Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth.

OBJECTIVE: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity. STUDY DESIGN: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut. RESULTS: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. CONCLUSIONS: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

Profiles of caregiving behaviors among children and adolescents with perinatally acquired HIV.

Although parenting behaviors are widely considered an important factor in the adjustment of children and adolescents with chronic physical health needs, few studies have addressed this topic as it pertains to youth with perinatally-acquired human immunodeficiency virus (PHIV). We examined profiles of child-centeredness, control through guilt, consistent discipline, and detachment, and whether these profiles differed in terms of parent- and youth-reported psychiatric disorder symptoms in a cohort of HIV infected youth (N = 314). Latent profile analyses of caregiving behaviors were conducted separately for children (6-12 years) and adolescents (13-18 years). Two profiles were identified among children: (a) moderate caregiving (87%, n = 130) and (b) high detachment caregiving (13%, n = 19), and three profiles were identified among adolescents: (a) moderate caregiving (55%, n = 88), (b) high detachment caregiving (19%, n = 30), and (c) high control through guilt caregiving (26%, n = 42). The high detachment and high control through guilt caregiving profiles displayed higher levels of parent-and youth-reported symptoms than the moderate caregiving profile. These findings suggest that caregiver behaviors of PHIV youth vary as a function of children's developmental period and differ in terms of youth psychological symptoms.

Psychiatric symptoms and antiretroviral nonadherence in US youth with perinatal HIV: a longitudinal study.

OBJECTIVES: The relationship of specific psychiatric conditions to adherence has not been examined in longitudinal studies of youth with perinatal HIV infection (PHIV). We examined associations between psychiatric conditions and antiretroviral nonadherence over 2 years. DESIGN: Longitudinal study in 294 PHIV youth, 6-17 years old, in the United States and Puerto Rico. METHODS: We annually assessed three nonadherence outcomes: missed above 5% of doses in the past 3 days, missed a dose within the past month, and unsuppressed viral load (>400 copies/ml). We fit multivariable logistic models for nonadherence using Generalized Estimating Equations, and evaluated associations of psychiatric conditions (attention deficit hyperactivity disorder, disruptive behavior, depression, anxiety) at entry with incident nonadherence using multivariable logistic regression. RESULTS: Nonadherence prevalence at study entry was 14% (3-day recall), 32% (past month nonadherence), and 38% (unsuppressed viral load), remaining similar over time. At entry, 38% met symptom cut-off criteria for at least one psychiatric condition. Greater odds of 3-day recall nonadherence were observed at week 96 for those with depression [adjusted odds ratio (aOR) 4.14, 95% confidence interval (CI) 1.11-15.42] or disruptive behavior (aOR 3.36, 95% CI 1.02-11.10], but not at entry. Those with vs. without attention deficit hyperactivity disorder had elevated odds of unsuppressed viral load at weeks 48 (aOR 2.46, 95% CI 1.27-4.78) and 96 (aOR 2.35, 95% CI 1.01-5.45), but not at entry. Among 232 youth adherent at entry, 16% reported incident 3-day recall nonadherence. Disruptive behavior conditions at entry were associated with incident 3-day recall nonadherence (aOR 3.01, 95% CI 1.24-7.31). CONCLUSION: In PHIV youth, comprehensive adherence interventions that address psychiatric conditions throughout the transition to adult care are needed.

Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus.

OBJECTIVE: To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). STUDY DESIGN: P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥ 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥ 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥ 15. RESULTS: Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. CONCLUSION: In youth infected with HIV with a CD4% ≥ 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.

Human immunodeficiency virus disease severity, psychiatric symptoms, and functional outcomes in perinatally infected youth.

OBJECTIVE: To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. DESIGN: Cross-sectional analysis of entry data from an observational,prospective 2-year study.Logistic and linear regression models adjusted for potential confounders were used. SETTING: Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. PARTICIPANTS: Youth aged 6 to 17 years who had HIV infection (N=319). MAIN EXPOSURES: Antiretroviral treatment and perinatal HIV infection. MAIN OUTCOME MEASURES: Youth and primary caregivers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social,and academic functioning; and quality of life. RESULTS: Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms,older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms,higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage atstudy entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms.A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. CONCLUSION: Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic,and social functioning, all of which warrant additional study.

Prevalence of pain and association with psychiatric symptom severity in perinatally HIV-infected children as compared to controls living in HIV-affected households.

