Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 68 Records) |
Query Trace: Belay ED[original query] |
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Suicides in National Hormone Pituitary Program recipients of cadaver-derived human growth hormone
Abrams JY , Mills JL , Schonberger LB , Chang D , Maddox RA , Belay ED , Leschek EW . J Endocr Soc 2023 7 (12) bvad130 CONTEXT: Numerous reports of suicide among individuals who received cadaver-derived human growth hormone (c-hGH) through the National Hormone Pituitary Program (NHPP) raised the alarm for potentially increased suicide risk. OBJECTIVE: We conducted a study to assess suicide risk in the NHPP cohort and identify contributing factors to facilitate early recognition and intervention. METHODS: The study population consisted of patients receiving NHPP c-hGH starting from 1957, and cohort deaths with an ICD code consistent with suicide or possible suicide through 2020 were evaluated. Descriptive data were extracted from medical records. Standardized mortality ratios (SMRs) to compare the observed number of suicide deaths in the cohort to the expected number were calculated using general population suicide rates by sex, age group, and time period. RESULTS: Among 6272 patients there were 1200 all-cause cohort deaths, of which 55 (52 male, 3 female) were attributed to suicide. Of these, 47 were identified by ICD code alone compared to an expected count of 37.8 (SMR = 1.25, 95% CI 0.91-1.66). Among male cohort members, the SMR was 1.33 (95% CI 0.97-1.78). Elevated risk of suicide was detected for cohort members aged 25-34 (SMR = 1.79, 95% CI 1.06-2.83) and during the period from September 19, 1985, to December 31, 1998 (SMR = 1.70, 95% CI 1.02-2.65). CONCLUSION: Overall, the observed number of suicides among NHPP c-hGH recipients was not significantly higher than expected. However, certain subgroups may be at elevated risk of suicide. Studies are needed to better understand the nature and magnitude of suicide risk among c-hGH recipients to facilitate early intervention to prevent suicide deaths. |
Clinical features, etiologies, and outcomes of central nervous system infections in intensive care: A multicentric retrospective study in a large Brazilian metropolitan area
Andrade HB , da Silva IRF , Espinoza R , Ferreira MT , da Silva MST , Theodoro PHN , Detepo PJT , Varela MC , Ramos GV , da Silva AR , Soares J , Belay ED , Sejvar JJ , Bozza FA , Cerbino-Neto J , Japiassú AM . J Crit Care 2023 79 154451 PURPOSE: The goal of this study was to investigate severe central nervous system infections (CNSI) in adults admitted to the intensive care unit (ICU). We analyzed the clinical presentation, causes, and outcomes of these infections, while also identifying factors linked to higher in-hospital mortality rates. MATERIALS AND METHODS: We conducted a retrospective multicenter study in Rio de Janeiro, Brazil, from 2012 to 2019. Using a prediction tool, we selected ICU patients suspected of having CNSI and reviewed their medical records. Multivariate analyses identified variables associated with in-hospital mortality. RESULTS: In a cohort of 451 CNSI patients, 69 (15.3%) died after a median 11-day hospitalization (5-25 IQR). The distribution of cases was as follows: 29 (6.4%) had brain abscess, 161 (35.7%) had encephalitis, and 261 (57.8%) had meningitis. Characteristics: median age 41 years (27-53 IQR), 260 (58%) male, and 77 (17%) HIV positive. The independent mortality predictors for encephalitis were AIDS (OR = 4.3, p = 0.01), ECOG functional capacity limitation (OR = 4.0, p < 0.01), ICU admission from ward (OR = 4.0, p < 0.01), mechanical ventilation ≥10 days (OR = 6.1, p = 0.04), SAPS 3 ≥ 55 points (OR = 3.2, p = 0.02). Meningitis: Age > 60 years (OR = 234.2, p = 0.04), delay >3 days for treatment (OR = 2.9, p = 0.04), mechanical ventilation ≥10 days (OR = 254.3, p = 0.04), SOFA >3 points (OR = 2.7, p = 0.03). Brain abscess: No associated factors found in multivariate regression. CONCLUSIONS: Patients' overall health, prompt treatment, infection severity, and prolonged respiratory support in the ICU all significantly affect in-hospital mortality rates. Additionally, the implementation of CNSI surveillance with the used prediction tool could enhance public health policies. |
Treatments and severe outcomes for patients diagnosed with MIS-C at four children's hospitals in the United States, March 16, 2020-March 10, 2021
Shah AB , Abrams JY , Godfred-Cato S , Kunkel A , Hammett TA , Perez MA , Hsiao HM , Baida N , Rostad CA , Ballan W , Ede K , Laham FR , Kao CM , Oster ME , Belay ED . Pediatr Infect Dis J 2023 42 (11) 990-998 BACKGROUND: Clinical management of multisystem inflammatory syndrome in children (MIS-C) has varied over time and by medical institution. METHODS: Data on patients with MIS-C were collected from 4 children's hospitals between March 16, 2020 and March 10, 2021. Relationships between MIS-C treatments and patient demographics, clinical characteristics, and outcomes were described. Propensity score matching was utilized to assess the relative risk of outcomes dependent on early treatment with intravenous immunoglobulin (IVIG) or low-dose steroids, controlling for potential confounding variables. RESULTS: Of 233 patients diagnosed with MIS-C, the most commonly administered treatments were steroids (88.4%), aspirin (81.1%), IVIG (77.7%) and anticoagulants (71.2%). Compared with those patients without respiratory features, patients with respiratory features were less likely to receive IVIG and steroids on the same day (combination treatment) (44.1%). Controlling for confounding variables, patients receiving IVIG within 1 day of hospitalization were less likely to have hospital length of stay ≥8 days (RR = 0.53, 95% CI: 0.31-0.88). Patients receiving low-dose steroids within 1 day of hospitalization were less likely to develop ventricular dysfunction (RR = 0.45, 95% CI: 0.26-0.77), have increasingly elevated troponin levels (RR = 0.55, 95% CI: 0.40-0.75) or have hospital length of stay ≥8 days (RR = 0.46, 95% CI: 0.29-0.74). CONCLUSION: Treatments for MIS-C differed by hospital, patient characteristics and illness severity. When IVIG and low-dose steroids were administered in combination or low-dose steroids were administered alone within 1 day of hospitalization, the risk of subsequent severe outcomes was decreased. |
