Pediatric Clinical Influenza Disease by Type and Subtype 2015-2020: A Multicenter, Prospective Study.

BACKGROUND: Previous investigations into clinical signs and symptoms associated with influenza types and subtypes have not definitively established differences in the clinical presentation or severity of influenza disease. METHODS: The study population included children 0 through 17 years old enrolled at 8 New Vaccine Surveillance Network sites between 2015 and 2020 who tested positive for influenza virus by molecular testing. Demographic and clinical data were collected for study participants via parent/guardian interview and medical chart review. Descriptive statistics were used to summarize demographic and clinical characteristics by influenza subtype. Multivariable logistic regression and Cox proportional hazard models were used to assess effects of age, sex, influenza subtype, and history of asthma on severity, including hospital admission, need for supplemental oxygen, and length of stay. RESULTS: Retractions, cyanosis, and need for supplemental oxygen were more frequently observed among patients with influenza A(H1N1)pdm09. Headaches and sore throat were more commonly reported among patients with influenza B. Children with influenza A(H1N1)pdm09 and children with asthma had significantly increased odds of hospital admission (adjusted odds ratio (AOR): 1.39, 95% CI: 1.14-1.69 and AOR: 2.14, 95% CI: 1.72-2.67, respectively). During admission, children with influenza A(H1N1)pdm09 had significantly increased use of supplemental oxygen compared to children with A(H3N2) (AOR: 0.60, 95% CI: 0.44-0.82) or B (AOR: 0.56, 95% CI: 0.41-0.76). CONCLUSIONS: Among children presenting to the emergency department and admitted to the hospital, influenza A(H1N1)pdm09 caused more severe disease compared to influenza A(H3N2) and influenza B. Asthma also contributed to severe influenza disease regardless of subtype.

RSV Neutralizing Antibodies Following Nirsevimab and Palivizumab Dosing.

BACKGROUND: Data describing respiratory syncytial virus (RSV) neutralizing antibody (nAb) levels for nirsevimab, a recently approved, extended half-life, anti-RSV fusion protein (F protein) monoclonal antibody, relative to the previous standard of care, palivizumab, have not been reported. METHODS: The MEDLEY trial was a randomized, palivizumab-controlled, phase 2/3 study of nirsevimab during 2 RSV seasons (season 1 and 2) in infants born preterm (≤35 weeks' gestational age; dosed season 1 only) or with congenital heart disease or chronic lung disease of prematurity (dosed seasons 1 and 2). Participants were randomly assigned to receive a single dose of nirsevimab followed by 4 monthly placebo doses, or 5 once-monthly doses of palivizumab. Anti-RSV fusion protein serology (ie, levels of prefusion [pre-F]/postfusion [post-F] conformation antibodies), nirsevimab and palivizumab serum concentrations, and RSV nAbs were measured in participant samples collected at baseline (pre-dose) and days 31, 151, and 361. RESULTS: Serologic data were similar in seasons 1 and 2. Nirsevimab predominately conferred pre-F antibodies, whereas palivizumab conferred pre-F and post-F antibodies. Nirsevimab and palivizumab serum concentrations were highly correlated with nAb levels in both seasons. In season 1, the nAb levels in nirsevimab recipients were highest in day 31 samples and gradually declined but remained 17-fold above baseline at day 361. nAb levels in palivizumab recipients increased incrementally with monthly doses to day 151. nAb levels followed similar patterns in season 2. nAb levels were ∼10-fold higher with nirsevimab compared with palivizumab across both seasons. CONCLUSIONS: Nirsevimab prophylaxis confers ∼10-fold higher and more sustained RSV nAb levels relative to palivizumab.

Clinical and Genomic Epidemiology of Coxsackievirus A21 and Enterovirus D68 in Homeless Shelters, King County, Washington, USA, 2019-2021.

Congregate homeless shelters are disproportionately affected by infectious disease outbreaks. We describe enterovirus epidemiology across 23 adult and family shelters in King County, Washington, USA, during October 2019-May 2021, by using repeated cross-sectional respiratory illness and environmental surveillance and viral genome sequencing. Among 3,281 participants >3 months of age, we identified coxsackievirus A21 (CVA21) in 39 adult residents (3.0% [95% CI 1.9%-4.8%] detection) across 7 shelters during October 2019-February 2020. We identified enterovirus D68 (EV-D68) in 5 adult residents in 2 shelters during October-November 2019. Of 812 environmental samples, 1 was EV-D68-positive and 5 were CVA21-positive. Other enteroviruses detected among residents, but not in environmental samples, included coxsackievirus A6/A4 in 3 children. No enteroviruses were detected during April 2020-May 2021. Phylogenetically clustered CVA21 and EV-D68 cases occurred in some shelters. Some shelters also hosted multiple CVA21 lineages.

