Revealing the Hidden Impacts: Insights into Biological Aging and Long-Term Effects in Pauci- and Asymptomatic COVID-19 Healthcare Workers.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers-DNA methylation age (DNAmAge) and telomere length (TL)-in blood leukocytes, nasal cells (NCs), and induced sputum (IS) one year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data from questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male sex, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p < 0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p < 0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p ≤ 0.05) and NCs (p < 0.001) and were biologically older than COPD patients (p < 0.05). These findings suggest the need to monitor aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Posterior Semicircular Canal Plugging Relieves Tumarkin's Crisis in Ménière's Disease Patients.

(1) Background: Patients affected by Ménière's disease can experience Tumarkin's syndrome, which is characterized by postural instability, gait abnormalities, and, occasionally, an abrupt loss of balance known as vestibular drop attack or Tumarkin's crisis. In this study, semicircular canal plugging is proposed as the definitive treatment for this condition. The outcomes of this type of surgery are discussed. (2) Methods: A total of 9 patients with a confirmed diagnosis of Ménière disease suffering from Tumarkin crisis underwent posterior semicircular canal plugging. These patients were assessed with Video Head Impulse Tests, vestibular evoked myogenic potentials, and Pure Tone Audiometry preoperatively and postoperatively. (3) Results: VHIT showed a postoperative decrease in PSC gain median (Preop. 0.86 and postop. 0.52; p < 0.009). No statistically significant differences were described for the anterior semicircular canal and the lateral semicircular canal. No patient experienced new Tumarkin crisis after the surgical treatment. (4) Conclusions: Our ten years of experience with posterior semicircular canal plugging in Ménière disease patients with Tumarkin's syndrome has shown that this type of surgical procedure is successful in controlling Tumarkin's crisis, with high patient satisfaction and little worsening in hearing level.

Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis.

Introduction: The Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and characteristic symptoms are deficits in smell and taste perception, which may last for weeks/months after COVID-19 diagnosis owing to mechanisms that are not fully elucidated. Methods: In order to identify the determinants of olfactory symptom persistence, we obtained olfactory mucosa (OM) from 21 subjects, grouped according to clinical criteria: i) with persistent olfactory symptoms; ii) with transient olfactory symptoms; iii) without olfactory symptoms; and iv) non-COVID-19 controls. Cells from the olfactory mucosa were harvested for transcriptome analyses. Results and discussion: RNA-Seq assays showed that gene expression levels are altered for a long time after infection. The expression profile of micro RNAs appeared significantly altered after infection, but no relationship with olfactory symptoms was found. On the other hand, patients with persistent olfactory deficits displayed increased levels of expression of genes involved in the inflammatory response and zinc homeostasis, suggesting an association with persistent or transient olfactory deficits in individuals who experienced SARS-CoV-2 infection.

Altered brain regional homogeneity is associated with depressive symptoms in COVID-19.

BACKGROUND: COVID-19 is an infectious disease that has spread worldwide in 2020, causing a severe pandemic. In addition to respiratory symptoms, neuropsychiatric manifestations are commonly observed, including chronic fatigue, depression, and anxiety. The neural correlates of neuropsychiatric symptoms in COVID-19 are still largely unknown. METHODS: A total of 79 patients with COVID-19 (COV) and 17 healthy controls (HC) underwent 3 T functional magnetic resonance imaging at rest, as well as structural imaging. Regional homogeneity (ReHo) was calculated. We also measured depressive symptoms with the Patient Health Questionnaire (PHQ-9), anxiety using the General Anxiety Disorder 7-item scale, and fatigue with the Multidimension Fatigue Inventory. RESULTS: In comparison with HC, COV showed significantly higher depressive scores. Moreover, COV presented reduced ReHo in the left angular gyrus, the right superior/middle temporal gyrus and the left inferior temporal gyrus, and higher ReHo in the right hippocampus. No differences in gray matter were detected in these areas. Furthermore, we observed a negative correlation between ReHo in the left angular gyrus and PHQ-9 scores and a trend toward a positive correlation between ReHo in the right hippocampus and PHQ-9 scores. LIMITATIONS: Heterogeneity in the clinical presentation in COV, the different timing from the first positive molecular swab test to the MRI, and the cross-sectional design of the study limit the generalizability of our findings. CONCLUSIONS: Our results suggest that COVID-19 infection may contribute to depressive symptoms via a modulation of local functional connectivity in cortico-limbic circuits.

