Objective The objective of this study is to present a novel clinical manifestation of infection with the Omicron variant of the SARS‐CoV‐2 virus affecting mainly young, vaccinated, and healthy adults. We describe a new group of COVID‐19 patients seeking emergency care with symptoms similar to the life‐threatening condition epiglottitis. Here, we present a case series and discuss management. Methods We performed a retrospective single‐center case study of patients diagnosed with COVID‐19 who were referred to the Ear, Nose, and Throat Emergency Department (ENT ED) between January 1 and January 23, 2022 with clinical symptoms such as acute odynophagia, severe sore throat, and fever. Ethical approval was obtained from the Swedish Ethical Review Authority (2020‐02579). Informed consent was obtained from all patients included in the study. Results Twenty patients meeting inclusion criteria were identified. Fifteen patients were fully vaccinated against COVID‐19. Four patients needed a short hospitalization for their symptoms. The most common diagnoses were COVID‐19‐associated acute viral laryngotracheitis and/or viral pharyngitis. Six patients presented with signs of secondary bacterial infection and were put on antibiotics. Conclusion Previous variants of SARS‐CoV‐2 infection affected predominantly the lower respiratory tract and were associated with loss of smell and taste in many patients. The Omicron variant seems to affect predominantly the upper airways and cause acute laryngitis without olfactory dysfunction. In some patients, the clinical manifestation is similar to the symptoms of epiglottitis. In such a case, a prompt examination of the larynx is the gold standard to exclude inflammatory edema in the upper airways. None of the patients described in this study developed epiglottitis. In this study, we discuss the management of acute odynophagia in COVID‐19 patients.

Objectives: To investigate the relationship between laryngopharyngeal reflux (LPR) and recurrent (ROM) or chronic otitis media with effusion (COME). Databases: PubMed, Scopus, and Cochrane Library. Methods: Three authors searched articles published between January 1980 and September 2020 about the association between LPR and the development of recurrent or chronic otitis media. Inclusion, exclusion, diagnostic criteria, and clinical outcome evaluation of included studies were analyzed using PRISMA criteria. The bias analysis of included studies was evaluated with the Tool to assess Risk of Bias of the CLARITY group. Results: Twenty-six clinical and three experimental articles met our inclusion criteria, accounting for 1,624 children and 144 adults with COME or ROM. According to the pH study type, the prevalence of LPR and gastroesophageal reflux disease (GERD) in OM patients were 28.7% (range, 8–100%) and 40.7 (range, 18–64%), respectively. The majority of studies identified pepsin or pepsinogen in middle ear effusion, with a range of mean concentrations depending on the technique used to measure pepsin. There was an important heterogeneity between studies regarding definition of COME, ROM, and LPR, exclusion criteria, methods used to measure pepsin/pepsinogen in middle ear secretions and outcome assessments. Conclusion: The association between LPR and OM is still unclear. Future clinical and experimental studies are needed to investigate the association between LPR and OM in both children and adults through extensive gastric content analysis in middle ear suppurations and impedance-pH monitoring considering acid, weakly acid, and alkaline reflux events.

Despite the introduction of vaccines, COVID-19 still affects millions of people worldwide. A better understanding of pathophysiology and the discovery of novel therapies are needed. One of the cells of interest in COVID-19 is the neutrophil. This cell type is being recruited to a site of inflammation as one of the first immune cells. In this project, we investigated a variety of neutrophils phenotypes during COVID-19 by measuring the expression of markers for migration, maturity, activation, gelatinase granules and secondary granules using flow cytometry. We show that neutrophils during COVID-19 exhibit altered phenotypes compared to healthy individuals. The activation level including NETs production and maturity of neutrophils seem to last longer during COVID-19 than expected for innate immunity. Neutrophils as one of the drivers of severe cases of COVID-19 are considered as potential treatment targets. However, for a successful implementation of treatment, there is a need for a better understanding of neutrophil functions and phenotypes in COVID-19. Our study answers some of those questions.

Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.

