Is There Risk of Flu Outbreaks in the 2021-22 Season?

COVID-19 was as rampant in the US as it had ever been in the very first days of 2021.

In the early January weeks following the winter holiday season—a time of mass indoor gathering and socializing—and just weeks before newly authorized vaccines from Pfizer-BioNTech and Moderna would begin reaching greater adult populations, the pandemic virus began its greatest climb in US daily cases.

The very peak of new daily COVID-19 cases, as of this writing in July 2021, came on January 12: more than 210,000 reported cases in a single day, per the Centers for Disease Control and Prevention (CDC).

At the very same time, influenza was a non-factor. There were just 273 total positive cases of the flu reported in the US for the week ending January 16, according CDC FluView data. Just a year before, positive flu cases in the same week had exceeded 3000.

After months of speculation that legitimate risk of a “twindemic” in the 2020-21 flu season could overwhelm already exhausted hospital systems, flu was a sparse infection risk in the US while another respiratory virus was uncontrolled at unprecedented rates.

The explanations for contrasting confirmed COVID-19 and flu cases in the US during the 2020-21 season are simply understood and widely accepted by clinicians; what such factors mean for the forecast of the next season remains unclear. As the 2021-22 flu season approaches during a critical period of evolving COVID-19 mitigation strategies, public health experts are utilizing recent history to interpret future outbreak risks.

A Quiet 2020-21 Season

It helps to first understand the influences of the minimal 2020-21 flu season.

Wary of COVID-19 spread risk during the fall and winter months, experts stressed the importance of annual flu vaccination access and administration. The approximate 194 million flu vaccine doses distributed in the US last season were the most ever—an 11% increase from total distribution the season before (174.5 million).

Even with record supply and heightened messaging, flu vaccination coverage actually dipped among key populations. The 58.2% vaccination rate among children in mid-April was 4.1 percentage points fewer than the year prior; among pregnant women, the drop was 4.2 percentage points (61.3% vs 65.5%).

All race ethnicity groups additionally reported decreased flu vaccination coverage rates last year; Black and non-Hispanic persons rates decreased from 43.5% in 2019-20, to 36.5% to 2020-21.

However, overall coverage among adults had improved. Per a CDC survey in early February, 55% of all US adults had already received a flu vaccine, versus the 48% reported at the end of the 2019-20 season.

Rates were greatest among the age groups at greatest risk of COVID-19 and flu severity: 60% of people aged 50-64 years were vaccinated against the flu last year, as were 80% of those aged ≥65 years old.

The next contributing factors were those which had primarily sought to mitigate COVID-19 spread, but experts believe ultimately helped limit the flu through the winter. Tim Uyeki, MD, MPH, MPP, Chief Medical Officer of the CDC’s Influenza Division, National Center for Immunization and Respiratory Diseases, told Contagion® a litany of COVID-19 measures may have reduced flu spread in often highly susceptible areas:

• Reduced traveling and limited international travel options
• Significant increases in remote work for adults and remote schooling for children
• Social distancing measures and regional/state mask mandates

“It’s possible that higher influenza vaccine coverage may have also contributed, but collectively all of these mitigation measures probably contributed,” Uyeki said. “How much one measure such as facemask wearing contributed to all of that, I think is impossible to really discern.

“It’s what local governments and local public health recommended or required, and then it’s people’s behaviors and interactions,” he explained.

Pandemic-driven public health guidance and collective behavior may have indeed contributed equally to the minimal flu spread thus far, but both factors are currently evolving. Just this week, the CDC announced updated recommendations advising that Americans vaccinated for COVID-19 should begin wearing masks again when in indoor areas of high transmission risk.

With the Delta variant of SARS-CoV-2 now lifting 7-day averages for new daily US cases back above 50,000 for the first time since April, federal health authorities are reconsidering the immunity and prevention assured by available COVID-19 vaccines.

Approximately half the country’s population is now fully vaccinated against COVID-19. Though mRNA vaccines BNT162b2 and mRNA-1273 remain significantly able to prevent symptomatic and severe cases driven by the Delta variant, breakthrough infection risk and the reported greater transmissibility of the dominant variant has driven the call for continued mask-wearing.

High flu transmission-risk areas such as schools will again be aided by masks; included in the CDC’s guidance this week was recommendation that all teachers, staff, students and visitors wear mask indoors when classrooms reopen this year—regardless of vaccination status.