Olfactory Dysfunction in COVID-19 Patients Who Do Not Report Olfactory Symptoms: A Pilot Study with Some Suggestions for Dentists.

BACKGROUND: Smell and taste dysfunction are frequently reported by SARS-CoV-2 positive patients. The degree of olfactory and gustatory dysfunction varies from a very mild reduction to their complete loss. Several studies have been performed to determine their prevalence in COVID-19 patients, mostly using subjective measurement methods. The literature lacks long-term studies regarding duration and recovery. METHODS: We assessed olfactory performance, using the Sniffin' Sticks olfactory test, in a group of patients who had not reported olfactory dysfunction, around 131 days after their COVID-19 diagnosis. RESULTS: 11 out of 20 subjects showed no olfactory reduction (65%), while 9 subjects showed reduced TDI score (45%). A total of 13 subjects (65%) scored above the cutoff point for Threshold, 16 subjects (80%) scored above the cutoff point for discrimination and 13 subjects (65%) scored above the cutoff point for identification. CONCLUSION: Objective measurement methods of olfactory performance show a higher prevalence of olfactory reduction compared to patients' self-reported questionnaires. Olfactory dysfunction can last even months after its onset and because of its high prevalence, it could be a screening symptom for suspect COVID-19 cases.

Manganese in Diagnostics: A Preformulatory Study.

This investigation aims to find lipid-based nanosystems to be used as tools to deliver manganese for diagnostic purposes in multimodal imaging techniques. In particular, the study describes the production and characterization of aqueous dispersions of anionic liposomes as delivery systems for two model manganese-based compounds, namely manganese chloride and manganese acetylacetonate. Negatively charged liposomes were obtained using four different anionic surfactants, namely sodium docusate (SD), N-lauroylsarcosine (NLS), Protelan AG8 (PAG) and sodium lauroyl lactylate (SLL). Liposomes were produced by the direct hydration method followed by extrusion and characterized in terms of size, polydispersity, surface charge and stability over time. After extrusion, liposomes are homogeneous and monodispersed with an average diameter not exceeding 200 nm and a negative surface charge as confirmed by ζ potential measurement. Moreover, as indicated by atomic absorption spectroscopy analyses, the loading of manganese-based compounds was almost quantitative. Liposomes containing NLS or SLL were the most stable over time and the presence of manganese-based compounds did not affect their size distribution. Liposomes containing PAG and SD were instable and therefore discarded. The in vitro cytotoxicity of the selected anionic liposomes was evaluated by MTT assay on human keratinocyte. The obtained results highlighted that the toxicity of the formulations is dose dependent.

Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: An international survey.

OBJECTIVES: To determine the prevalence of olfactory and taste dysfunction (OD; TD) among COVID-19 positive health care workers (HCWs), their associated risk factors and prognosis. METHODS: Between May and June 2020, a longitudinal multicenter study was conducted on symptomatic COVID-19 PCR confirmed HCWs (COVID-19 positive) in London and Padua. RESULTS: Hundred and fourteen COVID-19 positive HCWs were surveyed with a response rate of 70.6% over a median follow-up period of 52 days. UK prevalence of OD and TD was 73.1% and 69.2%, respectively. There was a male to female ratio of 1:3 with 81.6% being white, 43.7% being nurses/health care assistants (HCAs), and 39.3% being doctors. In addition, 53.2% of them worked on COVID-19 wards. Complete recovery was reported in 31.8% for OD and 47.1% for TD with a 52 days follow-up. The job role of doctors and nurses negatively influenced smell (P = .04 and P = .02) and taste recovery (P = .02 and P = .01). Ethnicity (being white) showed to positively influence only taste recovery (P = .04). Sex (being female) negatively influenced OD and TD recovery only in Paduan HCWs (P = .02 and P = .011, respectively). Working on a COVID-19 ward did not influence prognosis. CONCLUSIONS: The prevalence of OD and TD was considerably higher in HCWs. The prognosis for OD and TD recovery was worse for nurses/HCAs and doctors but working on a COVID-19 ward did not influence prognosis. Sixty-eight percent of surveyed HCWs at 52 days continued to experience OD or TD requiring additional future medical management capacity. LEVEL OF EVIDENCE: 4.

