Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.

Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4+ T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1fl/flMaffl/flCd4Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in TH1/NK/ILC1 effector genes in LPLs, while Prdm1fl/flCd4Cre and Maffl/flCd4Cre mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maffl/flCd4Cre mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell-myeloid-neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf, revealing potential mechanisms of human disease.

Publisher Correction: c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

In the version of this article initially published, the Supplementary Data file was an incorrect version. The correct version is now provided. The error has been corrected in the HTML and PDF version of the article.

c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in CD4+ T cells in vitro. However, the global effects of c-Maf on diverse immune responses in vivo are unknown. Here we found that c-Maf regulated IL-10 production in CD4+ T cells in disease models involving the TH1 subset of helper T cells (malaria), TH2 cells (allergy) and TH17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in TH1 and TH2 responses, TH17 cell-mediated pathology was reduced in this context, with an accompanying decrease in TH17 cells and increase in Foxp3+ regulatory T cells. Bivariate genomic footprinting elucidated the c-Maf transcription-factor network, including enhanced activity of NFAT; this led to the identification and validation of c-Maf as a negative regulator of IL-2. The decreased expression of the gene encoding the transcription factor RORγt (Rorc) that resulted from c-Maf deficiency was dependent on IL-2, which explained the in vivo observations. Thus, c-Maf is a positive and negative regulator of the expression of cytokine-encoding genes, with context-specific effects that allow each immune response to occur in a controlled yet effective manner.

Nobiletin regulates invasion, migration and metastasis in hypopharyngeal squamous cell carcinoma.

Head and neck squamous cell carcinoma carries a poor prognosis. Patients typically present with advanced disease and exhibit severe malnutrition at the time of diagnosis. Nobiletin (NOB) (5,6,7,8,3',4'-Hexamethoxyflavone) is a polymethoxyflavone that inhibits the proliferation and migration of various cancer cell types. To the best of our knowledge, its effects on hypopharyngeal squamous cell carcinoma have not been evaluated previously. This study examined the effects of NOB on the proliferation, migration, and invasiveness of the FaDu cell line derived from hypopharyngeal squamous cell carcinoma. We determined protein kinase phosphorylation by western blot analysis, migration by Transwell assay, and metastatic potential by enzyme-linked immunosorbent assay of vascular endothelial growth factor. NOB inhibited cell proliferation by 40% at concentrations of 15 µM and 40 µM, and reduced migration and induced apoptosis at 50 µM by downregulating extracellular signal-regulated kinase, protein kinase B, and phosphoinositide 3-kinase. Our results suggest that the effects of NOB on FaDu cells are associated with protein kinase inhibition.

Opioid prescriptions among the World Trade Center Health Program population.

BACKGROUND: The World Trade Center Health Program (Program) provides limited health care to those directly affected by the 9/11 terrorist attacks. Because of physical/mental trauma arising from the 9/11 attacks, Program members might be at high risk of opioid use. To prevent prescription opioid overuse, in 2018 the Program implemented various measures to improve opioid prescribing and expand access to non-opioid pain management among Program members. However, the characteristics of opioid prescriptions dispensed among this population has never been described. METHODS: Administrative and claims data from 07/01/2011 to 09/30/2022 were used to describe opioid prescriptions dispensed during 2013-2021. RESULTS: From 2013-2021, 108,285 members were Program-enrolled for ≥ 10 months, 4,053 (3.7%) had 22,938 outpatient opioid prescriptions, of which, 62.1% were for cancer-related pain, 11.1% for hospice/end of life care, 4.8% for surgery pain, and 9.8% for acute/chronic pain. Among members with Program-paid diagnostic/treatment claims (n = 70,721), the proportion with opioid prescriptions for cancer/hospice/end of life care increased from 0.5% in 2013 to 1.6% in 2018 (p = 0.010), then decreased to 1.1% in 2021 (p = 0.070), and the proportion for non-cancer surgery/acute/chronic pain decreased from 0.6% in 2013 to 0.23% in 2021 (p = 0.0005). Among members prescribed opioids without cancer/hospice/sickle cell disease, the proportion who started with long-acting opioids or had opioid prescriptions from ≥ 4 prescribers were below 6.5% annually; the proportion receiving a high-dose (≥ 90 morphine milligram equivalents per day [MED]), or with concurrent opioids and benzodiazepines use, or who started opioids with MED ≥ 50 or with long duration (≥ 7 days' supply) were above 10% annually, but decreased since 2017. CONCLUSIONS: Prevalence of outpatient opioid prescriptions paid by the Program was very low and prescriptions were primarily dispensed for cancer/hospice/end of life care. Although Program efforts to improve opioid prescribing coincided with improvements in outcomes, ongoing surveillance is needed.

Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021.

During June 2021, the highly transmissible† B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, became the predominant circulating strain in the United States. U.S. pediatric COVID-19-related hospitalizations increased during July-August 2021 following emergence of the Delta variant and peaked in September 2021.§ As of May 12, 2021, CDC recommended COVID-19 vaccinations for persons aged ≥12 years,¶ and on November 2, 2021, COVID-19 vaccinations were recommended for persons aged 5-11 years.** To date, clinical signs and symptoms, illness course, and factors contributing to hospitalizations during the period of Delta predominance have not been well described in pediatric patients. CDC partnered with six children's hospitals to review medical record data for patients aged <18 years with COVID-19-related hospitalizations during July-August 2021.†† Among 915 patients identified, 713 (77.9%) were hospitalized for COVID-19 (acute COVID-19 as the primary or contributing reason for hospitalization), 177 (19.3%) had incidental positive SARS-CoV-2 test results (asymptomatic or mild infection unrelated to the reason for hospitalization), and 25 (2.7%) had multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition associated with COVID-19.§§ Among the 713 patients hospitalized for COVID-19, 24.7% were aged <1 year, 17.1% were aged 1-4 years, 20.1% were aged 5-11 years, and 38.1% were aged 12-17 years. Approximately two thirds of patients (67.5%) had one or more underlying medical conditions, with obesity being the most common (32.4%); among patients aged 12-17 years, 61.4% had obesity. Among patients hospitalized for COVID-19, 15.8% had a viral coinfection¶¶ (66.4% of whom had respiratory syncytial virus [RSV] infection). Approximately one third (33.9%) of patients aged <5 years hospitalized for COVID-19 had a viral coinfection. Among 272 vaccine-eligible (aged 12-17 years) patients hospitalized for COVID-19, one (0.4%) was fully vaccinated.*** Approximately one half (54.0%) of patients hospitalized for COVID-19 received oxygen support, 29.5% were admitted to the intensive care unit (ICU), and 1.5% died; of those requiring respiratory support, 14.5% required invasive mechanical ventilation (IMV). Among pediatric patients with COVID-19-related hospitalizations, many had severe illness and viral coinfections, and few vaccine-eligible patients hospitalized for COVID-19 were vaccinated, highlighting the importance of vaccination for those aged ≥5 years and other prevention strategies to protect children and adolescents from COVID-19, particularly those with underlying medical conditions.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir with low-dose ribavirin in patients with chronic hepatitis C virus genotype 1a infection without cirrhosis.

Patients infected with hepatitis C virus (HCV) treated with interferon-free direct-acting antivirals may still require ribavirin. However, ribavirin is associated with adverse events that can limit its use. This open-label, multicentre, Phase 3 study evaluated the safety and efficacy of ombitasvir/paritaprevir/ritonavir + dasabuvir (OBV/PTV/r + DSV) with low-dose ribavirin for 12 weeks in genotype 1a-infected patients without cirrhosis. The primary efficacy endpoint was sustained virologic response at post-treatment Week 12 (SVR12). The primary safety endpoint was haemoglobin <10 g/dL during treatment and decreased from baseline. Overall, 105 patients enrolled. The SVR12 rate was 89.5% (n/N = 94/105; 95% CI, 83.7-95.4). The study did not achieve noninferiority versus the historic SVR12 rate for OBV/PTV/r + DSV plus weight-based ribavirin. Five patients experienced virologic failure, four discontinued, and two had missing SVR12 data. Excluding nonvirologic failures, the SVR12 rate was 94.9% (n/N = 94/99). One patient met the primary safety endpoint. OBV/PTV/r + DSV plus low-dose ribavirin offers an alternative option for patients in whom full-dose ribavirin may compromise tolerability, although noninferiority to the weight-based ribavirin regimen was not met.

