Hospital and ICU Admission Risk Associated With Comorbidities Among Children With COVID-19 Ancestral Strains.

A large proportion of children have been affected by COVID-19; we evaluated the association between comorbidities and hospitalization/ICU (intensive care unit) admission among 4097 children under age 21 years with symptomatic COVID-19 (not just polymerase chain reaction [PCR]-positive or multisystem inflammatory syndrome in children associated with COVID-19 [MIS-C]) from 2 large health systems from March 2020 to September 2021. Significant comorbidities and demographic factors identified by univariable analysis were included in a multivariable logistic regression compared with children ages 6 to 11 without comorbidities. In all, 475 children (11.6%) were hospitalized, of whom 25.5% required ICU admission. Children under 1 year had high hospitalization risk, but low risk of ICU admission. Presence of at least 1 comorbidity was associated with hospitalization and ICU admission (odds ratio [OR] > 4). Asthma, obesity, chronic kidney disease, sickle cell disease, bone marrow transplantation, and neurologic disorders were associated with hospitalization (adjusted odds ratio [AOR] > 2). Malignancy, intellectual disability, and prematurity were associated with ICU admission (AOR > 4). Comorbidities are significantly associated with hospitalization/ICU admission among children with COVID-19.

HIV Pre-Exposure Prophylaxis: What Do Pediatricians Need to Know?

Pediatricians and adolescent providers play an important role in the health and well-being of adolescents and young adults, including their sexual health. HIV remains an ongoing concern for young people, with 21% of new HIV diagnoses occurring in this age group. The use of antiretroviral therapy for pre-exposure prophylaxis (PrEP) to prevent transmission of HIV to people who are not infected has been proven safe and effective. PrEP can be considered as part of a comprehensive risk mitigation strategy for adolescents and young adults, with clear guidelines for baseline evaluation and ongoing management. [Pediatr Ann. 2022;51(5):e191-e195.].

SARS-CoV-2 Among Infants <90 Days of Age Admitted for Serious Bacterial Infection Evaluation.

OBJECTIVES: To determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants hospitalized for a serious bacterial infection (SBI) evaluation and clinically characterize young infants with SARS-CoV-2 infection. METHODS: A retrospective chart review was conducted on infants <90 days of age hospitalized for an SBI evaluation. The study was conducted at 4 inpatient facilities in New York City from March 15, 2020, to December 15, 2020. RESULTS: We identified 148 SBI evaluation infants who met inclusion criteria. A total of 22 infants (15%) tested positive for SARS-CoV-2 by nasopharyngeal reverse transcription polymerase chain reaction; 31% of infants admitted during periods of high community SARS-CoV-2 circulation tested positive for SARS-CoV-2, compared with 3% when community SARS-CoV-2 circulation was low (P < .001). The mean age of infants with SARS-CoV-2 was higher than that of SARS-CoV-2-negative infants (33 [SD: 17] days vs 23 [SD: 23] days, respectively; P = .03), although no age difference was observed when analysis was limited only to febrile infants. An isolated fever was the most common presentation of SARS-CoV-2 (n = 13; 59%). Admitted infants with SARS-CoV-2 were less likely to have positive urine culture results (n = 1 [5%] versus n = 25 [20%], respectively; P = .002), positive cerebrospinal culture results (n = 0 [0%] versus n = 5 [4%], respectively; P = .02), or be admitted to intensive care (n = 2 [9%] versus n = 47 [37%]; P < .001), compared with infants without SARS-CoV-2. CONCLUSIONS: SARS-CoV-2 was common among young infants hospitalized for an SBI evaluation during periods of high but not low community SARS-CoV-2 circulation in New York City, although most infants did not require intensive care admission.

Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children During the COVID-19 Pandemic.

Importance: To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms. Objective: To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020. Design, Setting, and Participants: A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C. Main Outcomes and Measures: Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists. Results: Twenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity. Conclusions and Relevance: In this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.

Multisystem inflammatory syndrome in children.

PURPOSE OF REVIEW: Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases. RECENT FINDINGS: Clinical presentation of MIS-C is dominated by significant inflammation. Fever, gastrointestinal symptoms, cardiac dysfunction, and hypotension are common features. Kawasaki disease-like findings are common, but epidemiologic data and recent mechanistic studies suggest that distinct inflammatory pathways mediate Kawasaki disease and MIS-C. A broad diagnostic approach is recommended, given overlapping presentations between MIS-C and many other disease processes. Current management of MIS-C is highly variable, depending on illness severity, and can range from supportive care to aggressive immune modulation. A multidisciplinary approach with early involvement of multiple pediatric subspecialists is recommended for complicated cases. SUMMARY: Several studies have described the clinical manifestations of MIS-C, but definitive diagnosis remains challenging. Robust information about long-term outcomes awaits further study, as do immunologic data to refine diagnostic and therapeutic strategies.

