different biological causes of each post-COVID condition we see,” she says.

Finding the risk factors
To understand how COVID-19 might cause long-term symptoms, Heath and his colleagues tapped into data from a cohort of people they had started studying at the beginning of the pandemic. Using medical records, surveys, blood samples, and nasal swabs, they mined the data for all sorts of biological and immunological patterns.

The investigation revealed that lingering symptoms were common, a finding that Heath and his team reported in the journal Cell in January. Three months after symptoms began, more than half of participants reported fatigue, a quarter were still coughing, and 18 percent still had trouble with their sense of taste or smell, among other issues. About 35 percent of patients in the study reported between three and 10 symptoms.

Of those with ongoing symptoms, virtually all had at least one of four distinct risk factors: type 2 diabetes; measurable levels of SARS-CoV-2 RNA in the blood during the initial COVID-19 infection; circulating Epstein-Barr virus early in the infection; and a high level of autoantibodies.

Autoantibodies, proteins made by the immune system, can start to attack the body rather than just viral invaders. Having elevated levels of these proteins before even getting an infection was the most common predictor, showing up in two-thirds of people with lingering COVID symptoms, Heath says. A resurgence of Epstein-Barr in people who were previously infected with the virus, which can cause infectious mononucleosis, appeared in one-third of their long COVID cohort. Diabetes and SARS-CoV-2 also showed up in one-third of the long-Covid group. Some patients had multiple factors.

Each risk factor was linked to specific long COVID symptoms. Those with autoantibodies, for example, tended to experience fatigue and respiratory symptoms. Type 2 diabetes was associated with the common symptoms of respiratory viruses, like fatigue. And reactivation of the Epstein-Barr virus was associated with neurological symptoms, such as brain fog, difficulty sleeping, and memory loss.

Those findings corroborated previous results, says Michael VanElzakker, a neuroscientist at Harvard Medical School and Massachusetts General Hospital. For instance, research has connected resurgence of Epstein-Barr with diseases such as multiple sclerosis and chronic fatigue syndrome, also known as ME/CFS.

“I think that the surprising thing is how much of the long COVID these past factors account for,” Heath says, “and the fact that you can see them all at diagnosis.”

The ecosystems inside us
In a review of research on SARS-CoV-2 and other RNA viruses published in October 2021, VanElzakker and his colleague Amy Proal, a microbiologist at PolyBio Research Foundation, a research nonprofit in Kenmore, Washington, proposed a number of other possible routes to long-term symptoms. Among them: The virus might injure organs, persist in tissues, or disrupt the microbiome in ways that could cause inflammation and trigger neurological symptoms. The virus might derail the immune system, spur blood-clots, or disturb nerve signaling in the brain stem and in the vagus nerve, which could lead to symptoms resembling chronic fatigue syndrome.

Or, much like the reactivation of Epstein-Barr, microorganisms that normally inhabit us without causing trouble may start sparking problems when a SARS-CoV-2 infection stresses the immune system.

One pathogen of concern is the parasite Toxoplasma gondii, which is found in cat feces and undercooked meat and lives in an estimated 11 percent of people past infancy in the U.S. It has been linked with cancers, epilepsy, Alzheimer’s disease, and schizophrenia. Studies have suggested that immunosuppressant medications that treat diseases like rheumatoid arthritis and Crohn’s disease—and now severe cases of COVID-19—might reactivate T. gondii into a pathogenic state. Depending on where the parasite ends up, scientists speculate it could cause eye problems, heart problems, or neuropsychiatric issues, among other issues.

That line of research spotlights the vast ecosystems of bacteria, viruses, and other microorganisms that occupy us and have the potential to affect our immune function and health, says VanElzakker.

“We have this ongoing Serengeti inside us,” he says. “When a pathogen comes in and disrupts the immune system, a lot of the stuff that's in us already can sort of gurgle up and change its behavior, because it's got the opportunity.”

Researchers are also trawling for genetic variants that raise the risk of severe or long COVID-19. In January, scientists linked two genes to the loss of taste or smell after an infection, which is a symptom that can linger.

Heping Zhang, a data scientist at Yale University, co-authored a study identifying eight genetic variants that confer a higher risk of mortality from COVID-19. Understanding how a gene variant influences the potential for an immune system overreaction, he says, could lead to medications that block that immune response from turning deadly.

Ongoing research is likely to turn up more pre-existing conditions as risk factors for long COVID, Heath says, but it will take larger studies to find them. Another limitation is that most current studies don’t distinguish between symptoms that linger for just a couple months and then go away from those that last longer. People with organ damage after spending time in the ICU are lumped together with people who developed fatigue, dizziness, or trouble concentrating a few weeks after a mild infection. They are not the same, Nath says.

It might also be worth casting a wider net to include environmental factors such as air pollution that might harm the immune system, VanElzakker adds. “That could be something that is a vulnerability factor that we haven't really thought about and isn't really being measured.”

Hope and caution for long COVID
Eventually, a biological understanding of long COVID could produce treatments that anyone could take to prevent lingering symptoms. “You get sick, you're treated aggressively, you're done,” Nath says. “You don't even need to know whether you are at risk or not.”

For people with reactivation of viruses like Epstein-Barr, for example, taking antiviral medications very early in an infection might help stave off lingering effects, Heath says. If autoantibodies are an issue, people might benefit from treatments for lupus, which also involves autoantibodies that interfere with the immune system. Identifying genetic links, Zhang adds, could illuminate mechanisms that would suggest other treatment strategies.

There is still a long way to go. Even the strongest predictors identified to date raise questions. Epstein-Barr infection is extremely common, for example; some 90 percent of people harbor the virus in their bodies, making it unclear why reactivation happens only in some cases. Then there are people with multiple risk factors who escape an infection unscathed, VanElzakker adds, while healthier people with fewer risks remain sick for months.

Given the vast and complex number of ways that long COVID can play out, there is unlikely to ever be a simple test or treatment that will work for everyone, VanElzakker says. Instead, his work with chronic fatigue syndrome suggests that multiple hits might be more important than any one risk factor.

“If I had diabetes and a history of clotting problems, and I had bad mononucleosis when I was younger, there'd be a list of things that would cause me to be think long COVID might be a little bit more of a risk for me and I better be extra careful when I go out,” he says. “It's unlikely that it's going to be a one-to-one where we just know, Oh, you better not get COVID because you'll definitely end up with long COVID.”

While researchers continue to probe the underlying mechanisms, one step people can take now to protect themselves is to get vaccinated, Ssentengo says.

In a study of healthcare workers in Israel, 19 percent of 39 people with breakthrough cases reported symptoms that persist beyond six weeks—a lower rate than in studies of unvaccinated people who developed long COVID.

“That study was definitely hopeful that the vaccine potentially could reduce your risk of long COVID,” says Ssentengo, who in the midst of larger studies to determine whether vaccines can avert long-term symptoms. It’s since been backed up by additional research, including an analysis of medical records from more than 240,000 people infected with COVID-19 that also showed far better outcomes for vaccinated people.

For people like Uku, who got sick before vaccines were available, efforts to understand long COVID offer hope for relief along with a sense of validation. She has been thinking back to her freshman year of college in 2011, when she had a serious case of mononucleosis. She wonders if that virus permanently altered her biology and set the stage up for what she’s experiencing now. Still unable to work and eager to start her graduate program, she’s hoping that more insights will come soon.

If she had known that she was vulnerable to long-term consequences of COVID-19, she says, she would’ve made different choices. “I was going into the office and going out up until the day that the lockdown started in New York, and so was my partner,” she says. “Had I known that I was high risk, I would have started isolating the day that the very first case was recorded in New York.”

New Coronavirus News from 21 Feb 2022

Boris Johnson Moves to Lift Coronavirus Restrictions in England [The New York Times, 21 Feb 2022]

By Stephen Castle

The British prime minister is shifting toward a strategy of living with Covid-19. Critics argue that the move is too soon, even as case numbers fall.

LONDON — After almost two years of restrictions, Prime Minister Boris Johnson of Britain said on Monday that it was time to live with the coronavirus, announcing an end to England’s remaining legal curbs and most free testing, and making his country an outlier in its handling of the pandemic.

Although careful not to declare the country’s health crisis officially over, Mr. Johnson sought to put the country firmly on the path to normalcy, albeit just a day after an announcement that Queen Elizabeth II had tested positive for the virus.

Some critics say that news underscores the risks of moving too quickly to scrap restrictions, while political opponents say that decisions are being taken in Downing Street to distract attention from a police investigation into whether Mr. Johnson broke the coronavirus laws he himself set.

However the statement is another political landmark for Mr. Johnson, putting his government ahead of most others in Europe in the speed with which it hopes to return to normal life.
Having initially claimed the virus would be sent packing in 12 weeks, Mr. Johnson — who was himself hospitalized after being infected in 2020 — withdrew many restrictions last year but was later forced to reintroduce some to cope with the arrival of the Omicron variant.

The new plan means that, starting Thursday, routine contact tracing will end and those who test positive will no longer be legally obliged to isolate themselves, although they will be urged to do so.

The supply of free tests, which are currently available widely, will end on April 1 for all except the most vulnerable, effectively forcing people to pay to find out whether or not they are infected. Enhanced sick pay to support those suffering from the coronavirus will end in late March.

Speaking to Parliament, Mr. Johnson said he was setting out a strategy for living with the coronavirus, rather than declaring the pandemic at an end.

“It is time that we got our confidence back, we don’t need laws to compel people to be considerate to others, we can rely on that sense of responsibility toward one another,” Mr. Johnson said. He added: “Let us learn to live with this virus.”

Wishing Queen Elizabeth a speedy recovery, Mr. Johnson said that her illness was a reminder that “the virus has not gone away.” But, he said, “Whilst the pandemic is not over we have now passed the peak of the Omicron wave.”

The rules, which still need approval in Parliament, would apply only to England. Scotland, Wales and Northern Ireland have their own powers over health issues and make their own rules and have usually been more cautious.

Even some of Mr. Johnson’s own lawmakers have expressed concern about the new strategy, particularly because of the restriction on the availability of free tests.

On Monday, a cabinet discussion on the details of the move to end most free testing was temporarily delayed at the last moment, with news reports saying there had been differences among ministers about the continuing costs of coronavirus measures. Over the weekend, Mr. Johnson said testing was costing taxpayers around 2 billion pounds, or $2.7 billion, a month.

Tim Loughton, a Conservative member of Parliament, said the country had to “learn to live with Covid and not lock everything down and retreat until it goes away.” But, speaking before the announcement, he told the BBC that he had “slight apprehensions in that I think we still do need to have testing available widely, because I think that is the reassurance people can have that they’ve taken all possible precautions and they don’t want to infect other people.”

The health secretary, Sajid Javid, said earlier Monday that a second booster vaccination would be offered to adults 75 and over, people living in care homes and those 12 and older who suffer from conditions that suppress their immune systems.

“We know immunity to Covid-19 begins to wane over time,” Mr. Javid said in a statement. “That’s why we’re offering a spring booster to those people at higher risk of serious Covid-19 to make sure they maintain a high level of protection.” So far almost 38 million Britons have had all three shots that have already been offered.

Medical professionals have urged the government to take a cautious approach, and there was a warning from the government’s chief scientific adviser, Patrick Vallance, who said he expected further variants and added that “they could be more severe.”

The current restrictions were scheduled to expire on March 24 and, given his precarious political position, Mr. Johnson might have struggled to persuade legislators from his own Conservative Party to agree to any extension of the legal requirement to self-isolate, with fines for those who break the rules.

Some on the libertarian wing of Mr. Johnson’s would like the government to withdraw its current guidance to wear face coverings in crowded and confined spaces, given the falling case numbers, though the government did not announce that step on Monday.

Nonethethess, Ian Blackford, leader of the Scottish National Party’s lawmakers in the British Parliament, accused Mr. Johnson of appeasing right-wing lawmakers whose support he may need to keep his job if the police investigation concludes that he broke coronavirus laws. “This statement is not about protecting the public it’s about the prime minister scrambling to save his own skin, Mr. Blackford said.

Few dispute that the pandemic is receding in Britain, and the latest available statistics show 38,409 daily cases and 15 deaths within 28 days of a positive test.

But the main opposition Labour Party called on the government to publish the scientific evidence behind its decision-making.

“This is a half-baked announcement from a government paralyzed by chaos and incompetence” said Keir Starmer, leader of the Labour Party, who criticized the decision to end free testing to most people.

The government, Mr. Starmer said, was advancing “an approach which seems to think that living with Covid means simply ignoring it.”

New Coronavirus News from 17 Feb 2022

Stealth Omicron BA.2 COVID Variant Could Be More Dangerous, Immune-Resistant Than BA.1—Study [Newsweek, 17 Feb 2022]

BY ED BROWNE

The Omicron COVID sub-variant BA.2 may be more dangerous than BA.1 and could pose a greater risk to public health, according to new research.

BA.2 has made headlines in recent weeks and is the subject of ongoing research after overtaking the previously dominant BA.1 Omicron type in countries like Denmark and South Africa.

Research has found that BA.2 has a significant transmission advantage over BA.1, meaning it has the potential to spread faster through populations. But other key characteristics about the variant, such as whether it leads to increased hospitalization or is more resistant to vaccines, have yet to be conclusively determined.

