Gender-based pay inequities persist in pediatrics, affecting women at all career stages and across subspecialties, even after accounting for work hours, duties, and productivity. These inequities are further pronounced between pediatrics, a women-dominated field, and men-dominated adult medicine and surgery. Contributing factors include systemic bias; unequal access to mentorship, sponsorship, and coaching; unequal promotion to leadership roles; part-time work; and inadequate parental leave policies. The consequences are profound, not only for the financial well-being and career satisfaction of women physicians, but also for the pediatric workforce and access to health care for pediatric patients. Subspecialties with more women often face workforce shortages and lower salaries for all. This policy statement from the American Academy of Pediatrics summarizes evidence of gender pay inequities, their causes, and strategies to achieve compensation equity. It recommends transparent pay practices, supportive parental leave policies, equitable promotion policies, and regular compensation reviews to address these inequities. Achieving pay equity is critical to building a diverse, sustainable, and fairly compensated pediatric workforce capable of meeting the health care needs of all children. Equity in pay is both a professional and public health imperative.

Patients with inflammatory bowel disease (IBD) have up to 3 times higher rates of influenza hospitalizations than healthy individuals. In adolescents with other immunocompromising conditions studies suggest that higher or repeated influenza vaccination (FluIV) doses induce better responses. In children with IBD annual FluIV is recommended, but how their baseline immune dysregulation and immunosuppressive treatments alter vaccine immunogenicity is poorly understood. Our goal was to evaluate longitudinal serologic and cellular responses after FluIV in IBD adolescents (IBDa) compared to healthy controls (HC).Figure 1.Anti-Influenza Antibody Optic Density Means by Patient Group before and after VaccineFigure 2.Interpersonal Variability of Anti-influenza Antibody Response before and after Vaccine IBDa (12-18 y) and matched HC vaccinated with the 2023-2024 inactivated quadrivalent FluIV were evaluated. Blood samples were obtained pre-vaccination (Pre-fluIV), 1 week (W1), 1 month (M1), 2 months (M2) and 6-8 months (M6) post-FluIV. Influenza antibodies (FluAb) were measured by ELISA and optical density (OD) values compared between groups using linear mixed models. In a subset of patients peripheral blood immunophenotype was analyzed, focusing on T-follicular helper cells (Tfh), T-regs, CD4 T-cells and B, which are key in humoral responses.Figure 3.Peripheral B- and T-cells responses to FluIV in HC and IBDa. From 9/2023-12/2023, we enrolled 35 IBDa, median age 16.5 (12-17) years, and 13 HC, median age 15.19 (12-16) years. 30% were female in both groups. Among IBDa 30 (86%) were treated with anti-TNF. Influenza specific antibodies were significantly lower in IBDa vs HC at 1 and 6 months (p=0.032, 0.036, Fig1), with significant variability within groups (Fig2). T and B cell phenotyping analyzed in 10 HC and 17 IBDa (all received anti-TNF), showed that IBDa had significantly higher CD4 T, Tfh, and Treg cells counts Pre-FluIV (p≤ 0.05), but decrease in Tfh cell counts from M1 to M6 (P = 0.055; Fig3). Further, memory B cells and CD4 T cells significantly decreased post vaccination only in IBDa (p< 0.05). Immune responses to FluIV differ between anti-TNF-treated IBDa and HC. Antibody responses to FluIV were significantly higher in HC vs IBDa and persisted until M6. A subset of IBDa had higher B and T cell counts Pre-FluIV, and limited B and T-cell responses post FluV, with significant individual variability in FluAb responses. These data suggest the need to improve FluIV strategies for IBDa. Cristina Tomatis Souverbielle, MD, Merck inc: Research support isp Asuncion Mejias, MD, PhD, MsCS, Enanta: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant Brendan Boyle, MD, MPH, Endo-Therapeutics: Endoscopic device - royalites Octavio Ramilo, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Honoraria

