Comparison of RT-PCR and antigen test sensitivity across nasopharyngeal, nares, and oropharyngeal swab, and saliva sample types during the SARS-CoV-2 omicron variant.

Limited data highlight the need to understand differences in SARS-CoV-2 omicron (B.1.1.529) variant viral load between the gold standard nasopharyngeal (NP) swab, mid-turbinate (MT)/anterior nasal swabs, oropharyngeal (OP) swabs, and saliva. MT, OP, and saliva samples from symptomatic individuals in Atlanta, GA, in January 2022 and longitudinal samples from a small familial cohort were tested by both RT-PCR and ultrasensitive antigen assays. Higher concentrations in the nares were observed in the familial cohort, but a dominant sample type was not found among 39 cases in the cross-sectional cohort. The composite of positive MT or OP assay for both RT-PCR and antigen assay trended toward higher diagnostic yield but did not achieve significant difference. Our data did not identify a singular preferred sample type for SARS-CoV-2 testing, but higher levels of saliva nucleocapsid, a trend toward higher yield of composite OP/MT result, and association of apparent MT or OP predominance with symptoms warrant further study.

Delivering Therapy to the Olfactory Cleft: A Comparison of the Various Methods of Administering Topical Nasal Medications.

Background and objective Chronic rhinosinusitis (CRS) is an inflammatory condition affecting the nasal mucosa, and it causes olfactory dysfunction (OD) in up to 78.2% of patients. Corticosteroids are the mainstay of treatment to shrink nasal polyposis, reduce inflammation, and improve olfactory function. While many delivery methods for topical nasal corticosteroids exist, there is scarce data on the efficacy of the various medication delivery methods to the olfactory cleft (OC). In light of this, this study aimed to compare the following delivery methods to the OC: conventional nasal spray (NS), nasal drops in the Kaiteki position (KP), and exhalation delivery system (EDS). Methods We evaluated 16 sinonasal cavities from eight cadaver specimens in this study. Each sinonasal cavity was administered fluorescein dye solution via NS, KP, and EDS. Following administration, nasal endoscopy was employed to capture staining patterns in the OC. OC staining was rated with scores ranging from 0 (no staining) to 3 (heavy staining) after each administration of dye solution. Mean OC staining ratings were calculated and compared using the Kruskal-Wallis rank sum test and the Wilcoxon signed-rank test. Results The mean OC staining score for the different delivery methods was as follows - NS: 1.095 ± 1.008, EDS: 0.670 ± 0.674, and KP: 2.038 ± 1.097. Nasal drops in the KP had a significantly higher staining score compared to NS (p=0.041) and EDS (p=0.003). However, there was no significant difference in staining scores between NS and EDS. Conclusions Nasal drops in the KP are more effective at reaching the OC than NS or EDS and should be considered as a first-line modality for administering topical medications when treating OD.

Clinical Practice Guideline: Immunotherapy for Inhalant Allergy.

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Executive Summary of Clinical Practice Guideline on Immunotherapy for Inhalant Allergy.

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Accessing the Eustachian tube: Conventional nasal spray vs. exhalation delivery system and the impact of targeted endoscopic sinus surgery on topical distribution patterns.

BACKGROUND: Eustachian tube dysfunction (ETD) may occur distinct from, or in conjunction with, chronic rhinosinusitis (CRS+ETD). Intranasal corticosteroid sprays are often prescribed for ETD, although ET distribution may be limited. To date, no anatomic studies compare nasopharynx (NP) distribution between conventional nasal sprays (NS) and exhalation delivery systems (EDS) after surgery. This study utilizes a cadaver model to examine topical NP delivery using EDS vs. NS before and after targeted endoscopic sinus surgery (ESS). METHODS: Sixteen sinonasal cavities were administered fluorescein solution via NS and EDS before and after maxillary antrostomy and anterior ethmoidectomy, followed by nasal endoscopy of the NP and ET orifice. Seven blinded experts submitted staining ratings of endoscopy images on a 0- to 3-point scale, with ratings averaged for analysis. RESULTS: Interrater reliability was excellent (intraclass correlation, 0.956). EDS was associated with significantly greater NP staining vs. NS in a pooled cohort of nonsurgical and ESS specimens (1.19 ± 0.81 vs. 0.78 ± 1.06; p = 0.043). Using a logistic regression model, EDS significantly outperformed NS in nonsurgical (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.21-10.09; p = 0.021) and post-ESS (OR, 9.00; 95% CI, 1.95-41.5; p = 0.005) specimens, with the greatest relative staining observed for EDS after targeted ESS (OR, 18.99; 95% CI, 3.44-104.85; p = 0.001). CONCLUSIONS: EDS is more effective than NS in topical delivery to the NP and ET orifices in cadavers. Targeted ESS may facilitate greater NP penetration by EDS compared with NS, with possible synergism after ESS for augmented delivery. These findings suggest a role for EDS delivery methods for ETD management and in CRS+ETD patients undergoing sinus surgery.

Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.

Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased ß-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1ß, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.

Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race.

Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (n = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (<16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), P = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), P = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.

An eosinophil peroxidase activity assay accurately predicts eosinophilic chronic rhinosinusitis.

BACKGROUND: A definitive diagnosis of eosinophilic chronic rhinosinusitis (eCRS) requires invasive surgical tissue sampling and histologic enumeration of intact eosinophils. Eosinophil peroxidase (EPX) is an accurate biomarker of sinonasal tissue eosinophilia in CRS regardless of polyp status. A less invasive and rapid method that accurately identifies tissue eosinophilia would be of great benefit to patients. OBJECTIVE: We sought to evaluate a new clinical tool that uses a nasal swab and colorimetric EPX activity assay to predict a diagnosis of eCRS. METHODS: A prospective, observational cohort study was conducted using nasal swabs and sinonasal tissue biopsies obtained from patients with CRS electing endoscopic sinus surgery. Patients were classified as non-eCRS (n = 19) and eCRS (n = 35) on the basis of pathologically determined eosinophil counts of less than 10 or greater than or equal to 10 eosinophils/HPF, respectively. Swab-deposited EPX activity was measured and compared with tissue eosinophil counts, EPX levels, and CRS-specific disease metrics. RESULTS: EPX activity was significantly increased in patients with eCRS than in patients without eCRS (P < .0001). With a relative absorbance unit cutoff value of greater than or equal to 0.80, the assay demonstrated high sensitivity (85.7%) and moderate specificity (79.0%) for confirming eCRS. Spearman correlations between EPX activity and tissue eosinophil counts (rs = 0.424), EPX levels (rs = 0.503), and Lund-Kennedy endoscopy scores (rs = 0.440) in eCRS were significant (P < .05). CONCLUSIONS: This investigation evaluates a nasal swab sampling method and EPX activity assay that accurately confirms eCRS. This method could potentially address the unmet need to identify sinonasal tissue eosinophilia at the point-of-care, as well as to longitudinally monitor eosinophil activity and treatment response.

The Effects of Endogenous Cannabinoids on the Mammalian Respiratory System: A Scoping Review of Cyclooxygenase-Dependent Pathways.

Introduction: The endogenous cannabinoid (endocannabinoid) system is an emerging target for the treatment of chronic inflammatory disease with the potential to advance treatment for many respiratory illnesses. The varied effects of endocannabinoids across tissue types makes it imperative that we explore their physiologic impact within unique tissue targets. The aim of this scoping review is to explore the impact of endocannabinoid activity on eicosanoid production as a measure of human airway inflammation. Methods: A scoping literature review was conducted according to PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Search strategies using MeSH terms related to cannabinoids, eicosanoids, cyclooxygenase (COX), and the respiratory system were used to query Medline, Embase, Cochrane, CINAHL, Web of Science, and Biosis Previews in December 2021. Only studies that investigated the relationship between endocannabinoids and the eicosanoid system in mammalian respiratory tissue after 1992 were included. Results: Sixteen studies were incorporated in the final qualitative review. Endocannabinoid activation increases COX-2 expression, potentially through ceramide-dependent or p38 and p42/44 Mitogen-Activated Protein Kinase pathways and is associated with a concentration-dependent increase in prostaglandin (PG)E2. Inhibitors of endocannabinoid hydrolysis found either an increase or no change in levels of PGE2 and PGD2 and decreased levels of leukotriene (LT)B4, PGI2, and thromboxane A2 (TXA2). Endocannabinoids increase bronchial epithelial cell permeability and have vasorelaxant effects in human pulmonary arteries and cause contraction of bronchi and decreased gas trapping in guinea pigs. Inhibitors of endocannabinoid hydrolysis were found to have anti-inflammatory effects on pulmonary tissue and are primarily mediated by COX-2 and activation of eicosanoid receptors. Direct agonism of endocannabinoid receptors appears to play a minor role. Conclusion: The endocannabinoid system has diverse effects on the mammalian airway. While endocannabinoid-derived PGs can have anti-inflammatory effects, endocannabinoids also produce proinflammatory conditions, such as increased epithelial permeability and bronchial contraction. These conflicting findings suggest that endocannabinoids produce a variety of effects depending on their local metabolism and receptor agonism. Elucidation of the complex interplay between the endocannabinoid and eicosanoid pathways is key to leveraging the endocannabinoid system as a potential therapeutic target for human airway disease.

