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.

Tonsillar origin of deep neck infection as a negative prognostic factor for developing complications.

<b>Aim:</b> The aim of this study was to compare the odontogenic and tonsillar origins of deep neck infection (DNI) as a negative prognostic factor for developing complications. </br></br> <b>Methods:</b> This was a retrospective study of 544 patients with tonsillar and odontogenic origins of DNI treated between 2006 and 2015 at 6 ENT Departments and Departments of Oral and Maxillofacial Surgery. Complications from DNI (descending mediastinitis, sepsis, thrombosis of the internal jugular vein, pneumonia, and pleuritis) were evaluated in both groups and compared. Associated comorbidities (cardiovascular involvement, hepatopathy, diabetes mellitus respiratory involvement, gastroduodenal involvement) were reviewed. </br></br> <b>Results:</b> Five hundred and forty-four patients were analyzed; 350/544 males (64.3%) and 19/544 females (35.7%). There were 505/544 cases (92.8%) with an odontogenic origin and 39/544 cases (7.2%) with a tonsillar origin of DNI. Complications occurred more frequently in the group with tonsillar origin of DNI (P < 0.001). There was no difference in diabetes mellitus between the two groups. </br></br> <b>Conclusions:</b> Currently, the tonsillar origin of DNI occurs much less frequently; nevertheless, it carries a much higher risk of developing complications than cases with an odontogenic origin. We recommend that these potentially high-risk patients with a tonsillar origin of deep neck infections should be more closely monitored.

Tonsil Riots and Vaccine Hesitancy: A 100-Year Legacy of Medical Mistrust.

The "tonsil riots" of 1906 were panics that developed at several public schools in historically immigrant-dominated neighborhoods of New York City (NYC). Per archived newspaper articles, several NYC public schools asked for parental consent to have Board of Health physicians come and perform tonsillectomy and adenoidectomy on their students. When children subsequently returned home from school "drooling mouthfuls of blood and barely able to speak," mothers reacted with panic and flocked to the schools demanding the safe return of their children. Police, ultimately, had to be called in to manage the crowds, and the events of 1906 largely faded from the public eye. However, these events can offer important lessons in communication and cultural humility as the United States continues its mass vaccination against coronavirus disease 2019.

Systemic Abscopal Effect of Low-dose Radiotherapy (2 Gy ×2) against Palatine Tonsil Follicular Lymphoma.

A 52-year-old man presented with palatine tonsillar swelling caused by follicular lymphoma. His tumor burden was low, but exacerbation of snoring and dysphagia was observed. Considering the first wave of coronavirus disease 2019 (COVID-19) pandemic, he received palliative 4-Gy irradiation to the tonsils in 2 fractions, which induced partial regression of tonsillar swellings and eradication of the circulating lymphoma cells. We suggest that low-dose radiotherapy triggered an abscopal effect of lymphoma, which allowed the patient time to receive COVID-19 vaccination before starting immunosuppressive chemo-immunotherapy.

Impact of COVID-19 on nationwide pediatric otolaryngology practice: Adenotonsillectomies (TA) and tonsil-related diagnoses trends.

OBJECTIVES/HYPOTHESIS: To determine the effects of the COVID-19 pandemic on Adenotonsillectomies (TA), Tonsil Related Cases (TC), and Peritonsillar Abscess (PTA) Trends. STUDY DESIGN: Retrospective Cohort Study. METHODS: This is a retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 51 children's hospitals. Regions were defined according to PHIS rules with at least five children's hospitals per region. We compared monthly total TA, TC, TC as a proportion of all hospital visits, and PTA from all encounters at each hospital from January 1, 2019, through December 31, 2021. RESULTS: Compared to 2019, April 2020 saw mean TC drop significantly from 371.62 to 68.37 (p < 0.001). Interestingly, June, September, and December 2020 had significantly higher mean TC compared to 2019. TC as a proportion of all hospital visits decreased significantly throughout the majority of 2021. Similarly, TA significantly decreased during 2020 and 2021 across all regions in the US, starting in March 2020 and this reduction in TA extended through the end of 2021 without any signs of recovery. PTA rates did not change significantly over the three years. CONCLUSIONS: The pandemic-plagued 2020 saw a noticeable decrease in overall TC and TA but then rebounded quickly to even higher than pre-pandemic levels. However, this rebound halted for the majority of 2021 and subsequently decreased to lower than pre-pandemic levels, which differs from other communicable pathologies such as otitis media which decreased initially then recovered to pre-pandemic levels by Summer of 2021.

