Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

To determine the preventive and therapeutic effect of dexmedetomidine on intensive care unit (ICU) delirium. The literature search using PubMed and the Cochrane Central Register of Controlled Trials was performed (August 1, 2018) to detect all randomized controlled trials (RCTs) of adult ICU patients receiving dexmedetomidine. Articles were included if they assessed the influence of dexmedetomidine compared to a sedative agent on incidence of ICU delirium or treatment of this syndrome. Accordingly, relevant articles were allocated to the following two groups: (1) articles that assessed the delirium incidence (incidence comparison) or articles that assessed the treatment of delirium (treatment comparison). Incidence of delirium and delirium resolution were the primary outcomes. We combined treatment effects comparing dexmedetomidine versus (1) placebo, (2) standard sedatives, and (3) opioids in random-effects meta-analyses. Risk of bias for each included RCT was assessed following Cochrane standards. The literature search resulted in 28 articles (25 articles/4975 patients for the incidence comparison and three articles/166 patients for the treatment comparison). In the incidence comparison, heterogeneity was present in different subgroups. Administration of dexmedetomidine was associated with significantly lower overall incidence of delirium when compared to placebo (RR 0.52; 95% CI 0.39–0.70; I2 = 37%), standard sedatives (RR 0.63; 95% CI 0.46–0.86; I2 = 69%), as well as to opioids (RR 0.61; 95% CI 0.44–0.83; I2 = 0%). Use of dexmedetomidine significantly increased the risks of bradycardia and hypotension. Limited data were available on circulatory insufficiency and mortality. In the treatment comparison, the comparison drugs in the three RCTs were placebo, midazolam, and haloperidol. The resolution of delirium was measured differently in each study. Two out of the three studies indicated clear favorable effects for dexmedetomidine (i.e., compared to placebo and midazolam). The study comparing dexmedetomidine with haloperidol was a pilot study (n = 20) with high variability in the results. Findings suggest that dexmedetomidine reduces incidence and duration of ICU delirium. Furthermore, our systematic searches show that there is limited evidence if a delirium shall be treated with dexmedetomidine.

Delirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment. The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100β were measured to investigate their dynamics in delirious and non-delirious patients after surgery. The Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial. Perioperative care. 182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia. Pre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo. Assessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay. None of the three study arms - haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100β levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups. The study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100β trajectories in patients with cognitive deterioration suggest affection of glial cells in particular. ClinicalTrials.govNCT02433041; registered on April 7, 2015.

Purpose: Screening for dysphagia at the intensive care unit (ICU) soon after extubation can prevent aspiration, pneumonia, lower mortality, and shorten re-feeding interval. This study aimed to modify the Gugging Swallowing Screen (GUSS), which was developed for acute stroke patients, and to validate it for extubated patients in the ICU. Methods: In this prospective study, forty-five patients who had been intubated for at least 24 h were recruited consecutively at the earliest 24 h after extubation. The modified GUSS-ICU was performed twice by two speech and language therapists independently. Concurrently, gold standard the flexible endoscopic evaluation of swallowing (FEES) was performed by an otorhinolaryngologist. Measurements were conducted within a three-hour period; all testers were blinded to each other’s results. Results: According to FEES, 36 of 45 (80%) participants were diagnosed with dysphagia; 13 of those were severe, 12 moderate, and 11 mild. Compared to FEES, the GUSS-ICU predicted dysphagia well (area under the curve for the initial rater pair: 0.923, 95% CI 0.832–1.000 and 0.923, 95% CI 0.836 -1.000 for the second rater pair). The sensitivity was 91.7% (95% CI 77.5–98.3%) and 94.4% (95% CI 81.3–99.3%); the specificity was 88.9% (51.8–99.7%) and 66.7% (29.9–92.5%); the positive predictive values were 97.1% (83.8–99.5%) and 91.9% (81.7–96.6%), and the negative predictive values were 72.7% (46.8–89%) and 75% (41.9–92.6%) for the first and second rater pairs, respectively. Dysphagia severity classification according to FEES and GUSS-ICU correlated strongly (Spearman’s rho: 0.61 for rater 1 and 0.60 for rater 2, p < 0.001). Agreement by all testers was good (Krippendorffs Alpha: 0.73). The interrater reliability showed good agreement (Cohen`s Kappa: 0.84, p < 0.001). Conclusion: The GUSS-ICU is a simple, reliable, and valid multi-consistency bedside swallowing screen to identify post-extubation dysphagia at the ICU. Trial registration: ClinicalTrials.gov Identifier: NCT04532398,31/08/2020.

Delirium after surgery and in the intensive care unit (ICU) remains a challenge for patients, families, and caregivers. Over the years, many promising biomarkers have been investigated as potential instruments for risk stratification of delirium. This review aimed to identify and assess the clinical usefulness of candidate serum biomarkers associated with hospital delirium in patients aged 60 years and older. We performed a time-unlimited review of publications indexed in PubMed, Cochrane, Embase, and MEDLINE databases until June 2019 that evaluated baseline and/or longitudinal biomarker measurements in patients suffering from delirium at some point during their hospital stay. A total of 32 studies were included in this review reporting information on 7610 patients. Of these 32 studies, twenty-four studies reported data from surgical patients including four studies in ICU cohorts, five studies reported data from medical patients (1026 patients), and three studies reported data from a mixed cohort (1086 patients), including one study in an ICU cohort. Findings confirm restricted clinical usefulness to predict or diagnose delirium due to limited evidence on which biomarkers can be used and limited availability due to non-routine use.