Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-30 (of 67 Records) |
Query Trace: Coates R[original query] |
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Durability of original monovalent mRNA vaccine effectiveness against COVID-19 Omicron-associated hospitalization in children and adolescents - United States, 2021-2023
Zambrano LD , Newhams MM , Simeone RM , Payne AB , Wu M , Orzel-Lockwood AO , Halasa NB , Calixte JM , Pannaraj PS , Mongkolrattanothai K , Boom JA , Sahni LC , Kamidani S , Chiotos K , Cameron MA , Maddux AB , Irby K , Schuster JE , Mack EH , Biggs A , Coates BM , Michelson KN , Bline KE , Nofziger RA , Crandall H , Hobbs CV , Gertz SJ , Heidemann SM , Bradford TT , Walker TC , Schwartz SP , Staat MA , Bhumbra SS , Hume JR , Kong M , Stockwell MS , Connors TJ , Cullimore ML , Flori HR , Levy ER , Cvijanovich NZ , Zinter MS , Maamari M , Bowens C , Zerr DM , Guzman-Cottrill JA , Gonzalez I , Campbell AP , Randolph AG . MMWR Morb Mortal Wkly Rep 2024 73 (15) 330-338 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. |
Pre-existing immunocompromising conditions and outcomes of acute COVID-19 patients admitted for pediatric intensive care
Rowan CM , LaBere B , Young CC , Zambrano LD , Newhams MM , Kucukak S , McNamara ER , Mack EH , Fitzgerald JC , Irby K , Maddux AB , Schuster JE , Kong M , Dapul H , Schwartz SP , Bembea MM , Loftis LL , Kolmar AR , Babbitt CJ , Nofziger RA , Hall MW , Gertz SJ , Cvijanovich NZ , Zinter MS , Halasa NB , Bradford TT , McLaughlin GE , Singh AR , Hobbs CV , Wellnitz K , Staat MA , Coates BM , Crandall HR , Maamari M , Havlin KM , Schwarz AJ , Carroll CL , Levy ER , Moffitt KL , Campbell AP , Randolph AG , Chou J . Clin Infect Dis 2024 BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities. |
Phenylketonuria Scientific Review Conference: state of the science and future research needs.
Camp KM , Parisi MA , Acosta PB , Berry GT , Bilder DA , Blau N , Bodamer OA , Brosco JP , Brown CS , Burlina AB , Burton BK , Chang CS , Coates PM , Cunningham AC , Dobrowolski SF , Ferguson JH , Franklin TD , Frazier DM , Grange DK , Greene CL , Groft SC , Harding CO , Howell RR , Huntington KL , Hyatt-Knorr HD , Jevaji IP , Levy HL , Lichter-Konecki U , Lindegren ML , Lloyd-Puryear MA , Matalon K , MacDonald A , McPheeters ML , Mitchell JJ , Mofidi S , Moseley KD , Mueller CM , Mulberg AE , Nerurkar LS , Ogata BN , Pariser AR , Prasad S , Pridjian G , Rasmussen SA , Reddy UM , Rohr FJ , Singh RH , Sirrs SM , Stremer SE , Tagle DA , Thompson SM , Urv TK , Utz JR , van Spronsen F , Vockley J , Waisbren SE , Weglicki LS , White DA , Whitley CB , Wilfond BS , Yannicelli S , Young JM . Mol Genet Metab 2014 112 (2) 87-122 New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism. |
Infants admitted to US intensive care units for RSV infection during the 2022 seasonal peak
Halasa N , Zambrano LD , Amarin JZ , Stewart LS , Newhams MM , Levy ER , Shein SL , Carroll CL , Fitzgerald JC , Michaels MG , Bline K , Cullimore ML , Loftis L , Montgomery VL , Jeyapalan AS , Pannaraj PS , Schwarz AJ , Cvijanovich NZ , Zinter MS , Maddux AB , Bembea MM , Irby K , Zerr DM , Kuebler JD , Babbitt CJ , Gaspers MG , Nofziger RA , Kong M , Coates BM , Schuster JE , Gertz SJ , Mack EH , White BR , Harvey H , Hobbs CV , Dapul H , Butler AD , Bradford TT , Rowan CM , Wellnitz K , Staat MA , Aguiar CL , Hymes SR , Randolph AG , Campbell AP . JAMA Netw Open 2023 6 (8) e2328950 IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. EXPOSURE: Respiratory syncytial virus. MAIN OUTCOMES AND MEASURES: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. RESULTS: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness. |
The modified clinical progression scale for pediatric patients: Evaluation as a severity metric and outcome measure in severe acute viral respiratory illness
