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Clinical Context

Vaccination against the influenza virus is the principal means to reduce the public health impact of this dangerous virus in the United States. How did influenza vaccination coverage fare during the COVID-19 pandemic? The National Flu Vaccination Dashboard by the Centers for Disease Control and Prevention (CDC)^[1] provides answers to this important question.

More than half (55%) of US adults had received the influenza vaccine by early February 2020, which compared favorably to the rate of 48% by the end of the 2019-2020 influenza season. Rates of vaccination among pregnant women declined slightly from 2019-2020 to 2020-2021, but they remained more than 60%.The news was not so positive among children: The coverage rate was 58%, which declined from 62% in 2019-2020; however, this decline in influenza vaccinations among children makes sense in light of lower rates of other childhood vaccination, as families avoided healthcare facilities during the COVID-19 pandemic.

Although there was no tremendous increase in uptake of the influenza vaccine in response to the COVID-19 pandemic, 2020-2021 was still a historic influenza season. The current study by Olsen and colleagues described why.

Study Synopsis and Perspective

Nonpharmaceutical interventions, such as masking, staying home, limiting travel, and social distancing, have been doing more than reducing the risk for COVID-19. They are also having an impact on infection rates and the timing of seasonal surges of other common respiratory diseases, according to an article published July 23 in Morbidity and Mortality Weekly Report.^[2]

Typically, respiratory pathogens such as respiratory syncytial virus (RSV), common cold coronaviruses, parainfluenza viruses, and respiratory adenoviruses increase in the fall and remain high throughout winter, following the same basic patterns as influenza. Although the historically low rates of influenza remained low into spring 2021, that is not the case for several other common respiratory viruses.

"Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases," wrote Sonja J. Olsen, PhD, and her colleagues at the CDC. She told Medscape Medical News that clinicians should use multipathogen testing to help guide treatment.

The authors also underscored the importance of fall influenza vaccination campaigns for anyone aged 6 months or older.

Timothy Brewer, MD, MPH, a professor of medicine in the division of infectious diseases at the David Geffen School of Medicine, University of California, Los Angeles (UCLA), and of epidemiology at the UCLA Fielding School of Public Health, agreed that it is important for healthcare professionals to consider off-season illnesses in their patients.

"Practitioners should be aware that if they see a sick child in the summer, outside of what normally might be influenza season, but they look like they have influenza, consider potentially influenza and test for it, because it might be possible that we may have disrupted that natural pattern," Brewer told Medscape Medical News. Brewer, who was not involved in the CDC research, said it is also "critically important" to encourage influenza vaccination as the season approaches.

The CDC researchers used the US World Health Organization Collaborating Laboratories System and the CDC's National Respiratory and Enteric Virus Surveillance System to analyze virologic data from October 3, 2020 to May 22, 2021 for influenza and January 4, 2020 to May 22, 2021 for other respiratory viruses. The authors compared virus circulation during these periods to circulation during the same dates from 4 previous years.

Data to calculate influenza and RSV hospitalization rates came from the Influenza Hospitalization Surveillance Network and the RSV Hospitalization Surveillance Network.

The authors reported that flu activity dropped dramatically in 2020-2021 to its lowest levels since 1997, the earliest season for which data are available. Only 0.2% of more than 1 million specimens tested positive for influenza; the rate of hospitalizations for lab-confirmed flu was 0.8 per 100,000 people. Flu levels remained low through the summer, fall, and through May 2021.

A potential drawback to this low activity, however, is a more prevalent and severe upcoming flu season, the authors wrote.

The repeated exposure to flu viruses every year often "does not lead to illness, but it does serve to boost our immune response to influenza viruses," Olsen told Medscape Medical News. "The absence of influenza viruses in the community over the last year means that we are not getting these regular boosts to our immune system. When we finally get exposed, our body may mount a weak response, and this could mean we develop a more clinically severe illness."

Children are most susceptible to that phenomenon because they have not had a lifetime of exposure to flu viruses, Olsen said.

"An immunologically naive child may be more likely to develop a severe illness than someone who has lived through several influenza seasons," she told Medscape. "This is why it is especially important for everyone 6 months and older to get vaccinated against influenza this season."

Rhinovirus and enterovirus infections rebounded fairly quickly after their decline in March 2020 and started increasing in May 2020 until they reached "near prepandemic seasonal levels," the authors wrote.

RSV infections dropped from 15.3% of weekly positive results in January 2020 to 1.4% by April 2020 and then stayed below 1% through the end of 2020. In past years, weekly positive results exceeded 3% in October and peaked at 12.5% to 16.7% in late December. Instead, RSV weekly positive results began increasing in April 2021, rising from 1.1% to 2.8% in May 2021.

