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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.

Social learning theory posits that adolescents learn to adopt social norms by observing the behaviors of others and internalizing the associated outcomes. However, the underlying neural processes by which social learning occurs is less well-understood, despite extensive neurobiological reorganization and a peak in social influence sensitivity during adolescence. Forty-four adolescents (Mage = 12.2 years) completed an fMRI scan while observing their older sibling within four years of age (Mage = 14.3 years) of age complete a risky decision-making task. Group iterative multiple model estimation (GIMME) was used to examine patterns of directional brain region connectivity supporting social learning. We identified group-level neural pathways underlying social observation including the anterior insula to the anterior cingulate cortex and mentalizing regions to social cognition regions. We also found neural states based on adolescent sensitivity to social learning via age, gender, modeling, differentiation, and behavior. Adolescents who were more likely to be influenced elicited neurological up-regulation whereas adolescents who were less likely to be socially influenced elicited neurological down-regulation during risk-taking. These findings highlight patterns of how adolescents process information while a salient influencer takes risks, as well as salient neural pathways that are dependent on similarity factors associated with social learning theory.

EML4-ALK is an oncogenic fusion protein present in approximately 5% of non–small cell lung cancers (NSCLC). Alternative breakpoints in the gene encoding EML4 result in distinct variants that are linked to markedly different patient outcomes. Patients with EML4-ALK variant 3 (V3) respond poorly to ALK inhibitors and have lower survival rates compared with patients with other common variants, such as V1. Here, we use isogenic Beas-2B bronchial epithelial cell lines expressing EML4-ALK V1 or V3, as well as ALK-positive NSCLC patient cells that express V1 (H3122 cells) or V3 (H2228 cells), to show that EML4-ALK V3 but not V1 leads to hyperstabilized K-fibers in mitosis, as well as errors in chromosome congression and segregation. This is consistent with our observation that EML4-ALK V3 but not V1 localizes to spindle microtubules and that wild-type EML4 is a microtubule stabilizing protein. In addition, cells expressing EML4-ALK V3 exhibit loss of spindle assembly checkpoint control that is at least in part dependent on ALK catalytic activity. Finally, we demonstrate that cells expressing EML4-ALK V3 have increased sensitivity to microtubule poisons that interfere with mitotic spindle assembly, whereas combination treatment with paclitaxel and clinically approved ALK inhibitors leads to a synergistic response in terms of reduced survival of H2228 cells. Implications: This study suggests that combining the microtubule poison, paclitaxel, with targeted ALK inhibitors may provide an effective new treatment option for patients with NSCLC with tumors that express the EML4-ALK V3 oncogenic fusion.

In the United States, infection with SARS-CoV-2 caused 380,000 reported deaths from March to December 2020.We adapted the Moving Epidemic Method to all-cause mortality data from the United States to assess the severity of the COVID-19 pandemic across age groups and all 50 states. By comparing all-cause mortality during the pandemic with intensity thresholds derived from recent, historical all-cause mortality, we categorized each week from March to December 2020 as either low severity, moderate severity, high severity, or very high severity.Nationally for all ages combined, all-cause mortality was in the very high severity category for 9 weeks. Among people 18 to 49 years of age, there were 29 weeks of consecutive very high severity mortality. Forty-seven states, the District of Columbia, and New York City each experienced at least 1 week of very high severity mortality for all ages combined.These periods of very high severity of mortality during March through December 2020 are likely directly or indirectly attributable to the COVID-19 pandemic. This method for standardized comparison of severity over time across different geographies and demographic groups provides valuable information to understand the impact of the COVID-19 pandemic and to identify specific locations or subgroups for deeper investigations into differences in severity.

Outcomes and costs of coronavirus disease (COVID-19) contact tracing are limited. During March-May 2020, we constructed transmission chains from 184 index cases and 1,499 contacts in Salt Lake County, Utah, USA, to assess outcomes and estimate staff time and salaries. We estimated 1,102 staff hours and $29,234 spent investigating index cases and contacts. Among contacts, 374 (25%) had COVID-19; secondary case detection rate was ≈31% among first-generation contacts, ≈16% among second- and third-generation contacts, and ≈12% among fourth-, fifth-, and sixth-generation contacts. At initial interview, 51% (187/370) of contacts were COVID-19-positive; 35% (98/277) became positive during 14-day quarantine. Median time from symptom onset to investigation was 7 days for index cases and 4 days for first-generation contacts. Contact tracing reduced the number of cases between contact generations and time between symptom onset and investigation but required substantial resources. Our findings can help jurisdictions allocate resources for contact tracing.

Previous infection with SARS-CoV-2 (the virus that causes COVID-19) or COVID-19 vaccination can provide immunity and protection from subsequent SARS-CoV-2 infection and illness. CDC used data from the VISION Network* to examine hospitalizations in adults with COVID-19-like illness and compared the odds of receiving a positive SARS-CoV-2 test result, and thus having laboratory-confirmed COVID-19, between unvaccinated patients with a previous SARS-CoV-2 infection occurring 90-179 days before COVID-19-like illness hospitalization, and patients who were fully vaccinated with an mRNA COVID-19 vaccine 90-179 days before hospitalization with no previous documented SARS-CoV-2 infection. Hospitalized adults aged ≥18 years with COVID-19-like illness were included if they had received testing at least twice: once associated with a COVID-19-like illness hospitalization during January-September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization). Among COVID-19-like illness hospitalizations in persons whose previous infection or vaccination occurred 90-179 days earlier, the odds of laboratory-confirmed COVID-19 (adjusted for sociodemographic and health characteristics) among unvaccinated, previously infected adults were higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine with no previous documented infection (adjusted odds ratio [aOR] = 5.49; 95% confidence interval [CI] = 2.75-10.99). These findings suggest that among hospitalized adults with COVID-19-like illness whose previous infection or vaccination occurred 90-179 days earlier, vaccine-induced immunity was more protective than infection-induced immunity against laboratory-confirmed COVID-19. All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.

