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.