Early data from the U.K.'s Health Security Agency (HSA) has suggested that vaccines are as effective against BA.2 as BA.1 in terms of preventing symptomatic disease, based on people who had a booster shot.

However, on Tuesday, dozens of researchers from Japan released a study in which they said they found that BA.2 may in fact be more pathogenic—capable of causing disease—and more resistant to previous immunity than BA.1. It should be noted that the study hasn't yet gone through the peer review process in which its quality and validity will be assessed.

The researchers infected hamsters with BA.1 and then obtained convalescent sera—essentially blood samples—from them after their bodies had elicited an immune response, meaning their blood contained antibodies.

They then exposed samples of BA.1 and BA.2 to these antibodies to see what would happen.
The researchers found that BA.2 was 2.9 times more resistant to the hamster samples than BA.1 was.

They further tested this finding in mice by immunizing them with cells expressing the spike protein of BA.1 and once again tested their antibodies against BA.1 and BA.2. This time, they found that BA.2 was 6.4 times more resistant than BA.1.

In addition, the researchers infected hamsters with BA.2 and BA.1 and found that the BA.2 group exhibited more health disorders such as body weight loss than in those infected with BA.1. They also found that the amount of BA.2 virus was higher in the hamsters' lungs than that of BA.1.

Recognition as a Variant of Concern
The researchers say that based on their findings, BA.2 should be given its own Greek alphabet letter and be "recognized as a unique variant of concern."

There are limitations to bear in mind, however. As mentioned, the study hasn't yet been peer reviewed and so its findings must be taken with a grain of salt for now. In addition, animal and cell culture models don't always translate accurately to humans.

Jeremy Kamil, associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek that the study "looks highly credible and rigorous" and was from "an excellent research group", but noted: "I think it's always hard to translate differences in animal and cell culture models to what's going on with regards to human disease. That said, the differences do look real.

"I'd also stress that immunity to BA.1 will mitigate against, and in most cases fully protect people from, BA.2 infection in the near term."

Ian Jones, professor of virology at the University of Reading in the U.K., said that he "can't see any flaws" in the Japanese study, but noted that cell and animal models do not perfectly mimic the situation in humans.

He agreed with the conclusion that BA.2 is "deserving of variant of concern (VOC) status," but said that current monitoring is sufficient and added: "The real experiment is ongoing in the populations of the world and, evidently, disease severity is considerably less than previously."

Mark Harris, a professor at the School of Molecular and Cellular Biology at the University of Leeds in the U.K., told Newsweek the study looked "interesting," but doubted the possibility of extrapolating lab-based data to real-world human infections.

New Coronavirus News from 16 Feb 2022

Research identifies differences between Omicron lineages BA.1 and BA.2 [News-Medical.Net, 16 Feb 2022]

By Jocelyn Solis-Moreira

Early data posted to the preprint server bioRxiv* suggests another Omicron lineage, called BA.2, is more contagious than BA.1 — the Omicron lineage that sparked the winter surge of coronavirus disease 2019 (COVID-19) cases in January 2022.

The current study identified the characteristics of the BA.2 variant and found that compared to the original Omicron strain, BA.2 is more immune resistant and shows greater cell fusion than BA.1.

As of February 2022, the Omicron variant has mutated into three lineages: BA.1, BA.2, and BA.3. A sublineage of BA.1 with an R346K substitution in the spike protein is classified as BA.1.1.

Evolutionary descent of Omicron lineages
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.1 emerged first followed by BA.2 and BA.3. Similar to BA.1 the earlier strains of BA.2, BA.3 and BA1.1 were detected in the Gauteng Province in South Africa suggesting the diversification of Omicron occurred there.

While BA.1 spread across the world at a faster rate than BA.2, the BA.2 lineage became more prevalent than BA.1 since January 2022 in multiple countries, including the Phillippines, India, Denmark, Singapore, Austria, and South Africa.

The study researchers created a model to analyze the epidemic dynamics of different SARS-CoV-2 lineages and estimate the number of COVID-19 cases for each country by each viral lineage. The frequency of BA.2 lineage was 1.40-fold higher than BA.1, suggesting cases caused by BA.2 will expand and spread more rapidly around the world than BA.1.

BA.2 shows resistance to monoclonal antibodies
The genetic sequence in the spike protein of the BA.2 lineage differs considerably from the BA.1 lineage suggesting it may confer greater immune resistance against antibodies.

To study this, the researchers performed neutralization assays with pseudoviruses and neutralizing antibodies that would be produced after vaccination. Results showed that BA.2 was similar to BA.1 in resistant vaccine-induced antibodies. BA.1 has shown to be highly resistant against mRNA vaccines and the AstraZeneca vaccine.

The Omicron BA.2 lineage was also completely resistant to two monoclonal antibodies known as Casirivimab and Imdevimab. Additionally, there was a 35-fold greater resistance to a therapeutic antibody, called Sotrovimab, compared to the B.1.1 virus containing D614G. Both BA.1 and BA.2 were highly resistant to convalescent serum samples containing antibodies after recovery from the original SARS-CoV-2 virus, the Alpha virus, and the Delta virus.

These data suggest that, similar to BA.1, BA.2 is highly resistant to the antisera induced by vaccination and infection with other SARS-CoV-2 variants as well as three antiviral therapeutic antibodies,” wrote the research team.

The researchers also studied convalescent samples infected with BA.1. Thirteen convalescent samples came from fully vaccinated individuals, 1 convalescent sample came from a person with one vaccine dose, and 3 convalescent samples came from unvaccinated individuals. While the results were not statistically significant, BA.2 appeared 1.4-fold more resistant to BA.1-infected sera.

Another observation was that convalescent samples from fully vaccinated individuals showed stronger antiviral effects against all variants compared to the 1-dose or unvaccinated serum samples.

Further investigation showed that BA.1-induced humoral immunity is less effective against BA.2. Using convalescent serum samples from infected hamsters 16 days after infection, the team found both BA.1 and BA.2 showed high resistance against B.1.1 and Delta-infected serum samples. BA.2 showed a 2.9-fold resistance against BA.1-infected convalescent hamster sera compared to BA.1.

Virological characteristics of BA.2 lineage
BA.2 was more contagious than BA.1 when studying the replication process in human nasal epithelial cells. BA.2 also showed significantly more cell fusion than BA.1. There were 1.52-fold larger syncytia seen in BA.2 than BA.1.

The greater fusogenic properties of BA.2 were hypothesized to come from more efficient cleaving of the spike protein than BA.1. However, a Western blot analysis showed the BA.2 spike protein was cleaved less than BA.1’s spike protein, indicating fusogenicity occurred independently of cleavage.

Instead, BA.2 may be more fusogenic and replicative than BA.1 in a TMPRSS2-dependent manner. Cell-based fusion assays revealed the fusogenicity of the BA.2.spike protein and the B.1.1 spike protein was similar in cells containing TMPRSS2 compared to those without it.

*Important notice
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
• Yamasoba D, et al. (2022). Virological characteristics of SARS-CoV-2 BA.2 variant. bioRxiv. doi: https://doi.org/10.1101/2022.02.14.480335 https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1

New Coronavirus News from 5 Feb 2022

UK Covid 5 February - 259 deaths and 60,578 cases - see additional data [West Bridgford Wire, 5 Feb 2022]

There were 1,224,823 tests reported on 3 February 2022. This shows a decrease of -7.3%compared to the previous 7 days.

Between 28 January 2022 and 3 February 2022, there have been 8,187,334 tests.

Cases
A confirmed case is someone who has tested positive for coronavirus.

60,578 new people had a confirmed positive test result reported on 5 February 2022.

Between 30 January 2022 and 5 February 2022, 599,229 people had a confirmed positive test result. This shows a decrease of -4.2% compared to the previous 7 days.

Vaccinations
Vaccines are currently given in 3 doses.

52,413,781 people had been given a first dose by the end of 4 February 2022.
48,549,079 people had been given a second dose by the end of 4 February 2022.
37,493,486 people had been given a booster or third dose by the end of 4 February 2022.

Healthcare
Some people with coronavirus have to go into hospital.
1,596 people with coronavirus went into hospital on 31 January 2022.
Between 25 January 2022 and 31 January 2022, 11,214 went into hospital with coronavirus. This shows a decrease of -8.7% compared to the previous 7 days.

There were 14,634 patients in hospital with coronavirus on 3 February 2022.
Some people in the hospital need to use a special device called a mechanical ventilator to help them breathe.
There were 478 coronavirus patients in hospital beds with a mechanical ventilator on 3 February 2022.

Deaths
There were 259 deaths within 28 days of a positive test for coronavirus reported on 5 February 2022.
Between 30 January 2022 and 5 February 2022, there have been 1,729 deaths within 28 days of a positive coronavirus test. This shows a decrease of -5.4% compared to the previous 7 days.

New Coronavirus News from 4 Feb 2022

Britain's pandemic modellers say future large waves of COVID possible [Reuters UK, 4 Feb 2022]

by Alistair Smout, Kate Holton and Andrew MacAskill

LONDON, Feb 4 (Reuters) - There is a realistic possibility of large waves of COVID-19 infection in the future in Britain and such waves might even be considered likely, epidemiologists who model the COVID-19 pandemic to inform government advice have said.

British Prime Minister Boris Johnson has ditched legal restrictions in England, saying that, while the pandemic was not over, Britain needs to learn to live with COVID.

The Scientific Pandemic Influenza Group on Modelling, Operational sub-group (SPI-M-O) said the emergence of new viral variants was the biggest unknown factor in the medium-to-long term, along with waning population immunity and changes in mixing patterns.

"Large future waves of infection that need active management to prevent detrimental pressure on the health and care sector are, at least, a realistic possibility (high confidence) or likely (medium confidence)," SPI-M-O said in a consensus statement published on Friday.

Britain has reported 157,730 deaths from COVID-19, the seventh highest total globally, and Johnson has faced heavy criticism for his handling of the pandemic, which has seen three national lockdowns.

The Omicron variant fuelled a spike in infections to new highs at the end of last year, prompting Johnson to reintroduce some limited measures, but deaths did not rise at the same pace.

He has now reopened the economy fully, citing the country's programme of booster shots, the availability of antivirals, and the lower severity of the Omicron variant, as breaking the link between infections and deaths.

England returned to Plan A last week, and the chair of SPI-M-O told Reuters that while each year should see the COVID situation improve, there may be times where the government has to go backwards and introduce measures. read more

"The next few years will be highly uncertain, and future outbreaks and waves will likely be noisy as things settle down," the SPI-M-O statement said.

"A steady, predictable pattern... may be many years away."

A ‘stealth’ Omicron subvariant is now spreading, worrying experts [National Geographic, 4 Feb 2022]

BY SANJAY MISHRA

Here's what the science shows so far about whether the BA.2 virus is more transmissible and how it holds up against available vaccines.

Cases of the Omicron variant are on the decline in U.S. and worldwide—but a different version of Omicron is now gaining traction. This so-called stealth variant, officially known as BA.2, is armed with even higher transmission potential, and possibly a greater ability to evade the immune response, than the original Omicron, leading experts to fear it could further prolong the COVID-19 pandemic.

The World Health Organization does not yet consider BA.2 to be a distinct “variant of concern” but is continuing to monitor its spread. BA.2 is beginning to replace the original Omicron strain in many countries. It is now the dominant variant in Denmark, which recorded more than 50,000 new infections in just one day last week. BA.2 also appears to be the major Omicron lineage in parts of India and the Philippines. It has already caused about 250 cases in the United States and been identified in more than half the states.

The BA.2 subvariant likely arose from a common ancestor around the same time as the original Omicron, also known as BA.1, so it is not a descendent but a sibling, says Cornelius Römer, a bioinformatician at the Biozentrum of the University of Basel in Switzerland.

“I would hypothesize that BA.1 dominated first simply because it started spreading earlier, and now BA.2 is catching up,” says Jesse Bloom, an evolutionary virologist at the Fred Hutchinson Cancer Research Center and a Howard Hughes Medical Institute investigator.

However, BA.2 has been sometimes dubbed a stealth variant because it is missing key mutations in its spike protein that are necessary for rapid PCR tests to distinguish it from previous variants, such as Delta. This difference also may be why BA.2 escaped attention earlier.

In fact, the two Omicron lineages have greater evolutionary divergences from each other than the differences between the original virus and the Alpha variant, the first variant of concern.
“BA.2 shares over 30 mutations with BA.1, but it also has 28 unique mutations,” says Shay Fleishon, an evolutionary geneticist and advisor to the Central Virology Laboratory in Israel.

This suggests that the common ancestor of both Omicron subvariants spread for quite some time, evolving into distinct subvariants before BA.1 was detected by a stroke of luck: A pair of mutations deleted two amino acids from its spike protein, making BA.1 easier to distinguish from Delta in rapid tests.

Still, BA.2 is “just as detectable by PCR as any other variant,” says Römer, referring to the “gold standard” tests that rely on time-consuming but highly accurate genetic techniques.

What makes BA.2 different?
Most of the differences between BA.2 and BA.1 are in the spike protein of the virus, which it uses to anchor to and infect human cells. BA.2 also has a large number of mutations in other parts of its viral sequence that are not well understood.

