Virus World

As a new version of bird flu spread through North America this spring, scientists began finding the virus in red foxes, bobcats and other mammals.  Something was wrong with the foxes. That was what callers to the Dane County Humane Society in Wisconsin kept saying in April, as they reported fox kits, or young foxes, behaving in strange ways: shaking, seizing or struggling to stand. The kits, which were often lethargic and wandering by themselves, also seemed unusually easy to approach, showing little fear of humans. “We just kept getting calls,” said Erin Lemley, a wildlife veterinary technician at the humane society’s wildlife center. “And the foxes started coming in.” Some of the kits that were admitted for treatment were quiet and withdrawn, she said. Others stumbled around or had seizures, their heads ticcing, their eyes flicking rhythmically. After the staff ruled out rabies, low blood sugar and other potential causes, laboratory testing revealed a surprising culprit: a highly virulent strain of avian influenza. “It was not a fun surprise,” said Dr. Shawna Hawkins, a zoo and wildlife veterinarian at the University of Wisconsin-Madison.

A newly arrived bird flu is sweeping through wild bird populations in the United States, and that may mean trouble for poultry farmers who have been doing their best to control this flu outbreak in their flocks. Some 24 million poultry birds like chicken and turkeys have already been lost, either because they died from the virus or were killed to prevent its spread. But unlike a similar bird flu outbreak seven years ago, this one is unlikely to just burn itself out. That's because this particular flu virus seems capable of hanging around in populations of wild birds, which can pass the virus on to poultry farms. While chickens and turkeys with the virus quickly sicken and die, some waterfowl can remain healthy with the virus and carry it long distances. Scientists believe that wild migratory birds brought this virus to North America a few months ago. Since then, more than 40 wild bird species in more than 30 states have tested positive. This strain of bird flu virus has turned up in everything from crows to pelicans to bald eagles.  "It's somewhat surprising how widespread it is already in North America," says Jonathan Runstadler, an influenza researcher at Tufts University. "It's clearly able to persist and transmit from year to year in parts of Asia, Europe, Africa, and I don't think we should be surprised if that's going to be the case here." As the virus moves across the country, and potentially settles in for the long haul, it will encounter new animal species that could get infected. This pathogen will also get a chance to genetically mingle with the flu viruses that are already circulating in the U.S. "What that means for the virus in terms of how it evolves, how it changes, we just don't really know," says Richard Webby, a flu researcher at St. Jude Children's Research Hospital.

There has been only one known human case

So far, the risk to humans seems low. But since related bird flu viruses have repeatedly jumped into people in the past, public health experts are watching for any signs of genetic changes that could make the virus able to move into humans. "We're concerned with any avian influenza virus that's circulating in domestic poultry or wild birds," says Todd Davis, an expert on animal-to-human diseases at the Centers for Disease Control and Prevention (CDC). "Because humans have no prior immunity to these viruses typically, if they were to be infected and spread the virus to other humans, then we could have another pandemic virus on our hands." This virus doesn't have genetic features previously associated with related bird flus that have infected humans. And the only person known to have contracted this particular bird flu virus was an elderly person in the United Kingdom who lived in close quarters with ducks; while some of the ducks got sick and died, their owner never had any symptoms. The CDC has been monitoring the health of more than 500 people in 25 states who were exposed to infected birds, says Davis. Although a few dozen people did develop flu-like symptoms, all were tested and none were positive for this virus.

Raptors could be especially hard hit

Wildlife experts have long known that highly pathogenic bird flus like this one were circulating in Europe and Asia. And they have worried about the possible threat these viruses might pose to American birds. Then, in December of 2021, chickens and other fowl got sick and started dying on a farm on the island of Newfoundland, Canada. Tests showed this deadly bird flu virus had made it across the Atlantic. "The very first moment it got to North America, it was a heads up to us," says Bryan Richards, the emerging diseases coordinator at the U.S. Geological Survey's National Wildlife Health Center. In January, government officials announced its arrival in the U.S. after a wigeon duck in South Carolina tested positive. The last time a dangerous bird flu entered the country, Richards says, "the number of instances where we picked that particular virus up in wild birds was very, very limited." In contrast, this latest bird flu virus is being detected in sick and dying birds all over. "This outbreak in the wild bird population is a lot more extensive than we saw in 2014 and 2015," says David Stallknecht, an avian influenza researcher with the University of Georgia. "Just a lot more birds appear to be affected." Waterfowl, and raptors that eat their dead bodies, are bearing the brunt of it. In Florida, for example, more than 1,000 lesser scaup ducks have succumbed to the virus. In New Hampshire, about 50 Canada geese died in a single event. In the Great Plains states, wildlife experts have seen mass die-offs in snow geese. "In addition, there's a host of other species, including black vultures and bald eagles and some of the other scavenging species, that were likely infected by consuming the carcasses of those waterfowl," says Richards. It remains to be seen how much of a toll this virus will take on American bird species. In Israel, when this virus hit an area where about 40,000 common cranes had gathered for the winter, "they lost a reported 8,000 of these birds over the course of a couple weeks," says Richards. "So when you start thinking about losing 20% of a specific population of wild birds, that's a pretty substantial impact."

Poultry farmers cull their flocks

Chickens and turkeys raised by the poultry industry have suffered the most deaths, and farmers are bracing themselves for even more. The bird flu that struck in 2014 and 2015 resulted in the deaths of more than 50 million birds and cost the industry billions of dollars. Back then, the greatest number of cases occurred in the month of April. "So I think I am kind of holding my breath this month," says Denise Heard, director of research programs for the U.S. Poultry & Egg Association. The virus has a number of ways to get from wild birds into poultry, says Heard. Since the last outbreak, the industry has worked to educate farmers about how to protect their flocks. "Wild migratory waterfowl are always flying over the top and when they poop, that poop gets on the ground," she says, explaining that the virus can then get tracked into bird houses on boots or inadvertently moved from farm to farm on vehicles. Heard says there currently seems to be less spread of the virus from farm to farm than was seen during the last major outbreak. Instead, there are more isolated cases popping up, perhaps because wild birds are bringing the viruses to farms and backyard flocks. If this virus sticks around in wild bird populations — which some scientists think is likely — poultry farmers may need to just learn to live with this problem. "I hope that this is not the case. I hope that in the U.S. this infection will die off soon, and the virus will go away again like it did in 2014," says Ron Fouchier, a virologist at Erasmus Medical Center in the Netherlands. "But there's no guarantee for that, as we've seen in Europe now that this virus has remained present for several years in a row." Since December, farmers in Europe have had to cull more than 17 million birds. "So that's very similar to the situation in the U.S.," says Fouchier. "And we are seeing massive die-offs in wild birds."

In 2009, global health officials started tracking a new kind of flu. It appeared first in Mexico, in March, and quickly infected thousands. Influenza tends to kill the very young and the very old, but this flu was different. It seemed to be severely affecting otherwise healthy young adults. American epidemiologists soon learned of cases in California, Texas, and Kansas. By the end of April, the virus had reached a high school in Queens, where a few kids, returning from a trip to Mexico, had infected a third of the student body. The Mexican government closed its schools and banned large gatherings, and the U.S. considered doing the same. “It was a very scary situation,” Richard Besser, who was then the acting director of the Centers for Disease Control and Prevention, told me. Early estimates suggested that the “swine flu,” as the new strain became known, killed as many as fourteen per cent of those it infected—a case fatality rate more than two hundred times higher than typical seasonal flu. The virus soon spread to more than a hundred and fifty countries, and the Obama Administration considered delaying the start of school until after Thanksgiving, when a second wave could be under way. Manufacturers worried about vaccine supplies. Like most flu vaccines, the one for the swine flu was grown in chicken eggs. “Even if you yell at them, they don’t grow faster,” Tom Frieden, who replaced Besser as the director of the C.D.C., said, at a press conference.

In the end, the world got lucky. The early stats were misleading: although swine flu was extremely contagious, it wasn’t especially deadly. Sometimes the reverse is true. Avian flu, which spread across the world during the winter of 2005-06, is not particularly transmissible but is highly lethal, killing more than half of those it infects. Each flu virus has its own epidemiological profile, determined by its genetic makeup, and flu genes shift every year. Howard Markel, a physician and historian of epidemics who, in the early two-thousands, helped invent the concept of “flattening the curve,” compared influenza’s swappable genetic components to “two wheels of fortune.” A double whammy—ease of spread combined with lethality—could make covid-19, or even the 1918 flu, which killed between forty million and a hundred million people, look like a twenty-four-hour bug.