"I probably shouldn't go in today": Inequitable access to paid sick leave and its impacts on health behaviors during the emergence of COVID-19 in the Seattle area.

This study examines inequities in access to paid sick leave (PSL) by race/ethnicity, income, and sex and the role of PSL access on leave-taking and care-seeking behaviors among Seattle-area workers in the months leading up to and during the emergence of COVID-19 in the region. Survey responses were collected online and in-person from individuals experiencing acute respiratory illness symptoms between November 2019 and March 2020 as part of a community-based respiratory viral surveillance study. Chi-square tests and log-binomial models were used to assess the association between PSL access and various socioeconomic indicators. A total of 66.6% (n = 2,276) respondents reported access to PSL. Proportionally, access to PSL was highest in respondents identifying as Asian (70.5%), followed by White (68.7%), Latine (58.4%), Multiracial (57.1%), Black (47.1%), and Other (43.1%). Access to PSL increased with household income. Eighty three percent of high-income respondents reported access compared to 52.9% of low-income households. Only 23.3% of the lowest-income households reported access to PSL. Fewer females (65.2%) than males (70.7%) reported access to PSL. Access to PSL is inequitably distributed across income, race/ethnicity, and sex. This study reinforces the vast body of knowledge on how socioeconomic inequalities increase individual and community-level vulnerability to the impacts of infectious disease outbreaks. It also supports the role of labor and economic policy in mitigating (or exacerbating) these impacts. Exemplified by the COVID-19 pandemic, universal access to PSL, especially for marginalized populations, benefits all.

Immunogenicity and Reactogenicity of High-dose or Standard-dose Influenza Vaccine in a Second Consecutive Influenza Season.

BACKGROUND: Pediatric hematopoietic cell transplant (HCT) recipients are at high-risk for morbidity from influenza virus infection. We demonstrated in a primary phase II randomized controlled trial that two post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart were more immunogenic than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen. METHODS: A subcohort of study participants re-enrolled and had hemagglutinin inhibition (HAI) titers measured at baseline and four weeks after each vaccine dose in year two. We estimated geometric mean fold rise (GMFR) in HAI titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (aGMR, comparing HD-TIV to SD-QIV) for each antigen at each time point. We described systemic and injection-site reactions. RESULTS: A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Post-vaccine GMFR and aGMR estimates were higher for both groups following a single influenza vaccine dose in year two compared to two doses of the same formulation in year one. Both groups had similar frequencies of injection-site and systemic reactions. CONCLUSIONS: A single dose of HD-TIV or SD-QIV was more immunogenic in year two than two doses of the same formulation in year one. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a two-dose schedule in the prior year post-HCT.

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022.

BACKGROUND: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). METHODS: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. RESULTS: Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. CONCLUSIONS: Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children.

Prevalence of SARS-CoV-2 in Children Identified by Preprocedural Testing at 5 US Children's Hospital Systems.

BACKGROUND: The burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic children was initially presumed to be high, which influenced hospital, school and childcare policies. Before vaccines were widely available, some hospitals implemented universal preprocedural SARS-CoV-2 polymerase chain reaction testing on asymptomatic patients. Understanding SARS-CoV-2 prevalence in asymptomatic children is needed to illuminate the diversity of viral characteristics and inform policies implemented during future pandemics. METHODS: Data were extracted from patient records of outpatient children who were preprocedurally tested for SARS-CoV-2 from 5 US hospital systems between March 1, 2020, and February 28, 2021. Prevalence was determined from positive test results. Adjusted odds ratios (AORs) were calculated using mixed logistic regression with the site as a random effect. RESULTS: This study analyzed 93,760 preprocedural SARS-CoV-2 test results from 74,382 patients and found 2693 infections (3.6%) from 2889 positive tests (3.1%). Site-specific prevalence varied across sites. Factors modestly associated with infection included being uninsured [AOR, 1.76 (95% confidence interval [CI], 1.45-2.13)], publicly insured [AOR, 1.17 (95% CI, 1.05-1.30)], Hispanic [AOR, 1.78 (95% CI, 1.59-1.99)], Black [AOR, 1.22 (95% CI, 1.06-1.39)], elementary school age [5-11 years; AOR, 1.15 (95% CI, 1.03-1.28)], or adolescent [12-17 years; AOR, 1.26 (95% CI, 1.13-1.41)]. CONCLUSIONS: SARS-CoV-2 prevalence was low in outpatient children undergoing preprocedural testing, a population that was predominantly asymptomatic at the time of testing. This study contributes evidence that suggests that undetected infection in children likely did not play a predominant role in SARS-CoV-2 transmission during the early prevaccine pandemic period when the general population was naive to the virus.