The "unusually timed" late spring increase in RSV "is probably associated with various nonpharmaceutical measures that have been in place but are now relaxing," Olsen told Medscape.

The RSV hospitalization rate was 0.3 per 100,000 people from October 2020 to April 2021 compared with 27.1 and 33.4 per 100,000 people in the previous 2 years. Of all RSV hospitalizations in the past year, 76.5% occurred in April 2021 and May 2021.

Rates of illness caused by the 4 common human coronaviruses (OC43, NL63, 229E, and HKU1) dropped from 7.5% of weekly positive results in January 2020 to 1.3% in April 2020 and stayed below 1% through February 2021. Then they climbed to 6.6% by May 2021. Infection rates of parainfluenza viruses types 1 to 4 similarly dropped from 2.6% in January 2020 to 1% in March 2020 and stayed below 1% until April 2021. Since then, rates of the common coronaviruses increased to 6.6% and parainfluenza viruses to 10.9% in May 2021.

Normally, parainfluenza viruses peak in October to November and May to June, so "the current increase could represent a return to prepandemic seasonality," the authors wrote.

Human metapneumoviruses' weekly positive results initially increased from 4.2% in January 2020 to 7% in March 2020 and then fell to 1.9% the second week of April 2020 and remained below 1% through May 2021. In typical years, these viruses peak from 6.2% to 7.7% in March to April. Respiratory adenovirus activity similarly dropped to historically low levels in April 2021 and then began increasing to reach 3% by May 2021, the usual level for that month.

"The different circulation patterns observed across respiratory viruses probably also reflect differences in the virus transmission routes and how effective various nonpharmaceutical measures are at stopping transmission," Olsen told Medscape. "As pandemic mitigation measures continue to be adjusted, we expect to see more changes in the circulation of these viruses, including a return to prepandemic circulation, as seen for rhinoviruses and enteroviruses."

Rhinovirus and enterovirus rates dropped from 14.9% in March 2020 to 3.2% in May 2020 -- lower than typical -- and then climbed to a peak in October 2020. The peak (21.7% weekly positive results) was, however, still lower than the usual median of 32.8%. After dropping to 9.9% in January 2021, it then rose 19.1% in May 2021, potentially reflecting "the usual spring peak that has occurred in previous years," the authors wrote.

The authors noted that it is not yet clear how the COVID-19 pandemic and related mitigation measures will continue to affect respiratory virus circulation.

The authors hypothesized that the reasons for a seeming return to seasonal activity of respiratory adenoviruses, rhinoviruses, and enteroviruses could involve "different transmission mechanisms, the role of asymptomatic transmission, and prolonged survival of these nonenveloped viruses on surfaces, all of which might make these viruses less susceptible to nonpharmaceutical interventions."

Brewer, of UCLA, agreed.

All the viruses basically "flatline except for adenoviruses and enteroviruses, and they behave a little differently in terms of how they spread," he told Medscape Medical News. "Enteroviruses are much more likely to be fecal-oral spread than the other viruses [in the study]."

The delayed circulation of parainfluenza and human coronaviruses may have resulted from suspension of in-person classes through late winter 2020, they write, but that doesn't explain the relative absence of pneumovirus activity, which usually affects the same young pediatric populations as RSV.

Brewer said California is seeing a surge of RSV right now, as are many states, especially throughout in the South. He's not surprised by RSV's deferred season, because those most affected -- children younger than 2 years -- are less likely to wear masks now and were "not going to daycare, not being out in public" in 2020.

"As people are doing more activities, that's probably why RSV has been starting to go up since April," he said.

Despite the fact that, unlike many East Asian cultures, the United States has not traditionally been a mask-wearing culture, Brewer would not be surprised if more Americans begin wearing masks during flu season.

"Hopefully another thing that will come out of this is better hand hygiene, with people just getting used to washing their hands more, particularly after they come home from being out," he added.

Brewer similarly emphasized the importance of flu vaccination for the upcoming season, especially for younger children who may have poorer natural immunity to influenza, owing to its low circulation rates in 2020–2021.

The study was funded by the CDC. Brewer and Olsen have disclosed no relevant financial relationships.

Clinical Implications

• Rates of influenza vaccination among adults increased slightly in comparing data from 2020-2021 with 2019-2020, but rates fell among children in comparing these 2 vaccination seasons.
• The 2020-2021 vaccination season was remarkable for very low rates of positive tests for influenza and RSV. In contrast, rhinovirus and enterovirus returned to typical seasonal patterns by mid-year 2020.
• Implications for the healthcare team: The profound decline in cases of influenza and RSV suggests that nonpharmaceutical interventions such as masking had an effect on respiratory infection beyond SARS-CoV-2, and members of the healthcare team play a pivotal role in providing education to the community on these mitigation measures.

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