Myeloid-derived suppressor cells (MDSC) were first recognized over twenty years ago as a key immunomodulatory cell population. Since their initial identification, a growing body of literature points to the importance of MDSC as a heterogeneous, immunosuppressive cell population and as a therapeutic target in adults with cancer. MDSC are potent suppressors of T cells and Natural Killer (NK) cells and can be helpful or harmful to the host depending on the pathophysiology. For example, MDSC are beneficial in pregnancy and prevent spontaneous abortion by promoting maternal-fetal tolerance. Increased MDSC are also associated with improved outcomes in patients with graft vs. host disease by decreasing T cell-driven inflammation. However, MDSC can also be harmful and are known to be pathologic in adults with cancer and chronic infections by promoting tumor escape and impairing pathogen clearance, respectively. Despite the widespread recognition of the importance of MDSC and their immune suppression effects in adults, much less is known regarding the role of MDSC in children. Research investigating MDSC in children lags significantly behind adult studies. In fact, while over 5,000 publications on PubMed discuss MDSC in immune regulation, fewer than 50 of these publications focus specifically on their role in children. This review aims to summarize the existing literature on the role of MDSC in children and identify important directions for future research, including targeting these cells in the pediatric population to improve clinical outcomes.

BACKGROUND:Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale-Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI. METHODS:We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 pediatric intensive care units in the United States from October through December 2022. We assigned CPS-Ped (0 = discharged home at respiratory baseline to 8 = death) at admission and days 2-7, 10, and 14. We identified predictors of clinical improvement (CPS-Ped ≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS). RESULTS:Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV) and 1 died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age <3 months, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2031 for hospital LOS. CONCLUSIONS:CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV.

BACKGROUND:Viral lower respiratory tract infections (LRTIs) are a leading cause of mortality among children. Bacterial coinfections in viral LRTI are associated with severe clinical outcomes. Identifying lower airway bacterial involvement in viral LRTI is challenging. Our objective was to define the concordance of bacterial detection between paired upper nasopharyngeal (NP) swabs and lower endotracheal airway samples (ETAs) in children with severe viral LRTI. METHODS:Convenience sample of children <5 years intubated with LRTI. Children were enrolled within 48 hours of ICU admission, and NP/ETAs were obtained for the detection of Moraxella catarrhalis , Streptococcus pneumoniae , Haemophilus influenzae and Staphylococcus aureus. Concordance was assessed via intraclass correlation coefficient (ICC), according to the respiratory virus and age. Clinical outcomes were also assessed. RESULTS:From 2017 to 2021, we enrolled 76 children [median age: 2.1 (1.2-4.3) months]. The most common respiratory virus was respiratory syncytial virus (RSV) (73.7%). Overall concordance for bacterial detection was high for M. catarrhalis , H. influenzae , and S. pneumoniae (ICC ≥0.75) but low for S. aureus (ICC 0.36). Detection rates varied by viral pathogen, with M. catarrhalis and S. pneumoniae showing the highest agreement in children with RSV. Agreement was higher in infants <6 months. Prolonged intubation was observed in children with RSV and NP codetection of S. pneumoniae or H. influenzae . CONCLUSIONS:Concordance was high for M. catarrhalis , H. influenzae , and S. pneumoniae, but not for S. aureus, and was influenced by the viral etiology and age. These findings suggest the applicability of NP swabs as surrogates for lower airway cultures for specific bacterial-virus combinations in children with severe LRTI.

Background and objectives: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. Methods: We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization]. Results: Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died. Conclusions: Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.

Primary infection related to the fungus, histoplasmosis, is generally asymptomatic in immunocompetent hosts. Calcified granulomas may be noted incidentally on radiologic imaging such as chest radiographs or computed tomography imaging. However, even in immunocompetent hosts, these primary infections occasionally result in end-organ involvement including respiratory compromise. Histoplasmosis should be included in the differential diagnosis of patients presenting with respiratory involvement and mediastinal adenopathy. We present two pediatric-aged patients who developed pulmonary involvement related to a primary histoplasmosis infection that resulted in mediastinal and tracheal lymphadenopathy. These led to respiratory compromise due to pleural effusion in the first patient and tracheal compression in the second. In this paper, the basic microbiology of Histoplasma capsulatum is presented, previous reports of primary respiratory involvement presented, and diagnostic and therapeutic options discussed.