Long-term repeatability of exhaled breath condensate pH in asthma.

Exhaled breath condensate (EBC) is being used increasingly to sample airway fluid. EBC pH may be a biomarker of airway inflammation in asthma. In this study, we assessed the long-term reproducibility of EBC pH in asthma. We examined 31 asthmatic patients and eight healthy subjects three times over a 1-year period (winter, autumn and summer). EBC pH was measured after argon deaeration. Repeatability of pH measurements was assessed using intraclass correlation coefficients (ICC) and the limits of agreement (LOA) between seasons were calculated according to Bland-Altman method. No significant differences in EBC pH between seasons were detected in healthy subjects and asthmatic patients. EBC pH showed high repeatability either in healthy subjects (ICC=0.94) or in asthmatics (ICC=0.97). Variability between seasons was greater in asthmatics than in healthy subjects: winter-autumn LOA -0.68/+0.52 and -0.31/+0.31, autumn-summer LOA -0.75/+0.67 and -0.24/+0.15, winter-summer LOA -0.92/+0.67 and -0.34/+0.23 in asthmatic and healthy subjects, respectively. In a subgroup of 11 asthmatics who remained in stable conditions during the study, no substantially different LOA were observed in EBC pH compared with the whole group of asthmatics. Asthmatic smokers (n=10) tended to have lower EBC pH (7.57+/-0.46) than asthmatic non-smokers (n=21) (7.74+/-0.21; p=0.063) and wider LOA. In conclusion, we demonstrated that EBC pH exhibits good repeatability in long-term assessment. EBC pH in asthmatics tended to fluctuate more than in healthy subjects. However, EBC pH variability in asthma was not influenced by changes in clinical status. Rather, we suggest that cigarette smoke may be implicated in EBC pH variability.

Effect of inhalation of thermal water on airway inflammation in chronic obstructive pulmonary disease.

Thermal water inhalations have been traditionally used in the treatment of upper and lower chronic airway diseases. However, the benefit and the mechanism of this treatment have not been properly assessed. To determine whether inhaled salt-bromide-iodine thermal water improves lung function, quality of life and airway inflammation, 39 patients with chronic obstructive pulmonary disease (COPD) were randomly assigned to receive 2-weeks inhalation treatment with thermal water (active, no. = 20) or normal saline (control, no. = 19) in single blind. Lung volumes were measured, Saint George's respiratory questionnaire (SGRQ) was administered and induced sputum was performed before and after treatment. No changes in pre- and post-salbutamol lung volumes was observed after inhalation treatment in both groups. SGRQ score showed a significant improvement in active group compared with control group at the end of the trial. The concentration of total cells in induced sputum increased significantly in both active (P < 0.05) and control groups (P < 0.05). Inhalation of thermal water induced a small but significant decrease in percentages of sputum neutrophils (P < 0.01) and a parallel increase in macrophages (P < 0.01). In contrast, normal saline inhalation was not associated with changes in differential sputum cell counts. In conclusion, treatment with inhaled salt-bromide-iodine thermal water in COPD is associated with a reduced proportion of neutrophils in induced sputum suggesting that thermal water may have a mild anti-inflammatory effect on the airways. However, the short-term improvement in some components health-related quality of life was not related with changes in lung function or with the degree of airway inflammation.