Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment: A longitudinal cohort study.

Objectives: Persistent olfactory dysfunction (OD) following loss of smell associated with SARS-CoV-2 infection is a major feature of long COVID. Perspectives on the prevalence of persistent OD predominantly rely on self-reported olfactory function. Few studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute recovery. Data anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of smell. This study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical OD. Methods: We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin' Sticks extended test at baseline and 1-year time points. Participants had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not available. Results: Baseline olfactory evaluation was completed by 122 participants, 53 of whom completed the 1-year follow-up assessment. Among participants presenting with perceived OD, 74.5% had confirmed psychophysical OD at baseline, with 55.1% at 1-year follow-up. Participants had reliable trends in self-rated versus psychophysically tested olfactory function at both time points. The total threshold, discrimination, and identification (TDI) score improved by +3.25 points in the cohort with psychophysical OD (p = 0.0005), with this improvement largely attributable to an increase in median threshold scores (+2.75 points; p = 0.0004). Conclusions: OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19, with many demonstrating lingering deficits at 1-year. Improvements in threshold, but not discrimination or identification, most significantly mediate improvement of total TDI score at follow-up.

Subjective Versus Psychophysical Measures of Chemosensory Alterations Following COVID-19.

INTRODUCTION: Olfactory dysfunction is a common symptom of COVID-19. However, subjective perception of olfactory function does not always correlate well with more objective measures. This study seeks to clarify associations between subjective and psychophysical measures of olfaction and gustation in patients with subjective chemosensory dysfunction following COVID-19. METHODS: Adults with persistent COVID-19-associated chemosensory disturbance were recruited for a prospective, longitudinal cohort study at a tertiary care institution. Participants provided subjective measures of olfactory and gustatory function and underwent psychophysical assessment using Sniffin' Sticks olfactory and Monell gustatory tests. RESULTS: Data analysis (n=65) showed a statistically significant association between subjective and psychophysical measures of olfaction (p<0.001). For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.11 (95% CI: 0.06, 0.16; p<0.001) point increase in TDI score while adjusting for age at baseline assessment, sex, and follow-up time. For each one-point increase in subjectively-reported olfactory ability, there is, on average, a 0.04 (95% CI: 0.02, 0.06; p<0.001) point and 0.05 (95% CI: 0.03, 0.07; p<0.001) point increase in discrimination and identification scores, respectively, when adjusting for age at baseline assessment, sex, and follow-up time. CONCLUSION: Subjective olfaction shows a mild to moderate association with psychophysical measures, but it fails to comprehensively assess persistent COVID-19-associated chemosensory deficits. The lack of significant association between subjective olfaction and threshold limits the utility of subjective olfaction in tracking recovery. These findings support the push for more widespread psychophysical chemosensory testing.

BMI Increases in Individuals with COVID-19-Associated Olfactory Dysfunction.

(1) Background: Reports suggest COVID-19-associated olfactory dysfunction (OD) may result in alterations in dietary behaviors and perceived weight change, but few studies using psychophysical evaluation of post-COVID-19-associated chemosensory dysfunction and body mass index (BMI) exist. The purpose of this study is to assess the impact of both quantitative and qualitative features of COVID-19-associated OD on BMI; (2) Methods: Recruitment of thirty-one participants with self-reported OD in the form of quantitative loss with and without qualitative features. Surveys with questions specific to qualitative olfactory function, Sniffin' Sticks tests, and BMI measures were completed at two visits, one year apart. Group differences were assessed with Wilcoxon signed-rank tests and the Holm-Bonferroni method; (3) Results: Individuals with persistent quantitative OD (n = 15) and self-reported parosmia (n = 19) showed statistically significant increases in BMI after 1 year (p = 0.004, adjusted α = 0.0125; p = 0.011, adjusted α = 0.0167). Controls with transient quantitative OD (n = 16) and participants without self-reported parosmia (n = 12) showed no statistically significant changes in BMI over the same time period (p = 0.079, adjusted α = 0.05; p = 0.028, adjusted α = 0.025); (4) Conclusions: This study shows an association between COVID-19-associated OD and BMI, suggesting olfaction may play a role in altering dietary habits and nutrition in this population. Larger study cohorts are needed to further evaluate this relationship.

Otolaryngologic manifestations among MPOX patients: A systematic review and meta-analysis.

