Currently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk ...factors for severe outcomes among adults hospitalized with COVID-19.
We analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March-2 May 2020, as identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality.
The data show that 92% of patients had ≥1 underlying condition; 32% required ICU admission; 19% required invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84, and ≥85 years versus 18-39 years (adjusted risk ratios aRRs, 1.53, 1.65, 1.84, and 1.43, respectively); male sex (aRR, 1.34); obesity (aRR, 1.31); immunosuppression (aRR, 1.29); and diabetes (aRR, 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84, and ≥ 85 years versus 18-39 years (aRRs, 3.11, 5.77, 7.67, and 10.98, respectively); male sex (aRR, 1.30); immunosuppression (aRR, 1.39); renal disease (aRR, 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR, 1.28); neurologic disorders (aRR, 1.25); and diabetes (aRR, 1.19).
In-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.
Abstract
Background
Data on risk factors for coronavirus disease 2019 (COVID-19)–associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors ...independently associated with COVID-19–associated hospitalizations.
Methods
Community-dwelling adults (aged ≥18 years) in the United States hospitalized with laboratory-confirmed COVID-19 during 1 March–23 June 2020 were identified from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), a multistate surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity, severe obesity, chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRRs) for hospitalization.
Results
Among 5416 adults, hospitalization rates (all reported as aRR 95% confidence interval) were higher among those with ≥3 underlying conditions (vs without) (5.0 3.9–6.3), severe obesity (4.4 3.4–5.7), chronic kidney disease (4.0 3.0–5.2), diabetes (3.2 2.5–4.1), obesity (2.9 2.3–3.5), hypertension (2.8 2.3–3.4), and asthma (1.4 1.1–1.7), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65 or 45–64 years (vs 18–44 years), males (vs females), and non-Hispanic black and other race/ethnicities (vs non-Hispanic whites).
Conclusions
Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.
Severe obesity, chronic kidney disease, diabetes, obesity, hypertension, asthma, age ≥45 years, male sex, and non-Hispanic black and other race/ethnicity are associated with increased risk of coronavirus disease 2019–associated hospitalizations.
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.
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.
Local chemotherapy is a clinically proven strategy in treating malignant brain tumors. Its benefits, however, are largely limited by the rapid release and clearance of therapeutic agents and the ...inability to penetrate through tumor tissues. We report here on a supramolecular tubustecan (TT) hydrogel as both a therapeutic and drug carrier that enables long-term, sustained drug release and improved tumor tissue penetration. Covalent linkage of a tissue penetrating cyclic peptide to two camptothecin drug units creates a TT prodrug amphiphile that can associate into tubular supramolecular polymers and subsequently form a well-defined sphere-shaped hydrogel after injection into tumor tissues. The hollow nature of the resultant tubular assemblies allows for encapsulation of doxorubicin or curcumin for combination therapy. Our in vitro and in vivo studies reveal that these dual drug-bearing supramolecular hydrogels enhance tumor retention and penetration, serving as a local therapeutic depot for potent tumor regression, inhibition of tumor metastasis and recurrence, and mitigation of the off-target side effects.
Abstract
Background
Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States ...included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season.
Methods
We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network.
Results
Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years.
Conclusions
Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.
We estimated that influenza vaccination prevented an estimated 4.4 million illnesses, 2.3 million medical visits, 58 000 hospitalizations, and 3500 deaths in the 2018–2019 influenza season.
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).
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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.
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.
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.
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.
Abstract
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.
During the 2017–2018 influenza season, we estimate that influenza vaccination reduced the risk of medically attended influenza by 38% and prevented 7 million illnesses, 4 million medical visits, 109 000 hospitalizations, and 8000 deaths in the United States.
Influenza may contribute to the burden of acute cardiovascular events during annual influenza epidemics.
To examine acute cardiovascular events and determine risk factors for acute heart failure ...(aHF) and acute ischemic heart disease (aIHD) in adults with a hospitalization associated with laboratory-confirmed influenza.
Cross-sectional study.
U.S. Influenza Hospitalization Surveillance Network during the 2010-to-2011 through 2017-to-2018 influenza seasons.
Adults hospitalized with laboratory-confirmed influenza and identified through influenza testing ordered by a practitioner.
Acute cardiovascular events were ascertained using discharge codes from the International Classification of Diseases (ICD), Ninth Revision, Clinical Modification, and ICD, 10th Revision. Age, sex, race/ethnicity, tobacco use, chronic conditions, influenza vaccination, influenza antiviral medication, and influenza type or subtype were included as exposures in logistic regression models, and marginal adjusted risk ratios and 95% CIs were estimated to describe factors associated with aHF or aIHD.
Among 89 999 adults with laboratory-confirmed influenza, 80 261 had complete medical record abstractions and available ICD codes (median age, 69 years interquartile range, 54 to 81 years) and 11.7% had an acute cardiovascular event. The most common such events (non-mutually exclusive) were aHF (6.2%) and aIHD (5.7%). Older age, tobacco use, underlying cardiovascular disease, diabetes, and renal disease were significantly associated with higher risk for aHF and aIHD in adults hospitalized with laboratory-confirmed influenza.
Underdetection of cases was likely because influenza testing was based on practitioner orders. Acute cardiovascular events were identified by ICD discharge codes and may be subject to misclassification bias.
In this population-based study of adults hospitalized with influenza, almost 12% of patients had an acute cardiovascular event. Clinicians should ensure high rates of influenza vaccination, especially in those with underlying chronic conditions, to protect against acute cardiovascular events associated with influenza.
Centers for Disease Control and Prevention.
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