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Single-cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype.

Immunoglobulin (Ig) E is central to the pathogenesis of allergic conditions, including allergic fungal rhinosinusitis. However, little is known about IgE antibody secreting cells (ASCs). We performed single-cell RNA sequencing from cluster of differentiation (CD)19+ and CD19- ASCs of nasal polyps from patients with allergic fungal rhinosinusitis (n = 3). Nasal polyps were highly enriched in CD19+ ASCs. Class-switched IgG and IgA ASCs were dominant (95.8%), whereas IgE ASCs were rare (2%) and found only in the CD19+ compartment. Through Ig gene repertoire analysis, IgE ASCs shared clones with IgD-CD27- "double-negative" B cells, IgD+CD27+ unswitched memory B cells, and IgD-CD27+ switched memory B cells, suggesting ontogeny from both IgD+ and memory B cells. Transcriptionally, mucosal IgE ASCs upregulate pathways related to antigen presentation, chemotaxis, B cell receptor stimulation, and survival compared with non-IgE ASCs. Additionally, IgE ASCs have a higher expression of genes encoding lysosomal-associated protein transmembrane 5 (LAPTM5) and CD23, as well as upregulation of CD74 (receptor for macrophage inhibitory factor), store-operated Calcium entry-associated regulatory factor (SARAF), and B cell activating factor receptor (BAFFR), which resemble an early minted ASC phenotype. Overall, these findings reinforce the paradigm that human ex vivo mucosal IgE ASCs have a more immature plasma cell phenotype than other class-switched mucosal ASCs and suggest unique functional roles for mucosal IgE ASCs in concert with Ig secretion.

Severe acute respiratory syndrome coronavirus 2 vaccine breakthrough infections: A single metro-based testing network experience.