Early estimates by Denmark’s State Serum Institute suggest BA.2 is about 50 percent more transmissible than the previous BA.1 strain. The Danish study, which is not yet peer reviewed, looked into the way COVID-19 spread in 8,541 households between late December and early January. About a quarter were BA.2 cases, and the data show that even fully vaccinated people are more susceptible to catching BA.2 than BA.1.

The United Kingdom Health Security Agency also estimates that BA.2 is more transmissible, though it puts the figure at roughly 30 percent higher than BA.1.

The genetic basis behind BA.2’s transmission advantage is not yet understood, says Bloom, who has combined computational and experimental methods to study the evolution of the SARS-CoV-2 virus and understand how specific mutations influence infection.

But the good news is that experts think it’s unlikely BA.2 will cause a spike in severe infections.
Another study that is not yet peer reviewed bolsters the case that the BA.1 version of Omicron causes less severe disease than previous variants, especially Delta; only half a percent of 52,297 Omicron cases in Southern California required hospital admissions. Similarly in the U.K., most admissions to the intensive care unit were caused by Delta until January 19, 2022, when the most recent data are available.

Although BA.2 looks quite different from the original Omicron, there is no evidence yet to suggest that it is any more severe than the previous variant. Neither the Danish nor the U.K. data show any difference in hospitalizations between BA.1 and BA.2 variants. And in other countries where BA.2 is now spreading, the WHO reports that hospitalizations are not rising any faster than what would otherwise be expected.

“We expect antibodies elicited by BA.1 will neutralize BA.2 fairly well, since the viruses are relatively similar in their [binding regions],” says Bloom. For this reason, Bloom thinks it is unlikely that massive BA.2 waves will follow in regions that just suffered from an Omicron surge.

Will vaccines protect against BA.2?
However, the results from preliminary data are mixed as to whether current vaccines will be more or less protective against BA.2 compared to BA.1, which has experts concerned about more potential breakthrough infections. For context, BA.1 is already very efficient at dodging previous immunity. It also reduces the efficacy of two doses of the Pfizer-BioNtech mRNA vaccine, though a third dose at least partially restores it.

The U.K. Health Security Agency estimates that existing vaccines are equally effective at preventing symptomatic disease caused by BA.2 and BA.1, though their data are based on a relatively small number of cases. The U.K. data showed that a booster dose administered two weeks after the second shot of a vaccine was 63 percent effective at preventing symptomatic disease from BA.1 and 70 percent effective for BA.2.

Preliminary studies with lab-synthesized versions of the coronavirus also suggest that neutralizing antibodies collected from the blood of vaccinated people are equally capable of blocking BA.1 and BA.2. And Fred Hutchinson’s Bloom and others have done modelling based on the subvariant’s specific mutations, and they predict that BA.2 won’t be as good as BA.1 at evading antibodies from vaccines.

By contrast, the Danish study is based on a larger case sample, and their data suggest the BA.2 subvariant is even better at evading immune protection provided by vaccines than the original version.

For now, it’s tough to say anything for sure until more real-world data come in. “Obviously, there are not yet direct experimental measurements for BA.2,” Bloom notes, “so we will know more soon.”

Zoonotic swine Flu News since 13 Oct 2021

District remains a swine flu hotspot with maximum deaths, cases in state [The Tribune India, 1 Dec 2022]

By Nitin Jain

10 succumb to H1N1 influenza, 154 test positive, 701 suspected cases
Ludhiana, December 1

Ludhiana district remains the hotspot for H1N1 influenza, commonly known as swine flu, with maximum deaths and cases in the state this season so far, the government has confirmed.

Health infra robust

To minimise public health risk, quality surveillance in both animal and human populations, thorough investigation of every human infection and risk-based pandemic planning are ensured. Besides, the health infrastructure has been made robust to deal with any eventuality. — Surabhi Malik, DC

With as many as 10 patients already succumbing to the infection caused by swine influenza virus (SIV) or swine-origin influenza virus, and 154 persons, including 58 local residents and 96 outsiders, testing positive, besides 701 suspected cases, comprising 271 local residents and 430 from outside, reported till Wednesday, Ludhiana has turned out to be the worst-hit district in the state, official figures have revealed.

Civil Surgeon Hitinder Kaur Sohal told The Tribune here on Wednesday that another fresh positive and one more suspected case of swine influenza virus subtype A (H1N1) were reported in the district on Wednesday and both cases were of local residents.

She said the district Health Department had made elaborate arrangements for the test, treatment and prevention of human infections that were primarily acquired through direct contact with infected animals or contaminated environments as these viruses have not acquired the ability of sustained transmission among humans. “We have set up exclusive isolation wards for swine flu patients and ensured adequate availability of drugs required for the treatment,” the Civil Surgeon said.

Dr Sohal said the condition of all positive cases of influenza virus disease ranging from mild upper respiratory tract infection (fever and cough), early sputum production and rapid progression to severe pneumonia, sepsis with shock and acute respiratory distress syndrome, was stable and recuperating at their own places while only two serious patients were still hospitalised in the district till this evening.

The H1N1 influenza virus, with the vast silent reservoir in aquatic birds, which was impossible to eradicate, has so far claimed 10 lives in the district. However, the Health Department had not yet confirmed the exact cause of these deaths and had classified them as suspected swine flu casualties.

In the state, as many as 41 swine flu deaths had been reported so far, of which 25 had been reviewed and confirmed as H1N1 casualties while the rest were still under review.

While Ludhiana topped the chart with the maximum of 10 deaths, Patiala had reported five casualties, four of which had been confirmed, Ropar also five with three confirmed, Moga three confirmed deaths, Malerkotla and Sangrur two each confirmed, Bathinda, Gurdaspur and Nawanshahr two each with one each confirmed, Amritsar, Faridkot, Fatehgarh Sahib, Ferozepur, Jalandhar, Mansa, Pathankot and Mohali had logged one confirmed swine flu death each so far.

Of the total 193 confirmed H1N1 virus cases reported across the state till date, Ludhiana had reported the maximum of 58 cases, followed by Mohali 21, Sangrur 13, Patiala 12, Jalandhar 11, Gurdaspur and Hoshiarpur seven each, Bathinda, Malerkotla and Nawanshahr six each, Ferozepur and Mansa five each, Amritsar, Fatehgarh Sahib and Kapurthala four each, Barnala, Faridkot and Muktsar three each and Fazilka and Pathankot had logged two swine flu cases each so far.

Signs & symptoms
Swine influenza infections in humans may cause disease ranging from mild upper respiratory infection (fever and cough) to rapid progression to severe pneumonia, acute respiratory distress syndrome, shock and even death.

Diagnosis
Laboratory tests are required to diagnose human infection with zoonotic influenza.

Treatment

Evidence suggests that some antiviral drugs, notably neuraminidase inhibitors (oseltamivir, zanamivir), can reduce the duration of viral replication and improve prospects of survival.

In suspected and confirmed cases, neuraminidase inhibitors should be prescribed as soon as possible (ideally, within 48 hours following symptom onset) to maximise therapeutic benefits. Treatment is recommended for a minimum of five days but can be extended till there is satisfactory clinical improvement.

Prevention
Besides antiviral treatment, the public health management includes personal protective measures such as regular hand washing with proper drying of the hands, good respiratory hygiene — covering mouth and nose when coughing or sneezing, using tissues and disposing of them correctly, early self-isolation of those feeling unwell, feverish and having other symptoms of influenza and avoiding close contact with sick people.

One Step Closer to a Universal Flu Vaccine? [The New York Times, 29 Nov 2022]

By Apoorva Mandavilli

Scientists have tested in animals a vaccine that may protect against 20 strains of influenza, helping to prevent another pandemic.

Imagine a single dose of vaccine that prepares your body to fight every known strain of influenza — a so-called universal flu vaccinethat scientists have been trying to create for decades.

A new study describes successful animal tests of just such a vaccine, offering hope that the country can be protected against future flu pandemics. Like the Covid vaccines made by Pfizer-BioNTech and Moderna, the experimental flu vaccine relies on mRNA.

It is in early stages — tested only in mice and ferrets — but the vaccine provides important proof that a single shot could be used against an entire family of viruses. If the vaccine succeeds in people, the approach could be used against other virus families, perhaps including the coronavirus.

The vaccine would not replace annual flu shots but would provide a shield against severe disease and death from potential pandemic threats.

“There’s a real need for new influenza vaccines to provide protection against pandemic threats that are out there,” said Scott Hensley, an immunologist at the University of Pennsylvania who led the work.

“If there’s a new influenza pandemic tomorrow, if we had a vaccine like this that was widely employed before that pandemic, we might not have to shut everything down,” he said. He and his colleagues described the vaccine last week in the journal Science.

By the age of 5, most children have been infected with the flu multiple times and have gained some immunity — but only against the strains they have encountered.

“Our childhood exposures to influenza lay down long-lived immune memory that can be recalled later in life,” Dr. Hensley. But “we’re sort of living the rest of our life dependent on the random chance of whatever we got infected with as a kid.”

Current influenza vaccines protect against seasonal flu but would provide little protection against a new strain that may emerge as a pandemic threat. During the 2009 H1N1 swine flu pandemic, for example, the conventional vaccine offered little defense against the virus. But older adults who had been exposed to H1N1 strains in childhood developed only mild symptoms.

Scientists have long tried to create a vaccine that would introduce children to every possible strain of flu they may encounter later in life. But researchers have been constrained by technical hurdles and by the diversity of the flu virus.

Broadly speaking, there are 20 subgroups of influenza that each represent thousands of viruses. Current vaccines can target four subgroups at most. But the experimental vaccine contains all 20, and it would be faster to produce.

The vaccine elicited high levels of antibodies to all 20 flu subtypes in ferrets and mice, the researchers found — a finding that several experts said was unexpected and promising.

If the vaccine behaves similarly in people, “we’ll have a more broad coverage of influenza viruses — not only those that are circulating, but those that might spill over from the animal reservoir that might cause the next pandemic,” Alyson Kelvin, a vaccinologist at the University of Saskatchewan in Canada, said.

Packing 20 targets into one vaccine does have a downside: Antibody levels in the test animals were lower than when they were given vaccines aimed at individual strains. But the levels were still high enough to be effective against influenza.

Because a new pandemic strain of influenza might differ from the 20 targets included in the experimental vaccine, the researchers also tested it against viruses that were imperfectly matched. The vaccine still provided strong protection, suggesting that it would prevent at least severe illness, if not infection, from a novel pandemic flu virus.

This phenomenon is akin to that with the current Covid vaccines: Although the latest Omicron variants are so different from the ancestral virus that the original vaccine does not prevent infections, it continues to help safeguard most people against severe illness.

This quality may be a particular advantage of mRNA vaccines, Dr. Kelvin said. Conventional flu vaccines target only the specific viruses they are designed for. But mRNA vaccines seem to produce antibodies that defend the body against a broader range of viruses than those included.

The experts noted some important caveats and questions that must be answered before the vaccine becomes a viable candidate.

The animals in the study built defenses against all 20 flu strains equally. But “these animals have not seen flu before,” said Richard J. Webby, an expert in influenza viruses at St. Jude Children’s Research Hospital in Memphis.

Such a complete lack of immunity against flu is only true of very young children, Dr. Webby noted. Older people are exposed to many different strains over their lifetimes, and it’s not clear whether their immune responses to a universal vaccine would be quite so uniform.

“The proof of the pudding will be what happens when it goes into humans and how going into a preimmune population skews the response to it,” Dr. Webby said.

Designing universal vaccines for varying age groups, if necessary, would be a challenge. It would also be important to see how long protection from such a vaccine lasts, some experts said.

“The biggest issue about universal flu is what you need to target and how long you can continue to use the same vaccine,” Ted Ross, director of Global Vaccine Development at the Cleveland Clinic, said. “If you have to keep updating it, it may not increase the advantage of how we do vaccines today.”

The next step for the vaccine would be to test it in monkeys and in people. But proving its effectiveness might be challenging. “How do you evaluate and regulate a vaccine where their targets aren’t circulating, and so you can’t really show effectiveness?” Dr. Kelvin said.

Perhaps the vaccine could be tested in small sporadic outbreaks, or in poultry workers who are at risk of becoming infected with an avian flu virus, she said: “Those are questions that I think we need to answer before we have our next pandemic.”

US flu hospitalization rate highest its been since 2009 swine flu pandemic, experts say [FOX 13 Tampa, 4 Nov 2022]

What is the difference? COVID-19, the flu, the common cold

Health experts advise getting tested by a health care provider but here are some key differences between COVID-19, the flu and the common cold as told by a nurse educator.

The U.S. flu season is off to an unusually fast start, adding to an autumn mix of viruses that have been filling hospitals and doctor waiting rooms.

Reports of flu are already high in 17 states, and the hospitalization rate hasn’t been this high this early since the 2009 swine flu pandemic, according to the Centers for Disease Control and Prevention. So far, there have been an estimated 730 flu deaths, including at least two children.

The winter flu season usually flu ramps up in December or January.

"We are seeing more cases than we would expect at this time," the CDC's Dr. José Romero said Friday.