The continuation of high-quality care is under threat for the over 70 million children in the United States. Inequities between Medicaid and Medicare payments and the current procedural-based reimbursement model have resulted in the undervaluing of pediatric medical care and lack of prioritization of children’s health by institutions. The number of pediatricians, including pediatric subspecialists, and pediatric healthcare centers are declining due to mounting financial obstacles and this crucial healthcare supply is no longer able to keep up with demand. The reasons contributing to these inequities are clear and rational: Medicaid has significantly lower rates of reimbursement compared to Medicare, yet Medicaid covers almost half of children in the United States and creates the natural incentive for medical institutions to prioritize the care of adults. Additionally, certain aspects of children’s healthcare are unique from adults and are not adequately covered in the current payment model. The result of decades of devaluing children’s healthcare has led to a substantial decrease in the availability of services, medications, and equipment needed to provide healthcare to children across the nation. Fortunately, the solution is just as clear as the problem: we must value the healthcare of children as much as that of adults by increasing Medicaid funding to be on par with Medicare and appreciate the complexities of care beyond procedures. If these changes are not made, the high-quality care for children in the US will continue to decline and increase strain on the overall healthcare system as these children age into adulthood.

BACKGROUND:The ACGME recently released its recommendation for updates to the program requirements for pediatrics. These updates proposed changes to allocation of resident clinical time and a greater emphasis on individualization. The potential impact of these changes on the training of physician-scientists is discussed.METHODS:Discussion of the proposed changes was held within the members of the National Pediatrician-Scientist Collaborative Workgroup, a group that represents scientists, trainees, program directors, chairs, and physician-scientist educators at nearly 30 residency programs from across the US with a focus on understanding and developing optimal approaches to physician-scientist training. Consideration was given to the both the personal and institutional impact of the proposal for physician-scientist development.RESULTS:Both threats and opportunities were identified. Key opportunities include the enhanced individualized training time that could be used to explore research. Threats include re-allocation of clinical training time that may strain institutions financially, expand clinical service requirements for other early career stage individuals, and alter exposure to a broad range of pediatric specialists and sub-specialists that impact career development.CONCLUSION:The NPSCW encourages consideration of the impact of changing program requirements on physician-scientist development to include ongoing discussion amongst mentors, programs, and trainees to understand and mitigate impact of new program requirements on the development of pediatrician-scientists.

Ernest, Emily1; Jedreski, Kathleen1; Snyder, Andrew2; Hensley, Josey3; Flowers, Maggie1; Bline, Katherine1; Hall, Mark4; Muszynski, Jennifer5 Author Information

Background: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in infancy and early childhood. Accurate diagnosis is essential to assess the true extent of RSV prevalence in the community and implement new preventative and therapeutic strategies effectively. Methods: RSV cell-free RNA (cfRNA) levels were measured in subjects with or without RSV-LRTI and mother/baby dyads infected in pregnancy. Diagnostic performance was first tested in nasopharyngeal (NP) swabs and serum specimens from two cohorts. Then, serum RSV-cfRNA levels from mother/baby dyads were used to investigate RSV transplacental transmission. Findings: A CRISPR-RSV assay detected RSV-cfRNA in NP swabs of RSV-infected subjects with 100% (95% CI: 91·0–100%) sensitivity and 100% (95% CI: 88·8–100%) specificity and in serum of RSV-infected children with 80·0 (95% CI: 44·4–97·5%) sensitivity and 100% (95% CI: 47·8–100%) specificity. CRISPR-RSV measurements of maternal and cord blood RSV-cfRNA levels correlated with the respective ddPCR results. Interpretation: This study validates a new CRISPR-based assay that rapidly detects RSV in respiratory secretions and serum samples with high specificity and sensitivity and is particularly useful in diagnosing congenital RSV infection. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases, U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, and National Cancer Institute. Declaration of Interest: We declare no competing interests. Ethical Approval: All study participants in the NCH and TTRSV cohorts were enrolled according to protocols approved by the Human Subjects Institutional Review Boards at Tulane University (TTRSV cohort) or Nationwide Children’s Hospital (NCH cohort). All participants or their legal guardians provided written informed consent.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.

