Sleep spindles changes in people with previous COVID-19 infection.

Stage 2 sleep spindles are considered useful biomarkers for the integrity of the central nervous system and for cognitive and memory skills. We investigated sleep spindles patterns in subjects after 12 months of their hospitalization in the intensive care unit (ICU) of the Padova Teaching Hospital due to COVID-19 between March and November 2020. Before the nap, participants (13 hospitalized in ICU - ICU; 9 hospitalized who received noninvasive ventilation - nonlCU; 9 age and sex-matched healthy controls - CTRL, i.e., not infected by COVID-19) underwent a cognitive and psychological as-sessment. During the nap, high-density electroencephalography (EEG) recordings were acquired. Slow (i.e., [9]-[12] Hz) and fast (i.e.,]12-16] Hz) spindles were automatically detected. Spindle density and spindle source reconstruction in brain grey matter were extracted. The psychological assessment revealed a statistical difference comparing CTRL and nonlCU in Beck Depression Inventory score and in the Physical Quality of Life index (pvalue = 0.03). The cognitive assessment revealed a trend of worsening results in executive functions in COVID-19 survivors. Slow spindle density significantly decreased comparing CTRL to COVID-19 survivors (pvalue= 0.001). There were statistically significant differences in EEG source-waveforms fast spindle amplitude onset among the three groups, mainly between CTRL and nonlCU. Clinical Relevance- Our results suggest that nonlCU were more susceptible to the hospitalization experience than ICU participants with a slight effect on cognitive tests. This impacted the spindle generation revealing a decreased density of slow spindles and affecting the generators of fast spindles in COVID-19 survivors especially in nonlCU.

Time-series analysis of multidimensional clinical-laboratory data by dynamic Bayesian networks reveals trajectories of COVID-19 outcomes.

BACKGROUND AND OBJECTIVE: COVID-19 severity spans an entire clinical spectrum from asymptomatic to fatal. Most patients who require in-hospital care are admitted to non-intensive wards, but their clinical conditions can deteriorate suddenly and some eventually die. Clinical data from patients' case series have identified pre-hospital and in-hospital risk factors for adverse COVID-19 outcomes. However, most prior studies used static variables or dynamic changes of a few selected variables of interest. In this study, we aimed at integrating the analysis of time-varying multidimensional clinical-laboratory data to describe the pathways leading to COVID-19 outcomes among patients initially hospitalised in a non-intensive care setting. METHODS: We collected the longitudinal retrospective data of 394 patients admitted to non-intensive care units at the University Hospital of Padova (Padova, Italy) due to COVID-19. We trained a dynamic Bayesian network (DBN) to encode the conditional probability relationships over time between death and all available demographics, pre-existing conditions, and clinical laboratory variables. We applied resampling, dynamic time warping, and prototyping to describe the typical trajectories of patients who died vs. those who survived. RESULTS: The DBN revealed that the trajectory linking demographics and pre-existing clinical conditions to death passed directly through kidney dysfunction or, more indirectly, through cardiac damage. As expected, admittance to the intensive care unit was linked to markers of respiratory function. Notably, death was linked to elevation in procalcitonin and D-dimer levels. Death was associated with persistently high levels of procalcitonin from admission and throughout the hospital stay, likely reflecting bacterial superinfection. A sudden raise in D-dimer levels 3-6 days after admission was also associated with subsequent death, possibly reflecting a worsening thrombotic microangiopathy. CONCLUSIONS: This innovative application of DBNs and prototyping to integrated data analysis enables visualising the patient's trajectories to COVID-19 outcomes and may instruct timely and appropriate clinical decisions.

High-density EEG sleep correlates of cognitive and affective impairment at 12-month follow-up after COVID-19.

OBJECTIVE: To disentangle the pathophysiology of cognitive/affective impairment in Coronavirus Disease-2019 (COVID-19), we studied long-term cognitive and affective sequelae and sleep high-density electroencephalography (EEG) at 12-month follow-up in people with a previous hospital admission for acute COVID-19. METHODS: People discharged from an intensive care unit (ICU) and a sub-intensive ward (nonICU) between March and May 2020 were contacted between March and June 2021. Participants underwent cognitive, psychological, and sleep assessment. High-density EEG recording was acquired during a nap. Slow and fast spindles density/amplitude/frequency and source reconstruction in brain gray matter were extracted. The relationship between psychological and cognitive findings was explored with Pearson correlation. RESULTS: We enrolled 33 participants ( 17 nonICU) and 12 controls. We observed a lower Physical Quality of Life index, higher post-traumatic stress disorder (PTSD) score, and a worse executive function performance in nonICU participants. Higher PTSD and Beck Depression Inventory scores correlated with lower executive performance. The same group showed a reorganization of spindle cortical generators. CONCLUSIONS: Our results show executive and psycho-affective deficits and spindle alterations in COVID-19 survivors - especially in nonICU participants - after 12 months from discharge. SIGNIFICANCE: These findings may be suggestive of a crucial contribution of stress experienced during hospital admission on long-term cognitive functioning.

Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study.

Because other coronaviruses enter the cells by binding to dipeptidyl-peptidase-4 (DPP-4), it has been speculated that DPP-4 inhibitors (DPP-4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP-4is among patients with type 2 diabetes (T2D) hospitalized for COVID-19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP-4is among matched patients with T2D in the same region. Of 403 hospitalized COVID-19 patients, 85 had T2D. The rate of exposure to DPP-4is was similar between T2D patients with COVID-19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID-19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID-19 who were on DPP-4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP-4is might affect hospitalization for COVID-19.