Possible exposures among mpox patients without reported male-to-male sexual contact - six U.S. Jurisdictions, November 1-December 14, 2022
Sharpe JD , Charniga K , Byrd KM , Stefanos R , Lewis L , Watson J , Feldpausch A , Pavlick J , Hand J , Sokol T , Ortega E , Pathela P , Hennessy RR , Dulcey M , McHugh L , Pietrowski M , Perella D , Shah S , Maroufi A , Taylor M , Cope A , Belay ED , Ellington S , McCollum AM , Zilversmit Pao L , Guagliardo SAJ , Dawson P . MMWR Morb Mortal Wkly Rep 2023 72 (35) 944-948 The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC. |
Profiling and benchmarking central nervous system infections in an infectious diseases intensive care unit
Andrade HB , Rocha Ferreira da Silva I , Espinoza R , da Silva MST , Theodoro PHN , Ferreira MT , Soares J , Belay ED , Sejvar JJ , Bozza FA , Cerbino-Neto J , Japiassú AM . J Intensive Care Med 2023 39 (1) 8850666231188665 BACKGROUND: There is little information comparing the performance of community acquired central nervous system infections (CNSI) treatment by intensive care units (ICUs) specialized in infectious diseases with treatment at other ICUs. Our objective was to reduce these gaps, creating bases for benchmarking and future case-mix classification. METHODS: This is a retrospective observational cohort of 785 admissions with 82 cases of CNSI admitted to the ICU of an important Brazilian referral center for infectious diseases (INI) between January 2012 and January 2019. Comparisons were made to data retrospectively collected from the 303,500 intensive care admissions from the Brazilian state health care system included in the Epimed Monitor database. Clinical, epidemiologic, and performance indicators: the standardized mortality rate (SMR) and the standardized resource use rate per ICU surviving patient (SRU) were collected. RESULTS: Case-mix infections profile and SMR/SRU data. SUS Mixed medical/surgical ICUs: SMR = 1.26, SRU = 1.59; SUS Neurological ICUs: SMR = 1.17, SRU = 2.23; INI ICU: SMR = 1.1, SRU = 1.1; INI ICU CNSI patients: SMR = 0.95, SRU = 1.01. CONCLUSIONS: Severe patients with CNSI can be efficiently and effectively treated in an ICU specialized in infectious diseases when compared to mixed medical/surgical and neurological ICUs from the public health system. At the same time, we provided profiling and a case-mix that can help and encourage benchmarking by other institutions and other countries. |
Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) Aged 12-20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021 (preprint)
Yousaf AR , Cortese MM , Taylor AW , Broder KR , Oster ME , Wong JM , Guh AY , McCormick DW , Kamidani S , Schlaudecker EP , Edwards K , Creech CB , Staat MA , Belay ED , Marquez P , Su JR , Salzman MB , Thompson D , Campbell AP , Museru O , Howard LM , Parise M , Finn LE , Kim M , Raman KV , Komatsu KK , Spiker BL , Burkholder CP , Lang SM , Soslow JH . medRxiv 2022 05 Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12-20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC. Method(s): We investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC's Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination. Finding(s): We identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12-20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12-20 years had received >=1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1.0 case per million persons receiving >=1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0.3 cases per million vaccinated persons. Interpretation(s): In our case series, we describe a small number of persons with MIS-C who had received >=1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
A multicenter retrospective cohort study to characterize patients hospitalized with MIS-A and COVID-19 in the United States, 2020-2021
Melgar M , Abrams JY , Godfred-Cato S , Shah AB , Garg A , Strunk A , Narasimhan M , Koptyev J , Norden A , Musheyev D , Rashid F , Tannenbaum R , Estrada YMartin RM , Patel B , Karanth S , Achenbach CJ , Hall GT , Hockney SM , Caputo M , Abbo LM , Beauchamps L , Morris SB , Cifuentes RO , de St Maurice A , Bell DS , Prabaker KK , Sanz Vidorreta FJ , Bryant E , Cohen DK , Mohan R , Libby CP , SooHoo S , Domingo TJ , Campbell AP , Belay ED . Clin Infect Dis 2023 BACKGROUND: The diagnosis of SARS-CoV-2-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute COVID-19 and may impact clinical management. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at six academic medical centers during March 1, 2020-December 31, 2021. MIS-A patients were matched on age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10,223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched COVID-19 patients, MIS-A patients were more likely to be non-Hispanic Black and less likely to be non-Hispanic White. MIS-A patients more likely had laboratory-confirmed COVID-19 ≥ 14 days prior to hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, MIS-A patients had higher neutrophil-to-lymphocyte ratio, C-reactive protein, ferritin, procalcitonin and D-dimer, compared with COVID-19 patients. MIS-A patients had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. Mortality was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management. |
Progress toward equitable mpox vaccination coverage: A shortfall analysis - United States, May 2022-April 2023