Background There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. Methods We conducted a study involving adults (≥50 years of age) with Covid-19–like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. Results The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19–associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. Conclusions Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.)

Background Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. Methods This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. Results A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2–48.0%). Conclusions This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715

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 (

Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,† COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.§ Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)¶ data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,†† and quarantining as recommended after exposure to persons with COVID-19.§§.

Background RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18–64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. Methods During the 2018–2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. Results In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2–1.9) for A/H1N1, 3.0 (95% CI: 2.4–3.7) for A/H3N2, 1.1 (95% CI: .9–1.4) for B/Yamagata, and 1.1 (95% CI: .9–1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. Conclusions RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4., In this randomized trial among healthcare personnel comparing antibody responses to cell-culture based and recombinant influenza vaccines (RIV4) versus standard-dose egg-based vaccines, RIV4 recipients had higher antibody responses against 3 cell-grown vaccine strains suggesting a possible additional benefit from RIV4.

Background: Auditory naming tests are superior to visual confrontation naming tests in revealing word-finding difficulties in many neuropathological conditions. Objective: To delineate characteristics of auditory naming most likely to reveal anomia in patients with dementia, and possibly improve diagnostic utility, we evaluated a large sample of patients referred with memory impairment complaints. Methods: Patients with dementia (N = 733) or other cognitive impairments and normal individuals (N = 69) were evaluated for frequency of impairment on variables of the Auditory Naming Test (ANT) of Hamberger & Seidel versus the Boston Naming Test (BNT). Results: Naming impairment occurred more frequently using the ANT total score (φ= 0.41) or ANT tip-of-the tongue score (TOT; φ= 0.19) but not ANT mean response time compared to the BNT in patients with dementia (p

The effect of influenza vaccination on influenza severity remains uncertain. We reviewed the literature for evidence to inform the question of whether influenza illness is less severe among individuals who received influenza vaccination compared with individuals with influenza illness who were unvaccinated prior to their illnesses. We conducted a narrative review to identify published findings comparing severity of influenza outcomes by vaccination status among community-dwelling adults and children ≥ 6 months of age with laboratory-confirmed influenza illness. When at least four effect estimates of the same type (e.g., odds ratio) were available for a specific outcome and age category (children versus adults), data were pooled with meta-analysis to generate a summary effect estimate. We identified 38 published articles reporting ≥ 1 association between influenza vaccination status and one of 21 indicators of severity of influenza illness among individuals with laboratory-confirmed influenza. Study methodologies and effect estimates were highly heterogenous, with only five severity indicators meeting criteria for calculating a combined effect. Among eight studies, influenza vaccination was associated with 26% reduction in odds of ICU admission among adults with influenza-associated hospitalization (OR = 0.74, 95% CI 0.58, 0.93). Among five studies of adults with influenza-associated hospitalization, vaccinated patients had 31% reduced risk of death compared with unvaccinated patients (OR = 0.69, 95% CI 0.52, 0.92). Among four studies of children with influenza virus infection, vaccination was associated with an estimated 45% reduction in the odds of manifesting fever (OR = 0.55, 95% CI 0.42, 0.71). Vaccination was not significantly associated with receiving a clinical diagnosis of pneumonia among adults hospitalized with influenza (OR = 0.92, 95% CI 0.82, 1.04) or with risk of hospitalization following outpatient influenza illness among adults (OR = 0.60, 95% CI 0.28, 1.28). Overall, our findings support the hypothesis that influenza vaccination may attenuate the course of disease among individuals with breakthrough influenza virus infection.

Residency specialty choice, a complex decision-making process, is often influenced by confidence level built upon knowledge, experience, and fit with the specialty. Despite the need for physiatrists with population growth, especially people with disability and older patients, limited growth in the number of residency positions and delayed exposure to the field of physical medicine and rehabilitation potentially contribute to a lack of confidence in pursuing physical medicine and rehabilitation. Early introduction to a specialty has been shown to impact specialty selection. Thus, this study aims to explore the impact of timing of exposure to physiatry on the confidence level of physical medicine and rehabilitation residents in their specialty choice. A survey for current physical medicine and rehabilitation residents was developed and distributed to residency program directors with a request to forward it to all residents. The response rate was low at 13%; however, the results provide a window into the experience of today's medical and premedical students. Interestingly, of the 175 respondents, a similar number reported first exposure to physiatry during third year and before medical school. In addition, earlier exposure was associated with higher confidence levels in specialty choice, the most powerful factor being the exposure to the specialty before starting medical school or during the preclinical years in medical school. These findings highlight opportunities to improve the physiatry workforce by providing earlier exposure to the specialty, even before medical school. Based on the results of the survey and ongoing discussions among medical students, residents, and faculty leaders, the authors review current recruitment efforts and new ideas.