COVID-19-Associated Myocarditis in an Adolescent.

A 17-year-old obese male was admitted to the pediatric intensive care unit after presenting with fluid-responsive septic shock following 7 days of fever, gastrointestinal symptoms and neck pain. Initial workup was positive for SARS-CoV-2 and elevated troponin I and brain natriuretic peptide. Echocardiography and cardiac magnetic resonance imaging confirmed acute myocarditis. One week after discharge, repeat echocardiogram demonstrated improved heart function with only residual myocardial dysfunction.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Febrile Infants Without Respiratory Distress.

We report 2 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time reverse-transcription polymerase chain reaction-based testing for SARS-CoV-2 for febrile infants in an outbreak setting.

Invasive group G streptococcal infection in a paediatric patient.

We present a paediatric case of group G streptococcal bacteraemia and vertebral osteomyelitis. The patient is a 14-year-old girl with Gaucher disease type 1 who presented with severe thoracolumbar pain. She was treated with a 4-week course of antibiotics for presumed osteomyelitis with clinical improvement.

Salvage Regimens Containing Darunavir, Etravirine, Raltegravir, or Enfuvirtide in Highly Treatment-Experienced Perinatally Infected Pregnant Women.

Combination antiretroviral therapy in pregnant women with human immunodeficiency virus has dramatically decreased maternal-to-child transmission. Highly treatment-experienced pregnant patients have limited effective treatment options due to past toxicities and viral resistance. We present 8 pregnancies in 7 perinatally infected women successfully treated with salvage regimens containing darunavir, etravirine, raltegravir, or enfuvirtide.

Changes in the soluble mucosal immune environment during genital herpes outbreaks.

BACKGROUND: Genital tract secretions provide variable inhibitory activity against herpes simplex virus (HSV) ex vivo. We hypothesize that the anti-HSV activity may prevent the spread of virus from the more commonly affected sites, such as the external genitalia, to the upper genital tract. METHODS: The antimicrobial activity of cervicovaginal lavage (CVL) and concentrations of mucosal immune mediators were measured in 10 HIV-seronegative women with an active external herpetic lesion and compared with 10 HIV-seronegative women who were HSV-1 and HSV-2 seronegative. Samples were obtained at the time of a symptomatic external lesion (day 0), after 1 week of oral acyclovir (day 7), and 1 week after completing treatment (day 14). Controls were evaluated at parallel intervals. RESULTS: The anti-HSV activity was higher in CVL obtained from cases compared to controls at presentation (day 0) (54.3% vs. 28%), fell to similar levels on day 7, and then rebounded on day 14 (69% vs. 25%). The anti-HSV activity correlated positively and significantly with the concentrations of several inflammatory proteins; the concentrations of these proteins tended to be higher in cases compared with controls and followed a similar temporal pattern. CONCLUSIONS: Increases in inflammatory immune mediators and anti-HSV activity were detected in CVL at the time of clinical outbreaks and after completion of a short course of acyclovir. These mucosal responses may protect against HSV spread but could facilitate HIV infection and contribute to the clinical observation that, independent of clinical lesions, HSV-2 is a risk factor for HIV acquisition.

Small for gestational age birth outcomes in pregnant women with perinatally acquired HIV.

OBJECTIVE: To compare small for gestational age (SGA) birth weight in children born to women with perinatally acquired HIV (PAH) vs. those with behaviorally acquired HIV (BAH). DESIGN: Retrospective cohort study of HIV-infected pregnant women who received care and delivered a live born at a single hospital in New York City from January 2004 to April 2011. METHODS: We collected data via chart review on demographics, behavioral risk factors, HIV clinical markers, antiretroviral therapy (ART), mode of HIV acquisition, and pregnancy outcomes on study participants. We compared rates of these exposures among participants by method of HIV acquisition. Generalized Estimating Equation was applied to evaluate the effect of HIV acquisition type on SGA birth weight, adjusting for potential confounders. RESULTS: Of 87 live births evaluated, 17 were born to 14 women with PAH. Overall, 20 (23%) were SGA. Eight of these SGA neonates were born preterm. Live births to women with PAH were more likely to be born SGA in our unadjusted analysis [odds ratio (OR) = 4.13, 95% confidence interval (CI) = 1.38-12.41). After adjusting for mother's age, substance use during pregnancy, nadir CD4 cell count during pregnancy, viral suppression at delivery, and second-line ART use during pregnancy, this relationship persisted with an adjusted OR of 5.7 (95% CI = 1.03-31.61). CONCLUSION: In comparison to infants born to women with BAH, infants born to women with PAH were at high risk for compromised intrauterine growth. Future studies are warranted to determine possible causal mechanisms.