Kota KK , Chesson H , Hong J , Zelaya C , Spicknall IH , Riser AP , Hurley E , Currie DW , Lash RR , Carnes N , Concepción-Acevedo J , Ellington S , Belay ED , Mermin J . MMWR Morb Mortal Wkly Rep 2023 72 (23) 627-632 More than 30,000 monkeypox (mpox) cases were reported in the United States during the 2022 multinational outbreak; cases disproportionately affected gay, bisexual, and other men who have sex with men (MSM). Substantial racial and ethnic disparities in incidence were also reported (1). The national mpox vaccination strategy* emphasizes that efforts to administer the JYNNEOS mpox vaccine should be focused among the populations at elevated risk for exposure to mpox (2). During May 2022-April 2023, a total of 748,329 first JYNNEOS vaccine doses (of the two recommended) were administered in the United States.(†) During the initial months of the outbreak, lower vaccination coverage rates among racial and ethnic minority groups were reported (1,3); however, after implementation of initiatives developed to expand access to mpox vaccination,(§) coverage among racial and ethnic minority groups increased (1,4). A shortfall analysis was conducted to examine whether the increase in mpox vaccination coverage was equitable across all racial and ethnic groups (5). Shortfall was defined as the percentage of the vaccine-eligible population that did not receive the vaccine (i.e., 100% minus the percentage of the eligible population that did receive a first dose). Monthly mpox vaccination shortfalls were calculated and were stratified by race and ethnicity; monthly percent reductions in shortfall were also calculated compared with the preceding month's shortfall (6). The mpox vaccination shortfall decreased among all racial and ethnic groups during May 2022-April 2023; however, based on analysis of vaccine administration data with race and ethnicity reported, 66.0% of vaccine-eligible persons remained unvaccinated at the end of this period. The shortfall was largest among non-Hispanic Black or African American (Black) (77.9%) and non-Hispanic American Indian or Alaska Native (AI/AN) (74.5%) persons, followed by non-Hispanic White (White) (66.6%) and Hispanic or Latino (Hispanic) (63.0%) persons, and was lowest among non-Hispanic Asian (Asian) (38.5%) and non-Hispanic Native Hawaiian and other Pacific Islander (NH/OPI) (43.7%) persons. The largest percentage decreases in the shortfall were achieved during August (17.7%) and September (8.5%). However, during these months, smaller percentage decreases were achieved among Black persons (12.2% and 4.9%, respectively), highlighting the need for a focus on equity for the entirety of a public health response. Achieving equitable progress in JYNNEOS vaccination coverage will require substantial decreases in shortfalls among Black and AI/AN persons. |
Falling Through the Cracks: The Current Gap in the Health Care Transition of Patients With Kawasaki Disease: A Scientific Statement From the American Heart Association
Dahdah N , Kung SC , Friedman KG , Marelli A , Gordon JB , Belay ED , Baker AL , Kazi DS , White PH , Tremoulet AH , American Heart Association Rheumatic Fever Endocarditis Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young , Council on Arteriosclerosis Thrombosis and Vascular Biology . J Am Heart Assoc 2021 10 (20) e023310 Background Health care transition (HCT) is a period of high vulnerability for patients with chronic childhood diseases, particularly when patients shift from a pediatric to an adult care setting. An increasing number of patients with Kawasaki disease (KD) who develop medium and large coronary artery aneurysms (classified by the American Heart Association according to maximal internal coronary artery diameter Z-scores ≥5 and ≥10, respectively) are becoming adults and thus undergoing an HCT. However, a poor transition to an adult provider represents a risk of loss to follow-up, which can result in increasing morbidity and mortality. Methods and Results This scientific statement provides a summary of available literature and expert opinion pertaining to KD and HCT of children as they reach adulthood. The statement reviews the existing life-long risks for patients with KD, explains current guidelines for long-term care of patients with KD, and offers guidance on assessment and preparation of patients with KD for HCT. The key element to a successful HCT, enabling successful transition outcomes, is having a structured intervention that incorporates the components of planning, transfer, and integration into adult care. This structured intervention can be accomplished by using the Six Core Elements approach that is recommended by the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians. Conclusions Formal HCT programs for patients with KD who develop aneurysms should be established to ensure a smooth transition with uninterrupted medical care as these youths become adults. |
COVID-19 vaccine reactogenicity and vaccine attitudes among children and parents/guardians after multisystem inflammatory syndrome in children or COVID-19 hospitalization: September 2021-May 2022