Objectives: Understanding the incidence and characteristics that influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections (VBIs) is imperative for developing public health policies to mitigate the coronavirus disease of 2019 (COVID-19) pandemic. We examined these factors and post-vaccination mitigation practices in individuals partially and fully vaccinated against SARS-CoV-2. Materials and methods: Adults >18 years old were voluntarily enrolled from a single metro-based SARS-CoV-2 testing network from January to July 2021. Participants were categorized as asymptomatic or symptomatic, and as unvaccinated, partially vaccinated, or fully vaccinated. All participants had confirmed SARS-CoV-2 infection based on standard of care (SOC) testing with nasopharyngeal swabs. Variant analysis by rRT-PCR was performed in a subset of time-matched vaccinated and unvaccinated individuals. A subgroup of partially and fully vaccinated individuals with a positive SARS-CoV-2 rRT-PCR was contacted to assess disease severity and post-vaccination mitigation practices. Results: Participants (n = 1,317) voluntarily underwent testing for SARS-CoV-2 during the enrollment period. A total of 29.5% of the population received at least one SARS-CoV-2 vaccine (n = 389), 12.8% partially vaccinated (n = 169); 16.1% fully vaccinated (n = 213). A total of 21.3% of partially vaccinated individuals tested positive (n = 36) and 9.4% of fully vaccinated individuals tested positive (n = 20) for SARS-CoV-2. Pfizer/BioNTech mRNA-1273 was the predominant vaccine received (1st dose = 66.8%, 2nd dose = 67.9%). Chronic liver disease and immunosuppression were more prevalent in the vaccinated (partially/fully) group compared to the unvaccinated group (p = 0.003, p = 0.021, respectively). There were more asymptomatic individuals in the vaccinated group compared to the unvaccinated group [n = 6 (10.7%), n = 16 (4.1%), p = 0.045]. CT values were lower for the unvaccinated group (median 24.3, IQR 19.1-30.5) compared to the vaccinated group (29.4, 22.0-33.7, p = 0.004). In the vaccinated group (n = 56), 18 participants were successfully contacted, 7 were lost to follow-up, and 2 were deceased. A total of 50% (n = 9) required hospitalization due to COVID-19 illness. Adherence to nationally endorsed mitigation strategies varied post-vaccination. Conclusion: The incidence of SARS-CoV-2 infection at this center was 21.3% in the partially vaccinated group and 9.4% in the fully vaccinated group. Chronic liver disease and immunosuppression were more prevalent in the vaccinated SARS-CoV-2 positive group, suggesting that these may be risk factors for VBIs. Partially and fully vaccinated individuals had a higher incidence of asymptomatic SARS-CoV-2 and higher CT values compared to unvaccinated SARS-CoV-2 positive individuals.

SARS-CoV-2 reliably detected in frozen saliva samples stored up to one year.

Viability of saliva samples stored for longer than 28 days has not been reported in the literature. The COVID-19 pandemic has spawned new research evaluating various sample types, thus large biobanks have been started. Residual saliva samples from university student surveillance testing were retested on SalivaDirect and compared with original RT-PCR (cycle threshold values) and quantitative antigen values for each month in storage. We conclude that saliva samples stored at -80°C are still viable in detecting SARS-CoV-2 after 12 months of storage, establishing the validity of these samples for future testing.

Concordance of SARS-CoV-2 Results in Self-collected Nasal Swabs vs Swabs Collected by Health Care Workers in Children and Adolescents.

Importance: Despite the expansion of SARS-CoV-2 testing, available tests have not received Emergency Use Authorization for performance with self-collected anterior nares (nasal) swabs from children younger than 14 years because the effect of pediatric self-swabbing on SARS-CoV-2 test sensitivity is unknown. Objective: To characterize the ability of school-aged children to self-collect nasal swabs for SARS-CoV-2 testing compared with collection by health care workers. Design, Setting, and Participants: Cross-sectional study of 197 symptomatic children and adolescents aged 4 to 14 years old. Individuals were recruited based on results of testing in the Children's Healthcare of Atlanta system from July to August 2021. Exposures: Children and adolescents were given instructional material consisting of a short instructional video and a handout with written and visual steps for self-swab collection. Participants first provided a self-collected nasal swab. Health care workers then collected a second specimen. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 detection and relative quantitation by cycle threshold (Ct) in self- vs health care worker-collected nasal swabs when tested with a real-time reverse transcriptase-polymerase chain reaction test with Emergency Use Authorization. Results: Among the study participants, 108 of 194 (55.7%) were male and the median age was 9 years (IQR, 6-11). Of the 196 participants, 87 (44.4%) tested positive for SARS-CoV-2 and 105 (53.6%) tested negative by both self- and health care worker-collected swabs. Two children tested positive by self- or health care worker-collected swab alone; 1 child had an invalid health care worker swab. Compared with health care worker-collected swabs, self-collected swabs had 97.8% (95% CI, 94.7%-100.0%) and 98.1% (95% CI, 95.6%-100.0%) positive and negative percent agreement, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups (mean [SD] Ct, self-swab: 26.7 [5.4] vs health care worker swab: 26.3 [6.0]; P = .65). Conclusions and Relevance: After hearing and seeing simple instructional materials, children and adolescents aged 4 to 14 years self-collected nasal swabs that closely agreed on SARS-CoV-2 detection with swabs collected by health care workers.

