Association of Chronic Medical Conditions With Severe Outcomes Among Nonpregnant Adults 18-49 Years Old Hospitalized With Influenza, FluSurv-NET, 2011-2019.

Background: Older age and chronic conditions are associated with severe influenza outcomes; however, data are only comprehensively available for adults ≥65 years old. Using data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), we identified characteristics associated with severe outcomes in adults 18-49 years old hospitalized with influenza. Methods: We included FluSurv-NET data from nonpregnant adults 18-49 years old hospitalized with laboratory-confirmed influenza during the 2011-2012 through 2018-2019 seasons. We used bivariate and multivariable logistic regression to determine associations between select characteristics and severe outcomes including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. Results: A total of 16 140 patients aged 18-49 years and hospitalized with influenza were included in the analysis; the median age was 39 years, and 26% received current-season influenza vaccine before hospitalization. Obesity, asthma, and diabetes mellitus were the most common chronic conditions. Conditions associated with a significantly increased risk of severe outcomes included age group 30-39 or 40-49 years (IMV, age group 30-39 years: adjusted odds ratio [aOR], 1.25; IMV, age group 40-49 years: aOR, 1.36; death, age group 30-39 years: aOR, 1.28; death, age group 40-49 years: aOR, 1.69), being unvaccinated (ICU: aOR, 1.18; IMV: aOR, 1.25; death: aOR, 1.48), and having chronic conditions including extreme obesity and chronic lung, cardiovascular, metabolic, neurologic, or liver diseases (ICU: range aOR, 1.22-1.56; IMV: range aOR, 1.17-1.54; death: range aOR, 1.43-2.36). Conclusions: To reduce the morbidity and mortality associated with influenza among adults aged 18-49 years, health care providers should strongly encourage receipt of annual influenza vaccine and lifestyle/behavioral modifications, particularly among those with chronic medical conditions.

Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018.

Background: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes. Methods: We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017-2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB-65, Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. Results: Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in-hospital mortality, at 0.78. Conclusions: We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision-making.

Constructing Antiretroviral Supramolecular Polymers as Long-Acting Injectables through Rational Design of Drug Amphiphiles with Alternating Antiretroviral-Based and Hydrophobic Residues.

One of the main challenges in the development of long-acting injectables for HIV treatment is the limited duration of drug release, which results in the need for frequent dosing and reduced patient adherence. In this context, we leverage the intrinsic reversible features of supramolecular polymers and their unique ability to form a three-dimensional network under physiological conditions to design a class of self-assembling drug amphiphiles (DAs) based upon lamivudine, a water-soluble antiretroviral (ARV) agent and nucleoside reverse transcriptase inhibitor. The designed ARV DAs contain three pairs of alternating hydrophobic valine (V) and hydrophilic lamivudine-modified lysine (K3TC) residues with a varying number of glutamic acids (E) placed on the C-terminus. Upon dissolution in deionized water, all three ARV DAs were found to spontaneously associate into supramolecular filaments of several micrometers in length, with varying levels of lateral stacking. Addition of 1× PBS triggered immediate gelation of the two ARV DAs with 2 or 3 E residues, and upon dilution in an in vitro setting, the dissociation from the supramolecular state to the monomeric state enabled a long-acting linear release of the ARV DAs. In vivo studies further confirmed their injectability, rapid in situ hydrogel formation, enhanced local retention, and long-acting therapeutic release over a month. Importantly, our pharmacokinetic studies suggest that the injected ARV supramolecular polymeric hydrogel was able to maintain a plasma concentration of lamivudine above its IC50 value for more than 40 days in mice and showed minimal systemic immunogenicity. We believe that these results shed important light on the rational design of long-acting injectables using the drug-based molecular assembly strategy, and the reported ARV supramolecular hydrogels hold great promise for improving HIV treatment outcomes.

Severity of influenza-associated hospitalisations by influenza virus type and subtype in the USA, 2010-19: a repeated cross-sectional study.

