There's a triple threat. It's tripledemic. The storm was a perfect one. The frightening phrases have dominated recent headlines as some health officials, clinicians, and scientists forecast that the respiratory syncytial virus (RSV) could surge at the same time in Northern Hemisphere locale that have relaxed masking, social distance, and other COVID-19 precautions.

There is a growing body of epidemiological and laboratory evidence that shows that respiratory viruses can interact with one another. Although waves of each virus may stress emergency rooms and intensive care units, the small group of researchers who study these viral collision say there is little chance they will peak together.

Richard Webby is an Influenza researcher at St. Jude Children's Research Hospital. It is not likely that they will circulate in the same way.

Ben Cowling is an epidemiologist at the University of Hong Kong. During the surge of the highly transmissible Omicron variant of SARS-coV-2 in Hong Kong in March, Cowling found that other respiratory Viruses came back again in April.

The number of respiratory viruses and the number of infections that escape notice make it difficult to untangle interference. Recent advances in technology make it easier to detect infections in people and study how multiple Viruses behave in the lab. Researchers are blaming the cause of the disease on the production of interferons.

Interferons can raise the body's defenses and temporarily build a populationwide immune barrier against respiratory viruses. Ellen Foxman, an immunologist at Yale University, has been studying the interference between the human airway and the Viruses in a lab model.

The most prevalent flu virus is the rhinoviruses. Human metapneumoviruses and rhinoviruses can be bumped. Influenza A can be defeated by its cousin, flu B. The co-author of a review on viral interference says there are a lot of health consequences from it.

It isn't a sure thing when multiple Viruses are circulating. The researchers concluded in a preprint that the flu and COVID-19 cases peaked at the same time in February. According to the researcher who led the study, interference is a small push. It depends on population immunity and vaccine rates.

The fluids come from the elves.

The National Institute for Medical Research in London reported in 1957 that one animal virus could cause another to go down. Chicken eggs that have been inoculated with a vaccine can't be used to transmit a live version of the flu. The chicken embryo had a chemical that accounted for the interference, which was discovered by the two men. This nonspecific, rapid response is part of the immune system's innate arm and is different from other immune responses.

It took a decade for interference between different Viruses in Humans to be noticed. The Academy of Medical Sciences wondered why weakened versions of the vaccine didn't grow in the guts of people who got them. She found that the enteroviruses in the gut were not harmful to theviruses. Large field trials were run of vaccines. They were able to ward off multiple respiratory Viruses. Increased levels of interferons were pegged as the reason for the protection against the respiratory Viruses.

Testing of people in Scotland who had respiratory problems and sought medical care shows peaks and troughs of the flu and rhinoviruses.

graph showing flu and rhinovirus prevalence

Many studies did not follow up on the findings. The majority of studies in the literature are based on the study of a single virus.

There have been reports of how waves of flu seemed to crowd out respiratory infections. The data was hard to read. Wouldn't it be great if sick children stayed home from school? culturing samples, which were cumbersome and often unreliable, were needed to confirm which virus had caused the illness.

The study of viral interference on more solid footing was put in motion by the H1N1 flu that hit in 2009. When populations have little immunity to a novel flu strain, it can spread widely outside of the winter season. The peak of the flu season in France and Sweden was delayed because of spikes of rhinoviruses in the summer.

More recently, in one of the largest, longest, and most comprehensive studies of respiratory virus infections in humans, Murcia and colleagues used a test that can identify members of 11 viral families to probe samples from more than 36,000 individuals who sought care from the National Health Service in Glasgow The group concluded in the December issue of the Proceedings of the National Academy of Sciences that there was a negative interaction between the twoviruses.

In the next year, Foxman and colleagues found interference after testing for 10 different viruses in 13,000 respiratory samples from people who sought care at the Yale New Haven hospital system. They reported in The Lancet Microbe that between 2016 and 2019, about 7% of people tested positive for rhinoviruses, but of these 1911 samples, only 12 had bothviruses, significantly less than expected. Murcia enjoyed seeing Ellen Foxman's paper. She showed similar results to ours.

Foxman pinned down the role of the drugs in the report. The organoids her team makes are similar to normal airways. The growth of influenza A viruses was almost halted by the infections with rhinoviruses. The study showed that the rhinoviruses caused the expression of genes related to interferon. She and her team treated the organoids with drugs that blocked their cells from responding to the interferon.

There is a lot of waiting.

Researchers are keeping a close eye on the newest respiratory virus. There could be interactions with other Viruses. Murcia wants to know what's going on. There are no robust epidemiological data today. There wasn't much chance to see interference in action because of the widespread social distance and mask. During the first three years of the Pandemic, there was almost no circulation of other respiratory Viruses. It is possible that the interactions with other viruses might be affected by the defense against interferons.

Foxman has published evidence that rhinoviruses can interfere with the disease. In cell studies, the two diseases can block each other.

Prospective studies that closely monitor the same populations for several seasons will be used to learn how the Viruses interfere with each other. People in Hong Kong often give blood and respiratory samples regardless of whether they have a disease or not. He says it's slow. Cowling says that Hong Kong doesn't have a lot of respiratory infections.

A lack of funding is limiting their ability to do large population studies. They and others are still optimistic that we will soon have the best data about the battle between the respiratory Viruses. Murcia says that this will be the first real winter where they have a normal mixing pattern. With multiple viruses running into each other for the first time in 3 years, he hopes to find out that interference is still alive and well.