BackgroundThe upper respiratory tract (URT) is the portal of entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-CoV-2 likely interacts with the URT microbiome. However, understanding of the associations between the URT microbiome and the severity of coronavirus disease 2019 (COVID-19) is still limited.ObjectiveOur primary objective was to identify URT microbiome signature/s that consistently changed over a spectrum of COVID-19 severity.MethodsUsing data from 103 adult participants from two cities in the United States, we compared the bacterial load and the URT microbiome between five groups: 20 asymptomatic SARS-CoV-2-negative participants, 27 participants with mild COVID-19, 28 participants with moderate COVID-19, 15 hospitalized patients with severe COVID-19, and 13 hospitalized patients in the ICU with very severe COVID-19.ResultsURT bacterial load, bacterial richness, and within-group microbiome composition dissimilarity consistently increased as COVID-19 severity increased, while the relative abundance of an amplicon sequence variant (ASV), Corynebacterium_unclassified.ASV0002, consistently decreased as COVID-19 severity increased.ConclusionsWe observed that the URT microbiome composition significantly changed as COVID-19 severity increased. The URT microbiome could potentially predict which patients may be more likely to progress to severe disease or be modified to decrease severity. However, further research in additional longitudinal cohorts is needed to better understand how the microbiome affects COVID-19 severity.

Background Anosmia and ageusia are symptoms commonly associated with COVID-19, but the relationship with disease severity, onset and recovery are unclear. Objective To examine factors associated with anosmia and ageusia and the recovery from these symptoms in an ethnically diverse cohort. Methods Individuals tested for SARS-CoV-2 between March and April 2020 were eligible for the study. Randomly selected participants answered a telephone questionnaire on COVID-19 symptoms with a focus on anosmia and ageusia. Additionally, relevant past medical history and data on the COVID-19 clinical course were obtained from electronic medical records. 486 patients were in the COVID-19 group and 103 were COVID-19-negative. Results Patients who were younger were more likely to report anosmia and/or ageusia (odds ratio (OR) for anosmia per 1-year increase in age: 0·98, 95%CI:0–97-0·99, p = 0·003; for ageusia: 0·98, 95%CI:0·97-0·99, p = 0·005) as were patients with lower eosinophil counts (OR for anosmia per 0.1-K/μL increase in eosinophils: 0·02, 95%CI:0·001-0·46, p = 0·01, for ageusia 0·10, 95%CI:0·01-0·97, p = 0·047). Male gender was independently associated with a lower probability of ageusia (OR:0·56, 95%CI:0·38-0·82, p = 0·003) and earlier sense of taste recovery (HR:1·44, 95%CI:1·05-1·98, p = 0·02). Latinos showed earlier sense of taste recovery than white patients (HR:1·82, 95%CI:1·05-3·18, p = 0·03). Conclusion Anosmia and ageusia were more common among younger patients and those with lower blood eosinophil counts. Ageusia was less commonly reported among men, and time to taste recovery was earlier among both men and Latinos.

The popularity of electronic cigarettes (e-cigs) that utilize nicotine salts has rapidly increased since the introduction of JUUL pods in 2015. The immunotoxicology of nicotine salts in the respiratory tract is understudied. We hypothesized that nicotine salt counteranions induce airway inflammation and alter immune responses to inhaled allergens independent of nicotine. METHODS: The nicotine salt counteranions lactate, levulinate, salicylate or benzoate (5% solution) were administered to C57BL/6J mice by oropharyngeal aspiration daily for three days (acute exposure model) or three times weekly for three weeks (persistent exposure model). In some studies, mice were also exposed to house dust mite (HDM) allergen alone or in combination with benzoate three times weekly for three weeks. Airway inflammation was assessed by enumeration of inflammatory cells in bronchoalveolar lavage fluid and lung histology. RESULTS: Acute exposure to nicotine salt counteranions induced an influx of neutrophils into the airways. Persistent exposure to nicotine salt counteranions resulted in a mixed neutrophilic and lymphocytic airway inflammatory response. Neither acute nor persistent exposure to nicotine salt counteranions caused airway eosinophilia. In a HDM-mediated allergic airway inflammation model, co-exposure to benzoate and HDM increased the percentage of airway neutrophils but decreased the percentage of eosinophils compared to HDM alone. CONCLUSIONS: Both acute and persistent exposure to nicotine salt counteranions induces airway inflammation in mice independent of nicotine. Benzoate also induced neutrophilic inflammation in a HDMmediated allergic airway inflammation model, suggesting that exposure to e-cigs containing nicotine salts may promote a neutrophilic asthma phenotype.

Non-steroidal Anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyposis, chronic rhinosinusitis, adult-onset asthma and hypersensitive reactions to cyclooxygenase-1 (COX-1) inhibitors. Among the available treatments for this disease, a combination of endoscopic sinus surgery followed by aspirin desensitization and aspirin maintenance therapy has been an effective approach. Studies have shown that long-term aspirin maintenance therapy can reduce the rate of nasal polyp recurrence in patients with N-ERD. However, the exact mechanism by which aspirin can both trigger and suppress airway disease in N-ERD remains poorly understood. In this review, we summarize current knowledge of aspirin effects in N-ERD, cardiovascular disease, and cancer, and consider potential mechanistic pathways accounting for the effects of aspirin in N-ERD.

To the Editor, Chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating inflammatory disease of the sinonasal cavities. 1 Concomitant CRSwNP and asthma, together with hypersensitivity reactions to cyclooxygenase-1 (COX-1) inhibitors, is a particular phenotype known as NSAID-exacerbated respiratory disease (N-ERD), which is associated with greater disease severity. 2 In this study, we attempted to characterize clinical, laboratory, and transcriptomic differences between CRSwNP patients with N-ERD (N-ERD; N = 13) and CRSwNP patients without N-ERD (non-N-ERD, N = 13).We compared patient demographics and clinical characteristics (Table 1). A more severe clinical phenotype with asthma presence and a higher number of sinus surgeries was observed in N-ERD patients. Lund-Mackay (LM) scores, definitive of radiographic severity of CRSwNP, 3 were significantly higher in N-ERD compared with non-N-ERD patients (20 (IQR 16-23) vs. 14 (IQR 14-18), re-LETTERS

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Purpose of reviewThe purpose of this review is to provide a comprehensive summary of the current understanding of the pathogenesis of aspirin-exacerbated respiratory disease (AERD), and an update on its management. Recent findingsElevated levels of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a newly described metabolite of arachidonic acid, have been identified in nasal polyps of AERD patients. In nasal polyps, activated basophils, and interleukin-5 -receptor-a-positive IL-5Ra þ plasma cells are associated with more severe nasal polyposis in AERD. Alveolar monocyte-derived macrophages and their persistent proinflammatory activation were suggested as putative factors contributing to AERD. Although not AERD-specific, three biological agents are now available for the management of both nasal polyposis and asthma. SummaryA newly downstream product of 15-lipoxygenase, 15-Oxo-ETE, was recently found to be significantly elevated in nasal polyps from AERD patients. This eicosanoid metabolite likely originates from an interplay between epithelial cells and mast cells. Nasal polyp basophils, IL-5Ra þ plasma cells, and alveolar macrophages were identified as important contributors to inflammation in AERD. Besides traditional aspirin desensitization and treatment for AERD management, several biologics for treatment of asthma are available, including three that have been approved for nasal polyposis. These biologic agents show variable rates of success in controlling AERD symptoms.

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