A busy flu season is not unexpected. The nation saw two mild seasons during the COVID-19 pandemic, and experts have worried that flu might come back strong as a COVID-weary public has moved away from masks and other measures that tamp the spread of respiratory viruses.

Community Montessori school in New Albany, Indiana, switched to virtual teaching at the end of the week because so many students were out sick with the flu. Beginning Monday, the school's 500 students will go back to wearing masks.

"Everybody just wants kids on campus, that is for sure," said the school's director, Burke Fondren. "We will do what we need to do."

There may be some good news: COVID-19 cases have been trending downwards and leveled off in the last three weeks, Romero said.

And in a few parts of the country, health officials think they may be seeing early signs that a wave of another respiratory virus may be starting to wane. RSV, or respiratory syncytial virus, is a common cause in kids of coldlike symptoms such as runny nose, cough and fever. While RSV continues to rise nationally, preliminary data suggest a decline in the Southeast, Southwest, and in an area that includes Rocky Mountain states and the Dakotas, CDC officials said.

Experts think infections from RSV increased recently because children are more vulnerable now, no longer sheltered from common bugs as they were during pandemic lockdowns. Also, the virus, which usually affects children at ages 1 and 2, is now sickening more kids up to age 5.

At the University of Chicago Medicine Comer Children’s Hospital, beds have been full for 54 days straight.

"The curves are all going up for RSV and influenza," said Dr. John Cunningham, Comer's physician-in-chief.

RSV illnesses seem to be unusually severe, he added.

Comer has had to turn down transfer requests from other hospitals because there was no room. Chicago-area hospitals had been able to transfer kids to Missouri, Iowa, and Wisconsin, but that's stopped. "They have no more beds, either," Cunningham said.

There’s not yet a vaccine against RSV, but there are shots for flu and COVID-19. Health officials say flu vaccinations are down in both kids and adults compared to before the pandemic, although up in children from last year.

So far this season, there have been an estimated 1.6 million flu illnesses and 13,000 hospitalizations. Flu activity is most intense in some of the areas where RSV is fading, including the Southeast, according to CDC data.

CDC confirms variant flu case in Michigan agricultural fair attendee [CIDRAP, 2４ Oct 2022]

Late last week, the Centers for Disease Control and Prevention (CDC) reported a further rise in US flu activity, particularly in the southeast and south central regions, along with another variant H3N2 (H3N2v) flu case, this time in a Michigan resident who had indirect exposure to swine at an agricultural fair.

The variant flu case occurred in a child who was not hospitalized and has recovered from his or her illness. No person-to-person transmission of H3N2v associated with this patient has been identified, the CDC said.

This is the ninth variant flu case detected in the United States this year, including 4 H3N2v cases (Michigan, 1; West Virginia, 3), and 5 H1N2v infections (Georgia, Michigan, Ohio, Oregon, and Wisconsin).

As flu activity rises across the country, clinical labs are reporting a 4.4% positivity rate for the past week, and 3% of outpatient visits have been for respiratory illnesses. Nonvariant H3N2 is the dominant strain this season, representing 79.5% of all cases detected thus far. The 2009 H1N1 strain represents 20.5% of cases.

“First time” achievements in pandemic influenza preparedness in two regions with high humanitarian and public health vulnerabilities, 2014-2021 [World Health Organization, 2１ Mar 2022]

The African (AFR) and Eastern Mediterranean (EMR) regions suffer a large burden of humanitarian vulnerabilities. Nine out of the 10 United Nations system-wide scale ups in response to emergencies occurred in these two regions since 2014. The two regions also have 21 out of the 28 (75%) countries with active health clusters highlighting the considerable challenges for addressing population health needs.

Since the beginning of PC implementation in 2014, investments were made in laboratory and surveillance capacities for strengthening pandemic influenza preparedness including in AFR and EMR. Despite the multiple emergencies experienced in these two regions, significant gains were made as shown below. The gains represent global solidarity to ensure that populations everywhere, regardless of context, are supported to strengthen their preparedness for a future influenza pandemic. The work operationalizes equity, which is at the heart of the PIP Framework, and WHO’s mandate to serve the vulnerable.

Increasing the number of National Influenza Centres (NICs) to facilitate global influenza monitoring and public health risk management

Four NICs were newly recognized by WHO in 3 African countries and 1 Eastern Mediterranean country, bringing the total number to 33 NICs in 31 countries in these two regions. Increasing the number of NICs was recognized, by the PIP Advisory Group in 2013, as the first objective for use of PC funds. Increasing the participation of countries in GISRS means that data and viruses shared are more representative for risk assessment and public health action. It will also facilitate a timely and effective response to an influenza pandemic as more countries will be able to rapidly detect a novel influenza virus.

Sharing influenza viruses to contribute to global surveillance and vaccine development
Fifteen countries started sharing influenza viruses or clinical specimens with WHO CCs since 2014 in AFR and EMR (respectively 12 and 3 countries). By sharing seasonal influenza viruses, countries increase the geographic representativeness of viruses available to inform the yearly composition of influenza vaccines. Through the sharing of seasonal influenza viruses, countries also show their capability to share influenza viruses with pandemic potential when the need arises.

Participating in WHO yearly EQAP to accurately detect emerging influenza viruses
Due to the continuous threat of pandemic influenza, quality laboratory diagnostics are essential. EQAP helps laboratories monitor, sustain and improve influenza virus detection capacity and performance standards. Since 2014, 5 African and 3 Eastern Mediterranean countries started participating in the WHO EQAP. EQAP helps WHO and GISRS institutions to focus capacity-strengthening initiatives to where they are most needed, and to ensure confidence in the underlying systems providing critical data for decision-making.

Sharing data to monitor influenza activity and inform risk assessments Fifteen countries from AFR and EMR started reporting epidemiological data to WHO’s influenza surveillance platform “FluID”, 6 started reporting virological data to “FluNet”, and 6 started reporting data to both platforms. The participation of more countries increases the geographical representativeness of the data in these two global systems. Routine data availability also means that situational analyses and risk assessments are up to date. These are critical for national and global preparedness.

Reporting influenza severity indicators to enable timely severity assessments and associated response recommendations
WHO’s pandemic influenza severity assessment (PISA) platform was developed to monitor and assess the severity of yearly influenza epidemics, so that when the time comes, it can also be used for pandemic influenza monitoring. Since its launch in 2017, 13 countries from AFR and EMR (respectively 10 and 3) have started reporting to the PISA platform. Country participation will streamline monitoring during the next pandemic, and the historical data will assist countries to determine the timing, scale, emphasis, intensity and urgency of the pandemic response actions needed.

Building resilient systems
WHO congratulates countries for these gains. However, the work is not done. Due to the humanitarian and fragile contexts in many countries, time is needed to stabilize participation in influenza preparedness systems. The COVID-19 pandemic also shed light on existing gaps in preparedness and the need to revisit surveillance platforms and approaches to be resilient within a broader acute respiratory disease context.

Denmark reports 'steep' increase in influenza cases - Outbreak News Today [Outbreak News Today, 2１ Mar 2022]

Since large parts of Danish society were shut down on 12 March 2020 due to Covid-19, the incidence of influenza has been at a very low level until the beginning of 2022. Now the number of people infected with influenza A is doubling from week to week.

In Denmark, the incidence of influenza tends to increase at the end of December. But this season, the flu has started very late, after being almost completely absent for the last two years during covid-19.

Currently, however, there is a steep increase in the number of flu cases in most of the country. In recent weeks, the number of infected has thus doubled from week to week and in week 10 reached 1,179 infected.

A total of 2,533 cases of influenza have been detected this season. The vast majority of cases – a total of 2,459 – are caused by the type of influenza virus called A / H3N2.

It is a well-known flu type, which is also circulating in other countries. H3N2 is included in the seasonal vaccine, but it is known to change and this may mean that the effect of the vaccine is reduced.

This season, changes have been seen in the H3N2 viruses in circulation, which may mean that the vaccine has a reduced effect.

Influenza has been detected in all age groups. At present, however, a predominance of children and the younger part of the population aged 15-44 as well as +85 year olds are affected by influenza.

It is now more than five months since seasonal flu vaccines became available. The late onset of influenza prevalence is therefore a challenge, as it is well known that the effect of vaccines decreases over time.

In the age group 2-6 years, the effect of the influenza vaccine, which is targeted at children, is calculated at 71% against influenza A. In the age group 7-44 years, the effect is calculated at 43%, while in the age group 45 years and over, no effect against the circulating influenza A type.

“Despite the fact that the vaccine effectiveness against influenza infection is not measurable in the age group 45 and above, the vaccine will probably still have some effect against serious illness if you become infected with influenza,” says section leader Ramon Trebbien from Stans Serum Institut ( SSI).

It is not so surprising that the best effect of the flu vaccine is seen among the children, as children generally have a good ability to form antibodies after being vaccinated.

In addition, vaccinated children aged 2-6 years have received two doses of the live attenuated childhood vaccine, which was introduced in the Danish vaccination program for the influenza season 2021/22.

The other age groups have received a single dose of the inactivated influenza vaccine known from previous flu seasons.

What happened when the 1918 flu pandemic met WWI [PBS NewsHour, 10 Mar 2022]

By Dr. Howard Markel

When it comes to the Russian invasion of Ukraine, it is safe to say that no one wins if the conflict helps spread the coronavirus.

Before Russia’s forces began attacking its neighbor, both countries had just hit records in new daily cases, peaking at an all-time high in Ukraine in early February. On Feb. 24, the day Russian President Vladimir Putin launched the assault, there were more than 25,000 new confirmed cases in Ukraine, according to the World Health Organization. While infections had begun to fall before Russia’s invasion, for multiple days in the past week the global health agency had reported no official data from the country – perhaps a reflection of the chaos and violence that has sent more than 2 million refugees to flee to other countries and scrambled its health infrastructure. No one has any real idea of how the virus may be spreading now.

“Low rates of testing since the start of the conflict mean there is likely to be significant undetected transmission,” WHO Director-General Tedros Adhanom Ghebreyesus said during a news briefing on March 2. “Coupled with low vaccination coverage, this increases the risk of large numbers of people developing severe disease.” Just 35 percent of Ukrainians are fully vaccinated against COVID, while 50 percent of Russians are – both below the worldwide average.

On every level, it is unwise to declare war during a pandemic. Infectious diseases have typically followed lines of humans engaged in travel, commerce and war. From the Civil War up until World War II, more soldiers died of infections than from bullets. Cholera, typhus fever, bubonic plague and other deadly microbes were all spread because germs also travel.

This was certainly the case with the influenza pandemic of 1918-1919, which was one of the worst contagion crises in the history of humankind. Around the world, anywhere from 40 to 100 million people died, according to various estimates, with 500,000 to 750,000 deaths in the United States alone. It was a particularly virulent and novel strain of influenza that attacked young adults most severely, in contrast to seasonal influenza’s typical victims, the very young and the elderly.

The United States entered World War I in 1918, four years into the conflict. In the months leading up, more than 4 million young men were sent to U.S. Army camps all over the country, traveling by train, cheek by jowl. They arrived to discover far-less-than-deluxe accommodations of crowded tents, dormitories, sloppy mess halls and poorly dug latrines. And when they were ready to ship out, they traveled—again by crowded trains—to the Atlantic seaboard where they boarded crowded troop ships taking them to the European theater, where many million more were already fighting. En route, many became seasick and vomited profusely; all of them slept in ridiculously close quarters, with the bunks resembling bookshelves stuffed with human cargo. Their destination was often the grimiest, filthiest trenches ever dug. To say troop conditions were not exactly sanitary is a gross understatement. Many of these young men were not only victims of influenza but terrific vectors for spreading microbes to others.

There were three waves across the 1918-1919 pandemic, and another in the winter of 1920. During the second wave, which lasted from September to December of 1918, soldiers, sailors and even ambulance drivers were among the hardest hit groups on both sides of the Atlantic Ocean. In recent years, some have claimed to pinpoint the outbreak’s origin to this Army camp in Kansas or that foxhole in Marne, but such microbe-gazing is a parlor game and impossible to prove. When discussing the coronavirus in 2022, however, origin stories no longer matter nearly as much as asking where the virus is spreading now and how it continues to make millions of people ill, or worse.

Unlike our current era, nobody knew much about virology at all back in 1918, and didn’t know exactly what caused the flu. Scientists had a better hand on bacteriology, but many experts incorrectly thought influenza was caused by the bacterium Haemophilus influenzae (hence, the quaint Latin last name). They had no medications yet that would work against bacteria – no antibiotics, let alone antivirals that could have helped in the pandemic. There were no intravenous fluids, respirators or intensive care units; nurses and doctors were in short supply; and medical care was more a form of warehousing these young men and women than what we would expect today. Working at these overcrowded base hospitals, let alone finding yourself in one, was a nightmare.

The ill soldiers were “placed on cots until every bed is full and yet others crowd in.”

Modern medical knowledge has greatly advanced, but the conditions on the ground are still dire. The United Nations has warned that Ukraine’s health care system is in grave danger. “As increasing numbers of people are displaced, the increased risk of COVID-19 contagion, combined with growing numbers of injured people in need of emergency medical services, will put additional pressure on the country’s already-stretched health system,” the U.N.
humanitarian agency wrote in a Feb. 26 report. On Wednesday, Ukrainian officials reported that Russia had bombed a maternity hospital in Mariupol, killing three and wounding more than a dozen people, including women waiting to give birth. Russia has attacked at least 18 medical facilities in two weeks, according to WHO.