PURPOSE: MPOX has numerous otolaryngologic presentations that have been recognized as clinically important, especially with the onset of the 2022 outbreak. However, how these features vary across region and outbreak have yet to be elucidated or supported by meta-analysis. The objective of this study is to identify the otolaryngologic manifestations of MPOX across previous and current outbreaks and among endemic and non-endemic regions. BASIC PROCEDURES: Data sources of MEDLINE (PubMed), the Cochrane Library, Scopus, Embase, Web of Science, Google Scholar, and OpenGrey were searched through August 2022. All observational studies reporting data on laboratory-confirmed MPOX patients with otolaryngologic symptoms were included. Two authors independently performed the screening process while a third resolved disagreements. Data were extracted into a structured form by two authors independently. We performed a meta-analysis of the prevalence of otorhinolaryngologic symptoms using MetaXL software (version 5.3) under a random-effects model. MAIN FINDINGS: 38 studies with 5952 patients were included. The four most prevalent manifestations were headache at 31 % (95 % CI [0.16-0.49], I 2  = 99 %), sore throat at 22 % (95 % CI [0.09-0.37], I 2  = 99 %), cough at 16 % (95 % CI [0.05-0.30], I 2  = 99 %), and cervical lymphadenopathy at 10 % (95 % CI [0.01-0.26], I 2  = 100 %). Otolaryngologic features were more prevalent in previous outbreaks as compared to the 2022 outbreak including 37 % prevalence of headache (95 % CI [0.11-0.66], I 2  = 100 %), 33 % prevalence of cough (95 % CI [0.21-0.47], I 2  = 98 %), 27 % prevalence of sore throat (95 % CI [0.07-0.53], I 2  = 99 %), 15 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.428], I 2  = 100 %), 13 % prevalence of oral ulcers (95 % CI [0.02-0.30], I 2  = 99 %), 6 % prevalence of oral exanthem (95 % CI [0.00-0.17], I 2  = 99 %), 5 % prevalence of dysphagia (95 % CI [0.00-0.18], I 2  = 99 %), and 5 % prevalence of tonsillar signs (95 % CI [0.00-0.13], I 2  = 99 %). Features that were more prevalent in endemic areas versus non-endemic areas include 27 % prevalence of cough (95 % CI [0.14-0.41], I 2  = 99 %), 15 % prevalence of oral ulcers (95 % CI [0.02-0.36], I 2  = 99 %), 6 % prevalence of tonsillar signs (95 % CI [0.00-0.18], I 2  = 99 %), and 19 % prevalence of cervical lymphadenopathy (95 % CI [0.00-0.48], I 2  = 100 %), while the only feature more prevalent in non-endemic areas was headache with a prevalence of 36 % (95 % CI [0.24-0.47], I 2  = 96 %). PRINCIPAL CONCLUSIONS: In this systematic review and meta-analysis, four symptoms - headache, sore throat, cough, and cervical lymphadenopathy - were found to be the most prevalent otolaryngologic features of MPOX. Otolaryngologic manifestations of MPOX were more pronounced in prior outbreaks and in endemic areas as compared to the 2022 outbreak and non-endemic areas. These findings may aid MPOX recognition in an otolaryngology setting.

Electrostatic loading and photoredox-based release of molecular cargo from oligoviologen-crosslinked microparticles.

Although on-demand cargo release has been demonstrated in a wide range of microparticle platforms, many existing methods lack specific loading interactions and/or undergo permanent damage to the microparticle to release the cargo. Here, we report a novel method for electrostatically loading negatively charged molecular cargo in oligoviologen-crosslinked microparticles, wherein the cargo can be released upon activation by visible light. A water-in-oil (W/O) emulsion polymerization method was used to fabricate narrowly dispersed microparticles crosslinked by a dicationic viologen-based dimer and a poly(ethylene glycol) diacrylate. A zinc-tetraphenyl porphyrin photocatalyst was also polymerized into the microparticle and used to photochemically reduce the viologen subunits to their monoradical cations through a visible-light-mediated photoredox mechanism with triethanolamine (TEOA) as a sacrificial reductant. The microparticles were characterized by microscopy methods revealing uniform, spherical microparticles 481 ± 20.9 nm in diameter. Negatively charged molecular cargo (methyl orange, MO) was electrostatically loaded into the microparticles through counteranion metathesis. Upon irradiation with blue (450 nm) light, the photo-reduced viologen crosslinker subunits lose positive charges, resulting in release of the anionic MO cargo. Controlled release of the dye, as tracked by absorption spectroscopy, was observed over time, yielding release of up to 40% of the cargo in 48 h and 60% in 120 h in single dynamic dialysis experiment. However, full release of cargo was achieved upon transferring the microparticles to a fresh TEOA solution after the initial 120 h period.

Iterative step-growth synthesis and degradation of unimolecular polyviologens under mild conditions.

An iterative step-growth addition method was used to expedite the gram-scale synthesis of main-chain polyviologens by several days, while also producing the longest main-chain polyviologen (i.e., 26 viologen subunits) reported to date. Facile degradation using inorganic and organic aqueous bases was also demonstrated for a representative oligoviologen (6V-Me·12Cl), a polyviologen (26V-Me·52Cl), and oligoviologen-crosslinked hydrogels.