A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

BACKGROUND: Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition. METHODS: 30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL) on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood. RESULTS: A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001) and fit a sigmoid E(max) pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators. CONCLUSIONS: Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development of models more predictive of microbicide efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00594373.

Postcoital bioavailability and antiviral activity of 0.5% PRO 2000 gel: implications for future microbicide clinical trials.

BACKGROUND: The pharmacokinetics and pharmacodynamics of vaginal microbicides are typically assessed among sexually abstinent women. However, the physical act of sex may modulate gel distribution, and preclinical studies demonstrate seminal plasma interferes with the antiviral activity of several microbicides. This study compared the biological activity and concentration of PRO 2000 in cervicovaginal lavage (CVL) collected in the absence or following coitus. METHODS: CVL samples were collected from ten heterosexual couples at baseline, after sex, after a single dose of 0.5% PRO 2000 gel and sex, and after gel application without sex. The impact of CVL on HIV-1 infection of TZM-bl cells and HSV-2 infection of CaSki cells was monitored by luciferase and plaque assay, respectively. PRO 2000 concentrations were measured by fluorescence. RESULTS: CVL collected after PRO 2000 application significantly inhibited HIV-1 and HSV-2 (p = 0.01). However, the antiviral activity was reduced following sex and no significant protective effect was observed in postcoital CVL obtained in the presence compared to the absence of PRO 2000 for HIV (p = 0.45) or HSV-2 (p = 0.56). Less PRO 2000 was recovered in postcoital CVL, which, in conjunction with interference by seminal plasma, may have contributed to lower antiviral activity. CONCLUSIONS: Postcoital responses to PRO 2000 differ from precoital measures and the results obtained may provide insights into the clinical trial findings in which there was no significant protection against HIV-1 or HSV-2. Postcoital studies should be incorporated into clinical studies before embarking on large-scale efficacy trials.

Female genital tract secretions inhibit herpes simplex virus infection: correlation with soluble mucosal immune mediators and impact of hormonal contraception.

PROBLEM: Female genital tract secretions inhibit herpes simplex virus (HSV) infection, however, the intra- and inter-subject variability, contribution of specific mediators, and impact of reproductive hormones have not been defined. METHOD: of study Cervicovaginal lavage (CVL) (n = 89) obtained from nine cyclers and seven women on hormonal contraception (HC), who completed between three and eight weekly visits, were examined for anti-herpes simplex virus activity and concentrations of mediators. RESULTS: The CVL inhibited HSV infection by a mean value of approximately 57% during the follicular or luteal phase, but only by 36% in hormonal contraceptive users. Human neutrophil peptides 1-3 (HNP1-3) (P = 0.03), IL-8 (P = 0.003), lactoferrin (P = 0.005), lysozyme (P = 0.003), IgA (P = 0.002), and IgG (P = 0.02) correlated with antiviral activity. Intra-subject and inter-subject variability was observed, suggesting that factors other than hormones contribute to innate defense. CONCLUSION: Endogenous antimicrobial activity may provide a biomarker of healthy mucosal immunity and may be reduced in the setting of HC. However, larger prospective studies are needed.

A hybrid strategy for the prevention of cytomegalovirus-related complications in pediatric liver transplantation recipients.

BACKGROUND: This single center, retrospective study describes experience with a hybrid prevention strategy combining short-course antiviral prophylaxis and preemptive cytomegalovirus (CMV) polymerase chain reaction (PCR) monitoring. METHODS: One hundred twenty-two pediatric liver transplantation recipients were followed up for a median of 2.3 years posttransplantation. Subjects received a minimum of 14 days of postoperative ganciclovir, followed by monthly CMV PCR monitoring. RESULTS: Forty-three CMV seronegative recipients received seropositive grafts and were considered high risk for CMV; 79 subjects were routine risk. CMV was detected by PCR in the absence of symptoms in 34.4% of subjects and was more likely in high risk than in routine risk recipients (58.1% vs. 21.8%, P=0.0001). Twelve subjects (9.8%) developed CMV disease (8 high risk vs. 4 routine risk, P=0.03). Three subjects developed acute rejection in the 6 months after detection of CMV, but CMV was preceded by rejection in 13 subjects. There were no mortalities secondary to CMV. A total of 38.5% of subjects were spared antiviral medications beyond their initial postoperative prophylaxis. CONCLUSIONS: These results suggest that a hybrid preventative approach for CMV is a reasonable alternative to prolonged antiviral prophylaxis and may reduce unnecessary exposure to antiviral therapy. However, patients who receive intensified immunosuppression after acute rejection are at increased risk for CMV and may require extended prophylaxis and closer monitoring.