Global influenza virus circulation declined and has been below traditional seasonal levels during the COVID-19 pandemic.1-3 We reviewed WHO influenza surveillance outputs from May 1-December 31, 2020 (epidemiologic weeks 18-53) from tropical Asian countries. For each country we report influenza surveillance specimens tested, and the percentage positive for influenza, by type and subtype. We compared current data to historical data from 2015-2019 in order to place the current season in historical context. Twelve included countries tested 17,407 surveillance specimens, with 592 (3.4%) testing positive for influenza viruses. From April 27-July 26, 2020 (epidemiologic weeks 18-30), specimens tested decreased from an average of 14,102 per year in 2015-2019 to 3,969 (71.9% decrease) and influenza positivity from 22% to 90% of weeks, influenza circulation was unseasonably low, or absent, during weeks 18-30, 2020. However, during weeks 31-53, the percentage of surveillance specimens testing positive for influenza approached or reached positivity rates of 2015-2019 in Bangladesh and Cambodia; and increased but remained lower than historical positivity in Lao PDR and Viet Nam. The data presented here are a reminder that the low levels of influenza circulation in the northern hemisphere in summer 2020 may not necessarily persist into the upcoming influenza season, and influenza surveillance and prevention strategies should continue as planned and not be delayed.

Background Anthropometric measurements and indices such as weight, height and Body Mass Index (BMI) are often used to assess overall health and nutritional status. Clinicians and epidemiologists often rely on self-reported weight and height to measure BMI. Differences between self-reported and measured weight and height can lead to differences between self-reported and measured BMI, biasing relative risks of diseases associated with differential BMI. Methods Applying regression analysis to a large nationally representative survey data with contemporaneous self-reports and measurements on 3412 individuals aged 65 or over, we provided estimates of the difference between self-reports and measurements of weight, height and BMI for older Australians, analysing demographic, socioeconomic and health correlates of estimated differences. Results We found both males and females underestimated weight, overestimated height and underestimated BMI and there was some evidence these differences increased with age. There was also evidence that these differences were associated with high levels of education and household composition. Conclusion Although average differences were small, for many individuals the differences may be significant, indicating measurements should be taken in clinically focused research and practice. This is important as systematic underestimation of BMI in older adults can have implications for estimating the size of populations at risk of many health conditions, including diabetes, hypertension and functional limitations.

In the 10 months since the first confirmed case of coronavirus disease 2019 (COVID-19) was reported in the United States on January 20, 2020 (1), approximately 13.8 million cases and 272,525 deaths have been reported in the United States. On October 30, the number of new cases reported in the United States in a single day exceeded 100,000 for the first time, and by December 2 had reached a daily high of 196,227.* With colder weather, more time spent indoors, the ongoing U.S. holiday season, and silent spread of disease, with approximately 50% of transmission from asymptomatic persons (2), the United States has entered a phase of high-level transmission where a multipronged approach to implementing all evidence-based public health strategies at both the individual and community levels is essential. This summary guidance highlights critical evidence-based CDC recommendations and sustainable strategies to reduce COVID-19 transmission. These strategies include 1) universal face mask use, 2) maintaining physical distance from other persons and limiting in-person contacts, 3) avoiding nonessential indoor spaces and crowded outdoor spaces, 4) increasing testing to rapidly identify and isolate infected persons, 5) promptly identifying, quarantining, and testing close contacts of persons with known COVID-19, 6) safeguarding persons most at risk for severe illness or death from infection with SARS-CoV-2, the virus that causes COVID-19, 7) protecting essential workers with provision of adequate personal protective equipment and safe work practices, 8) postponing travel, 9) increasing room air ventilation and enhancing hand hygiene and environmental disinfection, and 10) achieving widespread availability and high community coverage with effective COVID-19 vaccines. In combination, these strategies can reduce SARS-CoV-2 transmission, long-term sequelae or disability, and death, and mitigate the pandemic's economic impact. Consistent implementation of these strategies improves health equity, preserves health care capacity, maintains the function of essential businesses, and supports the availability of in-person instruction for kindergarten through grade 12 schools and preschool. Individual persons, households, and communities should take these actions now to reduce SARS-CoV-2 transmission from its current high level. These actions will provide a bridge to a future with wide availability and high community coverage of effective vaccines, when safe return to more everyday activities in a range of settings will be possible.

Transplant recipients are among the groups for whom the updated recommendations for 2020–2021 influenza vaccination should generally be considered essential, notably in the face of the COVID‐19 pandemic.

INTRODUCTION: Early intervention (EI) services provide essential support to families of children with delays or disabilities. Children can enter EI via a variety of routes, though all begin with a referral, and for children who require additional services, subsequent referrals are generally warranted. The referral process may be complicated by rurality, but little is known about families’ experiences with EI referrals in rural areas. This study focuses on better understanding rural families’ perspectives of the EI referral process. METHODS: Families with children in Part C services throughout Montana (N = 30) were interviewed regarding their referral experiences. A layered analysis was used to analyze initial and subsequent referrals, and investigate families’ experiences regarding the referral process. RESULTS: Families’ reports regarding which professionals provided referrals and who they provided referrals to were diverse. As part of qualitative content analysis three themes emerged: 1) the referral process is both challenging and complex; 2) professionals facilitate connections; and, 3) some professionals may have misconceptions or misunderstandings. Some families discussed how aspects of rurality may have exacerbated the complexities and challenges of the EI referral process. DISCUSSION: Based on families’ experiences, professional development related to when, how, and who to refer to EI services, and subsequent support of families during the referral process, may be of utmost importance. Furthermore, families discussed rurality in relationship to turnover rates, limited access to services or specialized knowledge, and travel distance required to receive services, demonstrating the importance of training and retaining rural EI professionals.