During WWI, most of the soldiers who died from the pandemic did not just die of influenza but of secondary bacterial pneumonia. As these poor souls’ lungs filled up with fluid, immune cells, and bacterial detritus, they turned blue from the lack of oxygen, often bled from the nose and mouth and ultimately suffocated.

The ill soldiers were “placed on cots until every bed is full and yet others crowd in. The faces soon wear a bluish cast; a distressing cough brings up the blood-stained sputum. In the morning the dead bodies are stacked about the morgue like cord wood,” recalled a doctor named Victor C. Vaughan. Years after witnessing influenza among “the stalwart young men” under his care at Camp Devens, Vaughan graphically recalled the carnage in his 1926 autobiography, “A Doctor’s Memories.”

Then the dean of the University of Michigan Medical School, Vaughan knew what he was talking about when it came to epidemics and combat. He had toured Army hospitals in 1898 during the Spanish American War and even contracted the dreaded yellow fever while doing so.

But Vaughan never forgot the horror he experienced in 1918 as a helpless doctor with nothing in his black bag, save morphine, to alleviate suffering. “This picture was painted on my memory cells,” he later wrote, “the deadly influenza virus [that] demonstrated the inferiority of human inventions in the destruction of human life… This infection. like war, kills the young, vigorous, robust adults …The husky male either made a speedy and rather abrupt recovery or was likely to die.”

A weakened or ill fighting force does not help anyone’s cause. When mated with 21st century technology, the incursion could spread infection from COVID far more quickly than tanks can travel, not only among soldiers but also among the civilians victimized by war.

Researchers getting closer to a “universal” flu vaccine [pnas.org, 1 Feb 2022]

Authored by Carolyn Beans

With new vaccine targets and more powerful delivery platforms, researchers are making inroads toward an influenza vaccine that could offer better, longer-lasting protection.

When urgent coronavirus disease 2019 (COVID-19) vaccine development efforts began in earnest in early 2020, researchers were by no means starting from scratch. That’s in part attributable to the decades of research dedicated to creating better influenza vaccines. Indeed, many flu vaccinologists pivoted to COVID-19 two years ago, bringing to bear the knowledge and tools they’d developed to fight a seasonal menace that has the potential to spark pandemics.

But these vaccinologists haven’t turned away from their longstanding goal: an influenza vaccine that protects against all strains. Such an achievement could save hundreds of thousands of lives every year. And COVID-19 vaccine efforts may end up helping to accelerate that work.

A universal influenza vaccine represents a game changer that could take the threat of both seasonal and pandemic influenza “off the table,” according to a November 2021 report, one of four from the National Academy of Medicine (NAM) on how to prepare for an influenza pandemic with lessons learned from COVID-19. As defined by the National Institute of Allergy and Infectious Diseases (NIAID) in 2018, a “universal” vaccine implies at least 75 percent effectiveness protecting all age groups for a minimum of one year against all strains of influenza A (1). Ideally, says the NAM report, a universal vaccine could also work against influenza B and offer protection for three to five years.

Seasonal flu vaccines—although valuable tools in mitigating flu—protect against only the narrow range of strains projected to be most problematic in a given year. When projections are off, the mismatch has led to vaccine effectiveness as low as 10 percent; even in a good year, vaccine effectiveness barely reaches 60 percent (2). There’s plenty at stake: Each year, influenza results in an estimated 290,000 to 650,000 deaths globally despite seasonal vaccines (3). A novel flu virus for which there’s no vaccine could lead to a pandemic that kills millions more.

A broadly protective flu vaccine has been a goal for decades, but it’s become more attainable in recent years thanks to new vaccine targets and more effective delivery platforms. When the coronavirus pandemic hit, influenza researchers were already making progress with platforms such as mRNA and viral vectors that have led to successful coronavirus vaccines.

All this means there’s good reason to believe that a universal flu vaccine is possible within a decade. But hurdles remain—from regulations designed to evaluate more traditional flu vaccines, to overcoming puzzling quirks of the human immune system.

A Moving Target An influenza virus particle looks much like the now infamous image of coronavirus. Proteins point outward from a sphere of lipids, forming a spikey ball. The most abundant of these protruding proteins is hemagglutinin, which, along with another surface protein called neuraminidase, is where influenza A viruses get their “H” and “N” designations (see Fig. 2).

Hemagglutinin is the key that unlocks host cells, letting the virus in. That makes it a main focus of the human immune system and the primary target of most flu vaccines. Flu vaccines aim to elicit long- and short-term immune responses, including antibodies that recognize specific locations on the hemagglutinin and attach to those spots, blocking the virus.

But hemagglutinin is a moving target. It consists of a stalk topped by a head that is especially prone to evolve, causing small changes to accumulate within each circulating strain. Since the 1970s, the World Health Organization has tried to stay ahead of these changes by recommending, months in advance, which of the circulating strains to include in seasonal flu vaccines (4). In recent years, those recommendations have included two influenza A and two influenza B strains, which are all incorporated into the single “quadrivalent” vaccine given in the United States (5).

In the late 2000s, several research groups made a key discovery that suggested it might be possible to end the race against evolving strains: Humans, it turned out, can generate flu-neutralizing antibodies against parts of the virus that remain largely unchanged (6). Since then, the search was on for the best of these “conserved” regions.

Viruses contain many proteins, all covered in antigenic sites, or epitopes, that trigger matching antibodies. But although hitting one antigenic site may deal the virus a lethal blow, hitting another may leave it relatively unscathed. “Your immune system doesn’t know the difference between what’s protective and what’s not,” explains immunologist Jenna Guthmiller, a postdoctoral fellow at the University of Chicago, IL, and an incoming assistant professor at the University of Colorado Anschutz Medical Campus in Aurora. Vaccination, she says, can teach our antibody-generating B cells to focus more on attacking critical regions of the virus. But first you have to get the cells’ attention.

Redirecting Attention
Many researchers developing vaccines against conserved parts of the flu virus have focused on the hemagglutinin stalk, which typically changes less than the head. Unfortunately, the stalk doesn’t generate as strong an immune response. The reason for the head’s “immunodominance” is not entirely clear, explains virologist and vaccinologist Florian Krammer of the Icahn School of Medicine at Mount Sinai in New York.

But Krammer, along with fellow virologist collaborators, is developing hemagglutinin proteins that attract the immune system’s attention to the stalk. They do so by taking advantage of another immune system tendency: to respond most readily to what it already knows. Even the strains included in seasonal flu vaccines from year to year, which may have sufficiently different hemagglutinin heads to evade antibodies tailored to a past version, also include many of the same or similar antigenic sites. So, the head is both immunodominant and very familiar. “The head domain has all of the advantages,” says Krammer.

Krammer’s group takes a hemagglutinin protein and swaps the familiar head for one from a distantly related strain. The head of this chimeric hemagglutinin is still immunodominant, but the stalk is the only familiar portion. “So you redistribute the advantages,” says Krammer. By delivering a second vaccination with the same stalk and another unfamiliar head, the stalk’s advantage grows.

The team recently designed a vaccine to protect against group 1 influenza A viruses—one of two groupings within influenza A based on the relatedness of their hemagglutinins (7). To make the H1 stalk the most familiar target presented in the vaccine, they topped their chimeric hemagglutinins with heads from avian H5 and H8 viruses. The results of their phase 1 clinical trial, published in January 2021, showed the vaccine induced a broad, durable immune response against the stalk (8). The team is similarly developing vaccines to protect against the more distantly related influenza A group 2 viruses and against influenza B, with the ultimate goal of creating a trivalent universal flu vaccine.

Despite much potential in the stalk, the head may hold some promise yet, says Guthmiller. She recently isolated antibodies produced by volunteers vaccinated against the 2009 H1N1 virus. Structural virologist Julianna Han of The Scripps Research Institute in La Jolla, CA, then used electron microscopy to reveal precisely how and where each antibody attached to the hemagglutinin head. Of the 66 individual antibodies identified, fully half targeted conserved head regions (9). In an in vitro study, these antibodies blocked nearly all human H1N1 viruses. And in mice, a representative sample of the antibodies provided 100% protection against weight loss and death from a mouse-adapted 2009 H1N1 virus.

Others are bringing computational brute force to the search for the best epitopes in an effort to “build” a better hemagglutinin for use as a vaccine antigen (10). Vaccinologist Eric Weaver, director of the Nebraska Center for Virology at the University of Nebraska–Lincoln, mines public databases to collect hemagglutinin gene sequence data for flu strains recorded over time. He and his team enter those data into the Epigraph vaccine designer, a computer algorithm that builds a new hemagglutinin based on the most common variations in the structure of the protein. To fill in potential gaps in protection, the algorithm can create another hemagglutinin protein using the most frequently occurring forms of each variable region not captured in the first protein, and so on for additional designs.

Working in pigs, which can serve as mixing vessels for avian, human, and pig strains to swap genome segments, Weaver’s team recently developed a vaccine aimed at protecting North American swine from H3 strains—a diverse influenza A subtype that circulates in both humans and pigs (11). Pigs vaccinated with a mixture of three synthetic hemagglutinin proteins generated antibodies that protected against 11 of 13 North American H3 swine strains tested. “If we can protect swine from humans, and if we can protect humans from swine,” Weaver says, “we’ll eliminate this mixing vessel.”

More than Packaging
In the United States, most influenza vaccines contain inactivated or weakened influenza viruses, which can require high doses to generate a sufficient immune response (12). But as researchers reveal new, more specific vaccine targets, they are also finding that the vaccine platform itself—the way an antigen is delivered to the body—can have huge impacts on the strength and quality of immune responses to those targets.

Lynda Coughlan, a vaccinologist at the University of Maryland School of Medicine in Baltimore, develops vaccines that harness another virus as a delivery tool (13). Adenoviruses naturally infect humans, causing a range of illnesses (14). Researchers can turn these adenoviruses into a “vector” for flu vaccines by deleting the genes that allow the adenoviruses to replicate. Inside this viral shell, researchers insert DNA sequences encoding whatever flu antigens they’d like to present.

A big advantage of these DNA viruses as vaccine vectors is that they use the vaccine recipient’s own gene-transcription and translation machinery to generate the antigen protein. And, in principle, the vaccine can keep producing antigen for weeks or longer, which researchers hypothesize could extend the immune response (15). Additionally, the way these vectors enter cells more closely mimics some real viral infections, which more actively engage the immune system.

COVID-19 vaccines currently on the market produced by AstraZeneca, China’s CanSino Biologics, Russia’s Gamaleya Institute, and Janssen (Johnson & Johnson) also use this adenoviral-delivery strategy, although interest in the technology long predates the pandemic. The University of Oxford’s (United Kingdom) Jenner Institute, where researchers developed the AstraZeneca COVID-19 vaccine, has tested its chimpanzee adenovirus vector against a range of diseases, including flu, although none had made it to market until the COVID vaccine.
Coughlan says that the precedent set with the use of adenovirus-vector vaccines against COVID-19 in humans may help pave the way for the flu field. And despite safety issues raised by the Centers for Disease Control and Prevention (CDC) in December regarding Johnson & Johnson's adenovirus-based COVID-19 vaccine as compared with mRNA products,* Coughlan says she’s confident that researchers can make modifications to adenoviral vectors to increase safety in the future.

In one recent study, Coughlan and colleagues at Mount Sinai and other institutions created a vaccine that triggered production of the hemagglutinin protein from the 2009 H1N1 virus; it protected mice from that strain (16). They also tested whether this adenoviral vaccine protected mice exposed to another virus—this one with a stalk that matched the hemagglutinin antigen in the vaccine but an entirely different head. All the mice survived, says Coughlan, compared with only a few animals that received a traditional H1N1 vaccine. When the team repeated the experiment with a still more distantly related virus, the difference was even more stark. Adenoviral-vaccinated mice survived, whereas none of the others did (16).

Messenger RNA (mRNA), a platform now famous for its use in the Moderna and Pfizer-BioNTech COVID-19 vaccines and the powerful immune responses they induce, was also in development by those companies as a flu vaccine before the coronavirus pandemic hit (17, 18).
The success of mRNA coronavirus vaccines is a testament to how well the platform can work, says vaccinologist Norbert Pardi of the University of Pennsylvania in Philadelphia, who in 2015, along with mRNA vaccine pioneers Katalin Karikó and Drew Weissman, and others, demonstrated that packaging mRNA within a protective coating of lipids prevents it from degrading too quickly and helps it enter cells (19).

mRNA vaccine technology enables researchers to quickly swap mRNA encoding for different antigens and include multiple antigens at once. In a 2020 study, Pardi, Coughlan, and others tested an mRNA vaccine that combined four influenza proteins. One of these proteins was a special hemagglutinin that contained only the stalk—another strategy for directing the immune response away from the head. In addition, the team included neuraminidase and two other viral proteins that tend to be more conserved. The idea is that incorporating multiple targets offers broader protection and also helps hedge bets. If one of these viral regions evolves to evade the immune system, says Pardi, the other targets could still potentially provide protection.