Barriers to access to care reported by women living with HIV across 27 countries.

Increased access to successful antiretroviral therapy (ART) is necessary in order to achieve an AIDS-free generation. Importantly, slightly over half of the people living with HIV are women. Small studies have described many barriers to accessing treatment and care among women living with HIV. This cross-sectional, non-interventional, epidemiological study assessed the prevalence of barriers to accessing care for women living with HIV across 27 countries, divided into four global regions. HIV-positive women attending routine clinical visits were offered the opportunity to participate in the study. Data describing the study sites and demographic characteristics of the participating women were collected. Participating women filled out questionnaires including the Barriers to Care Scale (BACS) questionnaire, on which they reported the extent to which they found each of the 12 potential barriers to accessing health care problematic. A total of 1931 women living with HIV were included in the study: 760 from Western Europe and Canada (WEC), 532 from Central and Eastern Europe (CEE), 519 from Latin America (LA), and 120 from China. The mean age of participating women was 40.1 ± 11.4 years. A total of 88.2% were currently taking ART. A total of 81.8% obtained HIV treatment under a government health plan. The most prevalent barrier to care was community HIV/AIDS stigma. Community HIV/AIDS knowledge, lack of supportive/understanding work environments, lack of employment opportunities, and personal financial resources were also highly prevalent barriers to accessing care. These findings indicate that, more than 30 years after the start of the AIDS epidemic, stigma is still a major issue for women living with HIV. Continued efforts are needed to improve community education on HIV/AIDS in order to maximize access to health care among women living with HIV.

Assessment of the effectiveness of an introductory general chemistry course in dentistry students enrolled in a biochemistry course.

As a strategy to carry out a better achievement in the Biochemistry course, undergraduate dentistry education manage a traditional course on the basic concepts of general chemistry necessary in the understanding of Biochemistry. In order to evaluate the effectiveness of learning outcome, we aimed to develop an evaluation tool that was applied to first-year dental students before and after receiving the general chemistry classes. Randomized trial consisted of 50 items distributed in 10 categories. The evaluation was applied to the students who took the Oral Biology course in the periods comprising 2020, 2021, and 2022 to a population of 109 students. Our results showed that after receiving the course the improvement rate was 20.71% with significant differences in each category. In conclusion, the introductory course allows students coming from different school systems to attend Biochemistry with similar knowledge of general chemistry.

Role of Angiotensin II in Non-Alcoholic Steatosis Development.

Fatty liver is a multifactorial disease characterized by excessive accumulation of lipids in hepatocytes (steatosis), insulin resistance, oxidative stress, and inflammation. This disease has a major public health impact because it is the first stage of a chronic and degenerative process in the liver that can lead to steatohepatitis, cirrhosis, and liver cancer. Although this disease is mainly diagnosed in patients with obesity, type 2 diabetes mellitus, and dyslipidemia, recent evidence indicates that vasoactive hormones such as angiotensin II (ANGII) not only promote endothelial dysfunction (ED) and hypertension, but also cause fatty liver, increase adipose tissue, and develop a pro-steatotic environment characterized by a low-grade systemic pro-inflammatory and pro-oxidant state, with elevated blood lipid levels. The role of ANGII in lipid accumulation has been little studied, so this review aims to summarize existing reports on the possible mechanism of action of ANGII in inducing lipid accumulation in hepatocytes.

Hydroalcoholic extract from Sechium edule (Jacq.) S.w. root reverses oleic acid-induced steatosis and insulin resistance in vitro.