This exploratory study examined whether social learning increases similarity in adolescent siblings' behavior and neural patterns during risky decision making. Participants included 86 adolescents (43 sibling dyads; younger siblings:M-age = 12.2 years; 22 females; older siblings:M-age = 14.6 years; 20 females) who completed questionnaires, and a decision-making task during an fMRI scan. Younger siblings became more similar to their older siblings' risky decision making after observing their older sibling take risks). Younger siblings who reported greater modeling of their older sibling, and less differentiation from them, showed increased neural similarity to their older siblings in the ventromedial prefrontal cortex, and the right anterior insula and ventral striatum, respectively. These findings highlight siblings as salient social agents in how adolescents process risky decision making. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01DA039923]; National Science FoundationNational Science Foundation (NSF) [SES 1459719] We greatly appreciate Elise Breitfeld, Sue Hyun Kwon, and Madison Marcus for their diligence in recruitment, data management, and data collection. We also thank Amanda Carter Benjamin, Susannah Ivory, and Virnaliz Jimenez for their assistance in collecting data. This work was supported by grants from the National Institutes of Health (R01DA039923) and National Science Foundation (SES 1459719).

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).

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.

Background Several observational studies have shown decreases in measured influenza vaccine effectiveness (mVE) during influenza seasons. One study found decreases of 6–11%/month during the 2011–2012 to 2014–2015 seasons. These findings could indicate waning immunity but could also occur if vaccine effectiveness is stable and vaccine provides partial protection in all vaccinees (“leaky”) rather than complete protection in a subset of vaccinees. Since it is unknown whether influenza vaccine is leaky, we simulated the 2011–2012 to 2014–2015 influenza seasons to estimate the potential contribution of leaky vaccine effect to the observed decline in mVE. Methods We used available data to estimate daily numbers of vaccinations and infections with A/H1N1, A/H3N2, and B viruses. We assumed that vaccine effect was leaky, calculated mVE as 1 minus the Mantel-Haenszel relative risk of vaccine on incident cases, and determined the mean mVE change per 30 days since vaccination. Because change in mVE was highly dependent on infection rates, we performed simulations using low (15%) and high (31%) total (including symptomatic and asymptomatic) seasonal infection rates. Results For the low infection rate, decreases (absolute) in mVE per 30 days after vaccination were 2% for A/H1N1 and 1% for A/H3N2and B viruses. For the high infection rate, decreases were 5% for A/H1N1, 4% for A/H3, and 3% for B viruses. Conclusions The leaky vaccine bias could account for some, but probably not all, of the observed intraseasonal decreases in mVE. These results underscore the need for strategies to deal with intraseasonal vaccine effectiveness decline.

Background Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children. Methods We included children aged 6 months–17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015–2016 influenza season. Documented influenza vaccination status was obtained from state immunization information systems, the electronic medical record, and/or provider records. Midturbinate nasal and throat swabs were tested for influenza using molecular assays. We estimated VE as 100% × (1 – odds ratio), comparing the odds of vaccination among subjects testing influenza positive with subjects testing negative, using multivariable logistic regression. Results Of 1653 participants, 36 of 707 (5%) of those fully vaccinated, 18 of 226 (8%) of those partially vaccinated, and 85 of 720 (12%) of unvaccinated children tested positive for influenza. Of those vaccinated, almost 90% were documented to have received inactivated vaccine. The majority (81%) of influenza cases were in children ≤ 8 years of age. Of the 139 influenza-positive cases, 42% were A(H1N1)pdm09, 42% were B viruses, and 14% were A(H3N2). Overall, adjusted VE for fully vaccinated children was 56% (95% confidence interval [CI], 34%–71%) against any influenza-associated hospitalization, 68% (95% CI, 36%–84%) for A(H1N1)pdm09, and 44% (95% CI, –1% to 69%) for B viruses. Conclusions These findings demonstrate the importance of annual influenza vaccination in prevention of severe influenza disease and of reducing the number of children who remain unvaccinated or partially vaccinated against influenza.