The vaccine protected mice from a broad range of group 1 influenza A viruses (20). Ultimately, the team plans to include about 10 to 12 antigens spanning influenza A and B. “This is how we believe that we can really develop a globally protective vaccine,” says Pardi.

"You want people to have some level of protective immunity, even if it’s not perfect, as quickly as possible without the lag phase of waiting for manufacturing of a perfectly matched vaccine." —Lynda Coughlan

Others are similarly combining multiple antigen targets into novel platforms with the goal of ramping up both the breadth and strength of the immune response. Researchers at NIAID’s Vaccine Research Center (VRC) in Bethesda, MD, are using nanoparticles to build multi-antigen influenza vaccines (see Fig. 1). It’s a “very strong way to stimulate the immune system,” says VRC vaccine immunologist Masaru Kanekiyo.

The team designs a genetic sequence encoding an antigen plus a nanoparticle piece at one end. They then mix this new protein with another nanoparticle piece whose shape is complementary to the first. The nanoparticles click into place like a three-dimensional puzzle, forming an “immunogen” sphere with antigens pointing outward.

In a recent test, Kanekiyo and collaborators showed that a vaccine nanoparticle displaying a total of 20 copies of four hemagglutinin proteins—one from each of the strains in a seasonal flu vaccine—generated strong immune responses in multiple animal models against these specific strains as well as or better than the commercial vaccine (21). But the nanoparticle vaccine also offered greater protection against more distantly related influenza strains, including avian strains with pandemic potential.

Kanekiyo suspects the physical spacing between antigens in the nanoparticle may create a structure that hits within the immune system’s “strike zone.” Whatever the mechanism, the nanoparticle platform seems to enhance the immune response, while also directing attention to the hemagglutinin stalks. The team is currently testing a similar vaccine in a phase 1 clinical trial.

Understanding the different types of immune responses induced by different vaccine platforms is a big research area, says Coughlan. Trials with COVID-19 vaccines have demonstrated that mixing and matching different platforms can provide the benefits of each while strengthening overall responses (22). Coughlan envisions that a truly universal influenza vaccine may similarly require multiple platforms. People might, for example, receive a two-shot “universal” flu vaccination with an adenoviral-based “prime” and then an mRNA “boost.”

Original Sin and Other Hurdles
Despite these advances, the winning formula for a universal flu vaccine is far from certain. The NAM report states that it “remains a difficult scientific problem with no guarantee that a vaccine can be developed that will provide long-term protection in people of all age groups" (23).

One major challenge is posed by a phenomenon sometimes called “original antigenic sin,” or imprinting (24). For reasons that are still not totally clear, the immune response to any influenza strain is launched in large part by the same B cells that developed upon a person’s first flu exposure, even when the strain is mismatched (unless the new strain is so significantly different that it’s beyond recognition). Guthmiller says that it’s not that subsequent exposures don’t matter; she likes to imagine a pyramid, with each exposure adding another level, although the B cells from that first exposure—the foundation of the pyramid—remain the most dominant.

A recent study by Guthmiller, Coughlan, Krammer, and others suggests that vaccination can sway the immune system more toward generating protective antibodies, whereas infection tends to result in more nonprotective antibodies linked to childhood infection (25). But it remains to be seen how universal vaccine candidates will perform in large numbers of people who have unique histories of exposure. Based on what we know right now, Han says, “even if you try to broaden an individual’s response to multiple strains of flu, you can only get so far based on the biases already present in that individual’s immune system.” One possible workaround, she suggests, might be to develop different universal flu vaccines for different age groups.

Another wildcard is durability—both in terms of how long vaccine-induced immune memory will remain active, and how long a particular vaccine formulation remains “universal” enough. “In a perfect world, you would get vaccinated at the age of six months or one year and then you wouldn’t need it again until you were 50,” says Weaver. “It’s more likely that evolution would continue to occur and that these would need to be updated.”

Given that a flu vaccine that is at once long lasting, broadly protective, and highly effective could prove a tall order, at least in the short term, Coughlan also sees a place for a vaccine that could limit the severity of illness for a broad range of flu strains—even if it does not prevent infection. This stopgap vaccine could be freeze-dried, stockpiled, and rolled out only in the event of a pandemic. “You want people to have some level of protective immunity, even if it’s not perfect, as quickly as possible without the lag phase of waiting for manufacturing of a perfectly matched vaccine,” she says.

Universal flu vaccines could face some regulatory hurdles (26). Most candidates would be sufficiently different from existing seasonal vaccines, meaning that getting them approved under current regulatory guidelines would require more than just showing so-called correlates of protection; vaccine developers would have to perform the extra step of demonstrating that the vaccine prevents people from getting sick, says Krammer. “That might be many million dollars’ difference in the cost of the clinical trial.”

But momentum is building and the pace of discovery may increase with fresh funding for efforts like NIAID’s Collaborative Influenza Vaccine Innovation Centers (CIVICs). Launched in fall 2019, CIVICs support collaborative research, vaccine manufacturing, and clinical trials—all at facilities within the CIVICs network. “I think that a lot of interesting vaccine approaches will come out of that structure,” says Krammer, who is co-principal investigator for one of three vaccine research centers within the network.

Like much influenza research, early work out of CIVICs was slowed by the coronavirus pandemic and supply chain issues. “That has impacted a lot of lab work,” says Krammer, adding that many influenza researchers—including himself—also shifted their attention to the new coronavirus for a time.

Still, he’s hopeful that the coronavirus pandemic may yet play some role in advancing a universal flu vaccine, both by renewing public enthusiasm for vaccines and by demonstrating how much can be accomplished with enough political will and financial support. “The public learned that pandemics happen and we need to be prepared,” says Krammer—but, he adds, researchers in the flu field “didn’t need that reminder.”

Footnotes
•↵*On December 16, 2021, the CDC endorsed updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for the prevention of COVID-19. The agency expressed a “clinical preference for individuals to receive an mRNA COVID-19 vaccine over Johnson & Johnson’s COVID-19 vaccine.” The agency cited ACIP’s unanimous recommendation based on “the latest evidence on vaccine effectiveness, vaccine safety and rare adverse events, and consideration of the U.S. vaccine supply.”
https://www.cdc.gov/media/releases/2021/s1216-covid-19-vaccines.html

References
1. ↵National Institute of Allergy and Infectious Diseases, Universal influenza vaccine research. https://www.niaid.nih.gov/diseases-conditions/universal-influenza-vaccine-research. Accessed 7 December 2021.
2. ↵Centers for Disease Control and Prevention, Past seasons vaccine effectiveness estimates. https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html. Accessed 7 December 2021.
3. ↵World Health Organization, Influenza (Seasonal) (2018) https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal). Accessed 7 December 2021.
4. ↵Influenza Research Database, World Health Organization recommendations for composition of influenza vaccines. https://www.fludb.org/brc/vaccineRecommend.spg?decorator=influenza. Accessed 7 December 2021.
5. ↵Centers for Disease Control and Prevention, Quadrivalent influenza vaccine. https://www.cdc.gov/flu/prevent/quadrivalent.htm. Accessed 7 December 2021.
6. ↵D. C. Ekiert et al., Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246–251 (2009).
7. ↵Centers for Disease Control and Prevention, Types of influenza viruses. https://www.cdc.gov/flu/about/viruses/types.htm. Accessed 7 December 2021.
8. ↵R. Nachbagauer et al., A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nat. Med. 27, 106–114 (2021).
9. ↵J. J. Guthmiller et al., First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes. Sci. Transl. Med. 13, eabg4535 (2021).
10. ↵J. Glanville et al., A general solution to broad-spectrum vaccine design for rapidly mutating viruses. https://doi.org/10.21203/rs.3.rs-100459/v1 (29 December 2020).
11. ↵B. L. Bullard et al., Epigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus. Nat. Commun. 12, 1203 (2021).
12. ↵Centers for Disease Control and Prevention, How influenza (flu) vaccines are made. https://www.cdc.gov/flu/prevent/how-fluvaccine-made.htm. Accessed 7 December 2021.
13. ↵L. J. Kerstetter, S. Buckley, C. M. Bliss, L. Coughlan, Adenoviral vectors as vaccines for emerging avian influenza viruses. Front. Immunol. 11, 607333 (2021).
14. ↵Centers for Disease Control and Prevention, Adenoviruses.
https://www.cdc.gov/adenovirus/index.html. Accessed 7 December 2021.
15. ↵S. Rauch, E. Jasny, K. E. Schmidt, B. Petsch, New vaccine technologies to combat outbreak situations. Front. Immunol. 9, 1963 (2018).
16. ↵C. M. Bliss et al., A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice. Mol. Ther., 10.1016/j.ymthe.2022.01.011 (2022).
17. ↵R. A. Feldman et al., mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37, 3326–3334 (2019).
18. ↵BioNTech, BioNTech signs collaboration agreement with Pfizer to develop mRNA-based vaccines for prevention of influenza.
https://investors.biontech.de/news-releases/news-release-details/biontech-signs-collaboration-agreement-pfizer-develop-mrna-based. Accessed 7 December 2021.
19. ↵N. Pardi et al., Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Control. Release 217, 345–351 (2015).
20. ↵A. W. Freyn et al., A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice. Mol. Ther. 28, 1569–1584 (2020).
21. ↵S. Boyoglu-Barnum et al., Quadrivalent influenza nanoparticle vaccines induce broad protection. Nature 592, 623–628 (2021).
22. ↵M. E. Deming, K. E. Lyke, A ‘mix and match’ approach to SARS-CoV-2 vaccination. Nat. Med. 27, 1510–1511 (2021).
23. ↵National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine, Countering the Pandemic Threat through Global Coordination on Vaccines: The Influenza Imperative (The National Academies Press, Washington, DC, 2021).
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Dangerous Flu Comeback Expected atop COVID This Winter [Scientific American, 25 Jan 2022]

By Tara Haelle

COVID shutdowns limited the spread of influenza in 2019–2020. Several factors could mean this season will be more severe

A feared “twindemic” of influenza and COVID never came to pass last year, but the outlook for such a confluence this winter is resurfacing similar concerns among epidemiologists and other infectious disease experts. Flu cases started to tick up in October and November, and those months saw an outbreak at the University of Michigan at Ann Arbor. These early signals suggest that, in the coming weeks, seasonal flu could wreak some havoc—especially in hospitals—simultaneously with the national surge of the novel coronavirus, or SARS-CoV-2.

Public health officials agree that last year’s flu season was a no-show because of COVID mitigation measures, including less travel, increased working from home and remote schooling, mask wearing and social distancing. The combined restrictions and limits on social interactions prevented flu from gaining a foothold, says Lynnette Brammer, the U.S. Centers for Disease Control and Prevention’s team lead for domestic influenza surveillance. This winter many pandemic restrictions have loosened or been lifted entirely, creating an opening for influenza and other respiratory viruses.

Current flu infection rates nearly match the expectations of the CDC for this time of year, Brammer says. “This looks like a regular start of a flu season,” she adds, noting that most outbreaks so far have been in young adults (particularly on college campuses) and that now the virus now is spreading to older adults. U.S. influenza mortality rates vary from season to season. The viral disease caused an estimated 20,000 deaths and 380,000 hospitalizations in 2019–2020. The most recent severe season, 2017–2018, is estimated to have killed 52,000 people and hospitalized 710,000.

Like COVID, flu can have serious long-term effects, says Melissa Andrew, an associate professor of medicine at Dalhousie University in Nova Scotia. “Influenza is an important trigger for heart attacks and strokes. And in older people, it can cause delirium,” she says. Delirium, also a risk factor for dementia, can lead to cognitive decline and can increase the risk of falls and hip fracture. “So it’s really important to remember not just the short-term impacts of an infection like influenza but the longer-term ones,” Andrew says.

Speculations about “flurona” emerging as a Frankenstein-like single pathogen combining flu- and COVID-causing viruses are nonsense—but it is possible to develop flu and COVID infections at the same time. “Either one of these diseases can be very bad in people who are susceptible, and if you put them together, it can only be worse. But we know very little about it,” says Edward Belongia, director of the Center for Clinical Epidemiology & Population Health at the Marshfield Clinic in Wisconsin. “Sadly, we may find out this winter.”

Some looming concerns could pertain more to larger systems instead of individuals. Before the pandemic, hospitals and their emergency departments would fill up annually during the winter viral season, Andrew says. “Now we’re seeing hospitals getting overwhelmed with these waves of COVID, but everybody else still needs their regular care, too. If we get a wave of influenza on top of that,” she adds, “we could be in for quite a ride.”

Even a mild flu season, Belongia says, could take a “health care system that is already at the tipping point and tip it over even further,” with severely ill flu patients competing for resources with very sick COVID patients.

One emerging trend signals a potentially severe flu season, Belongia says: During most seasons, influenza A subtypes dominate at the beginning, and influenza B subtypes dominate at the end. Right now, he says, an influenza A subtype called H3N2—which is causing nearly all flu infections—is one that tends to dominate during the most severe flu seasons.