After the swine flu’s relatively harmless nature became apparent, many people asked if the alarm it provoked had been warranted. A Swiss survey found that trust in institutions had decreased. Some scientists and officials accused the World Health Organization of stirring up a “faked” pandemic to justify its budget. But most drew the opposite conclusion from the experience. Trying to prepare for a deadly flu pandemic had left them more alarmed. “There was just a sense of overwhelming relief,” Besser said. “If this had been like 1918, we sure weren’t ready.” In truth, we’re never fully ready for the flu. We know it’s coming, like the first fall leaf, and yet three times in the past century—in 1918, 1957, and 1968—it has flattened us, killing a million or more each time. Even in ordinary years, the disease infects a billion people around the world, killing hundreds of thousands; one study estimated that it costs the United States economy close to a hundred billion dollars annually. Our primary weapon against the virus, the flu vaccine, is woefully inadequate. Over the last decade and a half in the United States, flu vaccines have prevented illness only forty per cent of the time; in particularly bad years, when vaccines were less fine-tuned to the strains that were circulating, they were only ten-per-cent protective. Today, the coronavirus pandemic is rightfully the object of our most strenuous efforts. And yet, as the infectious-disease specialists David Morens, Jeffrey Taubenberger, and Anthony Fauci wrote, in a 2009 article in The New England Journal of Medicine, that “we are living in a pandemic era that began around 1918,” when the flu used shipping networks to traverse the world. Since the 1918 pandemic, this century-long, multi-wave pandemic has killed roughly the same number of people.....

Vaccine makers are betting that the mRNA technology powering two successful Covid vaccines will help curb the tragic global death toll from the flu.  As the world grapples with Covid-19, influenza isn’t getting much attention these days. But the flu’s global impact is staggering: three million to five million cases of severe illness every year, and up to 650,000 deaths. Every few decades, a new flu strain spills over from animals and leads to a pandemic. The deadly toll of influenza is all the more striking when you consider that we have had vaccines to fight it for eight decades. But they remain mediocre. A flu shot is good for only one flu season, and its effectiveness typically reaches somewhere between 40 and 60 percent. In some years it’s as low as 10 percent. But a new generation of highly effective flu vaccines may emerge in the next few years, based on the same mRNA technology that has protected hundreds of millions of people against Covid-19. While traditional influenza vaccines are grown for months in chicken eggs, mRNA vaccines are manufactured relatively quickly from scratch. In theory, their faster production may make them better matched to each season’s flu strains. And when they’re injected into people, they may provoke a stronger immune response than traditional flu vaccines do.

Two companies — Moderna, the Massachusetts biotech company that produced one of the authorized mRNA vaccines for Covid-19, and Sanofi, a French vaccine maker — began trials for mRNA flu vaccines this summer. Pfizer and BioNTech, the companies that produced the other mRNA Covid-19 vaccine, started their own flu trial last month. And Seqirus, a vaccine producer based in England, is planning to test another mRNA vaccine for the flu early next year.  No one can say for sure how well any of these four seasonal flu vaccines will turn out, but many experts are optimistic. And further down the line, mRNA technology may be tailored to make vaccines that work for years against a wide range of influenza strains. “I am beyond excited for the future of flu vaccination,” said Jenna Bartley, an immunologist at the University of Connecticut. No one can say for sure how well any of these four seasonal flu vaccines will turn out, but many experts are optimistic. And further down the line, mRNA technology may be tailored to make vaccines that work for years against a wide range of influenza strains. “I am beyond excited for the future of flu vaccination,” said Jenna Bartley, an immunologist at the University of Connecticut.

Covid suppression measures may have solved the headache of correctly formulating flu shots to match a winter's dominant influenza strain. In the eight years leading up to the Covid-19 pandemic, one of the subtypes of influenza A viruses started acting bizarrely. Flu viruses continuously evolve, to evade the immune defenses humans develop to fend them off. But after 2012, H3N2 started to behave differently.  It was almost as if there was a falling out within a family. The viruses formed into factions — clades, in virologists’ language — drifting further and further apart with each passing year and making the process of choosing the version of H3N2 to include in flu shots an increasingly challenging task. The greater the genetic distance between the clades, the bigger the cost of making the wrong choice. Vaccine that protects reasonably well against one might perform poorly if the other turned out to be the dominant strain in a given winter. In fact, that’s precisely what happened in the 2017-18 season, when the flu shot failed to protect three-quarters of vaccinated people in the U.S. against the H3N2 strain in circulation.  But an unexpected upside of the Covid-19 pandemic may have solved this problem for us — or at least made flu’s diversity more manageable. With Covid suppression measures like mask wearing, school closures, and travel restrictions driving flu transmission rates to historically low levels around the world, it appears that one of the H3N2 clades may have disappeared — gone extinct. The same phenomenon may also have occurred with one of the two lineages of influenza B viruses, known as B/Yamagata. Neither has been spotted in over a year. In fact, March of 2020 was the last time viral sequences from B/Yamagata or the H3N2 clade known as 3c3.A were uploaded into the international databases used to monitor flu virus evolution, Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle, told STAT.

If the global pool of flu viruses has truly shrunk to this degree, it would be a welcome outcome, flu experts say, making the twice-a-year selection of viruses to be included in flu vaccines for the Northern and Southern hemispheres much easier work.  “I think it has a decent chance that it’s gone. But the world’s a big place,” Bedford said of the H3N2 clade that may have disappeared. Florian Krammer, a flu expert at Mount Sinai School of Medicine in Manhattan, has been scouring genetic databases looking for B/Yamagata viruses. He’s hoping the viruses in this lineage are gone for good. “Just because nobody saw it doesn’t mean it has disappeared completely, right? But it could,” Krammer said. Flu is complex and a brief primer might be helpful here. There are two key families that cause human disease, influenza A and influenza B. Two subtypes of flu A viruses currently transmit among people, H1N1 and H3N2. Within those two subtypes are subclassifications or clades, with H3N2 viruses having more diversity than H1N1. Flu B doesn’t have subtypes, but its viruses divide into two “lineages”, B/Victoria and B/Yamagata. In the not-too-distant past only one of the B viruses was included in flu shots every year, but now most brands are quadrivalent — four-in-one shots that include one version each of the H1N1 and H3N2 viruses, and both flu B viruses. “We work so hard to get quadrivalent vaccines … and now, if really Yamagata has disappeared, then actually trivalent [vaccine] would be okay again,” said Ben Cowling, a flu expert at Hong Kong University. For the record, Cowling is among the skeptics when it comes to the question of whether B/Yamagata is actually gone.  So is Cécile Viboud, a flu epidemiologist at the National Institutes of Health’s Fogerty International Center.  “It’s hard to rule out,” Viboud said, adding these viruses could be circulating at low levels in places that didn’t use the types of non-pharmaceutical interventions like mask wearing and social distancing that other countries have employed to suppress Covid transmission. “The world is a very big place.”

The measures used to slow the spread of Covid-19 have had a dramatic impact on transmission of a number of respiratory viruses. Flu, respiratory syncytial virus — known as RSV — and many of the other bugs that afflict us during cold and flu season have been mercifully absent during the pandemic.  During a typical year, the genetic sequences of about 20,000 flu viruses are logged into GISAID, a repository used by researchers and public health officials to monitor the evolution of influenza and coronaviruses. But in the past year, only 200 were uploaded, Bedford said. Part of that is likely due to the fact that labs that do viral sequencing are prioritizing work on SARS-CoV-2, the virus that causes Covid. But a big factor here is that there is just a lot less flu transmission occurring, around the globe. That has led to a substantial winnowing of the pool of human flu viruses. “There had been maybe five-ish, six-ish [H3N2] clades circulating and now there’s two or three that made it through that bottleneck,” Bedford said. Though there’s been little flu illness globally, there are places that have seen outbreaks during the pandemic, he noted, saying China recorded flu B transmission — the Victoria lineage — and West Africa, Bangladesh, and Cambodia had H3N2 activity. Richard Webby, director of the World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds, cautioned that only a portion of flu viruses ever undergo genetic sequencing, so predictions about which flu viruses may have disappeared that are based on what’s in the databases risk being wrong.

