A Phase 1, Double-blinded, Placebo-Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of HEV-239 (Hecolin®) Vaccine in Healthy US Adults.

INTRODUCTION: Establishing the safety and immunogenicity of a hepatitis E virus vaccine in multiple populations could facilitate broader access and prevent maternal and infant mortality. METHODS: We conducted a phase 1, randomized, double-blinded, placebo-controlled (4:1 vaccine: placebo) trial of 30 µg HEV-239 (Hecolin®, Xiamen Innovax Biotech Company Limited, China) administered intramuscularly in healthy US adults aged 18-45 years. Participants were vaccinated on days 1, 29, and 180. Participants reported solicited local and systemic reactions for 7 days following vaccination and were followed through 12 months after enrollment for safety and immunogenicity (IgG, IgM). RESULTS: Solicited local and systemic reactions between treatment and placebo group were similar and overall mild. No participants experienced serious adverse events related to HEV-239. All participants receiving HEV-239 seroconverted at one month following the first dose and remained seropositive throughout the study. HEV-239 elicited a robust hepatitis E IgG response that peaked one month following the second dose (Geometric Mean Concentration (GMC) 6.16; 95% CI 4.40-8.63), was boosted with the third dose (GMC 11.50; 95% CI 7.90-16.75) and persisted through 6 months. CONCLUSIONS: HEV-239 is safe and elicits a durable immune response through at least 6 months after the third dose in healthy US adults. CLINICAL TRIALS REGISTRATION: NCT03827395. Safety Study of Hepatitis E Vaccine (HEV239) - Full Text View - ClinicalTrials.gov.

A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered with and without AS03 Adjuvant in Healthy US Adults.

INTRODUCTION: A surge of human influenza A(H7N9) cases began in 2016 in China due to an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS: Healthy adults (n=180), ages 19-50 years, were enrolled into this partially-blinded, randomized, multi-center Phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with two different boost intervals (21 versus 120 days) and two dosages (3.75 or 15 µg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition (HAI) and neutralizing antibody titers were assessed. RESULTS: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest HAI GMT (95%CI) observed against the 2017 A(H7N9) strain was 133.4 (83.6, 212.6) among participants who received homologous, adjuvanted 3.75 ug+AS03/2017 doses with delayed boost interval. CONCLUSIONS: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. (NCT03589807).

Infection prevention-how can we prevent transmission of community-onset methicillin-resistant Staphylococcus aureus?

BACKGROUND: Staphylococcus aureus is a versatile organism, capable of existing as a commensal organism while also possessing pathogenic potential. The emergence of clinically and genetically distinct strains of methicillin-resistant S. aureus (MRSA), termed community-onset MRSA (CO-MRSA), resulted in an epidemic of invasive and skin and soft tissue infections (SSTI) in otherwise healthy individuals without traditional risk factors. Colonization with S. aureus is a risk factor for developing infection and also a source of transmission to close contacts. Outbreaks of S. aureus SSTI have been described in crowded settings and within households. Thus, preventive strategies are essential to interrupt recurrent infections. OBJECTIVES: The objective of this narrative review is to provide a comprehensive, evidence-based approach to prevent transmission of CO-MRSA. We highlight key clinical trials that emphasize the importance of household and environmental S. aureus colonization in propagating household transmission. Finally, we highlight research priorities to prevent S. aureus infection. SOURCES: We cite primary literature from peer-reviewed publications as sources for this review. CONTENT: Our recommended approach to the management of individuals presenting with skin abscesses includes optimal treatment of the initial infection and hygiene education. Decolonization measures should be recommended for individuals with recurrent SSTIs or whose household members have SSTIs. Targeted decolonization with topical antimicrobials should be prescribed to all affected individuals within the household. IMPLICATIONS: S. aureus infections result in substantial mortality and morbidity because of the high incidence of recurrent skin infections. Although current decolonization strategies are beneficial, interventions are often costly to families and effectiveness wanes over time. Results from a recently completed trial evaluating integrated periodic decolonization and household environmental hygiene will further add to our understanding of what constitutes a sustainable decolonization approach. In addition, novel preventive strategies are being developed such as S. aureus vaccines, lytic agents, probiotics, microbiota transplants, and phage therapy.

Overview of COVID-19 Infection, Treatment, and Prevention in Children.

Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) or long COVID. The case definitions of MIS-C and long COVID have continued to evolve with the increased understanding of these new entities; however, improved methods of diagnosis and determination of the optimal management are still needed. Furthermore, with the continued circulation of SARS-CoV-2 variants, there remains a need for clinicians to remain up-to-date on the latest treatment and prevention options. The purpose of this review is to provide an evidence-based review of what we have learned about COVID-19 in children since the start of the pandemic and how best to counsel children and their families on the best methods of prevention.

Approach to vaccinating the pediatric solid organ transplant candidate and recipient.

Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is to provide readers with a concise, practical, expert-opinion on the approach to vaccinating the SOT candidate and recipient and to supplement existing guidelines. In addition, pediatric-specific knowledge gaps in the field and future research priorities will be highlighted.

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.

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.

Serologic responses to COVID-19 vaccination in children with history of multisystem inflammatory syndrome (MIS-C).

Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled seven children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies variably waned following acute MIS-C, but were significantly boosted with vaccination and maintained for up to 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n = 16) and children with history of MIS-C (n = 7) or COVID-19 (n = 8). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were significantly reduced to the Omicron variant.

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.

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.

Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019.

BACKGROUND: The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood. METHODS: We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients. RESULTS: Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]). CONCLUSIONS: MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.

Management and Prevention of Staphylococcus aureus Infections in Children.

Staphylococcus aureus is a common skin commensal with the potential to cause severe infections resulting in significant morbidity and mortality. Up to 30% of individuals are colonized with S aureus, though infection typically does not occur without skin barrier disruption. Infection management includes promptly addressing the source of infection, including sites of metastatic infection, and initiation of effective antibiotics, which should be selected based on local antibiotic susceptibility patterns. Given that S aureus colonization is a risk factor for infection, preventive strategies are aimed at optimizing hygiene measures and decolonization regimens for outpatients and critically ill children with prolonged hospitalizations.

Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome.

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.

Intent to Vaccinate SARS-CoV-2 Infected Children in US Households: A Survey.

A paucity of data exists evaluating a guardian's intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April-November 2020) and 45 second (December-January 2020-2021) surveys to guardians of children (<18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of "if a safe and effective vaccine" became available, and a second question was added to second surveys using the objective language of "would prevent 19 of 20 people from getting disease". When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%, p = 0.03). Common reasons for declining vaccination were concerns about adverse effects and/or vaccine safety. Providing additional facts on vaccine efficacy increased vaccine acceptance. Evidence-based strategies are needed to increase pediatric COVID-19 vaccine uptake.

A Retrospective Test-Negative Case-Control Study to Evaluate Influenza Vaccine Effectiveness in Preventing Hospitalizations in Children.

BACKGROUND: Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains. METHODS: We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months-17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012-2013 to 2016-2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates. RESULTS: We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7-10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012-2013 to 2016-2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B. CONCLUSIONS: Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by >50% across 5 influenza seasons.

The Importance of Advancing Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Children.

While the role of children in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be defined, children likely play an important role based on our knowledge of other respiratory viruses. Children are more likely to be asymptomatic or have milder symptoms and less likely to present for healthcare and be tested for SARS-CoV-2. Thus, our current estimates are likely under-representative of the true burden of SARS-CoV-2 in children. Given the potential direct benefit of a SARS-CoV-2 vaccine in children and the substantial indirect benefit through community protection, or "herd immunity," we argue that planning and implementation of SARS-CoV-2 vaccines should include children. Furthermore, community protection occurred after widespread implementation of prior childhood vaccines against Streptococcus pneumoniae, rubella, and rotavirus. We detail considerations for vaccine clinical trials, potential barriers to the implementation of widespread vaccination and argue why children would be an ideal target population for vaccination.

Burden of Illness in Households With Severe Acute Respiratory Syndrome Coronavirus 2-Infected Children.

We investigated of illness among household members of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children receiving medical care (n = 32). We identified 144 household contacts (HCs): 58 children and 86 adults. Forty-six percent of HCs developed symptoms consistent with coronavirus disease. Child-to-adult transmission was suspected in 7 cases.

Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM. METHODS: The comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM. RESULTS: Review of 3553 patients (18 039 person-years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin-susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture-positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%). CONCLUSIONS: Distinction between OM and sickle-related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.

Influenza vaccine effectiveness and disease burden in children and adolescents with sickle cell disease: 2012-2017.