This cross-sectional study evaluated the prevalence of pain and psychiatric symptoms in perinatally HIV-infected children at entry into P1055, a multicenter investigation of the prevalence and severity of psychiatric symptoms in HIV-infected children. Subjects 6-17 years of age and their primary caregivers were recruited from 29 International Maternal Pediatric Adolescent AIDS Clinical Trials sites in the USA and Puerto Rico. A total of 576 children (320 HIV and 256 HIV- children) were enrolled from June 2005 to September 2006. Subject self-reports of pain were measured by the Wong-Baker visual analog scale and Short-Form McGill Pain Questionnaire. Symptomatology for anxiety, depression, and dysthymia was assessed through Symptom Inventory instruments. Caregiver's assessment of their child's pain and psychiatric symptomatology was similarly measured. Logistic regression models were used to evaluate predictors of pain. We found that a higher proportion of HIV-infected than uninfected subjects reported pain in the last two months (41% vs 32%, p=0.04), last two weeks (28% vs 19%, p=0.02), and lasting more than one week (20% vs 11%, p=0.03). Among HIV-infected youth, females (OR=1.53, p=0.09), White race (OR=2.15, p=0.04), and Centers for Disease Control (CDC) Class C (OR=1.83, p=0.04) were significantly more likely to report pain. For all subjects, only 52% of caregivers recognized their child's pain and just 22% were aware that pain affected their child's daily activities. The odds of reported pain in HIV increased with higher symptom severity for generalized anxiety (OR=1.14, p=0.03), major depression (OR=1.15, p=0.03), and dysthymia (OR=1.18, p=0.01). This study underscores the importance of queries concerning pain and emotional stressors in the care of HIV and uninfected children exposed to HIV individuals. The discordance between patient and caregiver reports of pain and its impact on activities of daily living highlights that pain in children is under-recognized and therefore potentially under-treated.

Co-occuring psychiatric symptoms in children perinatally infected with HIV and peer comparison sample.

OBJECTIVE: To compare the rates of psychopathology in youths perinatally infected with HIV (N = 319) with a comparison sample of peers (N = 256) either HIV-exposed or living in households with HIV-infected family members. METHOD: Participants were randomly recruited from 29 sites in the United States and Puerto Rico and completed an extensive battery of measures including standardized DSM-IV-referenced ratings scales. RESULTS: The HIV+ group was relatively healthy (73% with CD4% >25%), and 92% were actively receiving antiretroviral therapy. Youths with HIV (17%) met symptom and impairment criteria for the following disorders: attention-deficit/hyperactivity disorder (12%), oppositional defiant disorder (5%), conduct disorder (1%), generalized anxiety disorder (2%), separation anxiety disorder (1%), depressive disorder (2%), or manic episode (1%). Many youths with HIV (27%) and peers (26%) were rated (either self- or caregiver report) as having psychiatric problems that interfered with academic or social functioning. With the exception of somatization disorder, the HIV+ group did not evidence higher rates or severity of psychopathology than peers, although rates for both groups were higher than the general population. Nevertheless, self-awareness of HIV infection in younger children was associated with more severe symptomatology, and youths with HIV had higher lifetime rates of special education (44 vs 32%), psychopharmacological (23 vs 12%), or behavioral (27 vs 17%) interventions. Youth-caregiver agreement was modest, and youths reported more impairment. CONCLUSION: HIV infection was not associated with differentially greater levels of current psychopathology; nevertheless, investigation of relations with developmental changes and specific illness parameters and treatments are ongoing.

Viral coinfection in the oral cavity of HIV-infected children: relation among HIV viral load, CD4+ T lymphocyte count and detection of EBV, CMV and HSV.

Viral coinfection in the oral cavity associated to HIV infection was evaluated in 180 children from birth to 13 years of age of both sexes. The oral examinations were performed at the Pediatric AIDS Outpatient Clinic, São Lucas Hospital and Clinic Hospital, both in Porto Alegre, Brazil and at the School of Dental Medicine, University Hospital Center, State University of New York at Stony Brook, USA. The aim of this study was to identify the presence of viral infections in the oral cavity. PCR technique was used to determine opportunistic viral infections caused by CMV, EBV, and HSV in mucosal swabs. A high frequency of viral infection was detected in the oral cavity of HIV-infected children determined by the PCR technique. HIV-infected children with viruses had a favorable CD4+ T lymphocyte count and unfavorable viral load.