But Webby does believe there has been a large reduction in the diversity of the circulating flu viruses, saying it will be interesting to see how that plays out in coming years. “Without doubt this is definitely going to change something in terms of the diversity of flu viruses out there. The extent to which it changes and how long it stays changed are the big question marks. But we have never seen this before,” said Webby, whose center is based at St. Jude Children’s Hospital in Memphis. His bet is that the B/Yamagata viruses aren’t gone, noting the flu B virus lineages sometimes go quiet for a while, only to reappear later. “But I do think we’re likely to lose a little bit of the H3N2 diversity. That’s a great thing.  Currently when we sit down to make recommendations for vaccine strains, it’s always the headache virus,” Webby said. “If we have to pick a [subtype] to lose diversity in, that would be the one.”

Scientific American is the essential guide to the most awe-inspiring advances in science and technology, explaining how they change our understanding of the world and shape our lives. Since the novel coronavirus began its global spread, influenza cases reported to the World Health Organization have dropped to minuscule levels. The reason, epidemiologists think, is that the public health measures taken to keep the coronavirus from spreading also stop the flu. Influenza viruses are transmitted in much the same way as SARS-CoV-2, but they are less effective at jumping from host to host. As Scientific American reported last fall, the drop-off in flu numbers was both swift and universal. Since then, cases have stayed remarkably low. “There’s just no flu circulating,” says Greg Poland, who has studied the disease at the Mayo Clinic for decades. The U.S. saw about 600 deaths from influenza during the 2020-2021 flu season. In comparison, the Centers for Disease Control and Prevention estimated there were roughly 22,000 deaths in the prior season and 34,000 two seasons ago.

Because each year’s flu vaccine is based on strains that have been circulating during the past year, it is unclear how next year’s vaccine will fare, should the typical patterns of the disease return. The WHO made its flu strain recommendations for vaccines in late February as usual, but they were based on far fewer cases than in a common year. At the same time, with fewer virus particles circulating in the world, there is less chance of an upcoming mutation, so it is possible the 2021–2022 vaccine will prove extra effective. Public health experts are grateful for the reprieve. Some are also worried about a lost immune response, however. If influenza subsides for several years, today’s toddlers could miss a chance to have an early-age response imprinted on their immune system. That could be good or bad, depending on what strains circulate during the rest of their life. For now, future flu transmission remains a roll of the dice....

Russia has registered the first case of a strain of bird flu virus named A(H5N8) being passed to humans from birds and has reported the matter to the World Health Organization (WHO), Anna Popova, head of consumer health watchdog Rospotrebnadzor, said on Saturday.  Outbreaks of the H5N8 strain have been reported in Russia, Europe, China, the Middle East and North Africa in recent months but so far only in poultry. Other strains - H5N1, H7N9 and H9N2 - have been known here) to spread to humans. Russia reported the case of human infection to the WHO “several days ago, just as we became absolutely certain of our results,” Popova said on Rossiya 24 state TV. There was no sign yet of transmission between humans, she added. Seven workers at a poultry plant in Russia’s south had been infected with the H5N8 strain in an outbreak at the plant in December, Popova said, adding that the individuals involved felt fine now. “This situation did not develop further,” she said.

In an email WHO’s European arm said it had been notified by Russia about a case of human infection with H5N8 and acknowledged this would if confirmed be the first time the strain had infected people. “Preliminary information indicates that the reported cases were workers exposed to bird flocks,” the email said. “They were asymptomatic and no onward human to human transmission was reported. “We are in discussion with national authorities to gather more information and assess the public health impact of this event,” the email added.  The majority of human bird flu infections have been associated with direct contact with infected live or dead poultry, though properly cooked food is considered to be safe. Bird flu outbreaks often prompt poultry plants to kill their birds to prevent the virus from spreading, and avoid importing countries having to impose trade restrictions. The vast majority of cases are spread by migrating wild birds, so producing countries tend to keep their poultry indoors or protected from contact with wildlife. Siberia’s Vector Institute said on Saturday it would start developing human tests and a vaccine against H5N8, RIA news agency reported.

The U.S. Food and Drug Administration (FDA) expanded the approved indication for Xofluza (baloxavir marboxil) to include post-exposure prevention of influenza (flu) for patients 12 years of age and older after contact with a person who has the flu, according to press releases Xofluza, previously available only in tablet form, is also now available as granules for mixing in water. Xofluza was originally approved in 2018 for treating uncomplicated flu in patients 12 years of age and older who have been symptomatic for no more than 48 hours. “This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” said Debra Birnkrant, MD, Director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research. “Americans will have to be more vigilant than ever as these viruses spread concurrently.”

In addition, Roche, the developer of the product, said it is determining a path forward with the FDA for a potential indication for Xofluza as a treatment for acute uncomplicated influenza in otherwise healthy children from one to 12 years of age and for the prevention of influenza in the same age group who have been exposed to influenza. Xofluza is currently not approved for use in this population, Roche said. Xofluza’s safety and efficacy for post-flu exposure prevention is supported by one randomized, double-blind, controlled trial in which 607 subjects, 12 years of age and older who were exposed to a person with influenza in their household, received either a single dose of Xofluza or a single dose of a placebo. Of these 607 subjects, 303 received Xofluza and 304 received the placebo. The trial’s primary endpoint was the proportion of subjects who were infected with influenza virus and presented with fever and at least one respiratory symptom from day one to day 10. Of those who received Xofluza, 1 percent of subjects met these criteria, compared to 13 percent of subjects who received a placebo for the clinical trial.

FDA Press Release (Nov, 23, 2020):

https://www.fda.gov/news-events/press-announcements/fda-expands-approval-influenza-treatment-post-exposure-prevention

Experts have warned that if Covid-19 cases remain high as flu season begins, the country could face a “twindemic,” with both viruses at high levels. A person has tested positive for both the flu and the coronavirus in Solano County, California, the county health department said. Such co-infection is so far rare and is the first such case to be reported in the county but not the country. At least two such cases have been reported, in Texas and Northern California. Experts have warned that if Covid-19 cases remain high as flu season begins, the U.S. could face a “twindemic,” with both viruses circulating at high levels.  Much of that concern has been focused on health care systems, which could be overwhelmed with a surge of both Covid-19 patients and flu patients. If both viruses begin circulating at high levels, it raises the risk of being infected with both at the same time.

“With the likelihood of both Covid-19 and seasonal flu activity this winter, contracting either disease may weaken your immune system and make you more susceptible to the other disease,” Dr. Bela T. Matyas, Solano County Health Officer, said Thursday in a statement. Little information was provided about the Solano County patient, except that the individual is under 65. The first confirmed case of community spread of Covid-19 in the United States was reported in the county in February.  In March, a Texas doctor reportedly fell ill with both viruses at the same time. And a research letter published in April in the Journal of the American Medical Association noted a case of flu-coronavirus co-infection in Northern California. It's not yet clear how common co-infections will be. "We very much hope that it will not be," Dr. Tara Bouton, an assistant professor of medicine at Boston University School of Medicine. Dr. Peter Chin-Hong, a professor of medicine and infectious disease specialist at the University of California, San Francisco, predicted it's only a matter of time before there are similar cases.

How common it will be "depends on what the flu season is going to look like," Chin-Hong said. “There's nothing that would preclude co-infection. It’s not like Covid comes in and takes out all the flu." It's also not yet clear if patients with co-infection of the flu and Covid-19 will fare worse, Bouton said. "However, there are a few preliminary studies suggesting that this may in fact be the case." That's "all the more reason why people need to do everything they can to prevent that scenario, including getting vaccinated against flu, wearing a mask when appropriate social distancing is not possible, and washing hands," she said.