Steatosis is characterized by fat accumulation and insulin resistance (IR) in hepatocytes, which triggers a pro-oxidant, pro-inflammatory environment that may eventually lead to cirrhosis or liver carcinoma. This work was aimed to assess the effect of Sechium edule root hydroalcoholic extract (rSe-HA) (rich in cinnamic and coumaric acid, among other phenolic compounds) on triglyceride esterification, lipid degradation, AMPK expression, and the phosphorylation of insulin receptor in a Ser312 residue, as well as on the redox status, malondialdehyde (MDA) production, and the production of proinflammatory cytokines in an in vitro model of steatosis induced by oleic acid, to help develop a phytomedicine that could reverse this pathology. rSe-HA reduced triglyceride levels in hepatocyte lysates, increased lipolysis by activating AMPK at Thr172, and improved the redox status, as evidenced by the concentration of glycerol and formazan, respectively. It also prevented insulin resistance (IR), as measured by glucose consumption and the phosphorylation of the insulin receptor at Ser312. It also prevented TNFα and IL6 production and decreased the levels of MDA and nitric oxide (ON). Our results indicate that rSe-HA reversed steatosis and controlled the proinflammatory and prooxidant environment in oleic acid-induced dysfunctional HepG2 hepatocytes, supporting its potential use to control this disorder.

The tumour suppressor Fhit positively regulates MHC class I expression on cancer cells.

MHC class I (MHC-I) molecules are ubiquitously expressed on the cells of an organism. Study of the regulation of these molecules in normal and disease conditions is important. In tumour cells, the expression of MHC-I molecules is very frequently lost, allowing these cells to evade the immune response. Cancers of different histology have shown total loss of MHC-I molecule expression, due to a coordinated transcriptional down-regulation of various antigen-processing machinery (APM) components and/or MHC-I heavy chains. The mechanisms responsible for these alterations remain unclear. We determined the possible genes involved by comparing MHC-I-positive with MHC-I-negative murine metastases derived from the same fibrosarcoma tumour clone. MHC-I-negative metastases showed transcriptional down-regulation of APM and MHC-I heavy chains. The use of microarrays and subtraction cDNA libraries revealed four candidate genes responsible for this alteration, but two of them were ruled out by real-time RT-PCR analyses. The other two genes, AP-2α and Fhit tumour suppressors, were studied by using siRNA to silence their expression in a MHC-I-positive metastatic cell line. AP-2α inhibition did not modify transcriptional expression of APM components or MHC-I heavy chains or surface expression of MHC-I. In contrast, silencing of the Fhit gene produced the transcriptional down-regulation of APM components and MHC-I heavy chains and decreased MHC-I surface expression. Moreover, transfection of Fhit in MHC-I-negative tumour cell lines restored MHC-I cell surface expression. These data indicate that defects in Fhit expression may promote MHC-I down-regulation in cancer cells and allow escape from immunosurveillance(#).

Blimp-1 and c-Maf regulate Il10 and negatively regulate common and unique proinflammatory gene networks in IL-12 plus IL-27-driven T helper-1 cells.

Background: CD4 + Th1 cells producing IFN-γ are required to eradicate intracellular pathogens, however if uncontrolled these cells can cause immunopathology. The cytokine IL-10 is produced by multiple immune cells including Th1 cells during infection and regulates the immune response to minimise collateral host damage. In this study we aimed to elucidate the transcriptional network of genes controlling the expression of Il10 and proinflammatory cytokines, including Ifng in Th1 cells differentiated from mouse naive CD4 + T cells. Methods: We applied computational analysis of gene regulation derived from temporal profiling of gene expression clusters obtained from bulk RNA sequencing (RNA-seq) of flow cytometry sorted naïve CD4 + T cells from mouse spleens differentiated in vitro into Th1 effector cells with IL-12 and IL-27 to produce Ifng and Il10, compared to IL-27 alone which express Il10 only , or IL-12 alone which express Ifng and no Il10, or medium control driven-CD4 + T cells which do not express effector cytokines . Data were integrated with analysis of active genomic regions from these T cells using an assay for transposase-accessible chromatin with sequencing (ATAC)-seq, integrated with literature derived-Chromatin-immunoprecipitation (ChIP)-seq data and the RNA-seq data, to elucidate the transcriptional network of genes controlling expression of Il10 and pro-inflammatory effector genes in Th1 cells. The co-dominant role for the transcription factors, Prdm1 (encoding Blimp-1) and Maf (encoding c-Maf) , in cytokine gene regulation in Th1 cells, was confirmed using T cells obtained from mice with T-cell specific deletion of these transcription factors. Results: We show that the transcription factors Blimp-1 and c-Maf each have unique and common effects on cytokine gene regulation and not only co-operate to induce Il10 gene expression in IL-12 plus IL-27 differentiated mouse Th1 cells, but additionally directly negatively regulate key proinflammatory cytokines including Ifng, thus providing mechanisms for reinforcement of regulated Th1 cell responses. Conclusions: These data show that Blimp-1 and c-Maf positively and negatively regulate a network of both unique and common anti-inflammatory and pro-inflammatory genes to reinforce a Th1 response in mice that will eradicate pathogens with minimum immunopathology.