Anticancer immunotherapies have revolutionized cancer management, yet the effect of systemic anti‐programmed cell death protein 1 (PD‐1) treatment is predominantly studied in tumor‐infiltrating lymphocytes (TILs). Its impact on PD‐1 expressing cells in tumor‐draining lymph nodes (TDLNs) is not well understood and yet to be explored. Thus, further research aiming for better understanding of the PD‐1 pathway not only in tumor tissue but also in TDLNs is warranted. In this study, we investigated the expression of PD‐1, CD69, and HLA‐DR on CD4+ and CD8+ T cells by flow cytometry analysis of peripheral blood mononuclear cells (PBMCs), TDLNs, and tumor samples from patients with oral squamous cell carcinoma (OSCC). Our data showed that both helper and cytotoxic T lymphocytes in OSCC tissue were highly activated and expressed high level of PD‐1 (over 70% positivity). Lymphocytes in TDLNs and peripheral blood expressed significantly lower levels of PD‐1 and other activation markers compared to TILs. Moreover, we demonstrated that a significant fraction of PD‐1 negative TILs expressed high levels of human leukocyte antigen – DR isotype and CD69. In contrast, PD‐1 negative cells in TDLNs and PBMCs scarcely expressed the aforementioned activation markers. Furthermore, we proved that patients with a high percentage of CD3+ PD‐1+ cells in tumor‐draining lymph nodes had significantly lower disease‐free and overall survival rates (log‐rank test P = .0272 and P = .0276, respectively). Taken together, we proved that flow cytometry of lymph nodes in OSCC is feasible and may be used to investigate whether PD‐1 levels in TDLNs correspond with survival and potentially with response to anti‐PD‐1 therapy. Such knowledge may ultimately help guide anti‐PD‐1 treatment.

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The contribution of different immune cell subsets, especially T cells, in anti-tumor immune response is well established. In contrast to T cells, the anti-tumor contribution of B cells has been scarcely investigated. B-cells are often overlooked, even though they are important players in a fully integrated immune response and constitute a substantial fraction of tumor draining lymph nodes (TDLNs) known also as Sentinel Nodes. In this project, samples including TDLNs, non-TDLNs (nTDLNs) and metastatic lymph nodes from 21 patients with oral squamous cell carcinoma were analyzed by flow cytometry. TDLNs were characterized by a significantly higher proportion of B cells compared with nTDLNs (P = .0127). TDLNs-associated B cells contained high percentages of naïve B cells, in contrary to nTDLNs which contained significantly higher percentages of memory B cells. Patients having metastases in TDLNs showed a significantly higher presence of immunosuppressive B regulatory cells compared with metastasis-free patients (P = .0008). Elevated levels of regulatory B cells in TDLNs were associated with the advancement of the disease. B cells in TDLNs were characterized by significantly higher expression of an immunosuppressive cytokine-IL-10 compared with nTDLNs (P = .0077). Our data indicate that B cells in human TDLNs differ from B cells in nTDLNs and exhibit more naïve and immunosuppressive phenotypes. We identified a high accumulation of regulatory B cells within TDLNs which may be a potential obstacle in achieving response to novel cancer immunotherapies (ICIs) in head and neck cancer.

Interleukin-26 (IL-26) is released by several immune and structural cells following stimulation of toll-like receptors (TLRs), whereupon it can directly inhibit viral replication and enhance neutrophil chemotaxis. Given these unique properties, IL-26 has emerged as an intriguing mediator of host defense in the lungs. However, the role of IL-26 in COVID-19 has not been thoroughly investigated. Here, we characterized the involvement of IL-26 in the hyperinflammation and tissue damage that occurs in patients with acute COVID-19. We found that IL-26 is markedly increased in blood samples from these patients, and that the concentration of IL-26 correlates with those of the neutrophil-mobilizing cytokines IL-8 and TNFα, respectively. Moreover, the increase in blood IL-26 correlates with enhanced surface expression of the “don’t eat me” signal CD47 on blood neutrophils isolated from patients with acute COVID-19. Finally, we found that the blood concentration of IL-26 correlates with that of increased lactate dehydrogenase, an established marker of tissue damage, and decreased mean corpuscular hemoglobin (MCH), a previously verified hematological aberration in COVID-19, both of which are associated with severe disease. Thus, our findings indicate that increased systemic IL-26 associates with markers of hyperinflammation and tissue damage in patients with acute COVID-19, thereby forwarding the kinocidin IL-26 as a potential target for diagnosis, monitoring, and therapy in this deadly disease.