As the Northern Hemisphere braces for a coronavirus-flu double hit, it’s unclear if it’ll be a deadly combo or one virus will squeeze out the other. The specter of a “twindemic” — two epidemics at the same time — looms as cold and flu season is set to start in October in the Northern Hemisphere. No one can predict what will happen when flu meets COVID-19, but public health officials are urging people to prepare for the worst. In this case, the worst would be a bad year for influenza, which in the United States has killed 12,000 to 61,000 people annually and hospitalized between 140,000 and 810,000 each year since 2010, combined with a resurgence of coronavirus infections. Together, the two could stress health care and public health systems beyond their limits. “We could see a perfect storm of accelerated COVID-19 activity as people gather more inside in particular, as they become increasingly fatigued with the mask wearing, social distancing and the hand hygiene, and as they are exposed to seasonal influenza,” said Jeanne Marrazzo, director of the infectious diseases division of the University of Alabama at Birmingham, during a news briefing from the Infectious Diseases Society of America, or IDSA, on September 10. Some states are getting coronavirus spread under control, but hospitalization levels haven’t gone down much, she said. “Overall, we still are on … a razor’s edge when it comes to COVID,” and influenza remains unpredictable. “We really can’t be complacent about this.”

Infectious diseases experts worry about a conjunction of influenza and coronavirus for multiple reasons, beyond overburdened health systems. Teasing out whether a person has flu or coronavirus — which have very similar symptoms — will require testing for both viruses, at a time when turnaround for COVID-19 tests is often slow. And some people may get infected with multiple viruses simultaneously, which could make symptoms more severe. But hints from the Southern Hemisphere give hope that the worst may not happen. Scientists usually forecast flu seasons’ severity in the north by watching what happens south of the equator, where flu season falls in the middle of the year. This year, the preview held good news: a mild season for flu and some other respiratory viruses. Countries in the Southern Hemisphere normally start seeing flu cases in May, and the flu season typically peaks in July and peters out around October. For the past five to six years, flu seasons in Australia have been bad. For instance, in 2019, Australia got an early flu season that started in March and “went on for a very long time,” says Kanta Subbarao, a virologist who directs the World Health Organization’s Collaborating Centre for Reference and Research on Influenza at the Doherty Institute in Melbourne, Australia. It wasn’t looking good for 2020 either. This year, flu season started even earlier, she says. “We started seeing some flu activity in January and February,” summer in the Southern Hemisphere. “Then it just completely stopped. It just fell off a cliff at the end of March, essentially when COVID-19 started appearing.”

From April through July, only 33 people had positive flu results in Australia out of 60,031 people tested, an international group of influenza researchers report September 18 in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention. The flu was also nearly nonexistent in South Africa and Chile in the late spring and early summer months. Together, the three countries recorded just 51 flu cases among 83,307 people tested, for a positivity rate of 0.06 percent. By contrast, over the April through July periods in 2017, 2018 and 2019, a total of 24,512 out of 178,690 people had positive flu tests, a positivity rate of 13.7 percent.  Travel restrictions that closed Australia’s borders may have prevented influenza from being imported from elsewhere. Lockdowns, school closures, mask wearing, social distancing and hand washing — all measures taken to prevent the spread of COVID-19 — may have also quashed any influenza outbreaks that remained. Other Southern Hemisphere countries have also reported unexpectedly low levels of influenza and another common respiratory virus called respiratory syncytial virus, or RSV, she says. Public health officials anticipated a resurgence of influenza and RSV once Australia reopened schools, but that hasn’t happened, Subbarao says. “We have looked very long and hard,” but have found very little of either disease, Subbarao says. Instead, “what we’re finding is rhinovirus,” which cause colds, Subbarao says, suggesting that rhinovirus hasn’t been phased by all the public health measures. Flu season may also be lighter than usual in the Northern Hemisphere as a result of reduced travel, former CDC director Tom Frieden said in an IDSA news briefing on September 15. Flu “gets around the world when people travel, and there’s not much traveling going on.” But COVID-19 remains a threat, he warned “If you doubted that COVID was more infectious than flu, look at South Africa or Chile, where COVID is spreading like wildfire and flu isn’t spreading at all.” In the United States during the 2019–2020 flu season, flu cases also took a nose dive after public health measures were put in place to limit coronavirus spread. Flu cases started increasing in November 2019, and between December 15 and March 7, more than 20 percent of flu tests were coming back positive each week, according to the MMWR report. By the week of March 22, plenty of people were still getting flu tests, but only 2.3 percent of the results came back positive. Many of those influenza-like illnesses that weren’t due to flu may have been COVID-19 (SN: 6/25/20).  Since the week of April 5, fewer than 1 percent of flu tests have detected the virus, and off-season flu counts are at historical lows. From May 17 to August 8, only 0.2 percent of flu tests gave positive results, compared with 2.35 percent last year, 1.04 percent in 2018 and 2.36 percent in 2017. The sharp drop-off of flu cases might just have been the natural end of the flu season. However, the decrease in percent positivity after March 1 “was dramatic, suggesting other factors were at play,” the researchers wrote...

Two recent studies were unable to rule out that H1N1 ("swine flu") vaccination ("Pandemrix") and seasonal influenza vaccination given to pregnant women might be associated with autism-spectrum disorder in the offspring. Now, a large study by researchers at Karolinska Institutet in Sweden, published in the journal Annals of Internal Medicine, refutes any such association.  Autism spectrum disorder is a severe neurodevelopmental childhood disorder characterized by impaired communication, lack of social skills and repetitive behavior. The disease has its onset in childhood.  While some studies indicate that influenza vaccination during pregnancy protects against morbidity in both the woman and her offspring, the long-term risks of H1N1 vaccination during fetal life have not been examined in detail. However two recent studies were unable to rule out that offspring to women undergoing influenza or H1N1 influenza vaccination during pregnancy, and especially during the first trimester, were at increased risk of autism-spectrum disorder.  Researchers from Karolinska Institutet, linked vaccination data in pregnant women from seven Swedish healthcare regions in 2009-2010 to the Swedish Medical Birth Register and the Swedish National Patient Register to identify autism-spectrum disorder in the offspring.

Of the 39,726 vaccine-exposed children, 394 (cumulative incidence, 1.0%) had a diagnosis of autism-spectrum disorder during the six-year follow-up compared with 330 (1.1%) among 29,293 unexposed children. Adjusting for potential confounders, H1N1 vaccine exposure during fetal life was not associated with a later childhood diagnosis of autism-spectrum disorder (adjusted hazard ratio=0.95; 95%CI=0.81-1.12). Results were similar for vaccinations in the first pregnancy trimester.  “Our null findings are important since some people have suspected that vaccinations could cause autism, and the anti-vaccine movement seems to be growing in the Western world,” says lead author, Professor Jonas F Ludvigsson, pediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “H1N1 vaccination has previously been linked to an increased risk of narcolepsy in young people, but vaccinating pregnant women does not seem to influence the risk of autism-spectrum disorder in the offspring,”  He continues: “Vaccination research has never been more important. Anticipating a vaccine against COVID-19, millions of pregnant women are likely to be offered such a vaccination. While our research group did not study COVID-19 vaccine effects, our research on H1N1 vaccination adds to the current knowledge about vaccines, pregnancy, and offspring disease in general.”

Original study in Annals Int. Medicine (Sept. 1 , 2020):

https://doi.org/10.7326/M20-0167 

Northern Hemisphere prepares for winter with little insight about how the new coronavirus and other respiratory viruses interact.  In March, as the Southern Hemisphere braced for winter flu season while fighting COVID-19, epidemiologist Cheryl Cohen and colleagues at South Africa’s National Institute for Communicable Diseases (NICD) set up a plan to learn from the double whammy. They hoped to study interactions between seasonal respiratory viruses and SARS-CoV-2, which causes COVID-19. Does infection with one change a person’s risk of catching the other? How do people fare when they have both?  But the flu season—and the answers—never came. NICD’s Centre for Respiratory Disease and Meningitis, which Cohen leads, has logged only a single flu case since the end of March. In previous years, the country’s surveillance platforms have documented, on average, about 700 cases during that period, Cohen says. “We’ve been doing flu surveillance since 1984, and it’s unprecedented.”

