Since the beginning of the COVID-19 pandemic, public health experts have worried about people getting infected with the influenza virus and SARS-CoV-2 at the same time, a disease sometimes called flurona. Now, a multi-year study of hospital patients offers some of the most comprehensive data on how frequent flurona cases are—and who seems to be getting them the most.
The study, which is not yet peer reviewed, shows that flurona cases have been happening throughout the pandemic but are so far relatively rare. Out of more than 170,000 recorded cases of COVID-19 seen in hospital data from the Mayo Clinic, just 73 were co-infected with the flu. Alabama and Georgia had the highest percentage of hospitalized COVID-19 patients with influenza co-infections—0.8 percent and 0.7 percent, respectively. These flurona patients were all relatively young, and their illnesses were generally mild.
However, the study reveals that hospitalizations due to co-infection were highest in January 2022 compared to all previous months of the pandemic—an increase driven in part by the highly transmissible Omicron variant.
In addition to the Omicron surge, the flu has sickened a larger number of people this year than last flu season, according to the Centers for Disease Control and Prevention. This is probably because the dominant strain of influenza that's circulating—H3N2—has evolved several mutations, creating a mismatch with this year's flu vaccine that seems less protective.
“The Omicron wave coincided with a very active H3N2 flu season. This has … created a scenario where there are significantly more flurona cases now than ever before in the COVID-19 pandemic,” says study co-author Venky Soundararajan, co-founder and chief scientific officer of the biomedical data firm nference, based in Cambridge, Massachusetts.
However, experts stress that flurona is not at all likely to lead to genetic exchanges between viruses and cause more severe hybrid forms of either the flu or COVID-19. “While it's possible, in theory, for such gene swaps to occur, the chances of this occurring are very, very low and would almost certainly result in a non-viable virus,” says Stephen Goldstein, an evolutionary virologist at Eccles Institute of Human Genetics at the University of Utah.
Study co-author Andrew Badley, an infectious disease physician-scientist at the Mayo Clinic, Minnesota, adds that “the main take-home message of [our study] is that co-infections do occur, and therefore we have to take that concept seriously.”
The perfect viral storm
A co-infection occurs when a patient contracts multiple pathogens—either of same type, such as two or more viruses, or different classes, such as a virus and a bacterium or fungus. This happens during many diseases; estimates suggest that 43 percent of patients hospitalized with flu-like symptoms are actually infected with multiple viruses. During Delta wave in India, many COVID-19 patients also got infected with mucor or black fungus.
Knowing this possibility, scientists in China first investigated whether flu and SARS-CoV-2 co-infection could occur in January 2020, they didn’t find any cases in a study of 99 COVID-19 patients. But a follow up one month later found that about one in nine patients in a single hospital at the epicenter of the COVID-19 outbreak in Wuhan, China, had caught both diseases.
In the U.S., a study done between March 1 and April 4, 2020, in New York City showed that only one patient among 1,996 people hospitalized with COVID-19 was co-infected with influenza; 2 percent were co-infected with other respiratory viruses.
The reason for these initially low co-infection rates may have been an unusually mild flu season in 2020. The CDC estimated that the U.S. saw over 35 million flu cases and 380,000 hospitalizations in the 2019-2020 flu season. By contrast, only 1,675 confirmed cases of flu were reported between September 28, 2020 and May 22, 2021, with a hospitalization rate of less than one per 100,000 people.
It’s not clear why the cases of flu dropped so precipitously, but it’s possibly due in part to preventive measures taken for COVID-19, such as social distancing, lockdowns, hand hygiene, and use of face masks. In addition, the U.S. had a record number of flu vaccine doses—193.8 million—delivered during that season.
Flu season is worse this year, according to the CDC’s FluSurv-NET surveillance system. What’s more, it’s happening on top of a staggering wave of COVID-19 cases due to the Omicron variant, which has increased the odds of catching both viruses simultaneously. The upside is that flurona cases have been less severe, which may be due to the fact that most seem to be happening in people ages 14 to 41 who are generally less likely to develop severe outcomes.
So why would younger populations get flurona more often? “Social distancing and masking adherence is likely less in that population,” says Badley. “It is probable, although we didn't assess that, the rate of vaccination for both COVID-19 and influenza is likely lower in the younger [population].”
Still, other studies also show that co-infection has not significantly worsened the severity of disease.
Does co-infection increase the risk of new hybrid viruses?
As for concerns about flurona causing hybrid viruses to emerge, experts say there is no evidence of SARS-CoV-2 and flu viruses swapping genes while someone is co-infected.
“In my opinion [it’s] impossible,” says Susan Weiss, a virologist at the University of Pennsylvania who has been studying coronaviruses for more than four decades.
Two different strains of influenza viruses can easily exchange gene segments with each other during co-infections, but there are no examples of co-infections between influenza virus and a coronavirus leading to a more troublesome variant, Goldstein says.
While SARS-CoV-2 has and continues to evolve via transmission in humans, “I don't think co-infection creates any additional risk,” he adds.
Most experts also doubt that co-infections between SARS-CoV-2 and the common cold coronavirus, HCoV-229E, are a worry, despite a study, not yet peer reviewed, suggesting that such co-infections may have played a role in the evolution of Omicron.
“Common cold coronavirus 229E is evolutionarily different virus from SARS-CoV-2,” says Weiss. “Such experiments are not done in laboratories, so we can’t know how close coronaviruses have to be to recombine.”
It is possible to get two SARS-CoV-2 variants—like Alpha and Delta—to swap parts of their genetic codes during co-infection. Some experts even speculate that the Omicron sub-variants BA.2 and BA.3 may have arisen through such recombination events, but the evidence is elusive.
In the meantime, studies have shown that the risk of developing serious COVID-19 and dying is much lower among patients who had received an influenza vaccine before they caught COVID-19.
According to John O’Horo, an infectious disease physician at the Mayo Clinic, “the same things that have been able to hold this pandemic in check so far—namely, masking where appropriate, vaccination, and boosters for Omicron, and the good old-fashioned flu shot are still important.”