Leland SB , Staffa SJ , Newhams MM , Khemani RG , Marshall JC , Young CC , Maddux AB , Hall MW , Weiss SL , Schwarz AJ , Coates BM , Sanders RC Jr , Kong M , Thomas NJ , Nofziger RA , Cullimore ML , Halasa NB , Loftis LL , Cvijanovich NZ , Schuster JE , Flori H , Gertz SJ , Hume JR , Olson SM , Patel MM , Zurakowski D , Randolph AG . Pediatr Crit Care Med 2023 24 (12) 998-1009 OBJECTIVES: To develop, evaluate, and explore the use of a pediatric ordinal score as a potential clinical trial outcome metric in children hospitalized with acute hypoxic respiratory failure caused by viral respiratory infections. DESIGN: We modified the World Health Organization Clinical Progression Scale for pediatric patients (CPS-Ped) and assigned CPS-Ped at admission, days 2-4, 7, and 14. We identified predictors of clinical improvement (day 14 CPS-Ped ≤ 2 or a three-point decrease) using competing risks regression and compared clinical improvement to hospital length of stay (LOS) and ventilator-free days. We estimated sample sizes (80% power) to detect a 15% clinical improvement. SETTING: North American pediatric hospitals. PATIENTS: Three cohorts of pediatric patients with acute hypoxic respiratory failure receiving intensive care: two influenza (pediatric intensive care influenza [PICFLU], n = 263, 31 sites; PICFLU vaccine effectiveness [PICFLU-VE], n = 143, 17 sites) and one COVID-19 (n = 237, 47 sites). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive mechanical ventilation rates were 71.4%, 32.9%, and 37.1% for PICFLU, PICFLU-VE, and COVID-19 with less than 5% mortality for all three cohorts. Maximum CPS-Ped (0 = home at respiratory baseline to 8 = death) was positively associated with hospital LOS (p < 0.001, all cohorts). Across the three cohorts, many patients' CPS-Ped worsened after admission (39%, 18%, and 49%), with some patients progressing to invasive mechanical ventilation or death (19%, 11%, and 17%). Despite this, greater than 76% of patients across cohorts clinically improved by day 14. Estimated sample sizes per group using CPS-Ped to detect a percentage increase in clinical improvement were feasible (influenza 15%, n = 142; 10%, n = 225; COVID-19, 15% n = 208) compared with mortality (n > 21,000, all), and ventilator-free days (influenza 15%, n = 167). CONCLUSIONS: The CPS-Ped can be used to describe the time course of illness and threshold for clinical improvement in hospitalized children and adolescents with acute respiratory failure from viral infections. This outcome measure could feasibly be used in clinical trials to evaluate in-hospital recovery. |
A distinct cross-reactive autoimmune response in multisystem inflammatory syndrome in children (MIS-C) (preprint)
Bodansky A , Sabatino JJ , Vazquez SE , Chou J , Novak T , Moffitt KL , Miller HS , Kung AF , Rackaityte E , Zamecnik CR , Rajan JV , Kortbawi H , Mandel-Brehm C , Mitchell A , Wang CY , Saxena A , Zorn K , Yu DJL , Asaki J , Pluvinage JV , Wilson MR , Loftis LL , Hobbs CV , Tarquinio KM , Kong M , Fitzgerald JC , Espinal PS , Walker TC , Schwartz SP , Crandall H , Irby K , Staat MA , Rowan CM , Schuster JE , Halasa NB , Gertz SJ , Mack EH , Maddux AB , Cvijanovich NZ , Zinter MS , Zambrano LD , Campbell AP , Randolph AG , Anderson MS , DeRisi JL , Kelley H , Murdock M , Colston C , Typpo KV , Sanders RC , Yates M , Smith C , Port E , Mansour R , Shankman S , Baig N , Zorensky F , Chatani B , McLaughlin G , Jones K , Coates BM , Newhams MM , Kucukak S , McNamara ER , Moon HK , Kobayashi T , Melo J , Jackson SR , Rosales MKE , Young C , Chen SR , Da Costa Aguiar R , Gutierrez-Arcelus M , Elkins M , Williams D , Williams L , Cheng L , Zhang Y , Crethers D , Morley D , Steltz S , Zakar K , Armant MA , Ciuculescu F , Flori HR , Dahmer MK , Levy ER , Behl S , Drapeau NM , Kietzman A , Hill S , Cullimore ML , McCulloh RJ , Nofziger RA , Rohlfs CC , Burnett R , Bush J , Reed N , Ampofo KK , Patel MM . medRxiv 2023 30 Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Extracorporeal membrane oxygenation characteristics and outcomes in children and adolescents with COVID-19 or multisystem inflammatory syndrome admitted to U.S. ICUs
Bembea MM , Loftis LL , Thiagarajan RR , Young CC , McCadden TP , Newhams MM , Kucukak S , Mack EH , Fitzgerald JC , Rowan CM , Maddux AB , Kolmar AR , Irby K , Heidemann S , Schwartz SP , Kong M , Crandall H , Havlin KM , Singh AR , Schuster JE , Hall MW , Wellnitz KA , Maamari M , Gaspers MG , Nofziger RA , Lim PPC , Carroll RW , Coronado Munoz A , Bradford TT , Cullimore ML , Halasa NB , McLaughlin GE , Pannaraj PS , Cvijanovich NZ , Zinter MS , Coates BM , Horwitz SM , Hobbs CV , Dapul H , Graciano AL , Butler AD , Patel MM , Zambrano LD , Campbell AP , Randolph AG . Pediatr Crit Care Med 2023 24 (5) 356-71 OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C (n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 (n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge. |
NFKB2 haploinsufficiency identified via screening for IFNα2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.
