Concerns about a severe influenza season that might overwhelm health care systems already overburdened by the surge of patients with COVID-19 have not been realized. The 2020-2021 influenza season has been characterized by unusually low circulation of influenza viruses in the US. From September 2020 through the week ending May 15, 2021, only 0.051% of 485?637 respiratory specimens tested and reported to the US Centers for Disease Control and Prevention were positive for influenza viruses at US public health laboratories and only 0.18% of 1?054?101 respiratory specimens were positive at US clinical laboratories (compared with 10%-19% in recent years).1

Population-based surveillance indicates that the cumulative rate of laboratory-confirmed influenza-associated hospitalizations this season (reported at sites in 14 states [0.8/100?000 population] as of April 30, 2021) is the lowest since data collection started in 2005.1 In comparison, the median cumulative influenza-associated hospitalization rate was substantially higher (44.2/100?000; range, 8.2-106.0/100?000) for the same periods during the 2010-2019 seasons.1 The experience in the US during 2020-2021 is similar to the near absence of influenza viruses in some southern hemisphere countries during 2020.2

Multiple factors have likely contributed to the marked decline in circulation of influenza viruses, including implementation of community mitigation measures to control SARS-CoV-2 transmission (eg, wearing of face masks, social distancing, workplace closures, school closures, virtual school instruction, indoor dining restrictions), behavioral changes in response to the COVID-19 pandemic (eg, staying at home, working from home, reduced domestic and international travel, or international travel with subsequent quarantine upon arrival), and influenza vaccination.

Whether SARS-CoV-2 infection can confer protection (viral interference) against influenza virus infection is not well understood. However, a UK epidemiological study from January 20-April 25, 2020, that included 19?256 individuals reported influenza virus infection (n?=?992) was associated with a lower risk of SARS-CoV-2 infection (n?=?4443) (adjusted odds ratio [OR], 0.42; 95% CI, 0.31-0.56), but that SARS-CoV-2 and influenza virus co-infection (n?=?58) was associated with a higher risk of intensive care unit admission (adjusted OR, 2.08; 95% CI, 1.17-3.70) or death (adjusted OR, 2.27; 95% CI, 1.23-4.19) compared with SARS-CoV-2 infection alone.3

It is unknown whether influenza virus circulation might increase this summer as SARS-CoV-2 community mitigation measures are relaxed and international travel increases, although influenza activity during the summer months in the US is typically low. For example, relaxation of SARS-CoV-2 pandemic control measures in Cambodia was followed by increases in influenza A(H3N2) virus circulation during August and September 2020.4

Influenza vaccine effectiveness estimates for 2020-2021 are not available, but a record number of influenza vaccine doses were distributed in the US this season and the greater numbers of vaccinated persons could have contributed to reducing influenza activity. However, countries such as Australia, Chile, and South Africa that have much lower use of influenza vaccines compared with the US also experienced low influenza activity in 2020 after implementing control measures to prevent SARS-CoV-2 transmission compared with typical seasons.2

Clinical Implications

Currently available influenza tests in clinical settings are rapid antigen detection assays with moderate to moderately high sensitivity and high specificity to detect seasonal influenza A and B viruses in respiratory specimens compared with nucleic acid amplification tests (molecular assays) that have high sensitivity and high specificity.5 During periods of high influenza activity, rapid antigen detection assays might yield more false-negative results than nucleic acid detection assays, whereas when influenza prevalence is low, both rapid antigen and molecular assays can yield some false-positive results.

Therefore, during periods of low influenza prevalence, consideration should be given to confirming positive influenza test results by additional molecular testing, particularly for outbreaks of acute respiratory illness among persons in institutional settings. When influenza activity is low, clinical diagnosis of influenza is less likely to be accurate than during periods of high influenza activity, and influenza testing can help guide antiviral treatment for hospitalized patients and outpatients at increased risk for influenza complications.

The low circulation of influenza viruses during the COVID-19 pandemic also has implications for decisions regarding antibiotic treatment of patients diagnosed with community-acquired pneumonia (CAP) during influenza season. Influenza-associated CAP due to Staphylococcus aureus, Streptococcus pneumoniae, and group A Streptococcus can result in severe and fatal complications.6 In contrast, although hospital-acquired bacterial co-infection is a concern in intubated patients, secondary bacterial CAP at hospital admission appears to be an uncommon complication of COVID-19.7 Therefore, testing for SARS-CoV-2 and influenza viruses in patients with diagnosed with CAP can be helpful during the decision-making process regarding the use of empirical antibiotic treatment.

Public Health Implications

Even though influenza virus circulation has declined worldwide during 2020-2021, genetically diverse influenza A(H3N2) viruses have continued to circulate in tropical Asian countries, as reported in Bangladesh and Cambodia.8 Fewer influenza viruses were available for antigenic characterization in the US and worldwide than during a typical season to inform the biannual influenza vaccine strain selection process.9

Recently, the World Health Organization recommended updates to 2 (ie, A[H3N2] and A[H1N1]pdm09) of the 4 influenza vaccine antigens for the northern hemisphere 2021-2022 season.9 Among many questions in planning for the next influenza season is: What might happen if influenza A(H3N2) viruses circulate widely? Influenza A(H3N2) viruses are associated with more severe epidemics and high hospitalization and mortality rates among older adults. Influenza vaccine effectiveness against A(H3N2) viruses among older adults is often low. Because A(H3N2) viruses have not circulated widely in the US since the 2018-2019 season, waning immunity from past A(H3N2) virus infections, particularly among older adults, could pose public health challenges if influenza A(H3N2) viruses circulate widely next winter. Therefore, increasing influenza vaccine coverage, especially among persons at high risk for influenza complications, and other preventive measures, may be particularly important in the upcoming 2021-2022 influenza season.

Studies of face mask use, primarily conducted in households, have generally not reported benefit in reducing secondary influenza virus transmission,10 perhaps due to the short incubation period for influenza and the likelihood that by the time influenza was diagnosed in a household member, exposure and influenza virus infection of their household contacts had already occurred before donning face masks. Given the effect on influenza activity of multiple community interventions to control SARS-CoV-2, including routine wearing of face masks, consideration of these measures during periods of high influenza virus circulation in the future may be warranted and socially acceptable to the public.

Continuing use of properly fitted face masks for health care personnel, patients, and visitors can help to reduce influenza virus transmission in health care settings. Most influenza virus transmission is thought to occur from symptomatic persons, but more research is needed on the contribution of asymptomatic and presymptomatic transmission, and the effectiveness of face masks to reduce influenza virus transmission in public settings. The effects of a variety of SARS-CoV-2 community mitigation measures on reducing influenza virus spread have highlighted the potential for similar prevention efforts, combined with influenza vaccination, to control severe influenza epidemics and pandemics.