Epidemic Risks

The fear of recession in flu prevention is justified, particularly in an era when most common COVID-19 mitigation strategies are subject to dichotomized debate. But there is already a stable base of acceptance in flu vaccination and treatment that experts hope keeps the seasonal virus at bay.

Leslie Kantor, PhD, MPH, Chair and Professor of the Department of Urban-Global Public Health at the Rutgers School of Public Health, told Contagion there’s a greater acceptance of regular flu vaccination—one which adults generally pass down to their children and future generations as common practice.

“We’re all kind of in agreement on the flu. And I hope that that stays,” Kantor said. “My fear is that some of the same problems that have emerged and gotten stronger during COVID will cross the street and affect the flu response.”

Of greater concern is that the population is straying further away from virus infection-induced immunity from influenza strains. As Uyeki noted, flu virus circulation was not only limited in the 2020-21 season—it had been circulating at a significantly reduced rate since at least March 2020.

From season to season, he explained, the most severe flu epidemics have been associated with influenza type A (H3N2) variant virus. Such viruses have not circulated much at all in the US since 2018-19.

“The bottom line is we could be at risk on a population basis of a rather severe influenza epidemic with type A (H3N2) viruses, depending upon how antigenically similar the viruses are compared to what people have been exposed to in the past, and how well the H2N3 vaccine strain has been mapped to it,” Uyeki said.

The ‘anti-vax’ misinformation movement, and even the greater public hesitancy surrounding vaccines, has been exacerbated by the pandemic, Kantor noted. Whether that would apply to discourse around annual flu vaccine doses is inconclusive—if not disproven by last year’s record rate of distribution in the US.

But were last year’s flu vaccination rates actually just a byproduct of significantresourcing? Kantor described the US’ healthcare emergency funding as a reactive process: a crisis like COVID-19 begins, it overwhelms, resources and tools are expedited and provided, then the funding stops short.

“When ideally, if you wanted to avoid public health crises, you would have strong infrastructure, strong funding, strong coordination all the time,” she explained.

Given the emphasis on risk of twin respiratory virus outbreaks last flu season, the US set a new precedent for vaccination rollout. Would continuing to contain the flu during COVID-19 outbreaks be reliant on such resourcing?

Tools in Place

The US healthcare system is only as strong as its weakest links. And for some time—at least since the 2008 economic recession—its local health departments have been exceptionally weakened, Kantor said. The cracks of local care team understaffing and overburden were fully exposed when COVID-19 outbreaks began.

The US healthcare system is lauded for its world-leading advances in clinical and scientific innovation, and ability to prioritize top-down guidance for care teams. None of that matters if execution is lacking at the patient level.

“The only way to [contain COVID-19] is with testing and contact tracing,” Kantor said. “And in so many of these towns across America, you're lucky if you have one full time person doing that.”

The flu season, in theory, adds another risk factor to be monitored in a system that already cannot keep up with the pandemic. Kantor called it “fortunate” that last season’s flu circulation was minimal; what could easily occur this season is millions more needing testing for overlapping COVID-19, flu, and other respiratory virus symptoms.

The US industry’s delivery of dozens of PCR and antigen assays for COVID-19, as well as multiplex tests differentiating SARS-CoV-2 from flu and respiratory virus strains, have stocked local pharmacies, clinician offices, and even online consumer marketplaces. Pharmacies and community centers have become better-resourced vaccination sites during the pandemic; adding flu vaccine doses to their offerings is a simplistic strategy.

Supply meets demand—yet, as Kantor noted, testing utility has never been streamlined.

She prosed, for example, why there aren’t relatively cheap antigen testing stations established in COVID-19 outbreak-risk areas, such as schools or public transportation hubs? If local systems cannot prioritize testing standards for something as severe as the pandemic virus, there’s little hope they’d put stress on testing for and mitigating flu spread.

“I do think there will be a lot of people who will have to rule out one or the other,” Kantor said about this upcoming flu season. “But I’m always going to lean on, wouldn’t it be better to avoid this in the first place? We have been a country that has tolerated tens of thousands of deaths every from the flu, year after year.

“We’ve absorbed it, and we’ve absorbed these COVID-19 deaths,” Kantor said.

Though monitoring and spread prevention remain lackluster, reactive care has been bolstered for some time. Uyeki spoke to the availability and proven efficacy of flu antiviral therapy—a treatment option which has been generally linked to reduced risk of even household spread among patients with the flu.