A positive note is that flu appears to have returned without one of the four subtypes that typically circulate every season. A lineage of influenza B viruses, called Yamagata, has been missing in action for nearly two years. Unlike influenza A viruses, influenza B viruses almost exclusively infect humans, so researchers think the Yamagata lineage may have gone extinct.

There is another early signal of possibly milder outcomes: Current flu infections are hovering a little above those seen in the 2015–2016 season, which had one of the lowest death counts from influenza in the past nine years. Flu seasons vary greatly in how they play out, Belongia says.

Flu vaccination campaigns took a back seat to COVID-19 vaccinations this past fall. And while flu vaccine uptake is currently similar to what it was at this time last year in most of the country, it is lower in some jurisdictions, according to the CDC’s flu vaccination dashboard. Officials are most concerned about coverage among the most vulnerable groups, including children and pregnant people, whose vaccination rates are currently lower than they were at the same time last year. By the end of October just more than a third of older adults on Medicare had been vaccinated, compared with 49 percent at that time in 2020 and 42 percent in 2019.

Manufacturers reformulate the flu vaccine each year to include the four viral strains that the World Health Organization and U.S. Food and Drug Administration anticipate will predominate in the coming season. It is still unclear whether this season’s vaccine strains will closely match the viruses that are circulating. A December 2021 preprint study identified changes in the currently circulating H3N2 strain that differ enough from the expected one used for this year’s flu vaccine to potentially reduce the effectiveness of the shot.

The slight mismatch is unsurprising because the committees that selected the vaccine’s flu strains had limited data on the latest strains—a result of minimal influenza circulation for almost two years—says Kawsar Talaat, an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.

On top of that, flu vaccines have historically provided less protection against H3N2 than other strains, and H3N2 evolves faster than H1N1 and B strains, Talaat says. “But even in very mismatched years, being vaccinated still protects you against severe disease and hospitalization,” she adds. “So it’s still better than not being vaccinated.”

The flu-season gap year in 2020–2021 also may have left our immune system less prepared, setting us up for a more severe season this time around, some experts say. Typically, each season, millions of people produce antibodies after encountering that season’s flu strains. But much of that immunologic priming did not happen last year.

“We have a population of people who are more susceptible and whose immune systems haven’t really seen a flu virus for a couple of years or more,” Belongia says. “In that setting, you want all the protection you can get and to give your immune system a head start with the vaccine.”

Higher rates of flu vaccination can also help reduce the burden on the already severely strained health care system, Brammer says. “That’s one of the many reasons we want to encourage people to get vaccinated against flu,” she says.

It bears repeating that behaviors aimed at lowering the risk of a SARS-CoV-2 infection also help prevent flu, Talaat says. “Do the things that we know work against all of these viruses,” she adds. That means ensuring you have received the COVID and flu vaccines and, if eligible, the COVID booster shot and the pneumonia vaccine, Talaat says. The CDC recommends the pneumonia vaccine to adults age 65 and older and children younger than age two, as well as others with certain medical conditions.

Although flu is not as contagious as SARS-CoV-2, social distancing and mask wearing still reduce flu transmission, as does frequent and meticulous hand hygiene. If people develop the symptoms common to flu and COVID (such as fever, cough, congestion and body aches), most clinics can run tests that look for COVID and flu at the same time. The main reason to test for flu is to treat it with antivirals and thereby reduce the risk of severe disease, hospitalization and death, Brammer says.

If nothing else, like the past two years, the 2021–2022 flu season will be a learning experience. “Just like COVID, nobody really knows what's going to happen next” because the past six months alone have been unprecedented, Belongia says. “It really has given us a lot of humility that, for all of our knowledge of immunology and virology, really nobody had a clue what was going to happen next.”

Penn Vet opens institute to study diseases spread from animals to humans [witf.org, 6 Dec 2021]

Saying that 75 percent of all newly emerging infectious diseases are zoonotic – meaning passed from animals to humans – the University of Pennsylvania School of Veterinary Medicine has established an Institute for Infectious and Zoonotic Diseases. Is Covid-19 one of them?

Many, and probably most researchers, believe the virus came from bats and that humans may have come into contact with infected bats at a wet market in Wuhan, China.

There are other examples of zoonotic diseases – Ebola, Zika, swine flu, avian flu and West Nile virus to name a few from last twenty years.

Appearing on Tuesday’s Smart Talk are Christopher Hunter, PhD, Mindy Halikman Heyer Distinguished Professor of Pathobiology; director, Institute for Infectious and Zoonotic Diseases and Dr. Lisa Murphy, DVM, associate professor of Toxicology; resident director of the Pennsylvania Animal Diagnostic Laboratory System at New Bolton Center (Kennett Square, PA); co-director, Wildlife Futures Program; and associate director, Institute for Infectious and Zoonotic Diseases.

2nd Swine Flu Case Confirmed [PrecisionVaccinations, 29 Nov 2021]

(Precision Vaccinations)
The U.S. CDC FLUView reported today a new human infection with a novel influenza A virus was reported by the state of Oklahoma. The infection occurred in an adult who was hospitalized for an unrelated illness and has since been discharged.

The patient had direct swine contact at home and an agricultural event. No ongoing human-to-human transmission has been identified associated with this case.

This is the second human infection with a novel influenza A virus during the 2021-22 influenza season.

The previous infection was an influenza A (H3N2) variant reported by Ohio that occurred in a child.

Influenza is a contagious respiratory illness caused by various influenza viruses such as the seasonal flu, avian influenza, swine influenza, and pandemic influenza.

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a “variant influenza virus,” says the CDC.

Most human infections with variant influenza viruses occur following proximity to swine, but human-to-human transmission can occur. It is important to note that variant influenza viruses have not shown the ability to spread quickly and sustainably from person to person in most cases.

During the 2020-21 influenza season, 14 human infections with novel influenza A viruses were reported in the U.S., including two H3N2v (I.A., WI), four H1N2v (I.A., IN, OH (2)), and eight H1N1v (IA (3), N.C., ND, WI (3)) virus infections.

Coimbatore reports two cases of H1N1 infections [DTNext, 25 Nov 2021]

Coimbatore, already battling to control COVID and dengue cases, is now faced with a fresh challenge—H1N1 virus

Coimbatore:
Two H1N1 infections were reported in the district on Monday, reportedly for the first time this year. The infected persons, women aged 63 and 68, are undergoing treatment in a private hospital and said to be recovering well.

Officials suspect that the spread could have originated from Kerala as a relative of one of the patients had visited her from the neighbouring state recently. The other patient has no recent travel history and the source of infection is yet to be ascertained. The infected women’s family members were tested but were negative for the flu.

Meanwhile, the Coimbatore Corporation advised the public to wear masks while going out to prevent the spread of the flu. “People should wash their hands frequently and approach the nearby Primary Health Centre (PHC) in case of any symptoms like fever, cough or headache,” said Corporation Commissioner Raja Gopal Sunkara.

As it is the rainy season, 64 medical camps are being conducted in the Corporation on a daily basis.

Influenza H1N1 alert issued following recent spike in cases in SA [The South African, 17 Nov 2021]

By Corné van Zyl

An increase in influenza H1N1 cases, or incorrectly referred to as “swine flu”, has been reported in five provinces.

WHAT DO WE KNOW ABOUT IT INFLUENZA H1N1?

In addition, private laboratories have reported an increase in influenza case detections, and the NICD has received reports of clusters of cases in schools and workplaces.

The NICD said influenza A(H3N2), influenza A(H1N1)pdm09, and influenza B are seasonal virus strains that are common in human populations.

“Influenza A(H3N2), influenza A(H1N1)pdm09 and influenza B are seasonal influenza virus strains that are common in human populations. Influenza A(H1N1)pdm09, which is sometimes incorrectly referred to as “swine flu”, has been one of the circulating seasonal influenza strains following its emergence in 2009,” NICD said.

It said the term “swine flu” should not be used as it causes unnecessary panic.

“The clinical course of infection with this influenza strain and clinical management is similar to that of other influenza strains,” it said.

The NICD said even though the detection rates for influenza in its surveillance programme exceeded previous seasonal thresholds, absolute numbers remained relatively low compared with previous years, possibly as a result of reduced health-seeking behaviour following the SARS-CoV-2 pandemic.

“Though most people with influenza will present with mild illness, influenza may cause severe illness which may require hospitalisation or cause death, especially in individuals who are at risk of severe influenza complications,” said Dr Sibongile Walaza, a medical epidemiologist at the Centre for Respiratory Diseases and Meningitis (CRDM) at the NICD.

WHO IS MOST AT RISK?

The NICD said groups at an increased risk of severe complications of influenza H1N1 include pregnant women, HIV-infected individuals, those with chronic illnesses or conditions such as diabetes, lung disease, tuberculosis, heart disease, renal disease, and obesity, those 65 years and older and children under the age of two years.

It cautioned that these groups should be encouraged to seek medical help early.

Prof Cheryl Cohen, Head of the CRDM said the increase in influenza in the summer, which is not the typical time for the influenza season, is likely the result of relaxation of non-pharmaceutical interventions to control COVID-19. Combined with an immunity gap due to influenza not circulating for two years (2020 and 2021) in South Africa

HOW TO PREVENT CONTRACTING OR SPREADING IT:
• avoid close contact with sick people,
• stay home when you are sick,
• cover your mouth and nose when coughing or sneezing,
• wear your mask, clean your hands regularly,
• avoid touching your mouth, eyes, and nose
• clean and disinfect common places.

SYMPTOMS OF INFLUENZA H1N1:
• The most common symptoms in infected patients are sudden onset of:
• fever,
• muscle pains and body aches,
• dry cough,
• sore throat,
• runny nose,
• feeling tired or unwell,
• and headache.

The symptoms develop anywhere from 1 to 4 days after infection and last for 2 to 7 days. For the majority of people, the symptoms commonly resolve without treatment.

Complicated influenza infections can cause serious illness and in some cases, death.

Severely ill patients with influenza should be admitted to the hospital. The commonest complication of influenza is pneumonia.

Swine Flu in the USA [PrecisionVaccinations, 6 Nov 2021]

By Karen McClorey Hackett & Holly Lutmer

(Precision Vaccinations)

The U.S. Centers for Disease Control and Prevention (CDC) confirmed on November 5, 2021, three human infections with novel influenza A viruses occurred during the 2020-21 influenza season.

However, no human-to-human transmission was associated with these 'swine flu' patients.
The CDC confirmed one human infection with novel influenza A(H1N2) variant (A(H1N2)v) in Indiana.

And two human infections with influenza A(H1N1)v were reported by Iowa.

All three patients were adults ≥ 18 years of age, were not hospitalized, and recovered from their illness.

Furthermore, these patients had attended an agricultural event where swine were present and/or visited a farm where swine were present.

During the 2020-21 influenza season, 14 human infections with novel influenza A viruses were reported in the United States, including two H3N2v (I.A., WI), four H1N2v (I.A., IN, OH (2)), and eight H1N1v (IA (3), N.C., ND, WI (3)) virus infections.

So far in the 2021-22 influenza season, one human infection with a novel influenza A virus (H3N2v) has been reported in Ohio.

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a "variant influenza virus."

Most human infections with variant influenza viruses occur following proximity to swine, but human-to-human transmission can occur.

It is important to note that in most cases, variant influenza viruses have not shown the ability to spread efficiently and sustainably from person to person.

Additional information on influenza in swine, variant influenza virus infection in humans, and strategies to interact safely with swine can be found at www.cdc.gov/flu/swineflu. Further details regarding human infections with novel influenza A viruses can be found at http://gis.cdc.gov/grasp/fluview/Novel_Influenza.html.

If needed, the U.S. FDA approved one vaccine against the 2009 H1N1 influenza virus for persons ten years of age and older. The successful 2009 vaccine rollout helped to end the H1N1 influenza pandemic in 2010.

A study published in 2017 found that adjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were effective in preventing this type of influenza. Overall, the vaccines were also effective against influenza-related hospitalization.

For both outcomes, adjuvanted vaccines were more effective in children than in adults.

For current, updated information on seasonal flu, including information about H1N1, see the CDC Seasonal Flu website.

Mumbai: Swine flu cases increase by 38.63% this year; 61 cases reported till October in 2021 [Free Press Journal, 2 Nov 2021]

By Swapnil Mishra

The cases related to the swine flu have increased by 38.63 per cent until October compared to last year. According to the data, there were 44 cases of H1N1 in 2020 which has now increased to 61 until October. Health officials said there is no doubt that cases of H1N1 and H3N2 have increased in the city. But experts have advised doctors to think of H1N1 if a patient doesn’t respond to Covid-19 treatment.

Senior doctors from civic-run hospitals said they have come across many patients exhibiting the symptoms and most of them are testing positive for influenza A. They said last year there were hardly any cases of swine flu or influenza.

Last month, a doctor from KEM Hospital said that seven to eight patients have shown symptoms of fever, cough and sore throat, similar to Covid-19. “If I test 10 people with these symptoms, the majority are turning positive for influenza and swine flu,” the doctor said.
Another doctor said there are cases of other viral infections and respiratory syncytial virus (RSV), too. “Doctors should keep this in mind, especially when a patient is not responding to Covid treatment,” he said.