Bodansky A , Vazquez SE , Chou J , Novak T , Al-Musa A , Young C , Newhams M , Kucukak S , Zambrano LD , Mitchell A , Wang CY , Moffitt K , Halasa NB , Loftis LL , Schwartz SP , Walker TC , Mack EH , Fitzgerald JC , Gertz SJ , Rowan CM , Irby K , Sanders RC Jr , Kong M , Schuster JE , Staat MA , Zinter MS , Cvijanovich NZ , Tarquinio KM , Coates BM , Flori HR , Dahmer MK , Crandall H , Cullimore ML , Levy ER , Chatani B , Nofziger R , Geha RS , DeRisi J , Campbell AP , Anderson M , Randolph AG . J Allergy Clin Immunol 2023 151 (4) 926-930.e2 BACKGROUND: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. METHODS: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. RESULTS: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. CONCLUSIONS: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity. |
Association of asthma with treatments and outcomes in children with critical influenza
Maddux AB , Grunwell JR , Newhams MM , Chen SR , Olson SM , Halasa NB , Weiss SL , Coates BM , Schuster JE , Hall MW , Nofziger RA , Flori HR , Gertz SJ , Kong M , Sanders RCJr , Irby K , Hume JR , Cullimore ML , Shein SL , Thomas NJ , Miller K , Patel M , Fitzpatrick AM , Phipatanakul W , Randolph AG . J Allergy Clin Immunol Pract 2022 11 (3) 836-843 e3 BACKGROUND: Hospitalization for severe influenza infection in childhood may result in post-discharge sequelae. OBJECTIVE(S): To evaluate inpatient management and post-discharge sequelae in children with critical respiratory illness due to influenza with or without pre-existing asthma. METHODS: Prospective, observational multicenter study of children (8-months to 17-years-old) admitted to a pediatric intensive care or high-acuity unit (11/2019-4/2020) for influenza. Results were stratified by pre-existing asthma. Pre-hospital status, hospital treatments and outcomes were collected. Surveys at approximately 90 days post-discharge evaluated post-discharge health resource use, functional status, and respiratory symptoms. RESULTS: 165 children with influenza: 56 (33.9%) with and 109 (66.1%) without pre-existing asthma (41.1% and 39.4% fully vaccinated against influenza, respectively). Fifteen (26.7%) patients with and 34 (31.1%) without pre-existing asthma were intubated. More patients with versus without pre-existing asthma received pharmacologic asthma treatments during hospitalization (76.7% vs 28.4%). Of 136 (82.4%) patients with 90-day survey data (46 [33.8%] with and 90 [66.1%] without pre-existing asthma), a similar proportion had an Emergency Department/urgent care visit (4.3%, 6.6%) or hospital readmission (8.6%, 3.3%) for a respiratory condition. Patients with pre-existing asthma more frequently experienced asthma symptoms (78.2% vs 3.3%) and had respiratory specialist visits (52% vs 20%) post-discharge. Ten of 109 (11.1%) patients without pre-existing asthma reported being newly diagnosed with asthma. CONCLUSIONS: Respiratory health resource use and symptoms are important post-discharge outcomes after influenza critical illness in children with and without pre-existing asthma. Less than half of children were vaccinated for influenza, a tool that could mitigate critical illness and its sequelae. |
Factors associated with COVID-19 non-vaccination in adolescents hospitalized without COVID-19.
Sahni LC , Price AM , Olson SM , Newhams MM , Pannaraj PS , Maddux AB , Halasa NB , Bline KE , Cameron MA , Schwartz SP , Walker TC , Irby K , Chiotos K , Nofziger RA , Mack EH , Smallcomb L , Bradford TT , Kamidani S , Tarquinio KM , Cvijanovich NZ , Schuster JE , Bhumbra SS , Levy ER , Hobbs CV , Cullimore ML , Coates BM , Heidemann SM , Gertz SJ , Kong M , Flori HR , Staat MA , Zinter MS , Hume JR , Chatani BM , Gaspers MG , Maamari M , Randolph AG , Patel MM , Boom JA . J Pediatric Infect Dis Soc 2022 12 (1) 29-35 BACKGROUND: Pfizer-BioNTech COVID-19 vaccine received emergency use authorization for persons ≥16 years in December 2020 and for adolescents 12-15 years in May 2021. Despite the clear benefits and favorable safety profile, vaccine uptake in adolescents has been suboptimal. We sought to assess factors associated with COVID-19 non-vaccination in adolescents 12-18 years of age. METHODS: Between June 1, 2021 and April 29, 2022, we assessed factors associated with COVID-19 non-vaccination in hospitalized adolescents ages 12-18 years enrolled in the Overcoming COVID-19 vaccine effectiveness network. Demographic characteristics and clinical information were captured through parent interview and/or electronic medical record abstraction; COVID-19 vaccination was assessed through documented sources. We assessed associations between receipt of COVID-19 vaccine and demographic and clinical factors using univariate and multivariable logistic regression and estimated adjusted odds ratios (aOR) for each factor associated with non-vaccination. RESULTS: Among 1,665 hospitalized adolescents without COVID-19, 56% were unvaccinated. Unvaccinated adolescents were younger (median age 15.1 years vs. 15.4 years, p<0.01) and resided in areas with higher social vulnerability index (SVI) scores (median 0.6 vs 0.5, p<0.001) than vaccinated adolescents. Residence in the Midwest [aOR 2.60 (95% CI: 1.80, 3.79)] or South [aOR 2.49 (95% CI: 1.77, 3.54)] US census regions, rarely or never receiving influenza vaccine [aOR 5.31 (95% CI: 3.81, 7.47)], and rarely or never taking precautions against COVID-19 [aOR 3.17 (95% CI: 1.94, 5.31)] were associated with non-vaccination against COVID-19. CONCLUSIONS: Efforts to increase COVID-19 vaccination of adolescents should focus on persons with geographic, socioeconomic, and medical risk factors associated with non-vaccination. |
BNT162b2 mRNA Vaccination Against COVID-19 is Associated with Decreased Likelihood of Multisystem Inflammatory Syndrome in U.S. Children Ages 5-18 Years.