Viral coinfection in the oral cavity of HIV-infected children: relation among HIV viral load, CD4+T lymphocyte count and detection of EBV, CMV and HSV / Co-infecção viral na cavidade bucal de crianças infectadas pelo HIV: relação entre carga viral, contagem de linfócitos T-CD4+ e detecção de EBV, CMV e HSV

A relação entre a infecção pelo HIV e a presença de diferentes tipos de vírus na cavidade bucal foi estudada em 180 crianças HIV-positivo, com idades entre zero e 13 anos de idade, de ambos os sexos. Os exames foram realizados nos Ambulatórios de Aids Pediátrica dos Hospitais São Lucas e de Clínicas, ambos em Porto Alegre, RS, Brasil e no Centro Hospitalar Universitário da Universidade Estadual de Nova Iorque, em Stony Brook (EUA). O objetivo desta pesquisa foi usar a técnica da PCR para detectar a presença dos vírus CMV, EBV e HSV na cavidade bucal desses pacientes, independentemente da presença ou não de manifestações estomatológicas relacionadas aos mesmos. Pode-se concluir que foi alta a freqüência de vírus detectados na cavidade bucal das crianças da amostra através da técnica da PCR e que a contagem média de linfócitos T-CD4+ das crianças com a presença dos vírus encontrava-se próxima da normalidade, enquanto a Carga Viral do HIV encontrava-se elevada.

Freqüência da hipoplasia do esmalte em crianças infectadas pelo HIV / Enamel hypoplasia frequency in HIV infected children

A hipoplasia do esmalte é uma alteração do esmalte dental, decorrente da ação de diferentes fatores etiológicos durante o período de formação desse. Dentre os possíveis fatores etiológicos, merecem destaque as alterações sistêmicas presentes em crianças infectadas pelo HIV. O objetivo deste trabalho foi estudar a freqüência da hipoplasia do esmalte em crianças infectadas pelo HIV e a provável relação desta patologia dental com a classificação da AIDS pediátrica. A amostra foi composta por 156 crianças brasileiras e 42 crianças norte-americanas, de zero a treze anos de idade, infectadas pelo HIV. A metodologia incluiu o preechimento de uma ficha individual, o exame clínico odontológico buscando a presença de dentes com anomalia dental do tipo hipoplasia do esmalte e a revisão dos prontuários médicos das crianças. Na amostra estudada, 24 crianças (12,12%) apresentaram hipoplasia do esmalte, sendo 17 brasileiras e 7 norte-americanas. A freqüência de crianças com hipoplasia do esmalte na amostra estudada foi considerada baixa. A distribuição das 24 crianças com hipoplasia do esmalte, de acordo com a classificação da AIDS pediátrica foi: 12 (50%) na categoria clínica C, 8 (33,33%) na categoria B e 4 (16,67%) na categoria A. A maioria das crianças com hipoplasia do esmalte encontrava-se na categoria C da AIDS pediátrica, considerada a mais grave.

[The association between oral manifestations and the socioeconomic and cultural characteristics of HIV-infected children in Brazil and in the United States of America]. / Associação entre manifestações estomatológicas e características socioeconômicas e culturais de crianças brasileiras e norte-americanas infectadas pelo HIV.

OBJECTIVES: This study had two objectives: (1) to investigate the socioeconomic and cultural characteristics of HIV-infected children and their families in relation to the presence of oral manifestations of AIDS and (2) to identify the most frequent oral manifestations of AIDS in the sample of children studied. METHODS: The sample consisted of a total of 184 children - both boys and girls - from 0 to 13 years old. The children were receiving care at two hospitals in the city of Porto Alegre, Brazil (the Hospital de Clínicas de Porto Alegre and the Hospital São Lucas da Pontifícia Universidade Católica), and at Stony Brook University Hospital, which is in the state of New York, United States. Data were analyzed using the chisquare test, Student's t test, and analysis of variance. RESULTS: Of the 184 patients, 117 of them (63.59%) were receiving care at the Hospital de Clínicas de Porto Alegre, 26 (14.13%) at the Hospital São Lucas, and 41 (22.28%) at Stony Brook University Hospital. In the Brazilian sample (the two hospitals in Porto Alegre) 42.66% of the children were living with their natural parents (mostly with the mother), while in the United States 56.10% of the children were living with foster families. Concerning income, 39.86% of the Brazilian families had a monthly income ranging from US$ 180 to US$ 450, and 33.57% had no income or did not provide information. With the United States sample, we were not allowed to ask about income, but all the families were classified by the social workers as having a monthly income below US$ 1 000. HIV was acquired through vertical transmission by 97.20% of the Brazilian children and by 97.56% of the children in the United States sample. Oral manifestations were more frequent in the Brazilian children (72.73%) than in the children in the United States sample (53.66%) (P = 0.01). CONCLUSIONS: The frequency of oral manifestations in the samples in both Brazil and the United States was influenced by socioeconomic and cultural conditions, family structure and income, access to information concerning AIDS, and adherence to treatment.