BACKGROUND: Influenza burden varies across seasons, partly due to differences in circulating influenza virus types or subtypes. Using data from the US population-based surveillance system, Influenza Hospitalization Surveillance Network (FluSurv-NET), we aimed to assess the severity of influenza-associated outcomes in individuals hospitalised with laboratory-confirmed influenza virus infections during the 2010-11 to 2018-19 influenza seasons. METHODS: To evaluate the association between influenza virus type or subtype causing the infection (influenza A H3N2, A H1N1pdm09, and B viruses) and in-hospital severity outcomes (intensive care unit [ICU] admission, use of mechanical ventilation or extracorporeal membrane oxygenation [ECMO], and death), we used FluSurv-NET to capture data for laboratory-confirmed influenza-associated hospitalisations from the 2010-11 to 2018-19 influenza seasons for individuals of all ages living in select counties in 13 US states. All individuals had to have an influenza virus test within 14 days before or during their hospital stay and an admission date between Oct 1 and April 30 of an influenza season. Exclusion criteria were individuals who did not have a complete chart review; cases from sites that contributed data for three or fewer seasons; hospital-onset cases; cases with unidentified influenza type; cases of multiple influenza virus type or subtype co-infection; or individuals younger than 6 months and ineligible for the influenza vaccine. Logistic regression models adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site compared odds of in-hospital severity by virus type or subtype. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season. FINDINGS: Data for 122 941 individuals hospitalised with influenza were captured in FluSurv-NET from the 2010-11 to 2018-19 seasons; after exclusions were applied, 107 941 individuals remained and underwent influenza A virus imputation when missing A subtype (43·4%). After imputation, data for 104 969 remained and were included in the final analytic sample. Averaging across imputed datasets, 57·7% (weighted percentage) had influenza A H3N2, 24·6% had influenza A H1N1pdm09, and 17·7% had influenza B virus infections; 16·7% required ICU admission, 6·5% received mechanical ventilation or ECMO, and 3·0% died (95% CIs had a range of less than 0·1% and are not displayed). Individuals with A H1N1pdm09 had higher odds of in-hospital severe outcomes than those with A H3N2: adjusted odds ratios (ORs) for A H1N1pdm09 versus A H3N2 were 1·42 (95% CI 1·32-1·52) for ICU admission; 1·79 (1·60-2·00) for mechanical ventilation or ECMO use; and 1·25 (1·07-1·46) for death. The adjusted ORs for individuals infected with influenza B versus influenza A H3N2 were 1·06 (95% CI 1·01-1·12) for ICU admission, 1·14 (1·05-1·24) for mechanical ventilation or ECMO use, and 1·18 (1·07-1·31) for death. INTERPRETATION: Despite a higher burden of hospitalisations with influenza A H3N2, we found an increased likelihood of in-hospital severe outcomes in individuals hospitalised with influenza A H1N1pdm09 or influenza B virus. Thus, it is important for individuals to receive an annual influenza vaccine and for health-care providers to provide early antiviral treatment for patients with suspected influenza who are at increased risk of severe outcomes, not only when there is high influenza A H3N2 virus circulation but also when influenza A H1N1pdm09 and influenza B viruses are circulating. FUNDING: The US Centers for Disease Control and Prevention.

Self-assembling paclitaxel-mediated stimulation of tumor-associated macrophages for postoperative treatment of glioblastoma.

The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic "don't eat me" signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects.

Influenza Antiviral Use in Patients Hospitalized With Laboratory-Confirmed Influenza in the United States, FluSurv-NET, 2015-2019.

From surveillance data of patients hospitalized with laboratory-confirmed influenza in the United States during the 2015-2016 through 2018-2019 seasons, initiation of antiviral treatment increased from 86% to 94%, with increases seen across all age groups. However, 62% started therapy ≥3 days after illness onset, driven by late presentation to care.

Antiviral supramolecular polymeric hydrogels by self-assembly of tenofovir-bearing peptide amphiphiles.