Some cases probably got overlooked as clinics temporary closed and people with mild symptoms avoided medical offices and clinics, Cohen says. “But I don’t believe it possible that we’ve entirely missed the flu season with all of our [surveillance] programs.” Apparently, travel restrictions, school closures, social distancing, and mask wearing have all but stopped flu from spreading in South Africa. Similar stories have emerged from Australia, New Zealand, and parts of South America. The Northern Hemisphere hopes to be so lucky. Few cases in the south might mean little infection spreading north, says Pasi Penttinen, head of the influenza and respiratory illness program at the European Centre for Disease Prevention and Control (ECDC). But if lockdowns and social distancing measures aren’t in place in October, November, and December, flu will spread much more readily than it has in the south, warns virologist John McCauley, director of the Worldwide Influenza Centre at the Francis Crick Institute. The prospect of a flu season during the coronavirus pandemic is chilling to health experts. Hospitals and clinics already under strain dread a pileup of new respiratory infections, including influenza and respiratory syncytial virus (RSV), another seasonal pathogen that can cause serious illness in young children and the elderly. In the United States, where some areas already face long waits for COVID-19 test results, the delays could grow as flu symptoms boost demand. “The need to try to rule out SARS-CoV-2 will be intense,” says Marc Lipsitch of the Harvard T.H. Chan School of Public Health. Because the Southern Hemisphere has largely been spared, researchers have little evidence about how COVID-19 might influence the course of a flu outbreak. One big concern is coinfection—people getting COVID-19 and flu at once, says Ian Barr, deputy director of the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne, Australia. “Two or three viruses infecting you are normally worse than one,” he says.

But the consequences of coinfections with SARS-CoV-2 haven’t been thoroughly studied. In April, a team at Stanford University found that among 116 people in Northern California who tested positive for the coronavirus in March, 24 also tested positive for at least one other respiratory pathogen, most often rhinoviruses and enteroviruses that cause cold symptoms, as well as RSV. Only one of the patients had influenza, although there likely wasn’t much flu circulating so late in the U.S. season, says Stanford pathologist Benjamin Pinsky, a co-author. The study didn’t find a difference in outcomes between COVID-19 patients with and without other infections. But it was too small to draw broad conclusions. To make things more complicated, having one virus can change a person’s chance of getting infected with another. Epidemiologist Sema Nickbakhsh and her team at the University of Glasgow have found both positive and negative relationships between different pairs of respiratory viruses, even after adjusting for confounding factors that would cause two viruses to show up concurrently or at separate times, such as their tendencies to wax and wane with the seasons. Coinfections with flu and other respiratory viruses are relatively rare, Nickbakhsh says, and the interactions her group has documented between flu and other viruses have suggested protective effects. For example, being infected with one type of flu virus, influenza A, seemed to reduce the chance of also having a rhinovirus, the researchers reported in 2019. (The mechanism behind this effect isn’t yet clear.) Nickbakhsh is more concerned about RSV, which her team found to have positive interactions with CoV-OC43, a coronavirus species of the same genus as SARS-CoV-2. It’s possible, she says, that having COVID-19 could increase a person’s susceptibility to RSV, or vice versa. Pinning down possible interactions between COVID-19 and other infections requires a large number of patient samples tested for SARS-CoV-2 and other respiratory viruses. Rapid, dual diagnostic tests will be important for both research and treatment decisions, says Benjamin Singer, a pulmonary and critical care physician at Northwestern University. The U.S. Food and Drug Administration has issued emergency use authorizations for flu–COVID-19 combination tests developed by Qiagen, BioFire Diagnostics, and the U.S. Centers for Disease Control and Prevention (CDC).

The CDC announced late Thursday that a person in Colorado has tested positive for an H5 bird flu virus — the first such recorded infection in the U.S.  The CDC did not reveal the neuraminidase subtype of the virus — the N portion of an influenza A virus’ name. The country is currently experiencing an unprecedented outbreak of H5N1 bird flu in both wild birds and in commercial poultry flocks. The man, described by Colorado health officials as being younger than 40 years old, experienced only fatigue; he is now in isolation and being treated with the flu antiviral oseltamivir. A statement from Colorado’s Department of Public Health and Environment said he is incarcerated at a state correctional facility and was culling poultry as part of a pre-release employment program. The CDC described the poultry outbreak as presumptively having been caused by H5N1. Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy, was less sanguine, saying that while previous experience with H5N1 viruses suggests that human infections didn’t lead to sustained person-to-person spread, heightened surveillance is important. “Any time you’re dealing with H5N1, you sleep with one eye open,” he told STAT.

H5 viruses have long struck fear among scientists who study bird flu because of the economic damage they can wreak and their propensity to occasionally infect people. They are one of two subtypes — H7 viruses are the other — that can become highly pathogenic. That term refers to their deadliness when they infect birds. In the mid-aughts, H5N1 viruses decimated poultry flocks first in Southeast Asia and later into South Asia and North Africa. H5 viruses have also been seen to infect people from time to time, often with devastating consequences. Of just over 860 previously recorded human cases of H5N1 infection — from 19 countries — just over half have died. For a number of years, it was feared the virus might cause a potentially devastating pandemic. But when the first pandemic in decades finally occurred in 2009, it was caused by a mild swine flu virus, H1N1.  The CDC’s statement suggested it isn’t completely clear the Colorado man was actually infected. The test may have picked up virus that was “surface contaminant” — presumably virus picked up by a nose swab — that was present because of the man’s involvement in culling infected poultry. But the CDC said the individual meets the criteria as a positive case and had to be treated as such. “The appropriate public health response at this time is to assume this is an infection and take actions to contain and treat,” the statement said. The CDC statement also pointed out that the group of H5N1 viruses that are currently spreading throughout the U.S. and Europe are different from the H5N1 viruses that caused the earlier outbreaks in Asia and North Africa. This is only the second human infection caused by this clade of H5N1 viruses; the first was a man in the United Kingdom who was infected last December. His flock of poultry contracted the virus and the man tested positive for the virus, although he reportedly didn’t experience symptoms of illness.

More than 20 states have reported avian influenza in commercial and backyard farms.  A growing epidemic of bird flu across the East Coast and Midwest has led to more than 20 million birds dying or being destroyed since February, fueling a surge in egg and poultry prices. After circulating for months in Asia and Europe, highly pathogenic avian influenza (HPAI) has been detected in commercial and backyard farms in more than 20 states, according to the US Department of Agriculture. Individual farmers have been forced to cull hundreds of thousands -- sometimes millions -- of birds to check the spread of the disease.  Shell egg prices have jumped to $2.88 a dozen (up more than 50%) since Feb. 8, when the first case was identified in a commercial turkey flock in Indiana. No humans have tested positive in the US yet, but the economic toll could be major: The first US epidemic in 2015 cost the poultry industry more than $1.5 billion and caused egg prices to nearly double. Here's what you need to know about bird flu, including what the outbreak means for consumers, how the industry is combating it and if it poses a threat to humans.

What is bird flu?

Bird flu is caused by avian influenza Type A viruses, which spread naturally among waterfowl and can infect wild birds, domestic poultry and other animals, though rarely humans. There are more than a dozen strains of bird flu, which are classified as either "low pathogenic" or "highly pathogenic," depending on their ability to spread disease and kill poultry.   The strain bombarding the US right now, Eurasian H5N1, is considered highly pathogenic.

How is bird flu transmitted?

The main source of infection is migratory waterfowl, such as ducks and geese. "They get infected but don't get sick," Denise Derrer, public information director for the Indiana State Board of Animal Health, told CNET. "Then they shed the virus in their droppings or wherever the land." That means the spread could peak in a few weeks, when spring migration reaches its high point, and not abate until June, when the birds settle into their summer breeding grounds. How the virus gets from barn to barn is still not entirely clear, which makes it hard to get a grip on the situation, according to Dr. Yuko Sato, a professor at Iowa State's school of veterinary medicine. "There's no concluded study on how it's coming in," Sato told NPR. "We can identify some weak links -- for example, people tracking it in." 

Where have bird flu outbreaks been detected?

The current strain of H5N1 was first reported in Asia and Europe. In the UK, eggs can no longer be labeled free-range because hens have been cooped up for months to avoid infection. Since the USDA confirmed the first US case in a wild duck in South Carolina in mid-January, infections have been reported in commercial farms and backyard flocks in Connecticut, Delaware, Illinois, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, North Carolina, North Dakota, New Hampshire, New York, Ohio, South Dakota, Wisconsin and Wyoming.  As a result, more than 20 million egg-laying hens, poultry chickens and turkeys have been or will soon be "depopulated," or killed, with more infections detected nearly every day. On March 31 alone, infections were detected in five states.