Multiple genetically distinct influenza B/Victoria lineage viruses have cocirculated in the United States recently, circulating sporadically during the 2018-19 season and more frequently early during the 2019-20 season (1). The beginning of the 2019-20 influenza season in Louisiana was unusually early and intense, with infections primarily caused by influenza B/Victoria lineage viruses. One large pediatric health care facility in New Orleans (facility A) reported 1,268 laboratory-confirmed influenza B virus infections, including 23 hospitalizations from July 31 to November 21, 2019, a time when influenza activity is typically low. During this period, Louisiana also reported one pediatric death associated with influenza B virus infection. An investigation of the influenza B virus infections in Louisiana, including medical and vaccine record abstraction on 198 patients, primarily from facility A, with sporadic cases from other facilities in the state, found that none of the patients had received 2019-20 seasonal influenza vaccine, in part because influenza activity began before influenza vaccination typically occurs. Among 83 influenza B viruses sequenced from 198 patients in Louisiana, 81 (98%) belonged to the recently emerged B/Victoria V1A.3 genetic subclade. Nationally, to date, B/Victoria viruses are the most commonly reported influenza viruses among persons aged

We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected ≈6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

Identifying optimal priming strategies for children2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naïve children.We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs.Mean age was 28 months (range, 6-72 months). Children received vaccines with either 7.5 μg (6-35 months) or 15 μg (≥36 months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72 months, and point estimates were higher among children 6-35 months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p = 0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p = 0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p 0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6).Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35 months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.

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.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

Previous COVID-19 vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during 27 July 2020 to 27 August 2020 from COVID-19-unvaccinated persons with detectable anti-SARS-CoV-2 antibodies. Neutralizing and binding antibody concentrations were severalfold lower in the unvaccinated study population compared to published concentrations at 28 days postvaccination. In this convenience sample, ~88% of neutralizing and ~63 to 86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection; ~30% of neutralizing and 1 to 14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. Our study not only supports observations of infection-induced immunity and current recommendations for vaccination postinfection to maximize protection against COVID-19, but also provides a large data set of pre-COVID-19 vaccination anti-SARS-CoV-2 antibody concentrations that will serve as an important comparator in the current setting of vaccine-induced and hybrid immunity. As new SARS-CoV-2 variants emerge and displace circulating virus strains, we recommend that standardized binding antibody assays that include spike protein-based antigens be utilized to estimate antibody concentrations correlated with protection from COVID-19. These estimates will be helpful in informing public health guidance, such as the need for additional COVID-19 vaccine booster doses to prevent symptomatic infection.

Variants of the oncogenic EML4‐ALK fusion protein contain a similar region of ALK encompassing the kinase domain, but different portions of EML4. Here, we show that EML4‐ALK V1 and V3 proteins form cytoplasmic foci that contain components of the MAPK, PLCγ and PI3K signalling pathways. The ALK inhibitors ceritinib and lorlatinib dissolve these foci and EML4‐ALK V3 but not V1 protein re‐localises to microtubules, an effect recapitulated in a catalytically inactive EML4‐ALK mutant. Mutations that promote a constitutively active ALK stabilise the cytoplasmic foci even in the presence of these inhibitors. In contrast, the inhibitor alectinib increases foci formation of both wild‐type and catalytically inactive EML4‐ALK V3 proteins, but not a Lys‐Glu salt bridge mutant. We propose that EML4‐ALK foci formation occurs as a result of transient association of stable EML4‐ALK trimers mediated through an active conformation of the ALK kinase domain. Our results demonstrate the formation of EML4‐ALK cytoplasmic foci that orchestrate oncogenic signalling and reveal that their assembly depends upon the conformational state of the catalytic domain and can be differentially modulated by structurally divergent ALK inhibitors., EML4‐ALK fusion proteins phase separate into foci that contain oncogenic signaling factors, through a mechanism that depends on an active ALK kinase conformation. Variants have distinct dynamics determined by a specific region of EML4.

BackgroundThe COVID-19 pandemic has caused substantial morbidity and mortality.ObjectiveTo describe monthly clinical trends among adults hospitalized with COVID-19.DesignPooled cross-sectional study.Setting99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET).PatientsU.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020.MeasurementsMonthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients.ResultsAmong 116743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100000 persons), ICU admission (20.2 per 100000 persons), and death (11.7 per 100000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December.LimitationCOVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country.ConclusionRates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines.Primary funding sourceCenters for Disease Control and Prevention.

The human retinal pigment epithelial RPE-1 cell line immortalized with hTERT retains a stable karyotype with a modal chromosome number of 46 and has been widely used to study physiological events in human cell culture systems. To facilitate inducible knock-out or knock-in experiments in this cell line, we have modified the AAVS1 locus to harbour a DNA fragment encoding ERT2-Cre-ERT2 fusion protein under regulation of a Tet-On expression system. In the generated cell line, active Cre recombinase was induced by simple addition of doxycycline and tamoxifen to the culture medium. As proof of concept, we successfully introduced an oncogenic point mutation to the endogenous KRAS gene locus of this cell line. The cell line will serve as a powerful tool to conduct functional analyses of human genes.

Summary This report updates the 2020–21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021–22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4). The 2021–22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html. Recommendations for the use of COVID-19 vaccines are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html, and additional clinical guidance is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html. Updates described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021–22 season are expected to be quadrivalent. Second, the composition of 2021–22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture–based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture–based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4. This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021–22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration–licensed indications. Updates and other information are available from CDC’s influenza website (https://www.cdc.gov/flu); vaccination and health care providers should check this site periodically for additional information.