The development of long-acting antiviral therapeutic delivery systems is crucial to improve the current treatment and prevention of HIV and chronic HBV. We report here on the conjugation of tenofovir (TFV), an FDA approved nucleotide reverse transcriptase inhibitor (NRTI), to rationally designed peptide amphiphiles (PAs), to construct antiviral prodrug hydrogelators (TFV-PAs). The resultant conjugates can self-assemble into one-dimensional nanostructures in aqueous environments and consequently undergo rapid gelation upon injection into 1× PBS solution to create a drug depot. The TFV-PA designs containing two or three valines could attain instantaneous gelation, with one displaying sustained release for more than 28 days in vitro. Our studies suggest that minor changes in peptide design can result in differences in supramolecular morphology and structural stability, which impacted in vitro gelation and release. We envision the use of this system as an important delivery platform for the sustained, linear release of TFV at rates that can be precisely tuned to attain therapeutically relevant TFV plasma concentrations.

Leveraging the therapeutic, biological, and self-assembling potential of peptides for the treatment of viral infections.

Peptides and peptide-based materials have an increasing role in the treatment of viral infections through their use as active pharmaceutical ingredients, targeting moieties, excipients, carriers, or structural components in drug delivery systems. The discovery of peptide-based therapeutic compounds, coupled with the development of new stabilization and formulation strategies, has led to a resurgence of antiviral peptide therapeutics over the past two decades. The ability of peptides to bind cell receptors and to facilitate membrane penetration and subsequent intracellular trafficking enables their use in various antiviral systems for improved targeting efficiency and treatment efficacy. Importantly, the self-assembly of peptides into well-defined nanostructures provides a vast library of discrete constructs and supramolecular biomaterials for systemic and local delivery of antiviral agents. We review here the recent progress in exploiting the therapeutic, biological, and self-assembling potential of peptides, peptide conjugates, and their supramolecular assemblies in treating human viral infections, with an emphasis on the treatment strategies for Human Immunodeficiency Virus (HIV).

Supramolecular nanomedicines through rational design of self-assembling prodrugs.

Advancements in the development of nanomaterials have led to the creation of a plethora of functional constructs as drug delivery vehicles to address many dire medical needs. The emerging prodrug strategy provides an alternative solution to create nanomedicines of extreme simplicity by directly using the therapeutic agents as molecular building blocks. This Review outlines different prodrug-based drug delivery systems, highlights the advantages of the prodrug strategy for therapeutic delivery, and demonstrates how combinations of different functionalities - such as stimuli responsiveness, targeting propensity, and multidrug conjugation - can be incorporated into designed prodrug delivery systems. Furthermore, we discuss the opportunities and challenges facing this rapidly growing field.

Rates of Severe Influenza-Associated Outcomes Among Older Adults Living With Diabetes-Influenza Hospitalization Surveillance Network (FluSurv-NET), 2012-2017.

Background: Diabetes mellitus (DM) is common among older adults hospitalized with influenza, yet data are limited on the impact of DM on risk of severe influenza-associated outcomes. Methods: We included adults aged ≥65 years hospitalized with influenza during 2012-2013 through 2016-2017 from the Influenza Hospitalization Surveillance Network (FluSurv-NET), a population-based surveillance system for laboratory-confirmed influenza-associated hospitalizations conducted in defined counties within 13 states. We calculated population denominators using the Centers for Medicare and Medicaid Services county-specific DM prevalence estimates and National Center for Health Statistics population data. We present pooled rates and rate ratios (RRs) of intensive care unit (ICU) admission, pneumonia diagnosis, mechanical ventilation, and in-hospital death for persons with and without DM. We estimated RRs and 95% confidence intervals (CIs) using meta-analysis with site as a random effect in order to control for site differences in the estimates. Results: Of 31 934 hospitalized adults included in the analysis, 34% had DM. Compared to those without DM, adults with DM had higher rates of influenza-associated hospitalization (RR, 1.57 [95% CI, 1.43-1.72]), ICU admission (RR, 1.84 [95% CI, 1.67-2.04]), pneumonia (RR, 1.57 [95% CI, 1.42-1.73]), mechanical ventilation (RR, 1.95 [95% CI, 1.74-2.20]), and in-hospital death (RR, 1.48 [95% CI, 1.23-1.80]). Conclusions: Older adults with DM have higher rates of severe influenza-associated outcomes compared to those without DM. These findings reinforce the importance of preventing influenza virus infections through annual vaccination, and early treatment of influenza illness with antivirals in older adults with DM.