Among the worst outbreaks:

The vaccine was only about 16 percent effective at reducing a person’s chance of getting a mild or moderate infection, the agency said. Experts said a good rate would be at least 50 percent. This season’s flu vaccine has offered little to no protection against getting a mild or moderate case of influenza, the Centers for Disease Control and Prevention said this week.This season’s flu vaccine has offered little to no protection against getting a mild or moderate case of influenza, the Centers for Disease Control and Prevention said this week. In a study of more than 3,600 Americans in seven states, the C.D.C. said in a report that the vaccine was only around 16 percent effective, a rate that it said was “not statistically significant.” “It’s not ineffective, but it’s clearly suboptimal in its efficacy,” Dr. Jesse L. Goodman, a former chief scientist at the Food and Drug Administration, said on Thursday. He reviewed the report but was not associated with it. Still, despite the vaccine’s lackluster performance this season, which started in October and lasts through May, the C.D.C. suggested that people get inoculated, saying that it could “prevent serious outcomes.”

Scientists had warned in 2020 that the flu season, if it was severe, could possibly converge with Covid to create a dreaded “twindemic.” But coronavirus restrictions — including working from home and the use of masks — along with a high flu vaccine rate may have helped reduce caseloads the last few seasons, during which, the C.D.C. said, cases have been at a record low. Still, even a mild flu season can be devastating. The C.D.C. estimated that during the 2019-20 flu season, around 22,000 people in the country had died and 400,000 had been hospitalized. This season, the agency said, “influenza activity” declined in December and January, during the worst of the Omicron surge, but increased in early February. In October and November of 2021, the agency investigated a flu outbreak at the University of Michigan, where there were 745 cases, mostly involving students who had not been vaccinated against the flu. Investigators there also found that the vaccine did not offer much protection. Dr. Goodman said that this season’s results showed how much flu vaccines could be improved.

“The next pandemic could be an influenza pandemic,” Dr. Goodman said, “so we need better vaccines.” Every year, scientists decide whether they need to update the flu vaccine to protect against the strains that they predict will dominate the upcoming season. The low efficacy rate this season, Dr. Goodman said, “suggests that there was a mismatch between the strains of virus in the vaccine and what’s circulating.” Scientists updated this season’s vaccines to offer protection against four flu viruses, including H3N2, which ended up being this season’s dominant strain, the report said. H3N2 was also dominant during the 2017-18 flu season, which experts had said was “moderately severe.” Since the agency began calculating the vaccine’s effectiveness in 2004, the efficacy rate has been as high as 60 percent — for the 2010-11 season — and as low as 10 percent, during the first season the C.D.C. tracked it. Dr. Goodman said he would consider a rate between 50 and 80 percent to be good. The flu is a life-threatening respiratory illness that can fill up hospital beds. It shares symptoms with Covid, including fever, coughing, a sore throat and fatigue. Adults 65 and older, those who are pregnant or immunocompromised and children under 5 are most at risk of the flu.

CDC report (March 11, 2022) available at:

https://www.cdc.gov/mmwr/volumes/71/wr/mm7110a1.htm 

An influenza pandemic like the pandemic of 1918 could be even worse than Covid-19 has been, and the world is not ready to deal with it, the National Academy of Medicine said in a series of reports released Wednesday. Work needs to begin now to start developing next-generation vaccines, and to build up capacity in low- and middle-income countries so they can make their own vaccines without relying on wealthy nations to make them available, the reports recommended. And governments need to figure out how to make sure companies have the incentives to work on these vaccines without knowing whether they'll ever be used or needed.  Covid-19 has been terrible, the Academy, an independent body that advises the US federal government on matters of medicine and health, said in the first of the the reports. "Yet, from an epidemiological perspective, COVID-19 does not represent a 'worst-case' pandemic scenario, such as the 1918-19 influenza, which resulted in at least 50 million deaths worldwide," the report reads.  Flu kills anywhere between 290,000 and 650,000 people a year in a normal year, according to WHO. Covid-19 has killed 5.1 millon people globally. The next influenza pandemic could kill 33 million people, the Academy said.

More than 1,900 people are dying in the US daily on average – the highest level since early March. Covid-19 has now killed as many Americans as the 1918-19 flu pandemic, with more than 675,000 reported deaths. The US population a century ago was just a third of what it is today, meaning the flu cut a much bigger, more lethal swath through the country. But the Covid-19 crisis is by any measure a colossal tragedy in its own right, especially given major advances in scientific knowledge and the failure to take maximum advantage of vaccines. Unlike a century ago, vaccines have been made widely available. However, an extensive reticence to be inoculated, fueled in part by baseless fears about safety and efficacy, means that 36% of people in the US aged 12 and over have yet to be fully vaccinated, according to data from the federal Centers for Disease Control and Prevention (CDC).  “Big pockets of American society – and, worse, their leaders – have thrown this away,” said Dr Howard Markel a medical historian at the University of Michigan.

The White House initially forecast 100,000 to 240,000 deaths from Covid-19, if people socially distanced. Donald Trump, who erroneously predicted the coronavirus would simply vanish, oversaw the lower end of this forecast being reached in May last year, the latter death toll arriving in November. A surge in deaths in the spring of 2020 was surpassed by a larger wave of deaths over winter, with a record 4,197 people dying on a single day, 13 January, according to Johns Hopkins University. Since Joe Biden became president, the rollout of vaccines has helped push the rate of deaths down, although it started climbing again in August due to the spread of the Delta variant. The true death toll may be much higher than the official total because, like the previous pandemic, it is estimated. Also similar to the 1918-19 flu, the coronavirus may never entirely disappear. Scientists hope it will become a mild seasonal bug as human immunity strengthens through vaccination and repeated infection.  “We hope it will be like getting a cold, but there’s no guarantee,” said Rustom Antia, a biologist at Emory University, suggesting an optimistic scenario in which this could happen over a few years. For now, the pandemic still has the US and other parts of the world firmly in its jaws. While the Delta variant-fueled surge in infections may have peaked, US deaths are more than 1,900 a day on average – the highest level since early March – and the overall toll topped 675,000 on Monday, according to the count kept by Johns Hopkins.

Winter may bring a new surge, with the University of Washington’s influential model projecting an additional 100,000 or so Covid-19 deaths by 1 January, which would bring the overall US toll to 776,000.  The 1918-19 influenza pandemic killed 50 million globally, at a time when the world had a quarter the population it does now. Global deaths from Covid-19 stand at more than 4.6 million. The 1918-19 flu’s US death toll is a rough guess, given incomplete records of the era and the poor scientific understanding of what caused the illness. The 675,000 figure comes from the CDC. Before Covid-19, the 1918-19 flu was universally considered the worst pandemic in history. Whether the current scourge ultimately proves deadlier is unclear.  In many ways, the 1918-19 flu – which was wrongly named Spanish flu because it first received widespread news coverage in Spain – was worse. Spread by the mobility of the first world war, it killed young, healthy adults in vast numbers. No vaccine existed and there were no antibiotics to treat secondary infections.  Jet travel and mass migrations threaten to increase the toll of the current pandemic. Much of the world is unvaccinated. And the coronavirus has been full of surprises. Just under 64% of the US population has received as least one dose of the vaccine, with state rates ranging from a high of approximately 77% in Vermont and Massachusetts to lows around 46% to 49% in Idaho, Wyoming, West Virginia and Mississippi. Globally, about 43% of the population has received at least one dose, according to Our World in Data, with some African countries just beginning to give their first shots. “We know that all pandemics come to an end,” said Dr Jeremy Brown, director of emergency care research at the National Institutes of Health, who wrote a book on influenza. “They can do terrible things while they’re raging.” Covid-19 could have been far less lethal in the US if more people had gotten vaccinated faster, “and we still have an opportunity to turn it around”, Brown said. “We often lose sight of how lucky we are to take these things for granted.”

The emergence and global spread of the highly pathogenic H5N8 avian influenza virus (AIV), a pathogen that has caused continuous and ongoing outbreaks with massive mortality in both wild and farmed birds across Eurasia and Africa throughout 2020, represents a considerable public health concern — particularly considering the first human cases of H5N8 infection were first reported last December. In a Perspective, Weifeng Shi and George Gao discuss the emergence and zoonotic potential of the H5 AIV lineages. Shi and Gao argue that vigilant surveillance and rigorous infection control measures for these emerging viruses are critical to avoid further human spillovers that could result in new and devastating pandemics.

