Threefold threat. tripledemia. A viral perfect storm. These scary phrases have dominated recent headlines, as some health officials, doctors, and scientists predicted that SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) could emerge at the same time in parts of the northern hemisphere that have relaxed the use of masks and social distancing. and other COVID-19 precautions.
But a growing body of laboratory and epidemiological evidence offers some reassurance: SARS-CoV-2 and other respiratory viruses often “interfere” with each other. Although the surges of each virus can stress emergency rooms and intensive care units, the small cabal of researchers studying these viral collisions say there’s little chance the trio will peak and collectively shut down hospital systems as they did. did COVID-19 at the beginning of the pandemic.
“Influenza and other respiratory viruses and SARS-CoV-2 just don’t get along very well together,” says virologist Richard Webby, an influenza researcher at St. Jude Children’s Research Hospital. “It is unlikely that they would circulate widely at the same time.”
“One virus tends to intimidate others,” adds epidemiologist Ben Cowling of the University of Hong Kong School of Public Health. During the rise of the highly transmissible Omicron variant of SARS-CoV-2 in Hong Kong in March, Cowling found that other respiratory viruses “disappeared…and came back in April.”
Untangling that interference has not been easy given the number of respiratory viruses (coronavirus, rhinovirus, adenovirus, RSV, and influenza are just a few of the best known) and the many infections that go undetected. However, recent technological advances make it easier to detect infections in people and to study the behavior of various viruses in the laboratory, in cell cultures, or in tissues derived from stem cells known as organoids. Increasingly, researchers are pointing to a cause: chemical messengers produced by infected people called, appropriately, interferons.
When a respiratory virus spreads through a community, interferons can vastly increase the body’s defenses and temporarily erect a population-wide immune barrier against subsequent viruses that attack the respiratory system. “Basically, all viruses trigger the interferon response to some degree, and all viruses are susceptible to it,” says Yale University immunologist Ellen Foxman, who has been exploring crosstalk between SARS-CoV-2 and other viruses in a laboratory model of the human airway.
Rhinoviruses, which cause common colds, can trip up influenza A (the most common flu virus). RSV can clash with human rhinoviruses and metapneumoviruses. Influenza A can thwart its distant cousin, influenza B. “Viral interference has many important health implications,” says Guy Boivin, a virologist at Laval University and co-author of a review on viral interference earlier this year. .
Still, interference is not a sure thing when multiple viruses are circulating. A household survey of 2,117 people in Nicaragua, for example, found that flu and COVID-19 cases peaked at the same time in February, suggesting “limited viral interference,” the researchers concluded in a preprint. “I think of the interference as a little nudge,” says Aubree Gordon, a researcher at the University of Michigan, Ann Arbor, who led the study with colleagues from the Nicaraguan Ministry of Health. “It depends on the immunity of the population and when that virus last circulated and the vaccination rates against influenza and COVID.”
EGG TRACKS
As early as 1957, two virologists at the National Institute for Medical Research in London reported a convincing mechanism by which an animal virus could outwit another. Alick Isaacs and Jean Lindemann investigated a well-known mystery in virology circles: the membranes of chicken eggs inoculated with inactivated influenza virus cannot be infected with a live version. Isaacs and Lindemann discovered that the chick embryo secreted a chemical, which they called interferon, which explained the interference. Unlike other immune responses (antibodies, for example) that target specific pathogens an animal has seen in the past, this rapid, nonspecific response is part of what’s known as the innate arm of the immune system.
It took a decade before interference between different viruses in humans received serious attention. Soviet virologist Marina Voroshilova of the Academy of Medical Sciences wondered why live but weakened versions of the poliovirus used in vaccines sometimes did not grow in the guts of people who received them and did not trigger protective immune responses. She found that harmless enteroviruses in the intestinal tract seemed to interfere with polioviruses. Voroshilova then conducted large field trials of attenuated enterovirus composite vaccines. They worked against those gut pathogens and also surprisingly prevented multiple respiratory viruses. Her team linked protection against respiratory viruses to increased levels of interferons.
virus shock
Testing of people in Scotland who had respiratory problems and sought medical attention reveals peaks and valleys in the prevalence of influenza A and rhinoviruses indicating that the two viruses are likely to interfere with each other.