Epidemiology, Clinical Characteristics, and Outcomes of Influenza-Associated Hospitalizations in US Children Over 9 Seasons Following the 2009 H1N1 Pandemic.

BACKGROUND: Recent population-based data are limited regarding influenza-associated hospitalizations in US children. METHODS: We identified children <18 years hospitalized with laboratory-confirmed influenza during 2010-2019 seasons, through the Centers for Disease Control and Prevention's Influenza Hospitalization Surveillance Network. Adjusted hospitalization and in-hospital mortality rates were calculated, and multivariable logistic regression was conducted to evaluate risk factors for pneumonia, intensive care unit (ICU) admission, mechanical ventilation, and death. RESULTS: Over 9 seasons, adjusted influenza-associated hospitalization incidence rates ranged from 10 to 375 per 100 000 persons each season and were highest among infants <6 months old. Rates decreased with increasing age. The highest in-hospital mortality rates were observed in children <6 months old (0.73 per 100 000 persons). Over time, antiviral treatment significantly increased, from 56% to 85% (P < .001), and influenza vaccination rates increased from 33% to 44% (P = .003). Among the 13 235 hospitalized children, 2676 (20%) were admitted to the ICU, 2262 (17%) had pneumonia, 690 (5%) required mechanical ventilation, and 72 (0.5%) died during hospitalization. Compared with those <6 months of age, hospitalized children ≥13 years old had higher odds of pneumonia (adjusted odds ratio, 2.7 [95% confidence interval, 2.1-3.4], ICU admission (1.6 [1.3-1.9]), mechanical ventilation (1.6 [1.1-2.2]), and death (3.3 [1.2-9.3]). CONCLUSIONS: Hospitalization and death rates were greatest in younger children at the population level. Among hospitalized children, however, older children had a higher risk of severe outcomes. Continued efforts to prevent and attenuate influenza in children are needed.

Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with congestive heart failure-United States, 2015-2017.

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (<65 years and ≥65 years) RSV-associated hospitalization rates by CHF status. Estimates were adjusted for age and the under-detection of RSV. We also report rate differences (RD) and rate ratios (RR) by comparing the rates for those with and without CHF. RESULTS: 2042 hospitalized RSV cases with CHF status recorded were identified. Most (60.2%, n = 1230) were ≥65 years, and 28.3% (n = 577) had CHF. The adjusted RSV hospitalization rate was 26.7 (95% CI: 22.2, 31.8) per 10,000 population in adults with CHF versus 3.3 (95% CI: 3.3, 3.3) per 10,000 in adults without CHF (RR: 8.1, 95% CI: 6.8, 9.7; RD: 23.4, 95% CI: 18.9, 28.5). Adults with CHF had higher rates of RSV-associated hospitalization in both age groups (<65 years and ≥65 years). Adults ≥65 years with CHF had the highest rate (40.5 per 10,000 population, 95% CI: 35.1, 46.6). CONCLUSIONS: Adults with CHF had 8 times the rate of RSV-associated hospitalization compared with adults without CHF. Identifying high-risk populations for RSV infection can inform future RSV vaccination policies and recommendations.

Characteristics and Outcomes of Hospitalized Pregnant Women With Influenza, 2010 to 2019 : A Repeated Cross-Sectional Study.