Zambrano LD , Newhams MM , Olson SM , Halasa NB , Price AM , Orzel AO , Young CC , Boom JA , Sahni LC , Maddux AB , Bline KE , Kamidani S , Tarquinio KM , Chiotos K , Schuster JE , Cullimore ML , Heidemann SM , Hobbs CV , Nofziger RA , Pannaraj PS , Cameron MA , Walker TC , Schwartz SP , Michelson KN , Coates BM , Flori HR , Mack EH , Smallcomb L , Gertz SJ , Bhumbra SS , Bradford TT , Levy ER , Kong M , Irby K , Cvijanovich NZ , Zinter MS , Bowens C , Crandall H , Hume JR , Patel MM , Campbell AP , Randolph AG . Clin Infect Dis 2022 76 (3) e90-e100 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 July 1, 2021 to April 7, 2022, we compared the odds of being fully vaccinated (two 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 (aOR, 0.16 95% CI, 0.10-0.26), including among children ages 5-11 years (aOR, 0.22 95% CI, 0.10-0.52), ages 12-18 years (aOR, 0.10 95% CI, 0.05-0.19), and during the Delta (aOR, 0.06 95% CI, 0.02-0.15) and Omicron (aOR, 0.22 95% CI, 0.11-0.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR, 0.08, 95% CI, 0.03-0.22) in 12-18 year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible patients were unvaccinated. CONCLUSIONS: Vaccination with two 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. |
Life-Threatening Complications of Influenza versus COVID-19 in U.S. Children.
Halasa NB , Spieker AJ , Young CC , Olson SM , Newhams MM , Amarin JZ , Moffitt KL , Nakamura MM , Levy ER , Soma VL , Talj R , Weiss SL , Fitzgerald JC , Mack EH , Maddux AB , Schuster JE , Coates BM , Hall MW , Schwartz SP , Schwarz AJ , Kong M , Spinella PC , Loftis LL , McLaughlin GE , Hobbs CV , Rowan CM , Bembea MM , Nofziger RA , Babbitt CJ , Bowens C , Flori HR , Gertz SJ , Zinter MS , Giuliano JS , Hume JR , Cvijanovich NZ , Singh AR , Crandall HA , Thomas NJ , Cullimore ML , Patel MM , Randolph AG . Clin Infect Dis 2022 76 (3) e280-e290 BACKGROUND: Clinical differences between critical illness from influenza infection versus coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. METHODS: We compared U.S. children (8 months to 17 years) admitted to the intensive care or high acuity unit with influenza (17 hospitals, 12/19/2019-3/9/2020) or COVID-19 (52 hospitals, 3/15/2020-12/31/2020). We compared demographics, underlying conditions, clinical presentation, severity, and outcomes. Using mixed-effects models, we assessed the odds of death or requiring life-support for influenza versus COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. RESULTS: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median 5.2 vs. 13.8 years), less likely to be non-Hispanic black (14.5% vs. 27.6%) or Hispanic (24.0% vs. 36.2%), and less likely to have ≥1 underlying condition (66.4% vs. 78.5%) or be obese (21.4% vs. 42.2%). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life-support in children with influenza vs. COVID-19 were similar (adjusted odds ratio, 1.30 [95% CI: 0.78-2.15; P = 0.32]). Median duration of hospital stay was shorter for influenza than COVID-19 (5 versus 7 days). CONCLUSIONS: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19. |
Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants.
Halasa NB , Olson SM , Staat MA , Newhams MM , Price AM , Pannaraj PS , Boom JA , Sahni LC , Chiotos K , Cameron MA , Bline KE , Hobbs CV , Maddux AB , Coates BM , Michelson KN , Heidemann SM , Irby K , Nofziger RA , Mack EH , Smallcomb L , Schwartz SP , Walker TC , Gertz SJ , Schuster JE , Kamidani S , Tarquinio KM , Bhumbra SS , Maamari M , Hume JR , Crandall H , Levy ER , Zinter MS , Bradford TT , Flori HR , Cullimore ML , Kong M , Cvijanovich NZ , Gilboa SM , Polen KN , Campbell AP , Randolph AG , Patel MM . N Engl J Med 2022 387 (2) 109-119 BACKGROUND: Infants younger than 6 months of age are at high risk for complications of coronavirus disease 2019 (Covid-19) and are not eligible for vaccination. Transplacental transfer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after maternal Covid-19 vaccination may confer protection against Covid-19 in infants. METHODS: We used a case-control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than 6 months of age. Between July 1, 2021, and March 8, 2022, we enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 states. We estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant (July 1, 2021, to December 18, 2021) and the B.1.1.259 (omicron) variant (December 19, 2021, to March 8, 2022). RESULTS: A total of 537 case infants (181 of whom had been admitted to a hospital during the delta period and 356 during the omicron period; median age, 2 months) and 512 control infants were enrolled and included in the analyses; 16% of the case infants and 29% of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21%) received intensive care (64 [12%] received mechanical ventilation or vasoactive infusions). Two case infants died from Covid-19; neither infant's mother had been vaccinated during pregnancy. The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52% (95% confidence interval [CI], 33 to 65) overall, 80% (95% CI, 60 to 90) during the delta period, and 38% (95% CI, 8 to 58) during the omicron period. Effectiveness was 69% (95% CI, 50 to 80) when maternal vaccination occurred after 20 weeks of pregnancy and 38% (95% CI, 3 to 60) during the first 20 weeks of pregnancy. CONCLUSIONS: Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age. (Funded by the Centers for Disease Control and Prevention.). |
BNT162b2 Protection against the Omicron Variant in Children and Adolescents.
