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BackgroundClinical investigations have argued for long-term neurological manifestations in both hospitalised and non-hospitalised COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity.MethodsFrom a sample of 208 consecutive non-neurological patients hospitalised for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardised clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses.ResultsAt 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%) and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses.ConclusionsPremorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations.

BackgroundCognitive deficits have been increasingly reported as possible long-term manifestations after SARS-CoV-2 infection.AimsIn this study we aimed at evaluating the factors associated with cognitive deficits 6 months after hospitalization for Coronavirus Disease 2019 (COVID-19).MethodsOne hundred and six patients, discharged from a pneumology COVID-19 unit between March 1 and May 30 2020, accepted to be evaluated at 6 months according to an extensive neurological protocol, including the Montreal Cognitive Assessment (MoCA).ResultsAbnormal MoCA scores at 6 months follow-up were associated with higher pre-hospitalization National Health System (NHS) score (Duca et al. in Emerg Med Pract 22:1–2, 2020) (OR 1.27; 95% CI 1.05–1.6; p = 0.029) and more severe pulmonary disease expressed by the Brescia-COVID Respiratory Severity Scale (Duca et al. in Emerg Med Pract 22:1–2, 2020) (BCRSS > 1OR 4.73; 95% CI 1.53–14.63; p = 0.003) during the acute phase of the disease.DiscussionThis longitudinal study showed that the severity of COVID-19, indicated by BCRSS, and a complex score given by age and premorbid medical conditions, expressed by NHS, play a major role in modulating the long-term cognitive consequences of COVID-19 disease.ConclusionsThese findings indicate that the association of age and premorbid factors might identify people at risk for long-term neurological consequences of COVID-19 disease, thus deserving longer and proper follow-up.

Aim: Pneumothorax is a potentially life-threatening condition whose diagnosis can be challenging. Ultrasound chest examination is generally fast and user-friendly, but in non-expert hands or with uncooperative patients, it may still be difficult and time-consuming. Adding another tool to support the suspicion of pneumothorax might be useful, potentially enhancing the diagnostic accuracy of standard ultrasound chest examination. We evaluated the feasibility of standardized bilateral ultrasound image comparison as a potential new tool for pneumothorax diagnosis. Materials and methods: We enrolled 60 subjects (30 with pneumothorax and 30 controls) and collected bilateral ultrasound images of their chests (each image contained one frame from the left lung and one from the right lung). Ten physicians (eight blinded to diagnosis) divided into five groups according to expertise evaluated the images for potential grayscale differences and/or horizontal artifacts between the two frames. All images were then analyzed with image analysis software for grayscale pixel assessment (one sub-analysis for the entire area under the pleural line, one for a 100-pixel-wide rectangle under the pleural line). Results: All clinicians achieved good results in terms of diagnostic accuracy and inter-operator reliability, even those unexperienced in ultrasound. Mean, range, and median grayscale pixel ratio between the pneumothorax side and the healthy side in a single patient proved to be the most reliable parameters, reaching excellent sensitivity and specificity. Combining these parameters proved to be an excellent diagnostic tool (ROC area under curve = 1.00, p-value = 0.02). Conclusions: Standardized bilateral thoracic ultrasound image comparison may be a potential new tool for the diagnosis of pneumothorax.

Covid-19 in immunocompromised patients shows a prolonged course and may lead to a poor prognosis. Although data on hyperimmune plasma for treatment of Covid-19 suggest an improved outcome in immunocompetent patients, limited data are currently available in immunocompromised patients. We present the case of a 62-year-old Caucasian woman, who was previously treated with obinutuzumab and bendamustine for follicular lymphoma and showed a prolonged positive test for Covid-19. Since no improvement was observed with standard of care (including remdesivir), the possibility of hyperimmune plasma infusion was discussed. A first dose of hyperimmune plasma was administered, with subsequent onset of fever, increasing inflammatory indexes and worsening radiological findings. Three days later a second dose of plasma was administered. Within twelve hours cough and fever disappeared, and oxygen at rest was discontinued. The patient was discharged 5 days later, and sopharyngeal swabs resulted negative 16 days after discharge.

Background: Systematic assessment of lymph node status by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is indicated in (suspected) lung cancer. Sampling is herein guided by nodal size and FDG-PET characteristics. Ultrasound strain elastography (SE) might further improve risk stratification. By imaging tissue deformation over time, SE computes relative tissue strain. In several tissues, a lower strain (deformation) has been associated with a higher likelihood of malignancy. Objectives: To assess if EBUS-SE can independently help predict malignancy, and when combined with size and FDG uptake information. Methods: This multicenter (n = 5 centers) prospective trial included patients with suspected or proven lung cancer using a standardized measurement protocol. Cytopathology combined with surgery or follow-up imaging (>6 months) were used as reference standard. Results: Between June 2016 and July 2018, 327 patients and 525 lymph nodes were included (mean size 12.3 mm, malignancy prevalence 0.48). EBUS-SE had an overall AUC of 0.77. A mean strain <115 (range 0–255) showed 90% sensitivity, 43% specificity, 60% positive predictive value, and 82% negative predictive value. Combining EBUS-SE (<115) with size (<8 mm) and FDG-PET information into a risk stratification algorithm increased the accuracy. Combining size and SE showed that the 48% a priori chance of malignancy changed to 11 and 70% in double negative or positive nodes, respectively. In the subset where FDG-PET was available (n = 370), triple negative and positive nodes went from a 42% a priori chance of malignancy to 9 and 73%, respectively. Conclusions: EBUS-SE can help predict lymph node malignancy and may be useful for risk stratification when combined with size and PET information.