Cutting Edge: SARS-CoV-2 Infection Induces Robust Germinal Center Activity in the Human Tonsil.

Understanding the generation of immunity to SARS-CoV-2 in lymphoid tissues draining the site of infection has implications for immunity to SARS-CoV-2. We performed tonsil biopsies under local anesthesia in 19 subjects who had recovered from SARS-CoV-2 infection 24-225 d previously. The biopsies yielded >3 million cells for flow cytometric analysis in 17 subjects. Total and SARS-CoV-2 spike-specific germinal center B cells, and T follicular helper cells, were readily detectable in human tonsils early after SARS-CoV-2 infection, as assessed by flow cytometry. Responses were higher in samples within 2 mo of infection but still detectable in some subjects out to 7 mo following infection. We conclude the tonsils are a secondary lymphoid organ that develop germinal center responses to SARS-CoV-2 infection and could play a role in the long-term development of immunity.

Generation of human tonsil epithelial organoids as an ex vivo model for SARS-CoV-2 infection.

The palatine tonsils (hereinafter referred to as "tonsils") serve as a reservoir for viral infections and play roles in the immune system's first line of defense. The aims of this study were to establish tonsil epithelial cell-derived organoids and examine their feasibility as an ex vivo model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The tonsil organoids successfully recapitulated the key characteristics of the tonsil epithelium, including cellular composition, histologic properties, and biomarker distribution. Notably, the basal layer cells of the organoids express molecules essential for SARS-CoV-2 entry, such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin, being susceptible to the viral infection. Changes in the gene expression profile in tonsil organoids revealed that 395 genes associated with oncostatin M signaling and lipid metabolism were highly upregulated within 72 h after SARS-CoV-2 infection. Notably, remdesivir suppressed the viral RNA copy number in organoid culture supernatants and intracellular viral protein levels in a dose-dependent manner. Here, we suggest that tonsil epithelial organoids could provide a preclinical and translational research platform for investigating SARS-CoV-2 infectivity and transmissibility or for evaluating antiviral candidates.

Impact of the COVID-pandemic on the incidence of tonsil surgery and sore throat in Germany.

PURPOSE: To longitudinally evaluate the impact of the COVID-19-pandemic on the incidence of inpatient tonsil surgery and outpatient primary care of sore throat in Germany. METHODS: A retrospective interrupted time-series analysis was conducted. The national database of the Hospital Remuneration System was used to retrieve the number of operations performed between January 2019 and September 2021 including elective and non-elective cases with the exception of malign diseases. Three episodes were compared on a weekly basis: before, during, and after the first national lockdown (March 16-May 3, 2020). We also analysed the number of outpatient doctor contacts of sore throat patients in 2019 and 2020. RESULTS: Overall, 144,069 surgical cases were included in the analysis. The first lockdown resulted in an abrupt and significant decrease of all types of tonsil surgery (p < 0.01). The incidence of tonsillectomy decreased from 556 (before) to 111 (during) and 326 (after) cases per week (relative risk 0.24; 95% CI 0.19-0.30, and 0.82; 95% CI 0.73-0.92). After the lockdown, the incidence persisted on a lower level compared to 2019. The number of doctor contacts decreased from 2,967,322 in 2019 to 1,976,617 in 2020 (- 33.4%). CONCLUSIONS: The first lockdown was associated with a significant decrease of all types of tonsil surgery. A return to pre-pandemic surgical activity was not identified. The findings were accompanied by a significant decrease of outpatient doctor contacts of sore throat patients in primary care, particularly in the subgroup of children and adolescents. The impact of the second lockdown, starting in December 2020, was by far not comparable.

COVID-19 in the tonsillectomised population.