Price AM , Olson SM , Newhams MM , Halasa NB , Boom JA , Sahni LC , Pannaraj PS , Irby K , Bline KE , Maddux AB , Nofziger RA , Cameron MA , Walker TC , Schwartz SP , Mack EH , Smallcomb L , Schuster JE , Hobbs CV , Kamidani S , Tarquinio KM , Bradford TT , Levy ER , Chiotos K , Bhumbra SS , Cvijanovich NZ , Heidemann SM , Cullimore ML , Gertz SJ , Coates BM , Staat MA , Zinter MS , Kong M , Chatani BM , Hume JR , Typpo KV , Maamari M , Flori HR , Tenforde MW , Zambrano LD , Campbell AP , Patel MM , Randolph AG . N Engl J Med 2022 386 (20) 1899-1909 BACKGROUND: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. METHODS: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. RESULTS: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). CONCLUSIONS: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant. (Funded by the Centers for Disease Control and Prevention.). |
Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19-Associated Hospitalization in Infants Aged <6 Months - 17 States, July 2021-January 2022.
Halasa NB , Olson SM , Staat MA , Newhams MM , Price AM , Boom JA , Sahni LC , Cameron MA , Pannaraj PS , Bline KE , Bhumbra SS , Bradford TT , Chiotos K , Coates BM , Cullimore ML , Cvijanovich NZ , Flori HR , Gertz SJ , Heidemann SM , Hobbs CV , Hume JR , Irby K , Kamidani S , Kong M , Levy ER , Mack EH , Maddux AB , Michelson KN , Nofziger RA , Schuster JE , Schwartz SP , Smallcomb L , Tarquinio KM , Walker TC , Zinter MS , Gilboa SM , Polen KN , Campbell AP , Randolph AG , Patel MM . MMWR Morb Mortal Wkly Rep 2022 71 (7) 264-270 COVID-19 vaccination is recommended for persons who are pregnant, breastfeeding, trying to get pregnant now, or who might become pregnant in the future, to protect them from COVID-19.(§) Infants are at risk for life-threatening complications from COVID-19, including acute respiratory failure (1). Evidence from other vaccine-preventable diseases suggests that maternal immunization can provide protection to infants, especially during the high-risk first 6 months of life, through passive transplacental antibody transfer (2). Recent studies of COVID-19 vaccination during pregnancy suggest the possibility of transplacental transfer of SARS-CoV-2-specific antibodies that might provide protection to infants (3-5); however, no epidemiologic evidence currently exists for the protective benefits of maternal immunization during pregnancy against COVID-19 in infants. The Overcoming COVID-19 network conducted a test-negative, case-control study at 20 pediatric hospitals in 17 states during July 1, 2021-January 17, 2022, to assess effectiveness of maternal completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy against COVID-19 hospitalization in infants. Among 379 hospitalized infants aged <6 months (176 with COVID-19 [case-infants] and 203 without COVID-19 [control-infants]), the median age was 2 months, 21% had at least one underlying medical condition, and 22% of case- and control-infants were born premature (<37 weeks gestation). Effectiveness of maternal vaccination during pregnancy against COVID-19 hospitalization in infants aged <6 months was 61% (95% CI = 31%-78%). Completion of a 2-dose mRNA COVID-19 vaccination series during pregnancy might help prevent COVID-19 hospitalization among infants aged <6 months. |
Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children.
Olson SM , Newhams MM , Halasa NB , Feldstein LR , Novak T , Weiss SL , Coates BM , Schuster JE , Schwarz AJ , Maddux AB , Hall MW , Nofziger RA , Flori HR , Gertz SJ , Kong M , Sanders RC , Irby K , Hume JR , Cullimore ML , Shein SL , Thomas NJ , Stewart LS , Barnes JR , Patel MM , Randolph AG . Clin Infect Dis 2022 75 (2) 230-238 BACKGROUND: Predominance of 2 antigenically drifted influenza viruses during the 2019-2020 season offered an opportunity to assess vaccine effectiveness against life-threatening pediatric influenza disease from vaccine-mismatched viruses in the United States. METHODS: We enrolled children aged <18 years admitted to the intensive care unit with acute respiratory infection across 17 hospitals. Respiratory specimens were tested using reverse-transcription polymerase chain reaction for influenza viruses and sequenced. Using a test-negative design, we estimated vaccine effectiveness comparing odds of vaccination in test-positive case patients vs test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation. RESULTS: We enrolled 159 critically ill influenza case-patients (70% ≤8 years; 51% A/H1N1pdm09 and 25% B-Victoria viruses) and 132 controls (69% were aged ≤8 years). Among 56 sequenced A/H1N1pdm09 viruses, 29 (52%) were vaccine-mismatched (A/H1N1pdm09/5A+156K) and 23 (41%) were vaccine-matched (A/H1N1pdm09/5A+187A,189E). Among sequenced B-lineage viruses, majority (30 of 31) were vaccine-mismatched. Effectiveness against critical influenza was 63% (95% confidence interval [CI], 38% to 78%) and similar by age. Effectiveness was 75% (95% CI, 49% to 88%) against life-threatening influenza vs 57% (95% CI, 24% to 76%) against non-life-threating influenza. Effectiveness was 78% (95% CI, 41% to 92%) against matched A(H1N1)pdm09 viruses, 47% (95% CI, -21% to 77%) against mismatched A(H1N1)pdm09 viruses, and 75% (95% CI, 37% to 90%) against mismatched B-Victoria viruses. CONCLUSIONS: During a season when vaccine-mismatched influenza viruses predominated, vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children. |
Frequency, Characteristics and Complications of COVID-19 in Hospitalized Infants.