Yousaf AR , Kunkel A , Abrams JY , Shah AB , Hammett TA , Arnold KE , Beltran YL , Laham FR , Kao CM , Hunstad DA , Hussaini L , Baida N , Salazar L , Perez MA , Rostad CA , Godfred-Cato S , Campbell AP , Belay ED . Pediatr Infect Dis J 2023 42 (3) 252-259 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a multiorgan hyperinflammatory condition following SARS-CoV-2 infection. Data on COVID-19 vaccine adverse events and vaccine attitudes in children with prior MIS-C are limited. We described characteristics associated with COVID-19 vaccination, vaccine adverse events and vaccine attitudes in children with a history of MIS-C or COVID-19 and their parents/guardians. METHODS: We enrolled children previously hospitalized for MIS-C or COVID-19 from 3 academic institutions. We abstracted charts and interviewed children and parents/guardians regarding vaccine adverse events and acceptability. RESULTS: Of 163 vaccine-eligible children enrolled with a history of MIS-C and 70 with history of COVID-19, 51 (31%) and 34 (49%), respectively, received mRNA COVID-19 vaccine a median of 10 (Interquartile Range 6-13) months after hospital discharge. Among 20 children with MIS-C and parents/guardians who provided interviews, local injection site reaction of brief duration (mean 1.8 days) was most commonly reported; no children required medical care within 2 weeks postvaccination. Vaccine survey results of interviewed, vaccinated children and their parents/guardians: of 20 children with MIS-C and 15 children with COVID-19, 17 (85%) and 13 (87%), respectively, listed doctors in the top 3 most trusted sources for vaccine information; 13 (65%) and 9 (60%) discussed vaccination with their doctor. CONCLUSIONS: COVID-19 vaccination was well tolerated in children with prior MIS-C or COVID-19 participating in our investigation. Parents/guardians regarded their children's doctors as a trusted source of information for COVID-19 vaccines, and most vaccinated children's parents/guardians had discussed COVID-19 vaccination for their child with their doctor. |
First-line corticosteroids for Kawasaki disease: Pulse versus multiple dose
Abrams JY , Ae R , Maddox RA , Schonberger LB , Nakamura Y , Belay ED . Pediatr Int 2022 64 (1) e15112 BACKGROUND: Kawasaki disease (KD) can result in severe coronary artery abnormalities (CAAs). Corticosteroids added to initial standard intravenous immunoglobulin (IVIG) treatment may decrease the risk for these complications. Different corticosteroid regimens (single-day high dose pulse vs multiple lower doses) may contribute to the discrepant results of prior studies. METHODS: Using data from the 22nd, 23(rd) , and 24th Japanese nationwide KD surveys (2011-2016), we identified KD patients who did not have CAAs at first presentation and who were treated with either pulse or multiple-dose corticosteroids as part of their initial treatment. Occurrence of subsequent CAAs and treatment failure were compared between the treatment regimens and adjusted odds ratios were calculated controlling for sex, age group, illness day at first treatment, survey, and recurrent KD. RESULTS: There were 782 KD patients who received pulse corticosteroid treatment and 4,817 who received multiple dose treatment. Patients receiving multiple dose treatment were less likely to develop CAAs (5.5% vs 8.3%, OR 0.64; 95% CI: 0.48-0.85) or treatment failure (21.4% vs 41.6%; OR: 0.38; 95% CI: 0.33-0.45). Adjusted analyses showed similar protective effects of multiple-dose treatment against CAAs (OR: 0.67, 95% CI: 0.51-0.90) and treatment failure (OR: 0.39, 95% CI: 0.33-0.46). CONCLUSIONS: Multiple-dose corticosteroid combination treatment resulted in substantially improved outcomes in KD patients compared to pulse treatment. For patients who may be at elevated risk of treatment failure or CAA, use of multiple-dose corticosteroids in conjunction with IVIG is likely to provide considerable clinical benefit. |
Council of State and Territorial Epidemiologists/CDC Surveillance Case Definition for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection - United States.
Melgar M , Lee EH , Miller AD , Lim S , Brown CM , Yousaf AR , Zambrano LD , Belay ED , Godfred-Cato S , Abrams JY , Oster ME , Campbell AP . MMWR Recomm Rep 2022 71 (4) 1-14 THIS REPORT SUMMARIZES THE EVIDENCE AND RATIONALE SUPPORTING THE COMPONENTS OF THE CSTE/CDC MIS-C SURVEILLANCE CASE DEFINITION AND DESCRIBES THE METHODS USED TO DEVELOP THE DEFINITION. THESE METHODS INCLUDED CONVENING MIS-C CLINICAL EXPERTS (I.E., CONSULTANTS): regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC. |
Kawasaki disease following the 13-valent pneumococcal conjugate vaccine and rotavirus vaccines
Kamidani S , Panagiotakopoulos L , Licata C , Daley MF , Yih WK , Zerbo O , Tseng HF , DeSilva MB , Nelson JC , Groom HC , Williams JTB , Hambidge SJ , Donahue JG , Belay ED , Weintraub ES . Pediatrics 2022 150 (6) BACKGROUND: Temporal associations between Kawasaki disease (KD) and childhood vaccines have been reported. Limited data on KD following 13-valent pneumococcal conjugate (PCV13) and rotavirus vaccines are available. METHODS: We conducted a self-controlled risk interval study using Vaccine Safety Datalink electronic health record data to investigate the risk of KD following PCV13 and rotavirus vaccines in children <2 years of age who were born from 2006 to 2017. All hospitalized KD cases identified by International Classification of Diseases diagnosis codes that fell within predefined risk (days 1-28 postvaccination) and control (days 29-56 for doses 1 and 2, and days 43-70 for doses 3 and 4) intervals were confirmed by manual chart review. RESULTS: During the study period, 655 cases of KD were identified by International Classification of Diseases codes. Of these, 97 chart-confirmed cases were within risk or control intervals. In analyses, the age-adjusted relative risk for KD following any dose of PCV13 was 0.75 (95% confidence interval, 0.47-1.21). Similarly, the age-adjusted relative risk for KD following any dose of rotavirus vaccine was 0.66 (95% CI, 0.40-1.09). Overall, there was no evidence of an elevated risk of KD following PCV13 or rotavirus vaccines by dose. In addition, no statistically significant temporal clustering of KD cases was identified during days 1 to 70 postvaccination. CONCLUSIONS: PCV13 and rotavirus vaccination were not associated with an increased risk of KD in children <2 years of age. Our findings provide additional evidence for the overall safety of PCV13 and rotavirus vaccines. |
Trends in Treatments for Multisystem Inflammatory Syndrome in Children (MIS-C), United States, February 2020 - July 2021.