The pandemic also required most primary care settings begin providing telemedicine options. In the event a patient tests positive for the flu, they could be prescribed antiviral therapy remotely by their physician, further reducing the risk of community spread.

Equipped with antiviral options for the flu, as well as monoclonal antibody options for high-risk patients with COVID-19, frontline physicians have a critical role to play in distinguishing either respiratory virus and making a timely treatment decision this season, Uyeki said.

“Clinicians really are going to depend upon knowing what's the level of SARS-CoV-2 circulation in the community at that moment, whether there’s influenza virus circulation—and if yes, how much?” Uyeki said. “It's really a reliance upon local surveillance data, and that will help inform clinical management and testing for SARS-CoV-2 and influenza.”

Timely diagnosis is also vital to the potential efficacy of prescribed flu treatment. Being able to initiate therapy with 1-2 days of symptoms being present for influenza could reduce disease duration, complications, and risk of spread.

It will be real-time monitoring of circulating viruses that inform ideal mitigation measures, Uyeki explained. While vaccination should continue to be prioritized, it has risk to be a sometimes ineffective practice.

Limited Measures

As influenza strains annually fluctuate in circulation—first in the Southern Hemisphere, then in the Northern Hemisphere—available vaccine doses are often an imperfect, educated prediction of necessary immunity.

In the 2019-20 season alone, flu vaccine effectiveness varied from 37% to 50% in all persons aged ≥6 months old, depending on the virus strain, according to CDC data.

Everyone of such age should be annually vaccinated for the flu, Uyeki stressed. But that guidance comes with an understanding of possible limitations. Though the vaccines’ benefits in reducing hospitalization, severe flu progression, and even death are generally consistent attributes, overall symptomatic disease prevention is not assured due to the moving target of circulating strains.

Kantor noted that Northern Hemisphere flu vaccine development and rollout is often informed by trends observed in the Southern Hemisphere’s flu season. Given that the latter similarly saw little of the flu in the last season, the former’s vaccine “guessing game” is a bit greater than usual.

“There seems to be a reasonable scientific argument that we should go with the same strains that were around [last year] because they didn't have a chance to mutate,” Kantor said. “That should be a pretty good bet. But we might have a slightly less effective vaccine.”

Vaccination timing is also a concern for this flu season. Kantor prosed whether reported waning efficacy of COVID-19 mRNA vaccines over time, as well as against the dominant Delta variant, may hinder the general public’s drive to upkeep record vaccination rates from last year.

She also suggested that timing of a possible COVID-19 vaccine booster dose authorization—if it were to occur in the fall season—may reduce flu vaccination rates if the processes are not streamlined.

“Can we get this set up so that we're doing boosters and flu at the same time?” Kantor suggested. “Or does this become two separate things that people need to do, which we know would really cut down on the likelihood that people would do it, just because the logistics get complicated?”

Uyeki added there is concern as to whether the 2021-22 flu season could begin earlier than usual this fall. Though such an event is unpredictable, the reopening of school systems, resumption of international travel, and possible resurgence of the type A (H3N2) virus could spell flu outbreaks occurring before the general vaccination push.

“If this occurred in September or early October before a lot of people were vaccinated, then there would be a lot of susceptible people—and in particular, if the viruses were also not well matched by the vaccine strains,” he explained.

Finally Prioritizing the Flu

There is no crystal ball gazing into upcoming flu seasons. There is only understanding of what constitutes greater risk of viral outbreaks, and what could reduce the effect of such factors. For that reason, Uyeki concludes that there is likely to be more flu activity in 2021-22 than was observed in the past season. For that reason, he stressed the need for clinicians to get their flu shot by late October, and to impress the same need to their patients as well.

Kantor added that, along with getting vaccinated, clinicians and patients need to keep perspective on the dangers of the flu. Especially at a time when great stress is put upon the severe risks of COVID-19, a more familiar but nonetheless potentially deadly virus like the flu can’t be discounted.

“Because it comes around every year, that doesn't mean that it's not serious, right?” she said.

The history of familiarity with the flu, contrasted against the heightened concern of COVID-19, and combined with greater leniency in public health measures among a more vaccinated population could spell significant risks for the 2021-22 flu season.

The pandemic response, almost coincidentally, provided a blueprint to reducing flu spread and severity in the US. But now the public must embrace it regularly, regardless the status of COVID-19.