Detection of Novel Influenza Viruses Through Community and Healthcare Testing: Implications for Surveillance Efforts in the United States.

BACKGROUND: Novel influenza viruses pose a potential pandemic risk, and rapid detection of infections in humans is critical to characterizing the virus and facilitating the implementation of public health response measures. METHODS: We use a probabilistic framework to estimate the likelihood that novel influenza virus cases would be detected through testing in different community and healthcare settings (urgent care, emergency department, hospital, and intensive care unit [ICU]) while at low frequencies in the United States. Parameters were informed by data on seasonal influenza virus activity and existing testing practices. RESULTS: In a baseline scenario reflecting the presence of 100 novel virus infections with similar severity to seasonal influenza viruses, the median probability of detecting at least one infection per month was highest in urgent care settings (72%) and when community testing was conducted at random among the general population (77%). However, urgent care testing was over 15 times more efficient (estimated as the number of cases detected per 100,000 tests) due to the larger number of tests required for community testing. In scenarios that assumed increased clinical severity of novel virus infection, median detection probabilities increased across all healthcare settings, particularly in hospitals and ICUs (up to 100%) where testing also became more efficient. CONCLUSIONS: Our results suggest that novel influenza virus circulation is likely to be detected through existing healthcare surveillance, with the most efficient testing setting impacted by the disease severity profile. These analyses can help inform future testing strategies to maximize the likelihood of novel influenza detection.

Responding to the Return of Influenza in the United States by Applying Centers for Disease Control and Prevention Surveillance, Analysis, and Modeling to Inform Understanding of Seasonal Influenza.

We reviewed the tools that have been developed to characterize and communicate seasonal influenza activity in the United States. Here we focus on systematic surveillance and applied analytics, including seasonal burden and disease severity estimation, short-term forecasting, and longer-term modeling efforts. For each set of activities, we describe the challenges and opportunities that have arisen because of the COVID-19 pandemic. In conclusion, we highlight how collaboration and communication have been and will continue to be key components of reliable and actionable influenza monitoring, forecasting, and modeling activities.

High Influenza Incidence and Disease Severity Among Children and Adolescents Aged <18 Years - United States, 2022-23 Season.

During the 2022-23 influenza season, early increases in influenza activity, co-circulation of influenza with other respiratory viruses, and high influenza-associated hospitalization rates, particularly among children and adolescents, were observed. This report describes the 2022-23 influenza season among children and adolescents aged <18 years, including the seasonal severity assessment; estimates of U.S. influenza-associated medical visits, hospitalizations, and deaths; and characteristics of influenza-associated hospitalizations. The 2022-23 influenza season had high severity among children and adolescents compared with thresholds based on previous seasons' influenza-associated outpatient visits, hospitalization rates, and deaths. Nationally, the incidences of influenza-associated outpatient visits and hospitalization for the 2022-23 season were similar for children aged <5 years and higher for children and adolescents aged 5-17 years compared with previous seasons. Peak influenza-associated outpatient and hospitalization activity occurred in late November and early December. Among children and adolescents hospitalized with influenza during the 2022-23 season in hospitals participating in the Influenza Hospitalization Surveillance Network, a lower proportion were vaccinated (18.3%) compared with previous seasons (35.8%-41.8%). Early influenza circulation, before many children and adolescents had been vaccinated, might have contributed to the high hospitalization rates during the 2022-23 season. Among symptomatic hospitalized patients, receipt of influenza antiviral treatment (64.9%) was lower than during pre-COVID-19 pandemic seasons (80.8%-87.1%). CDC recommends that all persons aged ≥6 months without contraindications should receive the annual influenza vaccine, ideally by the end of October.

Database derived from an electronic medical record-based surveillance network of US emergency department patients with acute respiratory illness.