Abrams JY , Belay ED , Godfred-Cato S , Campbell AP , Zambrano LD , Kunkel A , Miller AD , Wu MJ , Meng L , Shah AB , Oster ME . Clin Infect Dis 2022 75 (7) 1201-1209 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel severe postinfectious condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The purpose of this report is to describe nationwide trends in the evolving clinical management of MIS-C. METHODS: Patients with MIS-C were reported from state and local jurisdictions to the Centers for Disease Control and Prevention's (CDC's) MIS-C national surveillance system. Patients' case reports were reviewed to ensure that they met the CDC MIS-C case definition and had sufficient data for analysis. The prevalence of use of treatments for MIS-C, temporal trends in use of these treatments, and frequency of administration of different treatment combinations were analyzed. RESULTS: There were 4470 patients meeting the MIS-C case definition with onset dates from 19 February 2020 to 31 July 2021. The proportion of patients admitted to an intensive care unit (ICU) has declined over time, from 78.7% in April 2020 to 57.5% in June 2021 (P = .001). The most common treatments were intravenous immunoglobulin (IVIG), given to 85.6% of patients; steroids (77.7%), and antiplatelet medications (73.7%); use of each of these treatments has increased over time, particularly in patients not requiring admission to an ICU (all P < .001). Older patients and non-Hispanic Black patients were more likely to receive additional modes of therapy including vasoactive medication, noninvasive respiratory support, anticoagulation medication, and intubation/mechanical ventilation. CONCLUSIONS: IVIG, steroids, and antiplatelet medication have become increasingly utilized as standard treatment for MIS-C patients, while the use of other treatments may be contingent on the type and severity of clinical findings. |
Multisystem inflammatory syndrome in adults (MIS-A): case finding through systematic review of electronic medical records.
Melgar M , Haston J , DeCuir J , Cheng Q , Arnold KE , Meng L , Murphy DJ , Overton E , Hollberg J , Tobin-D'Angelo M , Patel P , Campbell AP , Godfred-Cato Do S , Belay ED . Clin Infect Dis 2022 75 (11) 1903-1911 BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a severe condition temporally associated with SARS-CoV-2 infection. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention (CDC) case definition to identify diagnosed and undiagnosed MIS-A cases among adults discharged April 2020-January 2021 from four Atlanta, Georgia hospitals affiliated with a single medical center. Non-MIS-A COVID-19 hospitalizations were identified using International Classification of Diseases, Tenth Revision encounter code U07.1. We calculated the ratio of MIS-A to COVID-19 hospitalizations, compared demographic characteristics of the two cohorts, and described clinical characteristics of MIS-A patients. RESULTS: We identified 11 MIS-A cases, none of which were diagnosed by the treatment team, and 5,755 COVID-19 hospitalizations (ratio 1: 523). Compared with patients with COVID-19, patients with MIS-A were more likely to be younger than 50 years (72.7% vs. 26.1%, p < 0.01) and to be non-Hispanic Black persons (81.8% vs. 50.0%, p = 0.04). Ten patients with MIS-A (90.9%) had at least one underlying medical condition. Two MIS-A patients (18.2%) had a previous episode of laboratory-confirmed COVID-19, occurring 37 and 55 days prior to admission. All MIS-A patients developed left ventricular systolic dysfunction. None had documented mucocutaneous involvement. All required intensive care, all received systemic corticosteroids, eight (72.7%) required mechanical ventilation, two (18.2%) required mechanical cardiovascular circulatory support, and none received intravenous immunoglobulin. Two (18.2%) died or were discharged to hospice. CONCLUSIONS: MIS-A is severe but likely underrecognized complication of SARS-CoV-2 infection. Improved recognition of MIS-A is needed to quantify its burden and identify populations at highest risk. |
Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation.
Yousaf AR , Cortese MM , Taylor AW , Broder KR , Oster ME , Wong JM , Guh AY , McCormick DW , Kamidani S , Schlaudecker EP , Edwards KM , Creech CB , Staat MA , Belay ED , Marquez P , Su JR , Salzman MB , Thompson D , Campbell AP , Museru O , Howard LM , Parise M , Finn LE , Kim M , Raman KV , Komatsu KK , Spiker BL , Burkholder CP , Lang SM , Soslow JH . Lancet Child Adolesc Health 2022 6 (5) 303-312 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC). METHODS: In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data. FINDINGS: Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals. INTERPRETATION: Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. FUNDING: US Centers for Disease Control and Prevention. |
SARS-CoV-2 spread and hospitalisations in paediatric patients during the omicron surge.
Belay ED , Godfred-Cato S . Lancet Child Adolesc Health 2022 6 (5) 280-281 The omicron (B.1.1.529) variant of SARS-CoV-2 was first reported to WHO on Nov 24, 2021, and designated a variant of concern 2 days later.1 Since then, the variant has been detected in many countries and is causing new surges in the COVID-19 pandemic, which has now lasted for over 2 years. In Europe and the Americas, WHO data indicate that spread of the omicron variant has resulted in 5–6 times more confirmed COVID-19 cases during the reporting weeks of Jan 10 and Jan 17, 2022, compared with highest peaks reported in previous waves. The rapid spread of omicron is attributed to multiple mutations on the spike protein that might have conferred increased host-cell receptor binding affinity and the increased ability to escape immunity induced by COVID-19 vaccination and previous infection.2 Host-cell analysis using pseudotyped SARS-CoV-2 spike proteins indicated that these mutations might have resulted in the omicron variant being more infectious than the delta (B.1.617.2) variant and other variants of concern.2, 3 |
Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome.
Godfred-Cato S , Abrams JY , Balachandran N , Jaggi P , Jones K , Rostad CA , Lu AT , Fan L , Jabbar A , Anderson EJ , Kao CM , Hunstad DA , Rosenberg RB , Zafferani MJ , Ede KC , Ballan W , Laham FR , Beltran Y , Bryant B , Meng L , Hammett TA , Oster ME , BamrahMorris S , Belay ED . Pediatr Infect Dis J 2022 41 (4) 315-323 BACKGROUND: Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential. METHODS: Data were collected from patients <21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis. RESULTS: A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97. CONCLUSIONS: Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS. |
Identification and description of patients with multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection using the Premier Healthcare Database.