SARS-CoV-2 transmission from contaminated surfaces, or fomites, has been a concern during the COVID-19 pandemic. Households have been important sites of transmission throughout the COVID-19 pandemic, but there is limited information on SARS-CoV-2 contamination of surfaces in these settings. We describe environmental detection of SARS-CoV-2 in households of persons with COVID-19 to better characterize the potential risks of fomite transmission. Ten households with ≥1 person with laboratory-confirmed COVID-19 and with ≥2 members total were enrolled in Utah, U.S.A. Nasopharyngeal and anterior nasal swabs were collected from members and tested for the presence of SARS-CoV-2 by RT-PCR. Fifteen surfaces were sampled in each household and tested for presence and viability of SARS-CoV-2. SARS-CoV-2 RNA was detected in 23 (15%) of 150 environmental swab samples, most frequently on nightstands (4/6, 67%), pillows (4/23, 17%), and light switches (3/21, 14%). Viable SARS-CoV-2 was cultured from one sample. All households with SARS-CoV-2-positive surfaces had ≥1 person who first tested positive for SARS-CoV-2 ≤ 6 days prior to environmental sampling. SARS-CoV-2 surface contamination occurred early in the course of infection when respiratory transmission is most likely, notably on surfaces in close, prolonged contact with persons with COVID-19. While fomite transmission might be possible, risk is low.

Key Points Question Are rates of severe influenza disease associated with race and ethnicity? Findings In this cross-sectional study of influenza-associated outcomes among 113 352 patients hospitalized with influenza over the course of 10 influenza seasons, Black, Hispanic, and American Indian or Alaska Natives persons had higher rates of hospitalization and intensive care unit admission, even after adjusting for age. The greatest disparities were found in the youngest age groups. Meaning These findings suggest that targeted prevention and intervention efforts, such as improved influenza vaccine coverage and early use of antiviral treatment, could improve influenza-associated outcomes among racial and ethnic minority groups identified in this study as having higher rates of severe influenza disease., This cross-sectional study examines rates of influenza-associated hospitalization, intensive care unit (ICU) admission, and in-hospital death by race and ethnicity in the US from 2009 to 2019., Importance Racial and ethnic minority groups, such as Black, Hispanic, American Indian or Alaska Native, and Asian or Pacific Islander persons, often experience higher rates of severe influenza disease. Objective To describe rates of influenza-associated hospitalization, intensive care unit (ICU) admission, and in-hospital death by race and ethnicity over 10 influenza seasons. Design, Setting, and Participants This cross-sectional study used data from the Influenza-Associated Hospitalization Surveillance Network (FluSurv-NET), which conducts population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in selected counties, representing approximately 9% of the US population. Influenza hospitalizations from the 2009 to 2010 season to the 2018 to 2019 season were analyzed. Data were analyzed from October 2020 to July 2021. Main Outcomes and Measures The main outcomes were age-adjusted and age-stratified rates of influenza-associated hospitalization, ICU admission, and in-hospital death by race and ethnicity overall and by influenza season. Results Among 113 352 persons with an influenza-associated hospitalization (34 436 persons [32.0%] aged ≥75 years; 61 009 [53.8%] women), 70 225 persons (62.3%) were non-Hispanic White (White), 24 850 persons (21.6%) were non-Hispanic Black (Black), 11 903 persons (10.3%) were Hispanic, 5517 persons (5.1%) were non-Hispanic Asian or Pacific Islander, and 857 persons (0.7%) were non-Hispanic American Indian or Alaska Native. Among persons aged younger than 75 years and compared with White persons of the same ages, Black persons were more likely to be hospitalized (eg, age 50-64 years: rate ratio [RR], 2.50 95% CI, 2.43-2.57) and to be admitted to an ICU (eg, age 50-64 years: RR, 2.09; 95% CI, 1.96-2.23). Among persons aged younger than 50 years and compared with White persons of the same ages, American Indian or Alaska Native persons were more likely to be hospitalized (eg, age 18-49 years: RR, 1.72; 95% CI, 1.51-1.96) and to be admitted to an ICU (eg, age 18-49 years: RR, 1.84; 95% CI, 1.40-2.42). Among children aged 4 years or younger and compared with White children, hospitalization rates were higher in Black children (RR, 2.21; 95% CI, 2.10-2.33), Hispanic children (RR, 1.87; 95% CI, 1.77-1.97), American Indian or Alaska Native children (RR, 3.00; 95% CI, 2.55-3.53), and Asian or Pacific Islander children (RR, 1.26; 95% CI, 1.16-1.38), as were rates of ICU admission (Black children: RR, 2.74; 95% CI, 2.43-3.09; Hispanic children: RR, 1.96; 95% CI, 1.73-2.23; American Indian and Alaska Native children: RR, 3.51; 95% CI, 2.45-5.05). In this age group and compared with White children, in-hospital death rates were higher among Hispanic children (RR, 2.98; 95% CI, 1.23-7.19), Black children (RR, 3.39; 95% CI, 1.40-8.18), and Asian or Pacific Islander children (RR, 4.35; 95% CI, 1.55-12.22). Few differences were observed in rates of severe influenza-associated outcomes by race and ethnicity among adults aged 75 years or older. For example, in this age group, compared with White adults, hospitalization rates were slightly higher only among Black adults (RR, 1.05; 95% CI 1.02-1.09). Overall, Black persons had the highest age-adjusted hospitalization rate (68.8 [95% CI, 68.0-69.7] hospitalizations per 100 000 population) and ICU admission rate (11.6 [95% CI, 11.2-11.9] admissions per 100 000 population). Conclusions and Relevance This cross-sectional study found racial and ethnic disparities in rates of severe influenza-associated disease. These data identified subgroups for whom improvements in influenza prevention efforts could be targeted.