BACKGROUND: For surveillance of episodic illness, the emergency department (ED) represents one of the largest interfaces for generalizable data about segments of the US public experiencing a need for unscheduled care. This protocol manuscript describes the development and operation of a national network linking symptom, clinical, laboratory and disposition data that provides a public database dedicated to the surveillance of acute respiratory infections (ARIs) in EDs. METHODS: The Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) network includes 26 academic investigators, from 24 sites, with 91 hospitals, and the Centers for Disease Control and Prevention (CDC) to survey viral infections. All data originate from electronic medical records (EMRs) accessed by structured query language (SQL) coding. Each Tuesday, data are imported into the standard data form for ARI visits that occurred the prior week (termed the index file); outcomes at 30 days and ED volume are also recorded. Up to 325 data fields can be populated for each case. Data are transferred from sites into an encrypted Google Cloud Platform, then programmatically checked for compliance, parsed, and aggregated into a central database housed on a second cloud platform prior to transfer to CDC. RESULTS: As of August, 2023, the network has reported data on over 870,000 ARI cases selected from approximately 5.2 million ED encounters. Post-contracting challenges to network execution have included local shifts in testing policies and platforms, delays in ICD-10 coding to detect ARI cases, and site-level personnel turnover. The network is addressing these challenges and is poised to begin streaming weekly data for dissemination. CONCLUSIONS: The RESP-LENS network provides a weekly updated database that is a public health resource to survey the epidemiology, viral causes, and outcomes of ED patients with acute respiratory infections.

Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza - United States, 2021-22 Influenza Season.

The 2022-23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3-5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021-22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021-April 30, 2022),§ and notifiable pediatric deaths associated¶ with influenza virus and SARS-CoV-2 coinfection (October 3, 2021-October 1, 2022)** were analyzed. SARS-CoV-2 coinfections occurred in 6% (32 of 575) of pediatric influenza-associated hospitalizations and in 16% (seven of 44) of pediatric influenza-associated deaths. Compared with patients without coinfection, a higher proportion of those hospitalized with coinfection received invasive mechanical ventilation (4% versus 13%; p = 0.03) and bilevel positive airway pressure or continuous positive airway pressure (BiPAP/CPAP) (6% versus 16%; p = 0.05). Among seven coinfected patients who died, none had completed influenza vaccination, and only one received influenza antivirals.†† To help prevent severe outcomes, clinicians should follow recommended respiratory virus testing algorithms to guide treatment decisions and consider early antiviral treatment initiation for pediatric patients with suspected or confirmed influenza, including those with SARS-CoV-2 coinfection who are hospitalized or at increased risk for severe illness. The public and parents should adopt prevention strategies including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and staying up-to-date with recommended influenza and COVID-19 vaccinations for persons aged ≥6 months.

Influenza Activity and Composition of the 2022-23 Influenza Vaccine - United States, 2021-22 Season.

Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing for seasonal influenza viruses, and monitoring for novel influenza A virus infections are important. An outbreak of highly pathogenic avian influenza A(H5N1) is ongoing; health care providers and persons with exposure to sick or infected birds should remain vigilant for onset of symptoms consistent with influenza. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

Interim Estimates of 2021-22 Seasonal Influenza Vaccine Effectiveness - United States, February 2022.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season.

Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic - United States, 2020-2021.

The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.

Decreased Influenza Activity During the COVID-19 Pandemic - United States, Australia, Chile, and South Africa, 2020.

After recognition of widespread community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by mid- to late February 2020, indicators of influenza activity began to decline in the Northern Hemisphere. These changes were attributed to both artifactual changes related to declines in routine health seeking for respiratory illness as well as real changes in influenza virus circulation because of widespread implementation of measures to mitigate transmission of SARS-CoV-2. Data from clinical laboratories in the United States indicated a 61% decrease in the number of specimens submitted (from a median of 49,696 per week during September 29, 2019-February 29, 2020, to 19,537 during March 1-May 16, 2020) and a 98% decrease in influenza activity as measured by percentage of submitted specimens testing positive (from a median of 19.34% to 0.33%). Interseasonal (i.e., summer) circulation of influenza in the United States (May 17-August 8, 2020) is currently at historical lows (median = 0.20% tests positive in 2020 versus 2.35% in 2019, 1.04% in 2018, and 2.36% in 2017). Influenza data reported to the World Health Organization's (WHO's) FluNet platform from three Southern Hemisphere countries that serve as robust sentinel sites for influenza from Oceania (Australia), South America (Chile), and Southern Africa (South Africa) showed very low influenza activity during June-August 2020, the months that constitute the typical Southern Hemisphere influenza season. In countries or jurisdictions where extensive community mitigation measures are maintained (e.g., face masks, social distancing, school closures, and teleworking), those locations might have little influenza circulation during the upcoming 2020-21 Northern Hemisphere influenza season. The use of community mitigation measures for the COVID-19 pandemic, plus influenza vaccination, are likely to be effective in reducing the incidence and impact of influenza, and some of these mitigation measures could have a role in preventing influenza in future seasons. However, given the novelty of the COVID-19 pandemic and the uncertainty of continued community mitigation measures, it is important to plan for seasonal influenza circulation in the United States this fall and winter. Influenza vaccination of all persons aged ≥6 months remains the best method for influenza prevention and is especially important this season when SARS-CoV-2 and influenza virus might cocirculate (1).

Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020.

Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.

Spread of Antigenically Drifted Influenza A(H3N2) Viruses and Vaccine Effectiveness in the United States During the 2018-2019 Season.

BACKGROUND: Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness (VE) and vaccine strain selection. We used US virologic surveillance and US Influenza Vaccine Effectiveness (Flu VE) Network data to evaluate consequences of this clade. METHODS: Distribution of influenza viruses was described using virologic surveillance data. The Flu VE Network enrolled ambulatory care patients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by means of reverse-transcriptase polymerase chain reaction and were sequenced. Using a test-negative design, we estimated VE, comparing the odds of influenza among vaccinated versus unvaccinated participants. RESULTS: During the 2018-2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2763 Flu VE Network case patients, 1325 (48%) were infected with A(H1N1)pdm09 and 1350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval, 37%-51%) against A(H1N1)pdm09 and 9% (-4% to 20%) against A(H3N2); VE was 5% (-10% to 19%) against A(H3N2) clade 3C.3a viruses. CONCLUSIONS: The predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018-2019 season was associated with decreased VE, supporting the A(H3N2) vaccine component update for 2019-2020 northern hemisphere influenza vaccines.

Update: Influenza Activity - United States and Worldwide, May 19-September 28, 2019, and Composition of the 2020 Southern Hemisphere Influenza Vaccine.

During May 19-September 28, 2019,* low levels of influenza activity were reported in the United States, with cocirculation of influenza A and influenza B viruses. In the Southern Hemisphere seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries. In late September, the World Health Organization (WHO) recommended components for the 2020 Southern Hemisphere influenza vaccine and included an update to the A(H3N2) and B/Victoria-lineage components. Annual influenza vaccination is the best means for preventing influenza illness and its complications, and vaccination before influenza activity increases is optimal. Health care providers should recommend vaccination for all persons aged ≥6 months who do not have contraindications to vaccination (1).

Update: Influenza Activity in the United States During the 2018-19 Season and Composition of the 2019-20 Influenza Vaccine.

Influenza activity* in the United States during the 2018-19 season (September 30, 2018-May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)† activity began increasing in November, peaked during mid-February, and returned to below baseline in mid-April; the season lasted 21 weeks,§ making it the longest season in 10 years. Illness attributed to influenza A viruses predominated, with very little influenza B activity. Two waves of influenza A were notable during this extended season: influenza A(H1N1)pdm09 viruses from October 2018 to mid-February 2019 and influenza A(H3N2) viruses from February through May 2019. Compared with the 2017-18 influenza season, rates of hospitalization this season were lower for adults, but were similar for children. Although influenza activity is currently below surveillance baselines, testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

Birth Cohort Effects in Influenza Surveillance Data: Evidence That First Influenza Infection Affects Later Influenza-Associated Illness.

BACKGROUND: The evolution of influenza A viruses results in birth cohorts that have different initial influenza virus exposures. Historically, A/H3 predominant seasons have been associated with more severe influenza-associated disease; however, since the 2009 pandemic, there are suggestions that some birth cohorts experience more severe illness in A/H1 predominant seasons. METHODS: United States influenza virologic, hospitalization, and mortality surveillance data during 2000-2017 were analyzed for cohorts born between 1918 and 1989 that likely had different initial influenza virus exposures based on viruses circulating during early childhood. Relative risk/rate during H3 compared with H1 predominant seasons during prepandemic versus pandemic and later periods were calculated for each cohort. RESULTS: During the prepandemic period, all cohorts had more influenza-associated disease during H3 predominant seasons than H1 predominant seasons. During the pandemic and later period, 4 cohorts had higher hospitalization and mortality rates during H1 predominant seasons than H3 predominant seasons. CONCLUSIONS: Birth cohort differences in risk of influenza-associated disease by influenza A virus subtype can be seen in US influenza surveillance data and differ between prepandemic and pandemic and later periods. As the population ages, the amount of influenza-associated disease may be greater in future H1 predominant seasons than H3 predominant seasons.