DeCuir J , Baggs J , Melgar M , Patel P , Wong KK , Schwartz NG , Bamrah Morris S , Godfred-Cato S , Belay ED . Epidemiol Infect 2022 150 1-22 Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52-74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults. |
Multisystem Inflammatory Syndrome in Children-United States, February 2020-July 2021.
Miller AD , Zambrano LD , Yousaf AR , Abrams JY , Meng L , Wu MJ , Melgar M , Oster ME , Godfred Cato SE , Belay ED , Campbell AP . Clin Infect Dis 2021 75 (1) e1165-e1175 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory condition in persons aged <21 years associated with antecedent SARS-CoV-2 infection. Our objective was to describe MIS-C cases reported to CDC's national surveillance since the COVID-19 pandemic began. METHODS: We included patients meeting the MIS-C case definition with onset date from February 19, 2020 through July 31, 2021, using CDC's MIS-C case report form, which collects information on demographics, clinical presentation, and laboratory results. Trends over time across 3 MIS-C pandemic waves were assessed using Cochran-Armitage test for categorical and Jonckheere-Terpstra test for continuous variables. RESULTS: Of 4,901 reported cases, 4,470 met inclusion criteria. Median patient age increased over time (P<0.001), with a median of 9 years (interquartile range, 5-13 years) during the most recent (third) wave. Male predominance also increased (62% in third wave, P<0.001). A significant (P<0.001) increase in severe hematologic and gastrointestinal involvement was observed across the study period. Frequency of several cardiovascular complications (i.e., cardiac dysfunction, myocarditis, and shock/ vasopressor receipt) and renal failure declined (P<0.001). Provision of critical care including mechanical ventilation (P<0.001) and extracorporeal membrane oxygenation (ECMO; P=0.046) decreased, as did duration of hospitalization and mortality (each P<0.001). CONCLUSIONS: Over the first 3 pandemic waves of MIS-C in the United States, cardiovascular complications and clinical outcomes including length of hospitalization, receipt of ECMO, and death decreased over time. These data serve as a baseline for monitoring future trends associated with SARS-CoV-2 B.1.617.2 (Delta) or other variants and increased COVID-19 vaccination among children. |
Multisystem Inflammatory Syndrome in Adults After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Coronavirus Disease 2019 (COVID-19) Vaccination.
Belay ED , Godfred Cato S , Rao AK , Abrams J , Wilson WW , Lim S , Newton-Cheh C , Melgar M , DeCuir J , Webb B , Marquez P , Su JR , Meng L , Grome HN , Schlaudecker E , Talaat K , Edwards K , Barnett E , Campbell AP , Broder KR , Bamrah Morris S . Clin Infect Dis 2021 75 (1) e741-e748 BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the COVID-19 pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. METHODS: Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. RESULTS: From December 14, 2020 to April 30, 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of SARS-CoV-2 infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. CONCLUSIONS: Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring. |
Central nervous system infection in the intensive care unit: Development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients
Andrade HB , Ferreira da Silva IR , Sim JL , Mello-Neto JH , Theodoro PHN , Torres da Silva MS , Varela MC , Ramos GV , Ramos da Silva A , Bozza FA , Soares J , Belay ED , Sejvar JJ , Cerbino-Neto J , Japiassú AM . PLoS One 2021 16 (11) e0260551 BACKGROUND: Central nervous system infections (CNSI) are diseases with high morbidity and mortality, and their diagnosis in the intensive care environment can be challenging. Objective: To develop and validate a diagnostic model to quickly screen intensive care patients with suspected CNSI using readily available clinical data. METHODS: Derivation cohort: 783 patients admitted to an infectious diseases intensive care unit (ICU) in Oswaldo Cruz Foundation, Rio de Janeiro RJ, Brazil, for any reason, between 01/01/2012 and 06/30/2019, with a prevalence of 97 (12.4%) CNSI cases. Validation cohort 1: 163 patients prospectively collected, between 07/01/2019 and 07/01/2020, from the same ICU, with 15 (9.2%) CNSI cases. Validation cohort 2: 7,270 patients with 88 CNSI (1.21%) admitted to a neuro ICU in Chicago, IL, USA between 01/01/2014 and 06/30/2019. Prediction model: Multivariate logistic regression analysis was performed to construct the model, and Receiver Operating Characteristic (ROC) curve analysis was used for model validation. Eight predictors-age <56 years old, cerebrospinal fluid white blood cell count >2 cells/mm3, fever (≥38°C/100.4°F), focal neurologic deficit, Glasgow Coma Scale <14 points, AIDS/HIV, and seizure-were included in the development diagnostic model (P<0.05). RESULTS: The pool data's model had an Area Under the Receiver Operating Characteristics (AUC) curve of 0.892 (95% confidence interval 0.864-0.921, P<0.0001). CONCLUSIONS: A promising and straightforward screening tool for central nervous system infections, with few and readily available clinical variables, was developed and had good accuracy, with internal and external validity. |
Clinical Characteristics of Multisystem Inflammatory Syndrome in Adults: A Systematic Review.