Abstract Background Septic children can develop a severe compensatory anti-inflammatory response, termed “immunoparalysis (IP)”, which is strongly associated with adverse outcomes. IP can be defined as a reduced ability of innate immune cells to produce TNFα when whole blood is stimulated ex vivo with LPS (a TNFα response < 200 pg/ml). Adaptive (lymphocyte-based) immune function is poorly understood in IP. We hypothesize that septic children with IP will also have suppressed lymphocyte cytokine production capacity and reduced lymphocyte populations. Methods Single-center, prospective, observational study of children (< 18 yrs) with septic shock. Subjects were enrolled and sampled < 48 hrs from shock onset. Ex vivo whole blood stimulation assays were used to evaluate innate (LPS-induced) and adaptive (PHA-induced) cytokine production capacities (Fig1). Cell populations were measured by flow cytometry (Fig2). Identical sampling and processing were done in a cohort of healthy control children. Data represent median (IQR).Figure 1.Ex-vivo stimulation assays TNFα production after lipopolysacharide (LPS) stimulation (innate immune response) is measured by chemiluminescence (Siemens Healthcare Diagnostics). Cytokine production after phytohemagglutinin (PHA) stimulation (adaptive immune response) is measured by multiplex assay (Biorad). Table 1 Whole blood was stained within 30 minutes of collection and included the cell populations shown above. Samples were acquired on the cytometer within a week of staining and analyzed using FlowJo 10.8.0 software. Results 30 children with septic shock (15 [8,16] yrs; 64% male, 3% mortality) and 11 healthy controls (6 [3,8] yrs; 54% male) were enrolled. Among septic subjects, length of stay was 5 [2,18] days in the ICU and 17 [6, 38] days in the hospital. Etiologies and sites of infection are shown in Fig3. Septic subjects had lower ex vivo PHA-induced cytokine production (Fig4), and relative lymphopenia by flow cytometry vs healthy controls, especially double negative-T cells (3.7% vs 8.4%; p=0.03) and γδ-T cells (2.9% vs 7.6%; p=0.03). 12 septic subjects had IP. Rates of viral detection (50% vs 11%; p=0.03) and viral-bacterial co-detection (63% vs 9%; p=0.04) were higher in the IP group vs non-IP septic subjects. Subjects with IP had lower monocyte HLA-DR expression but no differences in lymphocyte populations. PHA-induced production of Th1 cytokines was lower in those with IP, while production of Th2 cytokines was preserved (Fig5). *Subjects where included in analysis if treated as presumed bacterial infections. Abbreviations: PCR: Polymerase chain reaction; GI: Gastrointestinal; MSSA: Methicillin susceptible S aureus; MRSA: Methicillin resistant S aureus; Rh/E: Rhinovirus/Enterovirus; RSV: Respiratory Syncytial virus; PIV: Parainfluenza Virus.Figure 4.PHA-induced cytokine production capacity in sepsis vs healthy controls Comparisons done by Mann-Whitney U test. Asterisks represent p-value <0.05.Figure 5.PHA-induced cytokine production capacity in children with and without immunoparalysis (IP) Comparisons done by Mann-Whitney U test. Asterisks represent p-value <0.05. Conclusion Children with septic shock have early innate and adaptive immune suppression. Immunoparalysis was associated with skewing to a Th2 profile of cytokine production, and with the presence of viral infections. This approach has the potential to drive enrollment into clinical trials of personalized immunomodulation in this population. Disclosures Mark Hall, MD FCCM, Abbvie: Advisor/Consultant|Kiadis: Honoraria|Partner Therapeutics: complementary study drug Sobi for a clinical trial for which I am the Principal Investigator|Sobi: Complementary study drug for a clinical trial for which I am the Principal Investigator