Clinical evaluation of the Diagnostic Analyzer for Selective Hybridization (DASH): A point-of-care PCR test for rapid detection of SARS-CoV-2 infection.

BACKGROUND: An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. We evaluated clinical performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC rapid PCR test. METHODS: We conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites where we collected two bilateral anterior nasal swabs and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard". RESULTS: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently SARS-CoV-2 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R = 0.89 [95% CI 0.81, 0.94]). CONCLUSIONS: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results (approximately 15 minutes) in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR.

Don't forget about human factors: Lessons learned from COVID-19 point-of-care testing.

During the COVID-19 pandemic, the development of point-of-care (POC) diagnostic testing accelerated in an unparalleled fashion. As a result, there has been an increased need for accurate, robust, and easy-to-use POC testing in a variety of non-traditional settings (i.e., pharmacies, drive-thru sites, schools). While stakeholders often express the desire for POC technologies that are "as simple as digital pregnancy tests," there is little discussion of what this means in regards to device design, development, and assessment. The design of POC technologies and systems should take into account the capabilities and limitations of the users and their environments. Such "human factors" are important tenets that can help technology developers create POC technologies that are effective for end-users in a multitude of settings. Here, we review the core principles of human factors and discuss lessons learned during the evaluation process of SARS-CoV-2 POC testing.

International consensus statement on allergy and rhinology: Olfaction.

BACKGROUND: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). METHODS: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. RESULTS: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. CONCLUSION: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

Machine Learning Approaches to Identify Discriminative Signatures of Volatile Organic Compounds (VOCs) from Bacteria and Fungi Using SPME-DART-MS.

Point-of-care screening tools are essential to expedite patient care and decrease reliance on slow diagnostic tools (e.g., microbial cultures) to identify pathogens and their associated antibiotic resistance. Analysis of volatile organic compounds (VOC) emitted from biological media has seen increased attention in recent years as a potential non-invasive diagnostic procedure. This work explores the use of solid phase micro-extraction (SPME) and ambient plasma ionization mass spectrometry (MS) to rapidly acquire VOC signatures of bacteria and fungi. The MS spectrum of each pathogen goes through a preprocessing and feature extraction pipeline. Various supervised and unsupervised machine learning (ML) classification algorithms are trained and evaluated on the extracted feature set. These are able to classify the type of pathogen as bacteria or fungi with high accuracy, while marked progress is also made in identifying specific strains of bacteria. This study presents a new approach for the identification of pathogens from VOC signatures collected using SPME and ambient ionization MS by training classifiers on just a few samples of data. This ambient plasma ionization and ML approach is robust, rapid, precise, and can potentially be used as a non-invasive clinical diagnostic tool for point-of-care applications.

Treatment strategies for postviral olfactory dysfunction: A systematic review.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been associated with a dramatic increase in postviral olfactory dysfunction (PVOD) among patients who are infected. A contemporary evidence-based review of current treatment options for PVOD is both timely and relevant to improve patient care. Objective: This review seeks to impact patient care by qualitatively reviewing available evidence in support of medical and procedural treatment options for PVOD. Systematic evaluation of data quality and of the level of evidence was completed to generate current treatment recommendations. Methods: A systematic review was conducted to identify primary studies that evaluated treatment outcomes for PVOD. A number of medical literature data bases were queried from January 1998 to May 2020, with completion of subsequent reference searches of retrieved articles to identify all relevant studies. Validated tools for the assessment of bias among both interventional and observational studies were used to complete quality assessment. The summary level of evidence and associated outcomes were used to generate treatment recommendations. Results: Twenty-two publications were identified for qualitative review. Outcomes of alpha-lipoic acid, intranasal and systemic corticosteroids, minocycline, zinc sulfate, vitamin A, sodium citrate, caroverine, intranasal insulin, theophylline, and Gingko biloba are reported. In addition, outcomes of traditional Chinese acupuncture and olfactory training are reviewed. Conclusion: Several medical and procedural treatments may expedite the return of olfactory function after PVOD. Current evidence supports olfactory training as a first-line intervention. Additional study is required to define specific treatment recommendations and expected outcomes for PVOD in the setting of COVID-19.