Patel P , DeCuir J , Abrams J , Campbell AP , Godfred-Cato S , Belay ED . JAMA Netw Open 2021 4 (9) e2126456 IMPORTANCE: Multisystem inflammatory syndrome in adults (MIS-A) has not been well described. Improved diagnosis and treatment of MIS-A might mitigate COVID-19 morbidity and mortality. OBJECTIVE: To summarize the descriptive epidemiology and clinical characteristics of MIS-A. EVIDENCE REVIEW: This systematic review identified patients with MIS-A using 3 strategies: (1) literature review from May 1, 2020, to May 25, 2021, by searching MEDLINE, Embase, Global Health, CAB Abstracts, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Academic Search Complete, Scopus, World Health Organization Global COVID-19 Literature Database, and Google Scholar; (2) voluntary reports of MIS-A to the Centers for Disease Control and Prevention (CDC); and (3) reports among persons aged 18 to 20 years in the CDC surveillance system for MIS in children. FINDINGS: Of 221 patients with MIS-A, the median age was 21 (interquartile range [IQR], 19-34) years, and 154 of 219 (70%) with data available were men. Sixty of 169 patients (36%) were non-Hispanic Black individuals, and 122 of 209 (58%) had no underlying comorbidity. One hundred two of 149 patients (68%) noted a previous symptomatic COVID-19-like illness (median, 28 [IQR, 20-36] days previously). Most patients with MIS-A presented with fever (197 of 205 [96%]), hypotension (133 of 220 [60%]), cardiac dysfunction (114 of 210 [54%]), shortness of breath (102 of 198 [52%]), and/or diarrhea (102 of 197 [52%]). The median number of organ systems involved was 5 (IQR, 4-6). Median hospital stay was 8 (IQR, 5-12) days; 115 of 201 patients (57%) were admitted to the intensive care unit; 101 of 213 (47%) required respiratory support, and 15 of 220 (7%) died. Most patients (176 of 195 [90%]) had elevated markers of coagulopathy and/or inflammation and a positive SARS-CoV-2 serologic finding (139 of 194 [72%]). Ten patients with MIS-A presented with Kawasaki disease. CONCLUSIONS AND RELEVANCE: These findings suggest that MIS-A is a serious hyperinflammatory condition that presents approximately 4 weeks after onset of acute COVID-19 with extrapulmonary multiorgan dysfunction. |
Demographic and Clinical Factors Associated With Death Among Persons <21 Years Old With Multisystem Inflammatory Syndrome in Children-United States, February 2020-March 2021.
Bowen A , Miller AD , Zambrano LD , Wu MJ , Oster ME , Godfred-Cato S , Belay ED , Campbell AP . Open Forum Infect Dis 2021 8 (8) ofab388 Multisystem inflammatory syndrome in children (MIS-C) occurs among persons aged <21 years following severe acute respiratory syndrome coronavirus 2 infection. Among 2818 MIS-C cases, 35 (1.2%) deaths were reported, primarily affecting racial/ethnic minority persons. Being 16-20 years old or having comorbidities was associated with death. Targeting coronavirus disease 2019 prevention among these groups and their caregivers might prevent MIS-C-related deaths. |
Racial and Ethnic Disparities in Multisystem Inflammatory Syndrome in Children in the United States, March 2020 to February 2021.
Stierman B , Abrams JY , Godfred-Cato SE , Oster ME , Meng L , Yip L , Patel P , Balachandran N , Prezzato E , Pierce T , Hsu KK , Burns M , Peterson Pompa X , Lauro P , Hartley A , Jones C , Gretsch S , Reid H , Lim S , Campbell AP , Belay ED . Pediatr Infect Dis J 2021 40 (11) e400-e406 BACKGROUND: The incidence of multisystem inflammatory syndrome in children (MIS-C) varies by race and ethnicity. This study assessed whether disparities in MIS-C in the United States by race and ethnicity exceed known disparities in coronavirus disease 2019 (COVID-19) incidence. METHODS: We compared the distribution of race and ethnicity among patients with MIS-C (aged <21 years, termed children) with onset March 2020 to February 2021 to that of children with COVID-19 and in the general population. Analysis was restricted to 369 counties with high completeness of race and ethnicity reporting for MIS-C and COVID-19. For each racial and ethnic group, observed numbers of patients with MIS-C were compared with expected numbers (observed/expected ratio) in children with COVID-19 and in the general population within these counties. RESULTS: Compared with children in the general population, MIS-C was more frequent among Hispanic (139% of expected) and non-Hispanic Black children (183%) and less frequent among non-Hispanic White (64%) and non-Hispanic Asian children (48%). Compared with children with COVID-19, MIS-C was more frequent in non-Hispanic Black children (207% of expected) and less frequent in non-Hispanic White children (68%); however, frequency was not different among Hispanic (102%) and non-Hispanic Asian (74%) children. CONCLUSIONS: Disparities in MIS-C by race and ethnicity exist, even after controlling for COVID-19 disparities and geographic variations. The high proportion of MIS-C among Hispanic children and low proportion among non-Hispanic Asian children align with COVID-19 rates, while the high proportion among non-Hispanic Black children and low proportion among non-Hispanic White children are not explainable by COVID-19 rates. |
Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.