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 (

Household Transmission of SARS-CoV-2 from Children In an outbreak of Covid-19 at a summer camp, 224 confirmed cases in children and adolescents 7 to 19 years of age were identified. After the campe...

Purpose To evaluate the agreement between Goldmann applanation tonometry (GAT; Haag-Streit, Bern, Switzerland) and several portable tonometers that could be used for glaucoma screening programs. Design Evaluation of a diagnostic test. Participants Three hundred twenty-one eyes of 168 participants seeking treatment at the glaucoma clinic of a tertiary eye hospital in India. Methods Participants underwent intraocular pressure (IOP) measurement with GAT and 4 index tests: the Icare TA01i rebound tonometer (Icare USA, Raleigh, NC), a noncontact tonometer (NCT; Topcon CT-80; Topcon; Tokyo, Japan), a pneumatonometer (Model 30; Reichert Technologies; Depew, NY), and the Tono-Pen AVIA (Reichert Technologies). Main Outcome Measures Estimates of reproducibility of IOP measurements between each index test and GAT, including the intraclass correlation coefficient (ICC) and the Bland-Altman 95% limits of agreement. Results The Icare showed the greatest agreement with GAT (ICC, 0.69; 95% confidence interval, 0.61–0.74), followed by the NCT (ICC, 0.65; 95% confidence interval, 0.58–0.71), the Tono-Pen (ICC, 0.51; 95% confidence interval, 0.43–0.59), and the pneumatonometer (ICC, 0.36; 95% confidence interval, 0.27–0.44). The pneumatonometer and Tono-Pen tended to overestimate IOP relative to GAT, with a mean difference of 3.4 mmHg (95% limits of agreement [LOA], –7.3 to 14.1 mmHg) for the pneumatonometer and 3.2 mmHg (95% LOA, –6.1 to 12.6 mmHg) for the Tono-Pen. In contrast, measurements from the Icare and NCT were on average within 1 point of those for GAT (mean difference, –0.4 mmHg [95% LOA, –8.4 to 7.6 mmHg] and –0.5 mmHg [95% LOA, –8.7 to 7.6 mmHg], respectively). Conclusions The Icare and NCT both demonstrated good agreement with GAT across a wide range of IOPs and could be considered for glaucoma screening programs.

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).

Background Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC). Methods For 3 influenza seasons (2011–12, 2015–16, and 2017–18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC. Results During the 2017–18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18–64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations. Conclusions Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18–49 years.

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.

Background The contribution of respiratory viruses to childhood pneumonia in tropical low- and middle-income countries is poorly understood. We used population-based respiratory illness surveillance in children 5 years of age or younger in Dhaka, Bangladesh, to characterize these illnesses. Methods We conducted weekly home visits to children who were referred to clinic for fever or respiratory symptoms. Standardized clinical data were collected. Nasopharyngeal washes were collected for one fifth of children diagnosed with a febrile or respiratory syndrome, with virus isolation testing for influenza and reverse transcription polymerase chain reaction testing for other viruses. Pneumonia was defined as age-specific tachypnea and crepitations on chest auscultation by study physicians. Results From April 2004 to February 2008, 17,584 children were followed for 17,644 child-years; 6335 children had 12,499 clinic visits with eligible illnesses, including 6345 pneumonia episodes (incidence of 36 episodes/100 child-years). Annual incidence of pneumonia/100 child-years ranged from 88.3 for children 0-6 months of age to 13.1 for those 36-60 months of age. Of 1248 pneumonia visits with laboratory testing, 803 (64%) had detection of viral pathogens, including 274 respiratory syncytial virus (22% of pneumonia visits with laboratory testing; incidence 7.9/100 child-years), 244 adenovirus (19%; 7.0/100 child-years), 198 human metapneumovirus (16%; 5.7/100 child-years), 174 parainfluenza (14.0%; 5.0/100 child-years), and 81 influenza (6.5%; 2.3/100 child years). Conclusions Viral pathogens contribute to a majority of childhood pneumonia episodes in Bangladesh, a setting with high pneumonia rates, especially in children 2 years of age or younger. Developing effective prevention strategies targeting these children is a high priority. Given less sensitive laboratory method used for influenza detection, influenza rates may be underestimated.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (https://www.cdc.gov/flu/protect/whoshouldvax.htm). Effectiveness of seasonal influenza vaccine varies by season. During each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report uses data from 3,254 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 23, 2018-February 2, 2019. During this period, overall adjusted vaccine effectiveness against all influenza virus infection associated with medically attended ARI was 47% (95% confidence interval [CI] = 34%-57%). For children aged 6 months-17 years, overall vaccine effectiveness was 61% (44%-73%). Seventy-four percent of influenza A infections for which subtype information was available were caused by A(H1N1)pdm09 viruses. Vaccine effectiveness was estimated to be 46% (30%-58%) against illness caused by influenza A(H1N1)pdm09 viruses. CDC recommends that health care providers continue to administer influenza vaccine because influenza activity is ongoing and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses, or other influenza viruses that might circulate later in the season. During the 2017-18 influenza season, in which influenza A(H3N2) predominated, vaccination was estimated to prevent 7.1 million illnesses, 3.7 million medical visits, 109,000 hospitalizations, and 8,000 deaths (1). Vaccination can also reduce the severity of influenza-associated illness (2). Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated.