BACKGROUND: Pregnant women may be at increased risk for severe influenza-associated outcomes. OBJECTIVE: To describe characteristics and outcomes of hospitalized pregnant women with influenza. DESIGN: Repeated cross-sectional study. SETTING: The population-based U.S. Influenza Hospitalization Surveillance Network during the 2010-2011 through 2018-2019 influenza seasons. PATIENTS: Pregnant women (aged 15 to 44 years) hospitalized with laboratory-confirmed influenza identified through provider-initiated or facility-based testing practices. MEASUREMENTS: Clinical characteristics, interventions, and in-hospital maternal and fetal outcomes were obtained through medical chart abstraction. Multivariable logistic regression was used to evaluate the association between influenza A subtype and severe maternal influenza-associated outcomes, including intensive care unit (ICU) admission, mechanical ventilation, extracorporeal membrane oxygenation, or in-hospital death. RESULTS: Of 9652 women aged 15 to 44 years and hospitalized with influenza, 2690 (27.9%) were pregnant. Among the 2690 pregnant women, the median age was 28 years, 62% were in their third trimester, and 42% had at least 1 underlying condition. Overall, 32% were vaccinated against influenza and 88% received antiviral treatment. Five percent required ICU admission, 2% required mechanical ventilation, and 0.3% (n = 8) died. Pregnant women with influenza A H1N1 were more likely to have severe outcomes than those with influenza A H3N2 (adjusted risk ratio, 1.9 [95% CI, 1.3 to 2.8]). Most women (71%) were still pregnant at hospital discharge. Among 754 women who were no longer pregnant at discharge, 96% had a pregnancy resulting in live birth, and 3% experienced fetal loss. LIMITATION: Maternal and fetal outcomes that occurred after hospital discharge were not captured. CONCLUSION: Over 9 influenza seasons, one third of reproductive-aged women hospitalized with influenza were pregnant. Influenza A H1N1 was associated with more severe maternal outcomes. Pregnant women remain a high-priority target group for vaccination. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Risk Factors for Severe COVID-19 in Children.

OBJECTIVES: Describe population-based rates and risk factors for severe coronavirus disease 2019 (COVID-19) (ie, ICU admission, invasive mechanical ventilation, or death) among hospitalized children. METHODS: During March 2020 to May 2021, the COVID-19-Associated Hospitalization Surveillance Network identified 3106 children hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in 14 states. Among 2293 children primarily admitted for COVID-19, multivariable generalized estimating equations generated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) of the associations between demographic and medical characteristics abstracted from medical records and severe COVID-19. We calculated age-adjusted cumulative population-based rates of severe COVID-19 among all children. RESULTS: Approximately 30% of hospitalized children had severe COVID-19; 0.5% died during hospitalization. Among hospitalized children aged <2 years, chronic lung disease (aRR: 2.2; 95% CI: 1.1-4.3), neurologic disorders (aRR: 2.0; 95% CI: 1.5‒2.6), cardiovascular disease (aRR: 1.7; 95% CI: 1.2‒2.3), prematurity (aRR: 1.6; 95% CI: 1.1‒2.2), and airway abnormality (aRR: 1.6; 95% CI: 1.1‒2.2) were associated with severe COVID-19. Among hospitalized children aged 2 to 17 years, feeding tube dependence (aRR: 2.0; 95% CI: 1.5‒2.5), diabetes mellitus (aRR: 1.9; 95% CI: 1.6‒2.3) and obesity (aRR: 1.2; 95% CI: 1.0‒1.4) were associated with severe COVID-19. Severe COVID-19 occurred among 12.0 per 100 000 children overall and was highest among infants, Hispanic children, and non-Hispanic Black children. CONCLUSIONS: Results identify children at potentially higher risk of severe COVID-19 who may benefit from prevention efforts, including vaccination. Rates establish a baseline for monitoring changes in pediatric illness severity after increased availability of COVID-19 vaccines and the emergence of new variants.

Racial and Ethnic Disparities in Rates of COVID-19-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death in the United States From March 2020 to February 2021.