Payne AB , Gilani Z , Godfred-Cato S , Belay ED , Feldstein LR , Patel MM , Randolph AG , Newhams M , Thomas D , Magleby R , Hsu K , Burns M , Dufort E , Maxted A , Pietrowski M , Longenberger A , Bidol S , Henderson J , Sosa L , Edmundson A , Tobin-D'Angelo M , Edison L , Heidemann S , Singh AR , Giuliano JSJr , Kleinman LC , Tarquinio KM , Walsh RF , Fitzgerald JC , Clouser KN , Gertz SJ , Carroll RW , Carroll CL , Hoots BE , Reed C , Dahlgren FS , Oster ME , Pierce TJ , Curns AT , Langley GE , Campbell AP , Balachandran N , Murray TS , Burkholder C , Brancard T , Lifshitz J , Leach D , Charpie I , Tice C , Coffin SE , Perella D , Jones K , Marohn KL , Yager PH , Fernandes ND , Flori HR , Koncicki ML , Walker KS , Di Pentima MC , Li S , Horwitz SM , Gaur S , Coffey DC , Harwayne-Gidansky I , Hymes SR , Thomas NJ , Ackerman KG , Cholette JM . JAMA Netw Open 2021 4 (6) e2116420 IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. EXPOSURES: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). MAIN OUTCOMES AND MEASURES: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. RESULTS: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group. |
Multisystem Inflammatory Syndrome in Infants <12 months of Age, United States, May 2020-January 2021.
Godfred-Cato S , Tsang CA , Giovanni J , Abrams J , Oster ME , Lee EH , Lash MK , Le Marchand C , Liu CY , Newhouse CN , Richardson G , Murray MT , Lim S , Haupt TE , Hartley A , Sosa LE , Ngamsnga K , Garcia A , Datta D , Belay ED . Pediatr Infect Dis J 2021 40 (7) 601-605 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in infants <12 months old. Clinical characteristics and follow-up data of MIS-C in infants have not been well described. We sought to describe the clinical course, laboratory findings, therapeutics and outcomes among infants diagnosed with MIS-C. METHODS: Infants of age <12 months with MIS-C were identified by reports to the CDC's MIS-C national surveillance system. Data were obtained on clinical signs and symptoms, complications, treatment, laboratory and imaging findings, and diagnostic SARS-CoV-2 testing. Jurisdictions that reported 2 or more infants were approached to participate in evaluation of outcomes of MIS-C. RESULTS: Eighty-five infants with MIS-C were identified and 83 (97.6%) tested positive for SARS-CoV-2 infection; median age was 7.7 months. Rash (62.4%), diarrhea (55.3%) and vomiting (55.3%) were the most common signs and symptoms reported. Other clinical findings included hypotension (21.2%), pneumonia (21.2%) and coronary artery dilatation or aneurysm (13.9%). Laboratory abnormalities included elevated C-reactive protein, ferritin, d-dimer and fibrinogen. Twenty-three infants had follow-up data; 3 of the 14 patients who received a follow-up echocardiogram had cardiac abnormalities during or after hospitalization. Nine infants had elevated inflammatory markers up to 98 days postdischarge. One infant (1.2%) died after experiencing multisystem organ failure secondary to MIS-C. CONCLUSIONS: Infants appear to have a milder course of MIS-C than older children with resolution of their illness after hospital discharge. The full clinical picture of MIS-C across the pediatric age spectrum is evolving. |
Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic.
Belay ED , Abrams J , Oster ME , Giovanni J , Pierce T , Meng L , Prezzato E , Balachandran N , Openshaw JJ , Rosen HE , Kim M , Richardson G , Hand J , Tobin-D'Angelo M , Wilson S , Hartley A , Jones C , Kolsin J , Mohamed H , Colles Z , Hammett T , Patel P , Stierman B , Campbell AP , Godfred-Cato S . JAMA Pediatr 2021 175 (8) 837-845 IMPORTANCE: Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic. OBJECTIVE: To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition. MAIN OUTCOMES AND MEASURES: Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19. RESULTS: A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19. |
Kawasaki Disease With Coronary Artery Lesions Detected at Initial Echocardiography
Ae R , Maddox RA , Abrams JY , Schonberger LB , Nakamura Y , Kuwabara M , Makino N , Kosami K , Matsubara Y , Matsubara D , Sasahara T , Belay ED . J Am Heart Assoc 2021 10 (7) e019853 Background Detection of coronary artery lesions (CALs) at initial echocardiography can aid in diagnosing Kawasaki disease (KD) and inform primary adjunctive treatments. We aimed to characterize patients with KD with CALs detected at initial echocardiography. Methods and Results We analyzed data from the nationwide Japanese KD survey that contained information on 103 222 population-based patients diagnosed with KD across Japan during 2011 to 2018. Patients with CALs detected at initial echocardiography were assessed by age, day of illness, and number of principal KD signs (≥3). Multivariable logistic regression analysis was performed to evaluate factors independently associated with CAL detection. Overall, 3707 (3.6%) patients had CALs detected at initial echocardiography. Patients aged <12 and ≥60 months were associated with CAL detection (adjusted odds ratio [95% CI], 1.28 [1.18‒1.39] and 1.32 [1.20‒1.45], respectively; reference, 12‒59 months). Patients with delayed hospital visits were increasingly at higher risk for CAL detection (days 7‒8, 1.84 [1.63‒2.08]; days 9-10, 4.30 [3.58-5.15]; and days ≥11, 9.12 [7.63‒10.90]; reference, days 1-4). Patients with 3 or 4 principal KD signs were independently associated with CAL detection (1.75 [1.63‒1.88]). These patients were significantly more likely to be aged <12 months but were not associated with delayed hospital visit. Younger patients visited at earlier days of illness. Conclusions Timely diagnosis could be beneficial for patients with KD. However, even when the hospital visit occurred early in the course of illness, patients with 3 or 4 principal KD signs, especially younger patients, were at higher risk of CAL detection at initial echocardiography. |
Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study.
Abrams JY , Oster ME , Godfred-Cato SE , Bryant B , Datta SD , Campbell AP , Leung JW , Tsang CA , Pierce TJ , Kennedy JL , Hammett TA , Belay ED . Lancet Child Adolesc Health 2021 5 (5) 323-331 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes. METHODS: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities. FINDINGS: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]). INTERPRETATION: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C. FUNDING: None. |
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