Associaçäo entre manifestaçöes estomatológicas e características socioeconômicas e culturais de crianças brasileiras e norte-americanas infectadas pelo HIV / The association between oral manifestations and the socioeconomic and cultural characteristics of HIV-infected children in Brazil and in the United States of America

OBJETIVO: Investigar as características socioeconômicas e culturais de crianças infectadas pelo HIV e de suas famílias, relacionando-as com a presença de manifestaçöes estomatológicas da AIDS, e identificar as manifestaçöes estomatológicas mais freqüentes na amostra estudada. MÉTODO: A amostra foi composta por 184 crianças de ambos os sexos, com idade entre 0 e 13 anos, atendidas no Hospital de Clínicas de Porto Alegre e Hospital Säo Lucas da Pontifícia Universidade Católica, em Porto Alegre, Brasil, e no hospital universitário da Universidade do Estado de Nova Iorque em Stony Brook, Estado de Nova Iorque, Estados Unidos. Os dados foram analisados pelos testes do qui-quadrado, t de Student e análise de variância. RESULTADOS: Dos 184 pacientes, 63,59 por cento eram do Hospital de Clínicas de Porto Alegre; 22,28 por cento do hospital de Stony Brook; e 14,13 por cento do Hospital Säo Lucas. Na amostra brasileira, 42,66 por cento das crianças residiam com os pais naturais (principalmente com a mäe), enquanto que nos Estados Unidos 56,10 por cento das crianças moravam com pais adotivos. Em relaçäo à renda, 39,86 por cento das famílias no Brasil ganhavam entre 180 e 450 dólares mensais; 33,57 por cento näo tinham renda ou näo forneceram seus dados. Nos Estados Unidos, a pergunta sobre renda näo foi autorizada, mas todas as famílias foram classificadas pelos assistentes sociais do hospital como tendo renda abaixo de 1 000 dólares. O HIV foi adquirido por transmissäo vertical em 97,20 por cento dos casos no Brasil e 97,56 por cento nos Estados Unidos. A freqüência das manifestaçöes estomatológicas foi maior nas crianças brasileiras (72,73 por cento) do que nas norte-americanas (53,66 por cento) (P = 0,01). CONCLUSÖES: As condiçöes socioeconômicas e culturais, estrutura e renda familiar, acesso a informaçäo sobre AIDS e a adesäo aos esquemas terapêuticos influenciaram a freqüência das manifestaçöes estomatológicas nas duas amostras.

Objectives. This study had two objectives: (1) to investigate the socioeconomic and cultural characteristics of HIV-infected children and their families in relation to the presence of oral manifestations of AIDS and (2) to identify the most frequent oral manifestations of AIDS in the sample of children studied. Methods. The sample consisted of a total of 184 children­both boys and girls­ from 0 to 13 years old. The children were receiving care at two hospitals in the city of Porto Alegre, Brazil (the Hospital de Clínicas de Porto Alegre and the Hospital São Lucas da Pontifícia Universidade Católica), and at Stony Brook University Hospital, which is in the state of New York, United States. Data were analyzed using the chisquare test, Student's t test, and analysis of variance. Results. Of the 184 patients, 117 of them (63.59%) were receiving care at the Hospital de Clínicas de Porto Alegre, 26 (14.13%) at the Hospital São Lucas, and 41 (22.28%) at Stony Brook University Hospital. In the Brazilian sample (the two hospitals in Porto Alegre) 42.66% of the children were living with their natural parents (mostly with the mother), while in the United States 56.10% of the children were living with foster families. Concerning income, 39.86% of the Brazilian families had a monthly income ranging from US$ 180 to US$ 450, and 33.57% had no income or did not provide information. With the United States sample, we were not allowed to ask about income, but all the families were classified by the social workers as having a monthly income below US$ 1 000. HIV was acquired through vertical transmission by 97.20% of the Brazilian children and by 97.56% of the children in the United States sample. Oral manifestations were more frequent in the Brazilian children (72.73%) than in the children in the United States sample (53.66%) (P = 0.01). Conclusions. The frequency of oral manifestations in the samples in both Brazil and the United States was influenced by socioeconomic and cultural conditions, family structure and income, access to information concerning AIDS, and adherence to treatment