Hobbs CV , Woodworth K , Young CC , Jackson AM , Newhams MM , Dapul H , Maamari M , Hall MW , Maddux AB , Singh AR , Schuster JE , Rowan CM , Fitzgerald JC , Irby K , Kong M , Mack EH , Staat MA , Cvijanovich NZ , Bembea MM , Coates BM , Halasa NB , Walker TC , McLaughlin GE , Babbitt CJ , Nofziger RA , Loftis LL , Bradford TT , Campbell AP , Patel MM , Randolph AG . Pediatr Infect Dis J 2021 41 (3) e81-e86 BACKGROUND: Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19. METHODS: Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients aged >7 days to <1 year hospitalized with symptomatic acute COVID-19. RESULTS: We report 232 infants aged >7 days to <1 year hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients aged >7 days to <18 years, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and <1% died. CONCLUSIONS: Infants accounted for over a fifth of children aged <18 years hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were <6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant. |
Concordance with comprehensive iron assessment, hepatitis A vaccination, and hepatitis B vaccination recommendations among patients with sickle cell disease and thalassaemia receiving chronic transfusions: an analysis from the Centers for Disease Control haemoglobinopathy blood safety project
Badawy SM , Payne AB , Hulihan MM , Coates TD , Majumdar S , Smith D , Thompson AA . Br J Haematol 2021 195 (5) e160-e164 Non-concordance with preventive recommendations is common among patients with chronic conditions, including sickle cell disease (SCD) and transfusion-dependent thalassaemia (TDT).1,2 Iron overload is common among chronically transfused patients with SCD and TDT leading to increased morbidity, mortality and cost of care, especially as they live longer.3-5 | | The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations support completion of hepatitis A (HepA) and hepatitis B (HepB) vaccinations, including SCD and TDT.6,7 Cardiac iron overload is the leading cause of mortality in TDT,8 while it is rare in SCD.9 Guidelines recommend liver iron overload assessment every 1–2 years for patients with SCD receiving chronic transfusions.10,11 The recommendation for TDT is annual assessment of liver and cardiac iron concentration.3,8 However, there are limited data on concordance with these recommendations. In the present study, our objective was to evaluate concordance with these preventive recommendations among chronically transfused patients with SCD and TDT. We hypothesised that concordance is suboptimal. |
Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.
Son MBF , Murray N , Friedman K , Young CC , Newhams MM , Feldstein LR , Loftis LL , Tarquinio KM , Singh AR , Heidemann SM , Soma VL , Riggs BJ , Fitzgerald JC , Kong M , Doymaz S , Giuliano JS Jr , Keenaghan MA , Hume JR , Hobbs CV , Schuster JE , Clouser KN , Hall MW , Smith LS , Horwitz SM , Schwartz SP , Irby K , Bradford TT , Maddux AB , Babbitt CJ , Rowan CM , McLaughlin GE , Yager PH , Maamari M , Mack EH , Carroll CL , Montgomery VL , Halasa NB , Cvijanovich NZ , Coates BM , Rose CE , Newburger JW , Patel MM , Randolph AG . N Engl J Med 2021 385 (1) 23-34 BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.). |
Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19.
Feldstein LR , Tenforde MW , Friedman KG , Newhams M , Rose EB , Dapul H , Soma VL , Maddux AB , Mourani PM , Bowens C , Maamari M , Hall MW , Riggs BJ , Giuliano JSJr , Singh AR , Li S , Kong M , Schuster JE , McLaughlin GE , Schwartz SP , Walker TC , Loftis LL , Hobbs CV , Halasa NB , Doymaz S , Babbitt CJ , Hume JR , Gertz SJ , Irby K , Clouser KN , Cvijanovich NZ , Bradford TT , Smith LS , Heidemann SM , Zackai SP , Wellnitz K , Nofziger RA , Horwitz SM , Carroll RW , Rowan CM , Tarquinio KM , Mack EH , Fitzgerald JC , Coates BM , Jackson AM , Young CC , Son MBF , Patel MM , Newburger JW , Randolph AG . JAMA 2021 325 (11) 1074-1087 IMPORTANCE: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. OBJECTIVE: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). SETTING, DESIGN, AND PARTICIPANTS: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. EXPOSURE: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. RESULTS: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. CONCLUSIONS AND RELEVANCE: This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19. |
What's the "secret sauce" How implementation variation affects the success of colorectal cancer screening outreach
Coury J , Miech EJ , Styer P , Petrik AF , Coates KE , Green BB , Baldwin LM , Shapiro JA , Coronado GD . Implement Sci Commun 2021 2 (1) 5 BACKGROUND: Mailed fecal immunochemical testing (FIT) programs can improve colorectal cancer (CRC) screening rates, but health systems vary how they implement (i.e., adapt) these programs for their organizations. A health insurance plan implemented a mailed FIT program (named BeneFIT), and participating health systems could adapt the program. This multi-method study explored which program adaptations might have resulted in higher screening rates. METHODS: First, we conducted a descriptive analysis of CRC screening rates by key health system characteristics and program adaptations. Second, we generated an overall model by fitting a weighted regression line to our data. Third, we applied Configurational Comparative Methods (CCMs) to determine how combinations of conditions were linked to higher screening rates. The main outcome measure was CRC screening rates. RESULTS: Seventeen health systems took part in at least 1 year of BeneFIT. The overall screening completion rate was 20% (4-28%) in year 1 and 25% (12-35%) in year 2 of the program. Health systems that used two or more adaptations had higher screening rates, and no single adaptation clearly led to higher screening rates. In year 1, small systems, with just one clinic, that used phone reminders (n = 2) met the implementation success threshold (≥ 19% screening rate) while systems with > 1 clinic were successful when offering a patient incentive (n = 4), scrubbing mailing lists (n = 4), or allowing mailed FIT returns with no other adaptations (n = 1). In year 2, larger systems with 2-4 clinics were successful with a phone reminder (n = 4) or a patient incentive (n = 3). Of the 10 systems that implemented BeneFIT in both years, seven improved their CRC screening rates in year 2. CONCLUSIONS: Health systems can choose among many adaptations and successfully implement a health plan's mailed FIT program. Different combinations of adaptations led to success with health system size emerging as an important contextual factor. |
Qualitative Variation Among Commercial Immunoassays to Detect Measles-Specific IgG.