Aqueous Fraction from Cucumis sativus Aerial Parts Attenuates Angiotensin II-Induced Endothelial Dysfunction In Vivo by Activating Akt.

BACKGROUND: Endothelial dysfunction (ED) is a marker of vascular damage and a precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO), produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium. METHODS: A combination of subfractions SF1 and SF3 (C4) of the aqueous fraction from Cucumis sativus (Cs-Aq) was evaluated to control endothelial dysfunction in vivo and on HMEC-1 cells to assess the involvement of pAkt in vitro. C57BL/6J mice were injected daily with angiotensin II (Ang-II) for 10 weeks. Once hypertension was established, either Cs-AqC4 or losartan was orally administered along with Ang-II for a further 10 weeks. Blood pressure (BP) was measured at weeks 0, 5, 10, 15, and 20. In addition, serum creatinine, inflammatory status (in the kidney), tissue damage, and vascular remodeling (in the liver and aorta) were evaluated. Cs-AqC4 was also tested in vitro on HMEC-1 cells stimulated by Ang-II to assess the involvement of Akt phosphorylation. RESULTS: Cs-AqC4 decreased systolic and diastolic BP, reversed vascular remodeling, decreased IL-1ß and TGF-ß, increased IL-10, and decreased kidney and liver damage. In HMEC-1 cells, AKT phosphorylation and NO production were increased. CONCLUSIONS: Cs-AqC4 controlled inflammation and vascular remodeling, alleviating hypertension; it also improved tissue damage associated with ED, probably via Akt activation.

Effect of Induced Mechanical Leaf Damage on the Yield and Content of Bioactive Molecules in Leaves and Seeds of Tepary Beans (Phaseolus acutifolius).

Growing interest has recently been shown in Tepary beans (Phaseolus acutifolius) because they contain lectins and protease inhibitors that have been shown to have a specific cytotoxic effect on human cancer cells. Bean lectins offer protection against biotic and abiotic stress factors, so it is possible that mechanical foliar damage may increase lectin production. This study evaluates the effect of mechanical stress (foliar damage) on lectin and protease inhibitor content in Tepary beans. Seed yield was also analyzed, and phenolic content and antioxidant capacity (DPPH and TEAC) were determined in the leaves. An experimental design with random blocks of three treatments (T1: control group, T2: 50% mechanical foliar damage and T3: 80% mechanical foliar damage) was carried out. Mechanical foliar damage increased the amount of lectin binding units (LBUs) fivefold (from 1280 to 6542 LBUs in T3) but did not affect units of enzymatic activity (UEA) against trypsin (from 60.8 to 51 UEA in T3). Results show that controlled mechanical foliar damage could be used to induce overexpression of lectins in the seeds of Tepary beans. Mechanical foliar damage reduced seed production (-14.6%: from 1890 g to 1615 g in T3) and did not significantly increase phenolic compound levels in leaves.

Near-Full-Length Genome Sequences Representing an Event of Zooanthroponotic Transmission of SARS-CoV-2 Lineage B.1.189 in Mexico during 2020.

Here, we report three near-full-length genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) obtained in Mexico City, Mexico, during the pandemic of coronavirus disease 19 (COVID-19) in 2020, representing a zooanthroponotic transmission event between humans and a dog. All three genomes belong to the B.1.189 lineage based on the pangolin classification.