C. BICKEL/SCIENCE
But few studies followed up on the early findings. “If you look at the virology literature, more than 95% of the studies are based on studying a single virus,” says Pablo Murcia, a virologist at the University of Glasgow.
Sporadic epidemiologic reports have documented how waves of influenza seemed to crowd out RSV, parainfluenza, and other respiratory viruses. But confounding variables plagued the data. What would happen if, for example, sick children who stayed home from school dodged the other viruses? And confirming which virus had made a person sick required culturing samples, which, until recently, was cumbersome and often inconclusive.
The 2009 influenza pandemic, fueled by a new influenza virus called pH1N1 that had recently emerged in pigs, put the study of viral interference on a more solid footing. When populations have little immunity to a new flu strain, it can circulate widely outside of the winter season, as pH1N1 did around the world. But groups from Sweden and France, using highly sensitive polymerase chain reaction (PCR) assays to detect viral genetic sequences, showed that in those countries, peaks of rhinovirus infections in late summer delayed influenza peaks until late fall, the normal beginning. of the flu season.
More recently, in one of the largest, largest, and most comprehensive studies of respiratory virus infections in humans, Murcia and colleagues used a PCR assay that can identify members of 11 viral families to analyze nasal and throat samples from more than 36 000 people seeking care from the Glasgow NHS over 9 years. Among other examples of viral interference, their data clearly showed that rhinovirus and influenza A peaked at different times (see graph above), demonstrating a “negative interaction” between the two viruses, the group concluded at the December 26, 2019 issue of Proceedings of the National Academy of Sciences.
The following year, Foxman and his colleagues reported finding interference after PCR testing for 10 different viruses in 13,000 respiratory samples from adults seeking care at the Yale New Haven hospital system. Between 2016 and 2019, about 7% of people tested positive for either rhinovirus or influenza A virus, but of these 1,911 samples, only 12 had both viruses, significantly fewer than expected, they reported in The Lancet Microbe. “It was great to see Ellen Foxman’s work,” says Murcia. “She showed essentially similar results to ours, and they are completely independent studies.”
In the same report, Foxman pinpointed the causative role of interferons. Like normal airways, the organoids his team produces from bronchial epithelial cells generate immune responses, including the secretion of interferons. Infection of organoids with rhinovirus nearly stopped the growth of later added influenza A viruses. Rhinovirus infections led to the expression of a flood of interferon-related genes, the study showed. And when her team treated the organoids with drugs that prevented their cells from mounting an interferon response, the influenza viruses thrived.
WATCHFUL WAIT
Now, viral interference researchers are taking a close look at the newest respiratory virus circulating the world. “What interactions could SARS-CoV-2 have with other viruses?” Murcia asks. “To this day, there is no solid epidemiological data.” For one, widespread social distancing and mask-wearing in many countries meant there was little chance of seeing interference in action. “There was almost no circulation of other respiratory viruses during the first 3 years of the pandemic,” says Boivin. Additionally, SARS-CoV-2 has many defenses against interferons, including preventing their production, which could affect its interactions with other viruses.
Still, Foxman has published evidence that, in his organoid model, rhinovirus can interfere with SARS-CoV-2. And Boivin’s team reported that influenza A and SARS-CoV-2 can block each other in cell studies.
Learning how SARS-CoV-2 and other viruses interfere with each other outside of the laboratory will require prospective studies that closely monitor the same populations over multiple seasons. Cowling now has several relatively small studies underway in Hong Kong, where people repeatedly give blood and respiratory samples, regardless of whether they have symptoms of the disease. It’s slow, she says. “At the moment, we don’t have a lot of respiratory infections in Hong Kong,” Cowling adds, noting that mask-wearing is still common.
Cowling, Murcia and Foxman say that the shortage of funds has limited their abilities to carry out large population studies. Still, they and others remain optimistic that we will soon have the best data yet on the fight between SARS-CoV-2 and other respiratory viruses. “This will be the first real winter where we have a normal mixing pattern of people, and hopefully we start to see some signs,” Murcia says. With multiple viruses colliding with each other for the first time in 3 years, he hopes to learn that interference is still alive and well, and capable of mitigating this winter’s triple threat.
Source: news.google.com