BACKGROUND: Data are limited on the burden of influenza and seasonal influenza vaccine effectiveness (VE) in children with sickle cell disease (SCD). METHODS: We used a prospectively collected clinical registry of SCD patients 6 months to 21 years of age to determine the influenza cases per 100 patient-years, vaccination rates, and a test-negative case-control study design to estimate influenza VE against medically attended laboratory-confirmed influenza infection. Influenza-positive cases were randomly matched to test-negative controls on age and influenza season in 1:1 ratio. We used adjusted logistic regression models to compare odds ratio (OR) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimate. RESULTS: There were 1037 children with SCD who were tested for influenza, 307 children (29.6%) had at least one influenza infection (338 infections, incidence rate 3.7 per 100 person-years; 95% CI, 3.4-4.1) and 56.2% of those tested received annual influenza vaccine. Overall VE pooled over five seasons was 22.3% (95% CI, -7.3% to 43.7%). Adjusted VE estimates ranged from 39.7% (95% CI, -70.1% to 78.6%) in 2015/2016 to -5.9% (95% CI, -88.4% to 40.4%) in the 2016/17 seasons. Influenza VE varied by age and was highest in children 1-5 years of age (66.6%; 95% CI, 30.3-84.0). Adjusted VE against acute chest syndrome during influenza infection was 39.4% (95% CI, -113.0 to 82.8%). CONCLUSIONS: Influenza VE in patients with SCD varies by season and age. Multicenter prospective studies are needed to better establish and monitor influenza VE among children with SCD.

Severe Pediatric COVID-19 Presenting With Respiratory Failure and Severe Thrombocytopenia.

The novel severe acute respiratory syndrome coronavirus 2 is a worldwide pandemic. The severe morbidity and mortality associated with coronavirus disease 2019 has mostly affected the elderly or those with underlying medical conditions. We present a case of a 12-year-old girl with no past medical history who presented with fever, cough, and vomiting. Laboratory evaluation revealed severe thrombocytopenia and elevated markers of inflammation. The patient progressed to respiratory failure, and testing results for the severe acute respiratory syndrome coronavirus 2 returned positive. Because of the severity of her thrombocytopenia, she was treated with intravenous immunoglobulin and steroids with prompt improvement in platelets. The patient's severe acute respiratory distress syndrome was managed with mechanical ventilation, inhaled nitric oxide, and then airway pressure release ventilation. After azithromycin and hydroxychloroquine were given without improvement, our patient received tocilizumab, an anti-interleukin-6 receptor antibody, and remdesivir, a broad antiviral agent, with significant clinical benefit soon afterward. Given that severe pediatric coronavirus disease 2019 is rare, we hope to inform pediatric providers on the clinical course and management considerations as this pandemic continues to spread.

Murine Model of Maternal Immunization Demonstrates Protective Role for Antibodies That Mediate Antibody-Dependent Cellular Cytotoxicity in Protecting Neonates From Herpes Simplex Virus Type 1 and Type 2.

BACKGROUND: Neonatal herpes simplex virus (HSV) disease results in unacceptable morbidity and mortality. The primary humoral immune response to natural infection is neutralizing antibodies (Abs). However, Abs that activate Fc gama receptors (FcγRs) and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) may play a dominant role in protection. In adult mice, a single-cycle HSV candidate vaccine deleted in glycoprotein-D (ΔgD-2) that induces ADCC provided complete protection against HSV disease and prevented the establishment of latency. Passive transfer studies showed that Abs were sufficient for protection. The current study tested the hypothesis that maternal immunization with ΔgD-2 would protect neonates. METHODS: C57BL/6 female mice were vaccinated 3 weeks apart with ΔgD-2, and pups were challenged at different times postnatally with lethal doses of HSV-1 or HSV-2. Concentration and functionality of Abs and immune cells were assessed. RESULTS: Maternal ΔgD-2 immunization provided significant protection and reduced viral dissemination after lethal challenge with HSV-1 or HSV-2. Protection correlated with Abs acquired transplacentally or from breastmilk that mediated ADCC. Protection was reduced when pups were challenged on Day 1 of life, and this was associated with decreased ability of newborn cells to mediate Ab-dependent cell killing. CONCLUSIONS: Antibodies mediating ADCC provide significant protection against neonatal HSV.