Evaluation of transplacental maternal SARS-CoV-2 antibody transfer in small for gestational age infants.

Little is known about the potential benefits of maternal immunization in the setting of high-risk pregnancies resulting in small-for-gestational-age (SGA) infants. This study compares transplacental transfer of maternal SARS-CoV-2 anti-Spike antibody in pregnancies with SGA compared to appropriate-for-gestational-age infants.

Evaluation of a Modified Vesikari Severity Score as a Research Tool for Assessing Pediatric Acute Gastroenteritis.

A modified Vesikari severity score (MVSS) is a useful research tool for assessing severity of acute gastroenteritis. We present a MVSS for studies in which a follow-up assessment of symptoms cannot be obtained. The MVSS significantly correlated with other markers of severity, including illness duration and work and school absenteeism.

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Absenteeism and Health Behavior Trends Associated With Acute Respiratory Illness Before and During the COVID-19 Pandemic in a Community Household Cohort, King County, Washington.

Introduction: Longitudinal data on how acute respiratory illness (ARI) affects behavior, namely school or work participation, and nonpharmaceutical intervention (NPI) usage before and during the COVID-19 pandemic is limited. The authors assessed how ARIs and specific symptoms affected school, work, and health-related behaviors over time. Methods: From November 2019 to June 2021, participating households with children in King County, Washington, were remotely monitored for ARI symptoms weekly. Following ARIs, participants reported illness-related effects on school, work, and NPI use. Using logistic regression with generalized estimating equations, the authors examined associations between symptoms and behaviors. Results: Of 1,861 participants, 581 (31%) from 293 households reported 884 ARIs and completed one-week follow-up surveys. Compared with the prepandemic period, during the period of the pandemic pre-COVID-19 vaccine, ARI-related school (56% vs 10%, p<0.001) absenteeism decreased and masking increased (3% vs 28%, p<0.001). After vaccine authorization in December 2020, more ARIs resulted in masking (3% vs 48%, p<0.001), avoiding contact with non-household members (26% vs 58%, p<0.001), and staying home (37% vs 69%, p<0.001) compared with the prepandemic period. Constitutional symptoms such as fever were associated with work disruptions (OR=1.91; 95% CI=1.06, 3.43), staying home (OR=1.55; 95% CI=1.06, 2.27), and decreased contact with non-household members (OR=1.58; 95% CI=1.05, 2.36). Conclusions: This remote household study permitted uninterrupted tracking of behavioral changes in families with children before and during the COVID-19 pandemic, identifying increased use of some NPIs when ill but no additional illness-associated work or school disruptions.

Transfer of Respiratory Syncytial Virus Prefusion F Protein Antibody in Low Birthweight Infants.

Background: Respiratory syncytial virus (RSV)-associated lower respiratory tract infection contributes significantly to morbidity/mortality worldwide in low birthweight (LBW) infants (<2500 g). Studies have demonstrated decreased maternal immunoglobulin G (IgG) transfer of various antibodies to LBW infants. We aimed to evaluate naturally acquired RSV anti-prefusion F protein (anti-preF) antibody transfer in pregnancies with LBW versus normal birthweight (NBW) infants. Methods: In this cohort study conducted among pregnant individuals and their infants, we tested paired maternal and singleton infant cord samples for RSV anti-preF IgG via an electrochemiluminescence immunoassay, using linear regression to evaluate associations between LBW and anti-preF IgG. Covariates included seasonality, insurance, small-for-gestational-age birthweight, and gestational age at delivery. Results: We tested maternal/cord RSV anti-preF IgG from 54 and 110 pregnancies with LBW and NBW infants, respectively. Of LBW infants, 22 (40.7%) were born both preterm and with small-for-gestational-age birthweight. The median (interquartile range) gestational age at delivery and birthweight were 34.0 (31.7-37.1) weeks and 1902 (1393-2276) g for LBW infants versus 39.1 (38.3-39.9) weeks and 3323 (3109-3565) g for NBW infants (both P < .001). In unadjusted comparisons, preterm infants had significantly lower cord anti-preF IgG levels and cord-maternal IgG ratios compared with full-term infants, while LBW infants had significantly lower cord-maternal IgG ratios than NBW infants (all P < .01). After adjustment for covariates, there was no difference in cord-maternal IgG ratios (ß =-0.29 [95% confidence interval, -.63 to .05]) between LBW and NBW infants. Conclusions: We documented robust transfer of maternal RSV anti-preF IgG in pregnancies with both LBW and NBW infants. Further studies are needed to assess immune protection in at-risk infants.