Background The severity of the 2017–2018 influenza season in the United States was high, with influenza A(H3N2) viruses predominating. Here, we report influenza vaccine effectiveness (VE) and estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the 2017–2018 influenza season. Methods We used national age-specific estimates of 2017–2018 influenza vaccine coverage and disease burden. We estimated VE against medically attended reverse-transcription polymerase chain reaction–confirmed influenza virus infection in the ambulatory setting using a test-negative design. We used a compartmental model to estimate numbers of influenza-associated outcomes prevented by vaccination. Results The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%–43%), including 22% (95% CI, 12%–31%) against influenza A(H3N2), 62% (95% CI, 50%–71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%–57%) against influenza B. We estimated that influenza vaccination prevented 7.1 million (95% CrI, 5.4 million–9.3 million) illnesses, 3.7 million (95% CrI, 2.8 million–4.9 million) medical visits, 109 000 (95% CrI, 39 000–231 000) hospitalizations, and 8000 (95% credible interval [CrI], 1100–21 000) deaths. Vaccination prevented 10% of expected hospitalizations overall and 41% among young children (6 months–4 years). Conclusions Despite 38% VE, influenza vaccination reduced a substantial burden of influenza-associated illness, medical visits, hospitalizations, and deaths in the United States during the 2017–2018 season. Our results demonstrate the benefit of current influenza vaccination and the need for improved vaccines.

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 (

Background Stool consistency is an important diagnostic criterion in both research and clinical medicine and is often used to define diarrheal disease. Methods We examine the pediatric enteric virome across stool consistencies to evaluate differences in richness and community composition using fecal samples collected from children aged 0 to 5 years participating in a clinical trial in the Amhara region of Ethiopia. The consistency of each sample was graded according to the modified Bristol Stool Form Scale for children (mBSFS-C) before a portion of stool was preserved for viral metagenomic analysis. Stool samples were grouped into 29 pools according to stool consistency type. Differential abundance was determined using negative-binomial modeling. Results Of 446 censused children who were eligible to participate, 317 presented for the study visit examination and 269 provided stool samples. The median age of children with stool samples was 36 months. Species richness was highest in watery-consistency stool and decreased as stool consistency became firmer (Spearman’s r = − 0.45, p = 0.013). The greatest differential abundance comparing loose or watery to formed stool was for norovirus GII (7.64, 95% CI 5.8, 9.5) followed by aichivirus A (5.93, 95% CI 4.0, 7.89) and adeno-associated virus 2 (5.81, 95%CI 3.9, 7.7). Conclusions In conclusion, we documented a difference in pediatric enteric viromes according to mBSFS-C stool consistency category, both in species richness and composition. Electronic supplementary material The online version of this article (10.1186/s12879-019-3674-3) contains supplementary material, which is available to authorized users.

The inability to regulate affective arousal in the context of frustration may jeopardize children's ability to form successful friendships, especially as new peer groups are formed during the transition to kindergarten. While substantial research has utilized teacher reports of children's socioemotional behavior, there is less empirical evidence on the peer perspective. The present study utilized data from n = 235 kindergarteners (54% high in disruptive behavior) recruited for a multicomponent intervention. We examined whether physiological reactivity to frustration was associated with children's social success. Peer nominations of liking or disliking to play with the child were used to compute a social preference score, where negative values reflect greater rejection than acceptance. Multilevel growth modeling was employed to capture changes in respiratory sinus arrhythmia (RSA) reactivity across a manipulated inhibitory control task administered in 3 blocks, with differing algorithms embedded to induce affect: points were earned in the 1st and 3rd blocks (reward) and lost during the 2nd block (frustration). Groups did not differ in RSA reactivity during the 1st block, but children who experience greater peer rejection showed significant decreases in RSA (increases in arousal) across frustration. This increased arousal persisted across the 3rd block despite the reinstatement of reward, indicating a greater degree of reactivity and a lack of recovery relative to peer-accepted children. Teacher screenings of disruptive behavior only partially aligned with peer ratings of acceptance, highlighting the benefits of leveraging peer report to capture regulatory functioning and identify children for intervention recruitment.

BACKGROUND Antiviral treatment is recommended for hospitalized patients with suspected and confirmed influenza, but evidence is limited among children. We evaluated the effect of antiviral treatment on hospital length of stay (LOS) among children hospitalized with influenza. METHODS We included children RESULTS Compared with those not receiving antiviral agents, LOS was shorter for those treated ≤2 days after illness onset in both the medical conditions (adjusted hazard ratio: 1.37, P = .02) and ICU (adjusted hazard ratio: 1.46, P = .007) cohorts, corresponding to 37% and 46% increases in daily discharge probability, respectively. Treatment ≥3 days after illness onset had no significant effect in either cohort. In the medical conditions cohort, median LOS was 3 days for those not treated versus 2 days for those treated ≤2 days after symptom onset (P = .005). CONCLUSIONS Early antiviral treatment was associated with significantly shorter hospitalizations in children with laboratory-confirmed influenza and high-risk medical conditions or children treated in the ICU. These results support Centers for Disease Control and Prevention recommendations for prompt empiric antiviral treatment in hospitalized patients with suspected or confirmed influenza.