Senior doctors from the civic-run hospitals said they have seen three cases of swine flu and two cases of H3N2, also a subtype of influenza A this year. Moreover, recently a patient who recovered from Covid-19 tested positive for H1N1.

“I have recently treated two patients who presented with cold, fever and headache. One of the patients, in his 30s, had recently recovered from Covid-19. Since it is rare for a patient to get a Covid-19 re-infection within 90 days, he was suggested to take an H1N1 test. The result of the test came positive,” said a doctor.

Infectious diseases expert Om Shrivastav said influenza A is the most dominant infection currently. “H1N1 and Covid-19 are from the same family. Rt-PCR cannot differentiate between any of them. Any diagnosis is based on clinical parameters and not lab testing,” he said.

Dr Pinak Pandya, Consultant, department of Critical Care Jaslok Hospital and Research Centre, said for the past two to four months there has been a rise in new variants of H1N1 in China.
As per researchers, the new variant is different and the disadvantage is that this new variant is initially mild and many remain asymptomatic so initial studies in pigs have shown that it doesn’t get detected until it has infected a majority of the herd.

“In Mumbai we have still not seen presentation of the new mutated variant of H1N1 in any patients but the overall swine flu cases have increased from the past one-and-a-half-year.
Importantly, care should be taken if anyone is showing respiratory symptoms , cough, breathlessness, joint pain, vomiting even if you tested negative for Covid19 and consult your physician immediately if symptoms persist,” he said.

Doctors urge people to get vaccinated against the flu [Live 5 News WCSC, 13 Oct 2021]

By Bill Sharpe

CHARLESTON, S.C. (WCSC) - There is good and bad news about the upcoming fall virus season. The number of COVID-19 cases is dropping nationwide, especially in South Carolina.

But doctors like Willie Underwood with the American Medical Association are worried the flu could be worse, and perhaps much worse, than last year.

He says that is partly because of the safety steps we took last year to prevent COVID-19, which worked to help stop the flu, as well.

Underwood listed some of the safety practices that worked, including social distancing, not interacting with others, wearing a mask, and children learning from home.

Dr. Leandris Liburd with the Centers for Disease Control and Prevention says it’s especially important for those in the Black and Hispanic communities to get flu shots because there is a historic pattern of fewer people in these two groups getting vaccinated.
She worries about underlying conditions like heart disease, lung disease, diabetes and other conditions that have compromised the immune system could make the flu worse or even deadly.

In the meantime, Underwood recommends getting a “twofer,” both a flu shot and COVID vaccine at the same time.

“So, if you’re getting one, get the other if you can, because we’ve tested it, they’ve looked at it and it’s extremely, extremely -- and I’m going to say it again -- extremely safe to do so,” Underwood says.

Liburd also says it’s really important for Black parents to make sure their kids get the flu shots because right now in the Black community, flu vaccine coverage is under 50 percent across the country.

New Coronavirus News from 7 Jan 2022

COVID-19 and Influenza Surveillance - Coronavirus [Virginia Department of Health, 7 Jan 2022]

How does COVID-19 relate to the flu?

People with COVID-19 and people with influenza (the flu) can have similar signs and symptoms or even none at all. Even though individual infections may look the same, there are some important differences between the two diseases.
• Both COVID-19 and flu can cause severe illness and even death, but a larger proportion of COVID-19 cases result in hospitalization or death.
• More severe outcomes of COVID-19 tend to increase with age, while negative outcomes for the flu affect the very young and the very old.
• The reproductive number, R0 (pronounced R naught), is a value that describes how contagious a disease is. For the flu, the R0 tends to be between 1 and 2, which means that for every person infected with the flu, they will infect one to two more people. For the original COVID-19 variant, the R0 is higher than the flu, between 2 and 3.
• Between July and December 2021, more than 97% of sequenced samples in Virginia have been identified as the Delta variant. Delta is more than twice as contagious as previous variants of COVID-19, with an R0 that is estimated to be between 5-7. To learn more about COVID-19 variants, visit the Variants web page.
• As of January 1 2022, the Omicron variant accounts for 95% of testing for variants of concern in the US according to the Centers for Disease Control and Prevention (CDC). A recent study estimated Omicron to be about 3 times as infectious as the Delta variant, and both variants are more contagious than previous variants.
• The incubation period, or the time between infection and when you have symptoms, and the length of illness are both shorter for the flu than they are for COVID-19.

It’s important for public health and healthcare providers to be able to tell the difference between the flu and COVID-19.

How does VDH track and measure COVID-19?
Surveillance is the practice of tracking and measuring the burden and trend of a disease’s impact on a community. VDH conducts surveillance for many diseases and conditions, but the specific methods can vary by disease or condition. For some diseases, including COVID-19, VDH conducts surveillance by counting every case and trying to measure the exact impact of the disease. The benefits of counting individual cases include:
• Identifying health behaviors and risk factors that may be associated with more severe illness. Interviewing individual people with COVID-19 allows us to do this. . For COVID-19, we’re asking questions about living conditions, symptoms, underlying health conditions, and travel history.
• Uncovering outbreaks. Interviewing people with COVID-19 also allows us to ask questions about exposure that may help uncover outbreaks. Asking each person about where they work or where they go to childcare or school may identify a cluster of illnesses that are connected.
This can help prevent more people from getting sick at those locations.

Helping public health prevent spread of COVID-19. Knowing who is sick with COVID-19 can help public health to contact them to give steps on how to isolate (stay home) to prevent further spread. It also allows public health to do contact tracing. Contact tracing notifies people of their exposure and provides quarantine (stay home) recommendations and support.
VDH is using the “Box It In” strategy to try and control the spread of COVID-19. This strategy is how countries like New Zealand, South Korea, and Singapore are able to control their outbreaks. This strategy requires that we count individual cases of COVID-19.

While there are benefits to counting individual cases, there are also challenges:
• The process of interviewing individual cases is very time-consuming for public health staff.
• The process of entering data for each case of a common disease can be time-consuming for healthcare providers.
• Individual case counts need a large data infrastructure for exchanging, storing, and processing a high volume of data very quickly. It also needs a large workforce to analyze the data and ensure data quality.

How does VDH track and measure the flu?
For some diseases, the benefits of counting individual cases outweigh the challenges. For others, they don’t. The flu is an example of a disease where VDH does not count individual cases. All the challenges above apply to flu surveillance as well as the others below:
• For people who do seek care, most are diagnosed with a rapid influenza diagnostic test (RIDT) or by their symptoms alone. Diagnosing flu like this works well in the clinical setting. It can provide access to antiviral medication that treats the flu. Unfortunately, neither RIDTs nor symptom-based diagnoses are consistent or detailed enough to meet the case classification. Because of this, public health cannot “count” the case.
• The confirmatory tests that are available (PCR, viral culture, and DFA [direct fluorescent antigen]) for the flu are more expensive and are not used for most cases. Counting cases based on these tests alone would introduce bias. This is because people who are wealthier, better insured, or sicker, or certain healthcare systems, may more often use these test types.

So instead of counting each case of flu, VDH uses other data sources to track each flu season.
These variables include:
• Influenza-like illness (ILI)
VDH receives data about every visit to an emergency department (ED) and a lot of visits to urgent care centers (UCCs) through its syndromic surveillance program. These data include some demographics and a chief complaint, or why the patient is seeking care. The chief complaint may include their specific symptoms, a specific disease, or a known exposure. VDH can track which of these visits meet the criteria of having an influenza-like illness (ILI). An ILI is a specific mention of flu, or as a fever with either a cough, a sore throat, or both.

This surveillance system is voluntary, and some healthcare systems have started participating in the last few years. Because more ED visits are being analyzed, VDH reports out the percentage of total ED and UCC visits that have an ILI .This data source is not a count of cases and not everyone who meets ILI criteria will have the flu. This source does provide a good estimation of the intensity and timing of the flu season.
• Confirmatory lab reports

As mentioned, some tests available for the flu are confirmatory tests. One of the major benefits to these test types is that they can provide more detailed information about what type of flu virus a person has. Knowing whether we’re experiencing a flu season with a certain type of flu can be important for identifying what communities are at highest risk for complications and negative outcomes. This information also helps us to evaluate the effectiveness of the vaccine each year.

This data source is not a count of cases. Instead, it’s intended to provide insight into which viruses are circulating at a given time.
• Outbreaks
Outbreaks of flu are common. VDH counts any cluster of illness with two or more lab-confirmed cases of flu as an outbreak. Reported outbreaks can be a good indicator of how much flu is spreading within a community.
• Geographic Spread

The geographic spread of the flu, sometimes called the activity level, calculates how many of the five health regions in Virginia are experiencing spread of the flu. This is a calculation based on ILI, confirmatory lab reports, and outbreaks. This isn’t a measure of intensity or severity.
Instead it answers a yes/no question of whether flu is circulating in a specific area of the state.
This can help make the data more local. Before the COVID-19 pandemic, some healthcare systems based their mask-wearing and visitation policies on the geographic spread of flu to avoid introduction of a deadly virus into communities at higher risk.
• Pneumonia and Influenza (P&I) Deaths
Patients who die from the flu most often die from a complication rather than from the infection itself. They could develop pneumonia, which is a bacterial co-infection. Or, their underlying conditions could get worse. Public health tracks deaths coded as pneumonia and/or influenza (flu) together to avoid underestimating deaths associated with the flu.
• Influenza-Associated Pediatric Mortality
Influenza-associated pediatric mortality is a flu-associated death of a child. It is a nationally notifiable condition. This means that VDH reports every case we receive to CDC. This data source helps to measure the severity specific to the younger population. While the numbers are usually small in most states, CDC analyzes data from around the country and reports on findings from these cases.

There are two conditions related to influenza where the benefits of counting individual cases outweigh the challenges. These are:
• Influenza-Associated Pediatric Mortality
It’s a tragedy when a child dies from a preventable disease. VDH counts individual cases of children who die from the flu. This helps to better define the risk factors and complications that result in this outcome. Since we started counting flu-associated deaths in children, there have been between one and six deaths each flu season.
• Novel Influenza A Infections
Flu viruses, especially flu A strains, are always changing or mutating. Human infections with novel (new) flu viruses can happen in three ways:
• spillover: where a sick animal infects a human,
• genetic drift:where small mutations in the viral genome result in a new virus, or
• genetic shift: (where two different flu viruses swap parts of their genomes to create something completely new).

All three of these instances can result in a new virus that the human population does not have any immunity to, potentially leading to a pandemic. The global community is very concerned about flu pandemics so we closely monitor for these situations, perform contact tracing, and investigate the circumstances. In the United States, there have been two cases of human infection with a novel flu A virus in the past two years. Neither of these occurred in Virginia and neither resulted in additional infections.

Both of these conditions are important, but relatively rare, so the time VDH spends investigating and counting these cases is worthwhile.

What does our data tell us about the 2021-2022 flu season so far?
For surveillance purposes, each flu season in the United States begins during week 40 and lasts until week 20 of the following year. For the 2021-2022 season this is October 9, 2021 to May 21, 2022. As of January 1, 2022, Virginia is at the ‘Widespread’ geographic activity level.

This means that there was elevated influenza activity in at least three out of five health regions in Virginia. All five regions are above ILI threshold, and six outbreaks have been identified to date. For the most up-to-date information, see the Weekly Influenza Activity Report.

Looking at the Southern Hemisphere’s previous flu season can help us know what to expect in the Northern Hemisphere for the upcoming flu season. This process does not allow us to predict the future, but it can provide context and clues. During the Southern Hemisphere’s 2021 winter, they observed almost no flu activity. You can see the World Health Organization’s data on flu surveillance.

There are a few factors that could contribute to seeing such low levels of flu activity:
• Lower attention or shifted priorities among healthcare providers. This could result in decreased testing and differences in coding behavior.
• Decreased public health capacity could result in delays in reporting data.
• Prevention measures put in place to stop the spread of COVID-19, such as physical distancing, mask wearing, hand hygiene, and staying home when sick, have also been effective in limiting the spread of flu..

Of these three possibilities, the third is the most likely to have a large impact, followed by the first. We know that the Southern Hemisphere did not test as many people for flu as they would have during a typical flu season. We also know that among those who were tested, a much smaller percentage were positive than we would have normally expected.

VDH will continue to track flu and publish the Weekly Influenza Activity Report throughout the 2021-2022 flu season.

As we face rising case counts of COVID-19 coming out of the holiday season, it’s very important to make sure there are hospital beds available for those who need them. This means taking all the recommended steps to protect ourselves and our families against COVID-19 and the flu:
• Get your flu vaccine and/or your COVID-19 vaccine (or booster) if you haven’t already done so! It’s not too late to vaccinate. Find a flu vaccine site near you. You can also find a COVID-19 vaccine near you.
• Wear a well-fitting mask. Limit close contact with others you do not live with, in both indoor and outdoor spaces.
• Practice good respiratory etiquette. Cough or sneeze away from other people into your elbow or a tissue.
• Practice good hand hygiene. Wash your hands with soap and water for 20 seconds. Use an alcohol-based hand sanitizer that contains at least 60% alcohol if soap and water aren’t available.
• Get tested if you have symptoms or think you’ve been exposed.
• Follow isolation recommendations if you test positive and quarantine recommendations if you’ve been exposed to someone who tested positive.