The Potential Benefits of Delaying Seasonal Influenza Vaccine Selections for the Northern Hemisphere: A Retrospective Modeling Study in the United States.

BACKGROUND: Antigenic similarity between vaccine viruses and circulating viruses is crucial for achieving high vaccine effectiveness against seasonal influenza. New non-egg-based vaccine production technologies could revise current vaccine formulation schedules. We aim to assess the potential benefit of delaying seasonal influenza vaccine virus selection decisions. METHODS: We identified seasons where season-dominant viruses presented increasing prevalence after vaccine formulation had been decided in February for the Northern Hemisphere, contributing to their antigenic discrepancy with vaccine viruses. Using a SEIR (susceptible-exposed-infectious-recovered) model of seasonal influenza in the United States, we evaluated the impact of updating vaccine decisions with more antigenically similar vaccine viruses on the influenza burden in the United States. RESULTS: In 2014-2015 and 2019-2020, the season-dominant A(H3N2) subclade and B/Victoria clade, respectively, presented increasing prevalence after vaccine decisions were already made for the Northern Hemisphere. Our model showed that the updated A(H3N2) vaccine could have averted 5000-65 000 influenza hospitalizations in the United States in 2014-2015, whereas updating the B/Victoria vaccine component did not substantially change influenza burden in the 2019-2020 season. CONCLUSIONS: With rapid vaccine production, revising current timelines for vaccine selection could result in substantial epidemiological benefits, particularly when additional data could help improve the antigenic match between vaccine and circulating viruses.

Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin.

Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.

Kinetics and Durability of Antibody and T-Cell Responses to SARS-CoV-2 in Children.

BACKGROUND: The kinetics and durability of T-cell responses to SARS-CoV-2 in children are not well characterized. We studied a cohort of children aged 6 months to 20 years with COVID-19 in whom peripheral blood mononuclear cells and sera were archived at approximately 1, 6, and 12 months after symptom onset. METHODS: We compared antibody responses (n = 85) and T-cell responses (n = 30) to nucleocapsid (N) and spike (S) glycoprotein over time across 4 age strata: 6 months to 5 years and 5-9, 10-14, and 15-20 years. RESULTS: N-specific antibody responses declined over time, becoming undetectable in 26 (81%) of 32 children by approximately 1 year postinfection. Functional breadth of anti-N CD4+ T-cell responses also declined over time and were positively correlated with N-antibody responses (Pearson r = .31, P = .008). CD4+ T-cell responses to S displayed greater functional breadth than N in unvaccinated children and, with neutralization titers, were stable over time and similar across age strata. Functional profiles of CD4+ T-cell responses against S were not significantly modulated by vaccination. CONCLUSIONS: Our data reveal durable age-independent T-cell immunity to SARS-CoV-2 structural proteins in children over time following COVID-19 infection as well as S-antibody responses in comparison with declining antibody responses to N.

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds.

BACKGROUND: With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important. METHODS: We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month- to <12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month- to <5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5- to <12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. RESULTS: In 6-month- to <5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5- to <12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable with dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6-month- to <12-year-olds. Reactogenicity events were generally mild to moderate. No adverse events led to discontinuation. CONCLUSIONS: These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.

Respiratory Syncytial Virus-Associated Hospitalizations in Children <5 Years: 2016-2022.

BACKGROUND: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. METHODS: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. RESULTS: There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. CONCLUSIONS: The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

How Immunocompromised Hosts Were Left Behind in the Quest to Control the COVID-19 Pandemic.

The immunocompromised population was disproportionately affected by the severe acute respiratory syndrome coronavirus 2 pandemic. However, these individuals were largely excluded from clinical trials of vaccines, monoclonal antibodies, and small molecule antivirals. Although the community of scientists, clinical researchers, and funding agencies have proven that these therapeutics can be made and tested in record time, extending this progress to vulnerable and medically complex individuals from the start has been a missed opportunity. Here, we advocate that it is paramount to plan for future pandemics by investing in specific clinical trial infrastructure for the immunocompromised population to be prepared when the need arises.

Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years.

Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses. Pathogen circulation dropped substantially after the initiation of COVID-19 stay-at-home orders in March 2020. During this period, mobility was a positive, leading indicator of transmission of all endemic viruses and lagging and negatively correlated with SARS-CoV-2 activity. Mobility was briefly predictive of SARS-CoV-2 transmission when restrictions relaxed but associations weakened in subsequent waves. The rebound of endemic viruses was heterogeneously timed but exhibited stronger, longer-lasting relationships with mobility than SARS-CoV-2. Overall, mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change and at the beginning of epidemic waves.