OBJECTIVE: Interactions between SARS-CoV-2 and pharyngeal associated lymphoid tissue are thought to influence the manifestations of COVID-19. We aimed to determine whether a previous history of tonsillectomy, as a surrogate indicator of a dysfunctional pharyngeal associated lymphoid tissue, could predict the presentation and course of COVID-19. METHODS: Multicentric cross-sectional observational study involving seven hospitals in Northern and Central Italy. Data on the clinical course and signs and symptoms of the infection were collected from 779 adults who tested positive for SARS-CoV-2, and analysed in relation to previous tonsillectomy, together with demographic and anamnestic data. RESULTS: Patients with previous tonsillectomy showed a greater risk of fever, temperature higher than 39°C, chills and malaise. No significant differences in hospital admissions were found. CONCLUSIONS: A previous history of tonsillectomy, as a surrogate indicator of immunological dysfunction of the pharyngeal associated lymphoid tissue, could predict a more intense systemic manifestation of COVID-19. These results could provide a simple clinical marker to discriminate suspected carriers and to delineate more precise prognostic models.

COVID-19 infection in the palatine tonsil tissue and detritus: the detection of the virus compartment with RT-PCR.

Two patients suffering from chronic recurrent tonsillitis were reported. The first patient was confirmed infected with COVID-19, 3 weeks prior to tonsillectomy. The detritus and tonsil specimen were further analysed through real-time PCR (RT-PCR) and revealed amplification of the fragment N and ORF1ab genes of SARS-CoV-2. The second patient had a negative IgM and positive IgG antibody for COVID-19; however, the nasopharyngeal swab indicated negative for SARS-CoV-2. Tonsillectomy was performed 2 weeks after the swab; the tonsil specimen was analysed through RT-PCR and revealed amplification of the N2 and RdRp gene of SARS-CoV-2. According to both results, the presence of the SARS-CoV-2 gene remains to be detected in tonsil and/or detritus after 2-3 weeks after recovery. Hence, it is suggested that it is necessary to use adequate protection when performing tonsillectomy on early recovered patients with COVID-19. Furthermore, tonsillectomy would be more advisable to be performed after the fourth week after recovery from COVID-19.

Modeling human adaptive immune responses with tonsil organoids.

Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.

Rare case of clear cell renal cell carcinoma presenting as a unilateral tonsil lesion.

A 70-year-old man presented with gradually worsening throat discomfort. He had no prior diagnosis of cancer and no travel history of note. Examination revealed a right-sided painless neck lump. He underwent an MRI of the neck, revealing a gadolinium-enhancing tonsillar mass and two brain lesions. Biopsy of the tonsil lesion was in keeping with an epithelial neoplasm, suggesting metastatic renal cell carcinoma. This was confirmed following a staging CT, which revealed a left renal mass and lung metastases. Due to his brain metastases, the patient has been started on the tyrosine kinase inhibitor cabozantinib. A brief discussion on the diagnostic evaluation of a tonsil mass as a rare presentation of renal cell cancer follows this report.

ENT manifestation in COVID-19 patients.

OBJECTIVE: to detect, analyze and discuss the different ear nose throat (ENT) manifestations those were reported in COVID19 positive patients in the reviewed and published literatures. METHODS: We performed a search in the PubMed databases, Web of Science, LILACS, MEDLINE, SciELO, and Cochrane Library using the keywords; COVID-19, Novel coronavirus, corona, 2019-nCoV, SARS-CoV-2, ENT, ear, nose, throat, otorhinolaryngology, ORL, pharynx, ORL, smell, larynx, different ENT related symptoms. We reviewed published and peer reviewed studies that reported the ENT manifestations in COVID-19 laboratory-confirmed positive patients. RESULTS: within the included 1773 COVID-19 laboratory-confirmed positive patients, the most common ENT manifestations of COVID-19 were sore throat (11.3%) and headache (10.7%). While the other reported ENT manifestations were pharyngeal erythema (5.3%), nasal congestion (4.1%), runny nose or rhinorrhea (2.1%), upper respiratory tract infection (URTI) (1.9%), and tonsil enlargement (1.3%). CONCLUSION: ENT manifestations for COVID-19 are not common as fever and cough. But, a universal questionnaire using well-defined COVID-19 manifestations is needed to make the COVID-19 data precisely defined, complete and homogenous.