Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children.

Most studies of adaptive immunity to SARS-CoV-2 infection focus on peripheral blood, which may not fully reflect immune responses at the site of infection. Using samples from 110 children undergoing tonsillectomy and adenoidectomy during the COVID-19 pandemic, we identified 24 samples with evidence of previous SARS-CoV-2 infection, including neutralizing antibodies in serum and SARS-CoV-2-specific germinal center and memory B cells in the tonsils and adenoids. Single-cell B cell receptor (BCR) sequencing indicated virus-specific BCRs were class-switched and somatically hypermutated, with overlapping clones in the two tissues. Expanded T cell clonotypes were found in tonsils, adenoids and blood post-COVID-19, some with CDR3 sequences identical to previously reported SARS-CoV-2-reactive T cell receptors (TCRs). Pharyngeal tissues from COVID-19-convalescent children showed persistent expansion of germinal center and antiviral lymphocyte populations associated with interferon (IFN)-γ-type responses, particularly in the adenoids, and viral RNA in both tissues. Our results provide evidence for persistent tissue-specific immunity to SARS-CoV-2 in the upper respiratory tract of children after infection.

Patterns of Orofacial Clefting in New York City From 1983 to 2010: Trends by Racial Background, Birthplace, and Public Health Strategies.

OBJECTIVE: To determine the role of racial background, public health initiatives, and residence on the prevalence of orofacial clefts (OFCs) in New York City (NYC). DESIGN/METHODS: Retrospective review of OFC cases from the New York State Congenital Malformations Registry. PATIENTS/PARTICIPANTS: Patients born with an OFC and all live births to mothers residing in NYC between 1983 and 2010. MAIN OUTCOME MEASURES: Orofacial cleft birth prevalence by cleft type, race, and borough of maternal residence for each year and by time period around the implementation of public health interventions including folate supplementation. RESULTS: A total of 3557 cases were reviewed. The prevalence remained stable for cleft palate and cleft lip with or without cleft palate (CL ± P) in sequential time periods of the study. Among CL ± P cases, cleft lip prevalence decreased early in the study compared to increases in cleft lip and palate prevalence. For most years, the prevalence of OFCs was lower among African Americans than whites. A total of 12% to 26% of mothers in 4 of the NYC boroughs deliver outside of their borough of residence, choosing to give birth in Manhattan most often. No difference in OFC prevalence was shown in any of the 5 NYC boroughs. CONCLUSIONS: The period prevalence remained relatively stable during the time periods before and after the implementation of folate supplementation for OFCs in NYC. Prevalence of OFC subtypes was lower for most time periods during this study among African Americans compared to whites. Several factors may explain the choice of birthplace outside of the mother's borough of residence.

Association of anosmia and neutralizing antibody production in adolescents with SARS-CoV-2.

BACKGROUND: To monitor olfactory/gustatory dysfunction and its relationship to SARS-CoV-2 IgG antibody responses in an adolescent population. METHODS: Adolescents with changes in olfactory/gustatory functions were enrolled in a 15-month study. The patients were evaluated with 1) SNOT-22, 2) pediatric smell wheel, and 3) SARS-CoV-2 antibody testing. The relationship between these scores and length of anosmia, and the amount of SARS-CoV-2 IgG antibodies were assessed. A brain MRI was performed in cases of persistent special sensory symptoms. RESULTS: Eighteen patients were identified with smell and/or taste complaints. Most of the patients were female (67%) and median age was 15 years (range 11-17). Twelve patients had prior SARS-CoV-2 PCR testing, with only five patients with a positive result. The median SNOT-22 score was 16 (range 0-52) and the median smell wheel score was 6.5 (range 1-11). Patients with taste difficulty were more likely to have a score less than eight. 78% of the patients tested positive for antibodies and there was a strong negative correlation between smell wheel score and antibody level (Spearman, ρ = -0.798, p = 0.002). Five patients underwent MRI scan, and all resulted as normal olfactory bulb structures. 66% received nasal corticosteroids. 11 patients presented in follow up. CONCLUSIONS: Adolescents presenting to a pediatric ENT clinic during the SARS-CoV-2 pandemic were likely to have prolonged (>6 weeks) symptoms of SARS-CoV-2. The majority do not report positive PCR testing result but do report systemic symptoms including anosmia. This suggests that anosmia may be both a late and prolonged symptom of SARS-CoV-2.

Examining multi-level immune response to determine prevalence of COVID-19 in pediatric tonsillectomy.

OBJECTIVE: To determine the prevalence of COVID-19 in a cohort of children undergoing tonsillectomy through assessment of B cell immune responses to SARS-CoV-2 in both peripheral blood and tonsil tissue. METHODS: In this cohort study at a tertiary pediatric hospital (Children's National Hospital) in Washington, DC, we recruited 100 children undergoing tonsillectomy from late September 2020 to January 2021. Serum, peripheral blood cells, and tonsil tissue were collected and examined for immune reactivity to SARS-CoV-2. Parent-reported clinical histories were compared to antibody and B-cell responses. RESULTS: Among 100 children undergoing tonsillectomy, 19% had evidence of immune responses to SARS-CoV-2 (CoV2+), indicating prior COVID-19. In all seropositive participants, we detected SARS-CoV-2 specific B cells in both peripheral blood mononuclear cells and tonsils, providing evidence for tissue-specific immunity in these children. Of the 19, 63% reported no known history of COVID-19, and an additional 3 were asymptomatic or unaware of an acute infection when detected on pre-surgery screen. Hispanic children represented 74% of CoV2+ subjects compared to 37% of the full cohort. 100% of CoV2+ children lived in a zip code with poverty level >10%. CONCLUSIONS: Nearly one-fifth of children undergoing tonsillectomy at an urban U.S. hospital had evidence of prior COVID-19 during the early pandemic, with the majority unaware of prior infection. Our results underscore the ethnic and socio-economic disparities of COVID-19. We found concordant evidence of humoral immune responses in children in both blood and tonsil tissue, providing evidence of local immune responses in the upper respiratory tract. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1993-1999, 2023.

Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children.

SARS-CoV-2 infection triggers adaptive immune responses from both T and B cells. However, most studies focus on peripheral blood, which may not fully reflect immune responses in lymphoid tissues at the site of infection. To evaluate both local and systemic adaptive immune responses to SARS-CoV-2, we collected peripheral blood, tonsils, and adenoids from 110 children undergoing tonsillectomy/adenoidectomy during the COVID-19 pandemic and found 24 with evidence of prior SARS-CoV-2 infection, including detectable neutralizing antibodies against multiple viral variants. We identified SARS-CoV-2-specific germinal center (GC) and memory B cells; single cell BCR sequencing showed that these virus-specific B cells were class-switched and somatically hypermutated, with overlapping clones in the adenoids and tonsils. Oropharyngeal tissues from COVID-19-convalescent children showed persistent expansion of GC and anti-viral lymphocyte populations associated with an IFN-γ-type response, with particularly prominent changes in the adenoids, as well as evidence of persistent viral RNA in both tonsil and adenoid tissues of many participants. Our results show robust, tissue-specific adaptive immune responses to SARS-CoV-2 in the upper respiratory tract of children weeks to months after acute infection, providing evidence of persistent localized immunity to this respiratory virus.

Tracheal Agenesis: Vertical Division of the Native Esophagus - A Novel Surgical Approach and Review of the Literature.

INTRODUCTION: Tracheal agenesis (TA) is rare and usually fatal. Few survivors with concomitant tracheoesophageal fistulae (TEF) who underwent ligation of the distal esophagus with creation of a spit-fistula and neo-trachea from the proximal esophagus exist. We report a novel surgical technique whereby the esophagus is divided longitudinally to preserve a functional alimentation tract and a parallel neo-trachea. We review the literature of reported cases, including survivors beyond 12 months. METHODS: Case report and literature review. RESULTS: A female infant with prenatal polyhydramnios was born at 35 weeks gestation with immediate respiratory distress and absent cry. Oxygenation was maintained with a laryngeal mask airway. Despite a normal appearing larynx, she could not be intubated and emergent neck exploration disclosed no cervical trachea. The patient was placed on extra corporeal membranous oxygenation (ECMO), and later diagnosed with TA, Floyd Type I. Parental desire for reconstruction but refusal of a spit-fistula necessitated a novel procedure. The esophagus was divided longitudinally via a microstapler to preserve the original alimentary tract and create a parallel neo-trachea originating from the TEF and terminating as a cervical stoma. The healing process was complicated but the baby was ultimately discharged to home where she developed normally neurologically until succumbing one night to accidental decannulation at 16 months of age. CONCLUSION: We describe a novel surgical approach to manage TA. This includes avoiding creation of a spit fistula and preserving the native esophagus. We then survey the literature, reporting the survivorship duration and operative management of 174 reported cases of TA.

Patient Safety in Audiology.

There is a need to educate audiologists, physicians, and other clinicians about patient safety in audiology. This article addresses the many aspects of patient safety and the applicability to the practice of audiology in health care. Clinical examples of strategies to build a culture of patient safety are provided.

Clinical characteristics of pediatric granular myringitis.

OBJECTIVE: To determine the clinical characteristics of children with granular myringitis. STUDY DESIGN: Case series with chart review of children with granular myringitis. SETTING: Tertiary care children's hospitals in Delaware and Florida. SUBJECTS AND METHODS: From July 1, 2006, to June 30, 2011, 15 patients were identified with granular myringitis based on International Classification of Diseases, Ninth Revision code 384.1 (10 male, 5 female; 10 left-sided, 5 right-sided). RESULTS: Average age at onset was 10 years (range, 4-18 years). Average length of symptoms was 21 months (range, 3-48 months). Thirteen of the 15 patients (87%) had myringotomy tube placement prior to diagnosis of myringitis, and 11 had a previous perforation (73%). Eleven myringoplasties were performed on 8 (53%) patients prior to the onset of granular myringitis (5 fascia, 2 fat, 2 cartilage, 1 paper patch, and 1 at an outside hospital that was unknown). A total of 27 otolaryngologic surgical procedures were done on 14 of 15 patients. Ten patients (67%) had audiometry performed, and 6 (40%) had ear cultures. Medical treatment included ciprofloxacin and dexamethasone otic drops in all patients, oral antibiotics in 4 patients, and additional topical agents in 8 patients. Two patients had laser resurfacing, and 1 patient had surgical curettage. Five patients had long-term remission, 8 had intermittent remission, and 2 had no remission of their symptoms. CONCLUSION: Granular myringitis is a chronic, recalcitrant disease typically preceded by myringotomy and tube placement or myringoplasty/tympanoplasty. Medical and surgical intervention is varied and often does not lead to permanent resolution of the disease.