Evolutionary Dynamics of Mexican Lineage H5N2 Avian Influenza Viruses.

We have demonstrated for the first time a comprehensive evolutionary analysis of the Mexican lineage H5N2 avian influenza virus (AIV) using complete genome sequences (n = 189), from its first isolation in 1993 until 2019. Our study showed that the Mexican lineage H5N2 AIV originated from the North American wild bird gene pool viruses around 1990 and is currently circulating in poultry populations of Mexico, the Dominican Republic, and Taiwan. Since the implementation of vaccination in 1995, the highly pathogenic AIV (HPAIV) H5N2 virus was eradicated from Mexican poultry in mid-1995. However, the low pathogenic AIV (LPAIV) H5N2 virus has continued to circulate in domestic poultry populations in Mexico, eventually evolving into five distinct clades. In the current study, we demonstrate that the evolution of Mexican lineage H5N2 AIVs involves gene reassortments and mutations gained over time. The current circulating Mexican lineage H5N2 AIVs are classified as LPAIV based on the amino acid sequences of the hemagglutinin (HA) protein cleavage site motif as well as the results of the intravenous pathogenicity index (IVPI). The immune pressure from vaccinations most likely has played a significant role in the positive selection of antigenic drift mutants within the Mexican H5N2 AIVs. Most of the identified substitutions in these viruses are located on the critical antigenic residues of the HA protein and as a result, might have contributed to vaccine failures. This study highlights and stresses the need for vaccine updates while emphasizing the importance of continued molecular monitoring of the HA protein for its antigenic changes compared to the vaccines used.

Nematicidal, Acaricidal and Plant Growth-Promoting Activity of Enterobacter Endophytic Strains and Identification of Genes Associated with These Biological Activities in the Genomes.

In the present study, the nematicidal and acaricidal activity of three Enterobacter endophytic strains isolated from Mimosa pudica nodules was evaluated. The percentages of mortality of Enterobacter NOD4 against Panagrellus redivivus was 81.2%, and against Nacobbus aberrans 70.1%, Enterobacter NOD8 72.4% and 62.5%, and Enterobacter NOD10 64.8% and 58.7%, respectively. While against the Tyrophagus putrescentiae mite, the mortality percentages were 68.2% due to Enterobacter NOD4, 64.3% due to Enterobacter NOD8 and 77.8% due to Enterobacter NOD10. On the other hand, the ability of the three Enterobacter strains to produce indole acetic acid and phosphate solubilization, characteristics related to plant growth-promoting bacteria, was detected. Bioinformatic analysis of the genomes showed the presence of genes related to IAA production, phosphate solubilization, and nitrogen fixation. Phylogenetic analyzes of the recA gene, phylogenomics, and average nucleotide identity (ANI) allowed us to identify the strain Enterobacter NOD8 related to E. mori and Enterobacter NOD10 as E. asburiae, while Enterobacter NOD4 was identified as a possible new species of this species. The plant growth-promoting, acaricidal and nematicidal activity of the three Enterobacter strains makes them a potential agent to include in biocontrol alternatives and as growth-promoting bacteria in crops of agricultural interest.

Factors Associated With Severe Illness in Patients Aged <21 Years Hospitalized for COVID-19.

OBJECTIVES: To describe coronavirus disease 2019 (COVID-19)-related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness. METHODS: We abstracted data from medical charts to conduct a cross-sectional study of patients aged <21 years hospitalized at 6 United States children's hospitals from July to August 2021 for COVID-19 or with an incidental positive severe acute respiratory syndrome coronavirus 2 test. Among patients with COVID-19, we assessed factors associated with severe illness by calculating age-stratified prevalence ratios (PR). We defined severe illness as receiving high-flow nasal cannula, positive airway pressure, or invasive mechanical ventilation. RESULTS: Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged <1 (PR 1.82), 5 to 11 (PR 3.72), and 12 to 17 years (PR 3.19). CONCLUSIONS: Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged <5 years, obesity in those aged 5 to 17 years, and other underlying conditions for all age groups <18 years. These findings can inform pediatric practice, risk communication, and prevention strategies, including vaccination against COVID-19.