Latner DR , Sowers SB , Anthony K , Colley H , Badeau C , Coates J , Wong P , Fakile Y , Interiano C , Pannell KB , Leung-Pineda V , Patel MM , Rota PA , Limbago BM , Hickman CJ . J Clin Microbiol 2020 58 (6) Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary re-vaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization (PRN), the gold standard method and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there was good agreement across platforms for IgG negative sera and for samples with intermediate to high levels of IgG. False negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody. |
Parvovirus B19 infection in sickle cell disease: An analysis from the Centers for Disease Control haemoglobinopathy blood surveillance project
Majumdar S , Bean CJ , De Staercke C , Bost J , Nickel R , Coates T , Campbell A , Thompson A . Transfus Med 2020 30 (3) 226-230 OBJECTIVE: In the multicentre Haemoglobinopathy Blood Surveillance Project, to evaluate the seroprevalence of parvovirus B19 and DNA viral load in sickle cell disease (SCD). BACKGROUND: Although the epidemiology of parvovirus B19 seropositivity in SCD has been well documented, there are few studies that have assessed possible persistent parvovirus DNAemia and associated risk factors including blood transfusion. METHODS: A qualitative analysis of parvovirus B19 serology using ELISA and quantitative parvovirus B19 DNA by RT-PCR was performed in patients with SCD. RESULTS: Of 322 patients, 113 (35%) were parvovirus IgG positive and 119 (37%) were IgM positive at enrolment. The prevalence of IgG positivity increased with age. 71/322 (22%) were parvovirus DNA positive at enrolment with a mean viral load of 15 227 +/- 55 227 SD. (range 72-329 238 IU/mL). Patients who were positive for parvovirus B19 DNA received a significantly higher red blood cell transfusion volume in the prior year compared to patients who were negative (mean RBC volume = 8310 mL vs 5435 mL, respectively; P = .0073). Seventy-seven patients had follow-up testing approximately 1 year after enrolment and 11/28 (39%) patients had persistently positive IgM. CONCLUSION: Further studies are needed to better understand the natural history of parvovirus B19 infection in SCD especially in relation to RBC transfusion as a risk factor, as well as disease outcome and severity. |
Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy
Brinton LA , Brogan DR , Coates RJ , Swanson CA , Potischman N , Stanford JL . Menopause 2018 25 (11) 1195-1200 OBJECTIVE: To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. DESIGN: A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. RESULTS: Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. CONCLUSIONS: Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy. |
Effectiveness of clinical decision support based intervention in the improvement of care for adult sickle cell disease patients in primary care
Mainous AG3rd , Carek PJ , Lynch K , Tanner RJ , Hulihan MM , Baskin J , Coates TD . J Am Board Fam Med 2018 31 (5) 812-816 INTRODUCTION: Although most patients with rare diseases like sickle cell disease (SCD) are treated in the primary care setting, primary care physicians may find it challenging to keep abreast of medication improvements and complications associated with treatment for rare and complex diseases. The purpose of this study was to evaluate the effectiveness of a clinical decision support (CDS) -based intervention system for transfusional iron overload in adults with SCD to improve management in primary care. METHODS: An electronic medical record based clinical decision support system for potential transfusional iron overload in SCD patients in primary care was evaluated. The intervention was implemented in 3 family medicine clinics with a control group of 3 general internal medicine clinics. Data were collected in the 6 months before the intervention and 6 months after the intervention. There were 47 patients in the family medicine group and 24 in the general internal medicine group. RESULTS: There was no management change in the control group while the intervention group improved primary care management from 0% to 44% (P < .001). CONCLUSION: A CDS tool can improve management of SCD patients in primary care. |
Performance standards for biological threat agent assays for Department of Defense applications
Beck L , Coates SG , Gee J , Hadfield T , Jackson P , Keim P , Lindler L , Olson V , Ostlund E , Roberto F , Samuel J , Sharma S , Tallent S , Wagner DM . J AOAC Int 2018 101 (6) 1665-1708 There has been a proliferation in the developmentof biological threat agent detection technologies foruse in the field by first responders and private-sectorend-users as well as in Department of Defense(DoD) applications in which active combat maybe occurring and in other parts of the world. Incontrast to the proliferation of detection methodology, there has been a lack of standards defining therequired performance of these technologies. Standardsare necessary to demonstrate the performanceand limitations of the tools, providing confidencein the data to allow appropriate response actions byend-users and responders. In the past, the Departmentof Homeland Security (DHS), Science andTechnology Directorate, funded AOAC to developstandards and perform conformity assessmentunder three efforts. The first effort began in 2003to evaluate the performance of lateral flow immunoassaydevices used by first responders to screensuspicious powders for Bacillus anthracis spores.These devices are colloquially known as "handheldassays" and are frequently referred to as"HHAs." AOAC formed the Task Force on Bacillusanthracis (TFBA), which created a specific set ofconsensus performance criteria and test protocols(i.e., standards). Five HHA manufacturers submittedtheir technologies to AOAC so that third-partylaboratories could evaluate the tools against the criteria. |
An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial.