Perhaps overshadowed by the ongoing global COVID-19 pandemic, over the past year, H5N8 infections in both wildfowl and poultry have been identified in at least 46 countries across Europe, Asia, and Africa. While these outbreaks have led to the death or slaughter of many millions of birds worldwide, they’ve also notably resulted in at least one spillover event in Russia, where seven poultry farm workers tested positive for H5N8 virus. According to the authors, the rapid global spread of this AIV and its demonstrated ability to cross the species barrier, transmitting to humans, makes it a major concern to not only farming and wildlife security, but also global public health. Shi and Gao suggest that the surveillance of highly pathogenic AIVs in poultry farms, live markets, and wild birds must become a global priority.

Cited publication available in Science (May 21, 2021):

https://doi.org/10.1126/science.abg6302

An international team of researchers has found that three commonly used antiviral and antimalarial drugs are effective in vitro at preventing replication of SARS-CoV-2, the virus that causes COVID-19. The work also underscores the necessity of testing compounds against multiple cell lines to rule out false negative results.  The team, which included researchers from North Carolina State University and Collaborations Pharmaceuticals, looked at three antiviral drugs that have proven effective against Ebola and the Marburg virus: tilorone, quinacrine and pyronaridine. "We were looking for compounds that could block the entry of the virus into the cell," says Ana Puhl, senior scientist at Collaborations Pharmaceuticals and co-corresponding author of the research. "We chose these compounds because we know that other antivirals which successfully act against Ebola are also effective inhibitors of SARS-CoV-2."

The compounds were tested in vitro against SARS-CoV-2, as well as against a common cold virus (HCoV 229E) and murine hepatitis virus (MHV). Researchers utilized a variety of cell lines that represented potential targets for SARS-CoV-2 infection in the human body. They infected the cell lines with the different viruses and then looked at how well the compounds prevented viral replication in the cells. The results were mixed, with the compounds' effectiveness depending upon whether they were used in human-derived cell lines versus monkey-derived cell lines, known as Vero cell lines. In the human-derived cell lines, we found that all three compounds worked similarly to remdesivir, which is currently being used to treat COVID-19," says Frank Scholle, associate professor of biology at NC State and co-author of the research. "However, they were not at all effective in the Vero cells." "Researchers saw similar results when these compounds were initially tested against Ebola," says Sean Ekins, CEO of Collaborations Pharmaceuticals and co-corresponding author of the research. "They were effective in human-derived cell lines, but not in Vero cells. This is important because Vero cells are one of the standard models used in this type of testing. In other words, different cells lines may have differing responses to a compound. It points to the necessity of testing compounds in many different cell lines to rule out false negatives."

Next steps for the research include testing the compounds' effectiveness in a mouse model and further work on understanding how they inhibit viral replication. "One of the more interesting findings here is that these compounds don't just prevent the virus from potentially binding to the cells, but that they may also inhibit viral activity because these compounds are acting on the lysosomes," Puhl says. "Lysosomes, which are important for normal cell function, are hijacked by the virus for entry and exit out of the cell. So, if that mechanism is disrupted, it cannot infect other cells." "It's also interesting that these compounds are effective not just against SARS-CoV-2, but against related coronaviruses," Scholle says. "It could give us a head start on therapies as new coronaviruses emerge."

Published  in ACS Omega (March 10, 2021):

Vaccine aims to elicit broadly protective antibodies against the “stalk” of a surface protein on influenza viruses. For epidemiologists, the COVID-19 pandemic has greatly intensified their long-standing nightmare about another virus: the emergence of a new and deadly strain of flu. A universal flu vaccine, effective against any strain of the influenza virus that can infect humans, could protect us from this peril, but progress has been slow. A novel concept for one universal vaccine candidate has now passed its first test in a small clinical trial, its developers report today in Nature Medicine.  “This is an important paper,” says Aubree Gordon, an epidemiologist at the University of Michigan School of Public Health who studies influenza transmission and vaccines. The influenza virus rapidly accumulates mutations and easily “reassorts,” or swaps, genes between strains, creating variants that can dodge any past immunity people had acquired naturally or from vaccines. That’s why a new flu vaccine must be developed each year.

Existing flu vaccines contain weakened or inactivated influenza viruses with a mix of hemagglutinins (HAs), the proteins that stud their surfaces. These vaccines primarily aim to trigger antibody responses against HA’s top part, or head. Genetic changes in flu viruses rarely alter most of the head. But a small part of the head does reassort, or mutate, frequently, which allows new viral strains to dodge any immune memory and forces flu vaccinemakers to prepare new formulations each year, with updated HAs. HA’s bottom portion, or stalk, is less apt to vary, and epidemiological studies have shown people who have been exposed to an influenza strain and developed antibodies to the stalk can ward off a wide variety of other strains. So, the new universal flu vaccine candidate, one of a handful in development, puts HA’s stalk front and center. The study shows for the first time that “you can develop a vaccine strategy that produces stalk-reactive antibodies in humans,” says virologist Florian Krammer of the Icahn School of Medicine at Mount Sinai, who co-leads a multi-institutional universal flu vaccines consortium funded by the U.S. National Institute of Allergy and Infectious Diseases and helped develop the candidate tested in the new trial. Other clinical trials testing stalk-based universal flu vaccine candidates have yet to report data. Targeting the stalk is harder than it sounds, because immune memory cells built up over a lifetime of flu infections react so strongly to the conserved region of HA’s head that this response overrides production of antibodies against the stalk. Some researchers have tried to make flu vaccines that only contain HA’s stalk, but this fragment is highly unstable. To get around this problem, Krammer and colleagues made what they call chimeric HAs, which link the protein’s conserved stalk to unusual heads that are entirely new to the human immune system and don’t trigger a person’s immune memory. Only low levels of head antibodies are produced, allowing a strong new immune response to stalk to dominate. In essence, the head of the chimera is only there to stabilize the stalk.

Influenza vaccines contain three to four strains of the virus that are classified as group A, which breaks into two other divisions, and group B strains. The researchers developed vaccines made from live, weakened versions of influenza viruses or inactivated viruses bearing chimeric HAs representing only one division of group A. In the trial, 51 participants received the various vaccines and their antibodies were compared with those of 15 people who received placebos. A single shot of vaccine with chimeric HA inactivated viruses, the researchers report, “induced remarkably high antistalk antibody titers.” The trial was only a phase I study to establish safety and measure immune responses, which means it didn’t test the ability of the vaccines to protect people from influenza. Still, when the researchers transferred human antibodies triggered by the experimental vaccines into mice and then “challenged” the rodents with the influenza virus, the mice lost far less weight than untreated mice who also were infected, suggesting the antibodies protected them. Immunologist James Crowe, who runs the vaccine center at Vanderbilt University, says the study is “a serious effort” to test the stalk antibody hypothesis and “an important first step.”  Krammer says it will likely take at least 2 years to develop chimeric HAs representing enough other strains from influenza groups A and B to be combined into a universal vaccine. That mix would then be tested in a large-scale, multiyear study designed to show that the vaccine candidate works better than the seasonal vaccine. The seasonal vaccine works fairly well in years when its HA closely matches the variants in circulation, so the chimeric HAs would only show their true power during one of the rarer years when there’s a mismatch. This “long development path,” Krammer suspects, is the main reason his team lost an initial corporate partner, GlaxoSmithKline, which has another universal flu vaccine in clinical trials. “It’s difficult to get to get a lot of interest for something like this,” Krammer says.

Cited Research Published in Nat. Medicine (Dec. 7, 2020):

https://doi.org/10.1038/s41591-020-1118-7

(HealthDay)—Influenza vaccination may have a protective effect for COVID-19-positive patients, according to a brief report recently published in the Journal of the American Board of Family Medicine. Ming-Jim Yang, M.D., from the University of Florida in Gainesville, and colleagues conducted a retrospective review involving 2,005 patients older than 18 years of age who tested positive for COVID-19. Influenza vaccination status and comorbidities were examined. Severity of disease as reflected by hospitalization and intensive care unit (ICU) admission was examined as the primary outcome. The association between influenza vaccination status and hospitalization was examined. The researchers found that compared with those who were vaccinated, COVID-19-positive patients who had not received the influenza vaccine within the last year had 2.44- and 3.29-fold increased odds of hospitalization and ICU admission, respectively. The results were adjusted for age, race, gender, hypertension, diabetes, chronic obstructive pulmonary disease, obesity, coronary artery disease, and congestive heart failure. "One of the biggest problems we have with any preventive measure is getting people to do it," a coauthor said in a statement. "So, maybe this would be a pretty good push for people to go out and get their flu shot."