The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD) patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM) area and the extracellular matrix (ECM) protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. These findings indicate that airway remodeling also affects the large airways in COPD patients who have greater deposition of ECM proteins in the subepithelial layer and a larger smooth muscle area than control smoker subjects. These changes may contribute to chronic airflow obstruction in COPD patients.

BackgroundSeveral people affected by COVID-19 experienced neurological manifestations, altered sleep quality, mood disorders, and disability following hospitalization for a long time.ObjectiveTo explore the impact of different neurological symptoms on sleep quality, mood, and disability in a consecutive series of patients previously hospitalized for COVID-19 disease.MethodsWe evaluated 83 patients with COVID-19 around 3 months after hospital discharge. They were divided into 3 groups according to their neurological involvement (i.e., mild, unspecific, or no neurological involvement). Socio-demographic, clinical data, disability level, emotional distress, and sleep quality were collected and compared between the three groups.ResultsWe found that higher disability, depressive symptoms, and lower sleep quality in patients with mild neurological involvement compared to patients with unspecific and no neurological involvement. Differences between groups were also found for clinical variables related to COVID-19 severity.ConclusionAfter 3 months from hospital discharge, patients with more severe COVID-19 and mild neurological involvement experienced more psychosocial alterations than patients with unspecific or no neurological involvement. Both COVID-19 and neurological manifestations’ severity should be considered in the clinical settings to plain tailored interventions for patients recovering from COVID-19.

IntroductionBrain fog has been described up to 1 year after SARS-CoV-2 infection, notwithstanding the underlying mechanisms are still poorly investigated. In this study, we aimed to evaluate the prevalence of cognitive complaints at 1-year follow-up and to identify the factors related to persistent brain fog in COVID-19 patients.MethodsOut of 246 COVID patients, hospitalized from March 1st to May 31st, a sample of 137 patients accepted to be evaluated at 1 year from discharge, through a full clinical, neurological, and psychological examination, including the Montreal Cognitive Assessment (MoCA), impact of event scale-revised (IES-R), Zung self-rating depression scale (SDS), Zung self-rating anxiety scale (SAS), and fatigue severity scale (FSS). Subjects with prior cognitive impairment and/or psychiatric disorders were excluded.ResultsPatients with cognitive disorders exhibited lower MoCA score (22.9 ± 4.3 vs. 26.3 ± 3.1, p = 0.002) and higher IES-R score (33.7 ± 18.5 vs. 26.4 ± 16.3, p = 0.050), SDS score (40.9 ± 6.5 vs. 35.5 ± 8.6, p = 0.004), and fatigue severity scale score (33.6 ± 16.1 vs. 23.7 ± 12.5, p = 0.001), compared to patients without cognitive complaints. Logistic regression showed a significant correlation between brain fog and the self-rating depression scale values (p = 0.020), adjusted for age (p = 0.445), sex (p = 0.178), premorbid Cumulative Illness Rating Scale (CIRS) (p = 0.288), COVID-19 severity (BCRSS) (p = 0.964), education level (p = 0.784) and MoCA score (p = 0.909).ConclusionsOur study showed depression as the strongest predictor of persistent brain fog, adjusting for demographic and clinical variables. Wider longitudinal studies are warranted to better explain cognitive difficulties after COVID-19.

We evaluated the impact of COVID-19 vaccination on disease outcome in hospitalized patients with SARS-CoV-2 infection with a prospective study. 745 vaccinated and 451 unvaccinated patients consecutively admitted to a COVID-19 Hospital from 1st September 2021 to 1st September 2022 were included. Compared with unvaccinated cases, vaccinated patients were older, had more comorbidities, but had a lower risk of O2 need (odds ratio, OR, 0.46; 95 % CI 0.32–0.65) by logistic regression analysis adjusted for age, sex, comorbidity and WHO COVID-19 Clinical Progression Scale at admission. The ORs for O2 need were 0.38 (0.24–0.61), 0.50 (0.30–0.83) and 0.57 (0.34–0.96) in patients vaccinated 14–120, 121–180 and > 180 days prior to hospitalization, respectively. An anti-spike Ig titer higher than 5000 U/ml was associated with a reduced risk of O2 need (OR 0.52; 95 % CI 0.30–0.92). This study shows that COVID-19 vaccination has a significant impact on COVID-19 outcomes in hospitalized patients.

Recent studies suggest that COVID-19 survivors may experience long-term health consequences: in particular, neurological and mental health symptoms might be associated with long-term negative outcomes. This study is a secondary analysis of a larger cohort study and aims to determine the extent to which neurological and mental health sequelae are associated with survivors’ disability. Participants include COVID-19 survivors, with no pre-morbid brain conditions, who were discharged from the COVID-19 Unit of the ASST Spedali Civili Hospital between February and April 2020. At an average of 3.5 months after discharge, they were submitted to a neurological examination and completed the WHO Disability Assessment Schedule (WHODAS-12), the Hospital Anxiety and Depression Score, the Pittsburgh Sleep Quality Index and the Montreal Cognitive Assessment. Multivariable regression analysis was carried out to analyze variables that explain WHODAS-12 variation. In total, 83 patients (63 males, average age 66.9, 95% CI: 64.2–69.7) were enrolled; average WHODAS-12 was 13.2 (95% CI: 9.7–16.6). Cognitive dysfunction, anxiety, fatigue, and hyposmia/hypogeusia explained 28.8% of WHODAS-12 variation. These findings underline the importance and need for longitudinal follow-up assessments after recovery from COVID-19 and suggest the need for early rehabilitation of residual symptoms to enhance patients’ functioning.