Importance: Racial and ethnic minority groups are disproportionately affected by COVID-19. Objectives: To evaluate whether rates of severe COVID-19, defined as hospitalization, intensive care unit (ICU) admission, or in-hospital death, are higher among racial and ethnic minority groups compared with non-Hispanic White persons. Design, Setting, and Participants: This cross-sectional study included 99 counties within 14 US states participating in the COVID-19-Associated Hospitalization Surveillance Network. Participants were persons of all ages hospitalized with COVID-19 from March 1, 2020, to February 28, 2021. Exposures: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test within 14 days prior to or during hospitalization. Main Outcomes and Measures: Cumulative age-adjusted rates (per 100 000 population) of hospitalization, ICU admission, and death by race and ethnicity. Rate ratios (RR) were calculated for each racial and ethnic group compared with White persons. Results: Among 153 692 patients with COVID-19-associated hospitalizations, 143 342 (93.3%) with information on race and ethnicity were included in the analysis. Of these, 105 421 (73.5%) were 50 years or older, 72 159 (50.3%) were male, 28 762 (20.1%) were Hispanic or Latino, 2056 (1.4%) were non-Hispanic American Indian or Alaska Native, 7737 (5.4%) were non-Hispanic Asian or Pacific Islander, 40 806 (28.5%) were non-Hispanic Black, and 63 981 (44.6%) were White. Compared with White persons, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely to have higher cumulative age-adjusted rates of hospitalization, ICU admission, and death as follows: American Indian or Alaska Native (hospitalization: RR, 3.70; 95% CI, 3.54-3.87; ICU admission: RR, 6.49; 95% CI, 6.01-7.01; death: RR, 7.19; 95% CI, 6.47-7.99); Latino (hospitalization: RR, 3.06; 95% CI, 3.01-3.10; ICU admission: RR, 4.20; 95% CI, 4.08-4.33; death: RR, 3.85; 95% CI, 3.68-4.01); Black (hospitalization: RR, 2.85; 95% CI, 2.81-2.89; ICU admission: RR, 3.17; 95% CI, 3.09-3.26; death: RR, 2.58; 95% CI, 2.48-2.69); and Asian or Pacific Islander (hospitalization: RR, 1.03; 95% CI, 1.01-1.06; ICU admission: RR, 1.91; 95% CI, 1.83-1.98; death: RR, 1.64; 95% CI, 1.55-1.74). Conclusions and Relevance: In this cross-sectional analysis, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely than White persons to have a COVID-19-associated hospitalization, ICU admission, or in-hospital death during the first year of the US COVID-19 pandemic. Equitable access to COVID-19 preventive measures, including vaccination, is needed to minimize the gap in racial and ethnic disparities of severe COVID-19.

Therapeutic supramolecular tubustecan hydrogel combined with checkpoint inhibitor elicits immunity to combat cancer.

The clinical benefit of PD-1/PD-L1 blockade immunotherapy is substantially restricted by insufficient infiltration of T lymphocytes into tumors and compromised therapeutic effects due to immune-related adverse events following systemic administration. Some chemotherapeutic agents have been reported to trigger tumor-associated T cell responses, providing a promising strategy to achieve potent immune activation in a synergistic manner with PD-1 blockade immunotherapy. In light of this, a localized chemoimmunotherapy system was developed using an anti-cancer drug-based supramolecular polymer (SP) hydrogel to "re-edit" the host's immune system to combat cancer. This in situ forming injectable aPD1/TT6 SP hydrogel serves as a drug-delivery depot for sustained release of bioactive camptothecin (CPT) and aPD1 into the tumor microenvironment, priming the tumor for robust infiltration of tumor-associated T cells and subsequently prompting a response to the immune checkpoint blockade. Our in vivo results demonstrate that this chemoimmunotherapy hydrogel provokes a long-term and systemic anticancer T cell immune response, which elicits tumor regression while also inhibiting tumor recurrence and potential metastasis.

Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance - COVID-NET, 14 States, January-August 2021.

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.

Census tract socioeconomic indicators and COVID-19-associated hospitalization rates-COVID-NET surveillance areas in 14 states, March 1-April 30, 2020.

OBJECTIVES: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. METHODS: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. RESULTS: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts. CONCLUSIONS: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.

Influenza Antiviral Treatment and Length of Stay.

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 <18 years hospitalized with laboratory-confirmed influenza in the US Influenza Hospitalization Surveillance Network. We collected data for 2 cohorts: 1 with underlying medical conditions not admitted to the ICU (n = 309, 2012-2013) and an ICU cohort (including children with and without underlying conditions; n = 299, 2010-2011 to 2012-2013). We used a Cox model with antiviral receipt as a time-dependent variable to estimate hazard of discharge and a Kaplan-Meier survival analysis to determine LOS. 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.

Clinical Trends Among U.S. Adults Hospitalized With COVID-19, March to December 2020 : A Cross-Sectional Study.

BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 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. RESULTS: Among 116 743 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 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 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 18 508 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. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates 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 SOURCE: Centers for Disease Control and Prevention.