Abstract Introduction Lower respiratory tract infections (LRTI) caused by respiratory syncytial virus (RSV) result in over 100,000 deaths of infants globally. Though adults account for most COVID-19 hospitalizations, children also develop severe disease due to SARS-CoV-2. Children with severe illness due to LRTI demonstrate evidence of impaired adaptive immune function. MDSC are an immature, heterogenous cell population that expands significantly during inflammatory conditions. MDSC suppress T cell proliferation and function resulting in immunosuppression. MDSC subsets (granulocytic (G) MDSC and the monocytic (M-)MDSC) suppress T cells via distinct mechanisms. In a previous study, we observed a significant increase in G-MDSC in children with septic shock. We hypothesize that children with severe LRTI with RSV or COVID-19 will have expansion of MDSC that will be associated with differences in T cell subset composition and worse clinical outcomes. Methods Prospective, observational study in children admitted to the pediatric intensive care unit (PICU) with symptomatic RSV or COVID-19, defined by a positive polymerase chain reaction test. Children with multi-system inflammatory syndrome or positive for both RSV and COVID-19 were excluded. Pre-pandemic healthy control samples were obtained from children requiring IV placement for outpatient MRI. Peripheral blood mononuclear cells were isolated by ficoll gradient and stained for surface markers to identify MDSC (CD45+, HLA-DR-, CD33+ and CD11b+), including G- (CD15+, CD14-) and M-MDSC (CD14+, CD15-), and T cell populations. Clinical and demographic data were collected from the electronic medical record and stored in a secure database. Results We enrolled 30 children, 20 with RSV (50% male, median age 2 [1.2-5] months), 10 with COVID-19 (30 % male, median age 25 [ 3.8 – 215] months), and 30 healthy controls (64% male, median age 73.2 [57.6, 98.4] months. Children with severe LRTI due to RSV or COVID-19 have significantly increased percentage MDSC of PBMC compared to healthy controls (13% [5.6,22] vs 9.9% [5.2, 23] vs 0.95 [0.34, 2.8] respectively). Compared to children with COVID-19, children with RSV had higher percentage M-MDSC of total MDSC (90% [87,97] vs 45% (8.4, 71], p< 0.0001) and lower G-MDSC (1.1% [0.44, 3.0] vs 38% [17,90], p<0.0001). Children with RSV had a larger percentage of T regulatory cells of total CD4+ T cells (8.0% [6.1, 9.0] vs 4.3% [3.3, 5.8], p=0.01) and were more likely require non-invasive or invasive ventilatory respiratory support than those with COVID-19 (75% vs 30%, p=0.04). Conclusions Total MDSC are significantly expanded in children with severe LRTI due to RSV and COVID-19 compared to healthy controls, but with significantly different subset distributions. Children with RSV demonstrate a predominance of M-MDSC, while children with COVID-19 demonstrate significantly higher G-MDSC. Children with RSV were also more likely to have expanded Treg cell population and require higher level respiratory support. These findings suggest that MDSC composition and suppressive mechanisms may be partially driven by viral pathogen. Larger studies are needed to confirm these findings and to investigate the role of MDSC-mediated immune suppression in children with severe LRTI to identify this cell population as a potential therapeutic target.

Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged <6 months and 54% (95% CI = 32%-68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19.

We conducted a multicenter public health investigation of hospitalized vaccine-eligible US patients ages 5-18 years comparing 304 MIS-C patients with 502 SARS-CoV-2-negative controls. BNT162b2 vaccination was associated with a decreased likelihood of MIS-C across periods of Delta and Omicron predominance. Background Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. Methods In a multicenter, case-control, public health investigation of children ages 5-18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine >= 28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. Results We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR [aOR]: .16; 95% CI: .10-.26), including among children ages 5-11 years (aOR: .22; 95% CI: .10-.52), ages 12-18 years (aOR: .10; 95% CI: .05-.19), and during the Delta (aOR: .06; 95% CI: .02-.15) and Omicron (aOR: .22; 95% CI: .11-.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03-.22) in 12-18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated. Conclusions Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5-18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.

BACKGROUND:Multisystem inflammatory syndrome in children (MIS-C) represents a hyperinflammatory state that can result in multi-organ dysfunction and death. Myeloid-derived suppressor cells (MDSC) are an immunosuppressive cell population that expands under inflammatory conditions and suppresses T cell function. We hypothesized that MDSC would be increased in children with MIS-C and that MDSC expansion would be associated with T cell lymphopenia. METHODS:We conducted a prospective, observational study. Initial blood samples were collected within 48 h of admission. Age-matched healthy controls underwent sampling once. MDSC and T cell populations were identified by flow cytometric methods. RESULTS:We enrolled 22 children with MIS-C (12 ICU, 10 ward) and 21 healthy controls (HC). Children with MIS-C demonstrated significantly higher MDSC compared to HC, and MDSC expansion persisted for >3 weeks in the ICU group. Children with MIS-C admitted to the ICU demonstrated significantly lower absolute numbers of T cells and natural killer cells. There were no significant associations between MDSC and cardiac dysfunction, duration of hospitalization, or vasoactive inotrope score. CONCLUSIONS:Our study suggests that children critically ill with MIS-C have expansion of MDSC and associated decreased T cell and NK cell populations. Our results did not demonstrate associations between MDSC and clinical outcomes. IMPACT:Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated immune response occurring several weeks after SARS-CoV-2 infection that can result in multi-organ dysfunction and death. Children severely ill with MIS-C demonstrated increased myeloid-derived suppressor cells and decreased absolute numbers of CD4+ and CD8 + T cells and NK cells compared to healthy controls. There was no significant association between MDSC numbers and clinical outcomes; including cardiac dysfunction, length of stay, or requirement of vasoactive support, in children with MIS-C.