Update: Influenza Activity - United States, September 30, 2018-February 2, 2019.

CDC collects, compiles, and analyzes data on influenza activity and viruses in the United States. During September 30, 2018-February 2, 2019,* influenza activity† in the United States was low during October and November, increased in late December, and remained elevated through early February. As of February 2, 2019, this has been a low-severity influenza season (1), with a lower percentage of outpatient visits for influenza-like illness (ILI), lower rates of hospitalization, and fewer deaths attributed to pneumonia and influenza, compared with recent seasons. Influenza-associated hospitalization rates among children are similar to those observed in influenza A(H1N1)pdm09 predominant seasons; 28 influenza-associated pediatric deaths occurring during the 2018-19 season have been reported to CDC. Whereas influenza A(H1N1)pdm09 viruses predominated in most areas of the country, influenza A(H3N2) viruses have predominated in the southeastern United States, and in recent weeks accounted for a growing proportion of influenza viruses detected in several other regions. Small numbers of influenza B viruses (<3% of all influenza-positive tests performed by public health laboratories) also were reported. The majority of the influenza viruses characterized antigenically are similar to the cell culture-propagated reference viruses representing the 2018-19 Northern Hemisphere influenza vaccine viruses. Health care providers should continue to offer and encourage vaccination to all unvaccinated persons aged ≥6 months as long as influenza viruses are circulating. Finally, regardless of vaccination status, it is important that persons with confirmed or suspected influenza who have severe, complicated, or progressive illness; who require hospitalization; or who are at high risk for influenza complications be treated with antiviral medications.

Influenza Activity - United States, September 30-December 1, 2018.

Influenza activity in the United States was low during October 2018, and, although it increased slowly during November, activity remains low across most of the country.* During the week ending December 1, 2018, the percentage of outpatient visits for influenza-like illness† (ILI) was equal to the national baseline§ (Figure) and was at or slightly above the region-specific baseline in four of the 10 U.S. Department of Health and Human Services regions¶ (Regions 4 and 7-9). The majority of jurisdictions experienced minimal or low ILI activity since September 30; however, two experienced moderate ILI activity, and two experienced high ILI activity** during the week ending December 1. The percentage of deaths attributed to pneumonia and influenza remains below the epidemic threshold,†† and the rate of influenza-associated hospitalizations remains low. Five laboratory-confirmed, influenza-associated pediatric deaths occurring since September 30 have been reported to CDC. During the week ending December 1, the majority of jurisdictions (40 states, the District of Columbia, Puerto Rico, and U.S. Virgin Islands) reported sporadic or local geographic spread of influenza activity, nine states reported regional activity, and one state reported widespread activity.§§.

Update: Influenza Activity - United States and Worldwide, May 20-October 13, 2018.

During May 20-October 13, 2018,* low levels of influenza activity were reported in the United States, with a mix of influenza A and B viruses circulating. Seasonal influenza activity in the Southern Hemisphere was low overall, with influenza A(H1N1)pdm09 predominating in many regions. Antigenic testing of available influenza A and B viruses indicated that no significant antigenic drift in circulating viruses had emerged. In late September, the components for the 2019 Southern Hemisphere influenza vaccine were selected and included an incremental update to the A(H3N2) vaccine virus used in egg-based vaccine manufacturing; no change was recommended for the A(H3N2) component of cell-manufactured or recombinant influenza vaccines. Annual influenza vaccination is the best method for preventing influenza illness and its complications, and all persons aged ≥6 months who do not have contraindications should receive influenza vaccine, preferably before the onset of influenza circulation in their community, which often begins in October and peaks during December-February. Health care providers should offer vaccination by the end of October and should continue to recommend and administer influenza vaccine to previously unvaccinated patients throughout the 2018-19 influenza season (1). In addition, during May 20-October 13, a small number of nonhuman influenza "variant" virus infections† were reported in the United States; most were associated with exposure to swine. Although limited human-to-human transmission might have occurred in one instance, no ongoing community transmission was identified. Vulnerable populations, especially young children and other persons at high risk for serious influenza complications, should avoid swine barns at agricultural fairs, or close contact with swine.§.