DeZure AD , Coates EE , Hu Z , Yamshchikov GV , Zephir KL , Enama ME , Plummer SH , Gordon IJ , Kaltovich F , Andrews S , McDermott A , Crank MC , Koup RA , Schwartz RM , Bailer RT , Sun X , Mascola JR , Tumpey TM , Graham BS , Ledgerwood JE . NPJ Vaccines 2017 2 15 A novel avian influenza subtype, A/H7N9, emerged in 2013 and represents a public health threat with pandemic potential. We have previously shown that DNA vaccine priming increases the magnitude and quality of antibody responses to H5N1 monovalent inactivated boost. We now report the safety and immunogenicity of a H7 DNA-H7N9 monovalent inactivated vaccine prime-boost regimen. In this Phase 1, open label, randomized clinical trial, we evaluated three H7N9 vaccination regimens in healthy adults, with a prime-boost interval of 16 weeks. Group 1 received H7 DNA vaccine prime and H7N9 monovalent inactivated vaccine boost. Group 2 received H7 DNA and H7N9 monovalent inactivated vaccine as a prime and H7N9 monovalent inactivated vaccine as a boost. Group 3 received H7N9 monovalent inactivated vaccine in a homologous prime-boost regimen. Overall, 30 individuals between 20 to 60 years old enrolled and 28 completed both vaccinations. All injections were well tolerated with no serious adverse events. 2 weeks post-boost, 50% of Group 1 and 33% of Group 2 achieved a HAI titer >/=1:40 compared with 11% of Group 3. Also, at least a fourfold increase in neutralizing antibody responses was seen in 90% of Group 1, 100% of Group 2, and 78% of Group 3 subjects. Peak neutralizing antibody geometric mean titers were significantly greater for Group 1 (GMT = 440.61, p < 0.05) and Group 2 (GMT = 331, p = 0.02) when compared with Group 3 (GMT = 86.11). A novel H7 DNA vaccine was safe, well-tolerated, and immunogenic when boosted with H7N9 monovalent inactivated vaccine, while priming for higher HAI and neutralizing antibody titers than H7N9 monovalent inactivated vaccine alone. |
Summary of notifiable noninfectious conditions and disease outbreaks: Surveillance data published between April 1, 2016 and January 31, 2017 - United States
Thomas K , Jajosky R , Coates RJ , Calvert GM , Dewey-Mattia D , Raymond J , Singh SD . MMWR Morb Mortal Wkly Rep 2017 64 (54) 1-6 The Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Surveillance Data Published Between April 1, 2016 and January 31, 2017 - United States, herein referred to as the Summary (Noninfectious), contains official statistics for nationally notifiable noninfectious conditions and disease outbreaks. This Summary (Noninfectious) is being published in the same volume of MMWR as the annual Summary of Notifiable Infectious Diseases and Conditions. Data on notifiable noninfectious conditions and disease outbreaks from prior years have been published previously. |
Development of an improved standard reference material for vitamin D metabolites in human serum
Phinney KW , Tai SS , Bedner M , Camara JE , Chia RRC , Sander LC , Sharpless KE , Wise SA , Yen JH , Schleicher RL , Chaudhary-Webb M , Maw KL , Rahmani Y , Betz JM , Merkel J , Sempos CT , Coates PM , Durazo-Arvizu RA , Sarafin K , Brooks SPJ . Anal Chem 2017 89 (9) 4907-4913 The National Institute of Standards and Technology (NIST) has developed Standard Reference Material (SRM) 972a Vitamin D Metabolites in Frozen Human Serum as a replacement for SRM 972, which is no longer available. SRM 972a was developed in collaboration with the National Institutes of Health's Office of Dietary Supplements. In contrast to the previous reference material, three of the four levels of SRM 972a are composed of unmodified human serum. This SRM has certified and reference values for the following 25-hydroxyvitamin D [25(OH)D] species: 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3. The value assignment and certification process included three isotope-dilution mass spectrometry approaches, with measurements performed at NIST and at the Centers for Disease Control and Prevention (CDC). The value assignment methods employed have been modified from those utilized for the previous SRM, and all three approaches now incorporate chromatographic resolution of the stereoisomers, 25(OH)D3 and 3-epi-25(OH)D3. |
AOAC SMPR 2016.009: Standard Method Performance Requirements (SMPRs) for DNA-based methods of detecting Brucella suis in field-deployable, Department of Defense aerosol collection devices
Roberto F , Arce J , Beck LC , Blank TR , Cahall R , Damer K , Ficht T , Foster J , Kiss K , Nikolich M , Olsen S , Ozanich R , Rozak D , Schaefer F , Sozhamannan S , Tiller R , Coates SG . J AOAC Int 2017 100 (1) 255-260 Intended Use: Field-deployed use for analysis of | aerosol collection filters and/or liquids | 1 Applicability | Detection of Brucella suis in collection buffers from aerosol | collection devices. Field-deployable assays are preferred. | 2 Analytical Technique | Molecular detection of nucleic acid. | 3 Definitions | Acceptable minimum detection level (AMDL).— | Predetermined minimum level of an analyte, as specified by | an expert committee which must be detected by the candidate | method at a specified probability of detection (POD). | Exclusivity.—Study involving pure nontarget strains, which | are potentially cross-reactive, that shall not be detected or | enumerated by the candidate method. | Inclusivity.—Study involving pure target strains that shall be | detected or enumerated by the candidate method. | Maximum time-to-result.—Maximum time to complete an | analysis starting from the collection buffer to assay result. | Probability of detection (POD).—Proportion of positive | analytical outcomes for a qualitative method for a given matrix | at a specified analyte level or concentration with a ≥0.95 | confidence interval. | System false-negative rate.—Proportion of test results that | are negative contained within a population of known positives. | System false-positive rate.—Proportion of test results that are | positive contained within a population of known negatives. | 4 Method Performance Requirements | See Table 1. | 5 System Suitability Tests and/or Analytical Quality control | The controls listed in Table 2 shall be embedded in assays as | appropriate. Manufacturer must provide written justification if | controls are not embedded in the assay |
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