Study published in JABFM:

https://www.jabfm.org/sites/default/files/COVID_20-0528.pdf

A new Cleveland Clinic study has found that receiving the influenza vaccine does not increase a person's risk for contracting COVID-19 or worsen associated morbidity or mortality. Published in the Journal of Clinical and Translational Science, the study shows the flu vaccine is the single most important intervention to help stay healthy this fall and winter. Seasonal flu activity is unpredictable, and otherwise healthy people are hospitalized due to serious respiratory infection each year. This year, it's even more important to receive the flu vaccination to help prevent a twindemic of flu and COVID-19. In this new study, a team of researchers led by Joe Zein, M.D. - a pulmonologist at Cleveland Clinic—analyzed more than 13,000 patients tested for COVID-19 at Cleveland Clinic between early March and mid-April of this year. Comparing those who had received unadjuvanted influenza vaccines in the fall or winter of 2019 (4,138 patients) against those who did not received the vaccine (9,082 patients) revealed that influenza vaccination was not associated with increased COVID-19 incidence or disease severity, including risk for hospitalization, admission to the intensive care unit or mortality. "Our findings suggest that we should proceed as usual with our vaccination strategy for global influenza this flu season," said Dr. Zein. "Getting the annual flu vaccine remains the best safeguard against the influenza virus—both for yourself and the people around you."

Since much is still unknown about the possible outcomes of concurrent SARS-CoV-2 (the virus that causes COVID-19) and influenza infection—including disease pathology and burden to the healthcare system—researchers and clinicians believe that the population's adherence to widespread and early flu vaccination while researchers continue to collect data will help to mitigate the risk of simultaneous viral infections and epidemics/pandemics. "We have already seen the stress that COVID-19 can put on our hospitals and resources," said Dr. Zein. "While we're not yet sure how flu season will affect COVID-19 susceptibility and infections, we strongly advise people to get their influenza vaccines, both for their individual health and the collective health of our care systems." This study is the latest to utilize data from patients enrolled in Cleveland Clinic's COVID-19 Registry, which includes all individuals tested at Cleveland Clinic for the disease, not just those that test positive. Cleveland Clinic was one of the first organizations to develop a data registry and biobank for the emergent disease. Data from the registry has already been used in several landmark COVID-19 studies, including those that have led to the development of models that can predict a patient's likelihood of testing positive for COVID-19 and being hospitalized due to the disease.

Original study published in J. Clin. and Translational Science (Sept. 17, 2020):

 https://doi.org/10.1017/cts.2020.543

As the flu season approaches, a strained public health system may have a surprising ally — the common cold virus.Rhinovirus, the most frequent cause of common colds, can prevent the flu virus from infecting airways by jumpstarting the body’s antiviral defenses, Yale researchers report today (September 4, 2020) in the journal The Lancet Microbe. The findings help answer a mystery surrounding the 2009 H1N1 swine flu pandemic: An expected surge in swine flu cases never materialized in Europe during the fall, a period when the common cold becomes widespread. A Yale team led by Dr. Ellen Foxman studied three years of clinical data from more than 13,000 patients seen at Yale New Haven Hospital with symptoms of respiratory infection. The researchers found that even during months when both viruses were active, if the common cold virus was present, the flu virus was not. “When we looked at the data, it became clear that very few people had both viruses at the same time,” said Foxman, assistant professor of laboratory medicine and immunobiology and senior author of the study. Foxman stressed that scientists do not know whether the annual seasonal spread of the common cold virus will have a similar impact on infection rates of those exposed to the coronavirus that causes COVID-19. “It is impossible to predict how two viruses will interact without doing the research,” she said.

To test how the rhinovirus and the influenza virus interact, Foxman’s lab created human airway tissue from stem cells that give rise to epithelial cells, which line the airways of the lung and are a chief target of respiratory viruses. They found that after the tissue had been exposed to rhinovirus, the influenza virus was unable to infect the tissue. “The antiviral defenses were already turned on before the flu virus arrived,” she said. The presence of rhinovirus triggered production of the antiviral agent interferon, which is part of the early immune system response to invasion of pathogens, Foxman said. “The effect lasted for at least five days,” she said. Foxman said her lab has begun to study whether introduction of the cold virus before infection by the COVID-19 virus offers a similar type of protection.

Published in the Lancet Microbe (Sept. 4, 2020):

https://doi.org/10.1016/S2666-5247(20)30114-2

The results of 3 new studies reveal unknown ways until now that COVID-19 spreads, leading scientists to urge the use of face coverings in public. Research from various parts of the world considered three separate factors in each study: low humidity, public restrooms and airborne dust. The implications from all three of these studies? Mask up!

Low Humidity

A study just published in Transboundary and Emerging Diseases confirms an earlier study conducted in the Greater Sydney, Australia area during the early stages of the pandemic that reported a link between low humidity and community spread of COVID-19. The new research led by Dr. Michael Ward in the Sydney School of Veterinary Science adds to the growing body of evidence that low humidity is a key factor in the spread of the Coronavirus. The scientists estimated that for a 1% decrease in relative humidity, COVID-19 cases increase by 7 to 8%. The same link was not found in other weather patterns such as rainfall, temperature or wind. According to Ward, dry air favors the spread of the virus: “”When the humidity is lower, the air is drier and it makes the aerosols smaller,” he said, adding that aerosols are smaller than droplets. “When you sneeze and cough those smaller infectious aerosols can stay suspended in the air for longer. That increases the exposure for other people. When the air is humid and the aerosols are larger and heavier, they fall and hit surfaces quicker.” These findings add to a growing body of research that recommends wearing a mask.

Public Restrooms

A second study conducted by Chinese researchers from Yangzhou University reported that flushing a public restroom toilet or urinal can release clouds of virus-laden aerosols that can be inhaled, posing a serious public health challenge. The scientists simulated and tracked virus-laden particle movements when toilets and urinals were flushed. They discovered that flushing involves an interaction between gas and liquid, resulting in a large spread of aerosol particles. The disturbing results revealed that the trajectory of the particles ejected from flushing showed that more than 57% of the particles traveled away from the urinal. The researchers further point out that when men use urinals in a public restroom, these tiny particles can reach their thigh within 5.5 seconds when compared to the toilet flush, which takes 35 seconds to reach slightly higher. “From our work, it can be inferred that urnial flushing indeed promotes the spread of bacteria and viruses,” said Xiang-Dong Liu, one of the study’s authors. “Wearing a mask should be mandatory within public restrooms during the pandemic, and anti-diffusion improvements are urgently needed to prevent the spread of COVID-19.”

Airborne Dust

A third study from the University of California, Davis and the Icahn School of Medicine at Mt. Sinai reported that influenza viruses can spread through the air on dust, fibers and other microscopic particles. Until now, scientists assumed airborne transmission occurred mainly due to respiratory droplets by coughing, sneezing or talking. The scientists examined whether tiny, non-respiratory particles could carry influenza between guinea pigs. Using an automated particle sizer to count airborne particles, they found that uninfected guinea pigs give off spikes of up to 1,000 particles per second as they move around the cage. Particles given off by the animals’ breathing were at a constant but lower rate. Immune guinea pigs with influenza virus painted on their fur could transmit the virus through the air to other, susceptible guinea pigs, showing that the virus did not have to come directly from the respiratory tract to be infectious. Next the researchers tested whether microscopic fibers from an inanimate object could carry infectious viruses. They treated paper facial tissues with influenza virus, let them dry out and then crumpled them in front of the automated particle sizer. Crumpling the tissues released up to 900 particles per second in a size range that could be inhaled. They were also able to infect cells from these particles released from the virus-contaminated paper tissues. According to the researchers, the surprising findings that dust can spread viruses have obvious implications for Coronavirus transmission and use of masks for protection. Plus, they said, it opens up an entire new field of investigation on how outbreaks are interpreted.

Original studies available in these sites:

https://doi.org/10.1063/5.0021450

https://doi.org/10.1038/s41467-020-17888-w

https://doi.org/10.1111/tbed.13766