Body Composition and Physical Performance 1 Year After COVID-19.

OBJECTIVE: Long-term consequences after COVID-19 include physical complaints, which may impair physical recovery and quality of life. DESIGN: We assessed body composition and physical ability in patients 12 months after COVID-19. Consecutively recruited patients recovering from mild to severe COVID-19 were assessed using bioelectrical impedance analysis, 6-min-walk test, additional scales for physical performance and health-related quality of life. RESULTS: Overall physical recovery was good (i.e., Glasgow Outcome Scale-Extended ≥7 in 96%, Modified Rankin Scale ≤1 in 87%, Eastern Cooperative Oncology Group ≤1 in 99%). Forty-four percent of the 69 patients experienced a significant body mass index increase in the year after COVID-19 (≥1 kg/m 2 ), whereas skeletal muscle mass index was reduced in only 12%. Patients requiring intensive care treatment ( n = 15, 22%) during acute COVID-19 more often had a body mass index increase ( P = 0.002), worse 6-min-walk test-performance ( P = 0.044), and higher body fat mass ( P = 0.030) at the 1-yr follow-up when compared with patients with mild ( n = 22, 32%) and moderate ( n = 32, 46%) acute COVID-19. Body mass index increase was also more frequent in patients who had no professional rehabilitation ( P = 0.014). CONCLUSIONS: Although patients with severe COVID-19 had increased body mass index and body fat and performed worse in physical outcome measures 1 yr after COVID-19, overall physical recovery was satisfying. Translating these findings to variants beyond the Alpha strain of severe acute respiratory syndrome coronavirus 2 virus needs further studies.

Cognitive, Mental Health, Functional, and Quality of Life Outcomes 1 Year After Spontaneous Subarachnoid Hemorrhage: A Prospective Observational Study.

BACKGROUND: Patients with spontaneous subarachnoid hemorrhage (SAH) frequently encounter cognitive dysfunction and mental health issues with negative effects on health-related quality of life (HR-QoL). Here, we aimed to describe the prevalence of cognitive deficits, mental health problems, and HR-QoL impairments 1 year after SAH. METHODS: In this prospective observational study, 177 patients with SAH admitted to our neurointensive care unit over a time span of ten years followed the invitation for an in-person 1-year follow-up, including a standardized neuropsychological test battery. Mental health issues (anxiety and depression) and HR-QoL were evaluated using questionnaires (Hospital Anxiety and Depression Scale; 36-item Short Form questionnaire). Functional outcome was assessed with the modified Rankin Scale (mRS) score. RESULTS: Patients were 54 years of age (interquartile range 47-62 years) and presented with a median Hunt and Hess score of 2 (interquartile range 1-3) at admission. Most patients (93%) achieved good functional 1-year outcomes (mRS score 0-2). Seventy-one percent of patients had deficits in at least one cognitive domain, with memory deficits being the most prevalent (51%), followed by deficits in executive functions (36%), visuoconstruction (34%), and attention (21%). Even patients with perimesencephalic SAH (18%) or with full functional recovery (mRS score = 0, 46%) had a comparable prevalence of cognitive deficits (61% and 60%, respectively). Symptoms of depression and anxiety were reported by 16% and 33% of patients, respectively. HR-QoL was impaired in 37% (55 of 147). Patients with cognitive deficits (p = 0.001) or mental health issues (p < 0.001) more frequently reported impaired HR-QoL. CONCLUSIONS: Most patients with SAH have cognitive deficits and mental health issues 1 year after SAH. These deficits impair patients' quality of life.

Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae.

PURPOSE: Olfactory dysfunction (OD) commonly accompanies coronavirus disease 2019 (COVID-19). We investigated the kinetics of OD resolution following SARS-CoV-2 infection (wild-type and alpha variant) and its impact on quality of life, physical and mental health. METHODS: OD prevalence was assessed in an ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and an observational cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up). Co-occurrence of OD with other symptoms and effects on quality of life, physical and mental health were analyzed by multi-dimensional scaling, association rule mining and semi-supervised clustering. RESULTS: Both in the ambulatory COVID-19 survey study (72%) and the observational ambulatory and hospitalized cohort (41%) self-reported OD was frequent during acute COVID-19. Recovery from self-reported OD was slow (survey: median 28 days, observational cohort: 90 days). By clustering of the survey data, we identified a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorders (median recovery: 90 days) but low frequency of post-acute fatigue, respiratory or neurocognitive symptoms. This smell and taste disorder cluster was characterized by a high rating of physical performance, mental health, and quality of life as compared with convalescents affected by prolonged fatigue or neurocognitive complaints. CONCLUSION: Our results underline the heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype is characterized by good clinical, physical, and mental recovery and may pose a minor challenge for public health. STUDY REGISTRATION: ClinicalTrials.gov: NCT04661462 (survey study), NCT04416100 (observational cohort).

Blood Pressure Changes in Association with Nimodipine Therapy in Patients with Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: Nimodipine is recommended to prevent delayed cerebral ischemia in patients with spontaneous subarachnoid hemorrhage (SAH). Here, we studied hemodynamic side effects of different nimodipine formulations (per os [PO] and intravenous [IV]) in patients with SAH undergoing continuous blood pressure monitoring. METHODS: This observational cohort study includes consecutive patients with SAH (271 included in the IV group, 49 in the PO group) admitted to a tertiary care center between 2010 and 2021. All patients received prophylactic IV or PO nimodipine. Hemodynamic responses were evaluated based on median values within the first hour after continuous IV nimodipine initiation or PO nimodipine application (601 intakes within 15 days). Significant changes were defined as > 10% drop in systolic blood pressure (SBP) or diastolic blood pressure from baseline (median values 30 min before nimodipine application). With the use of multivariable logistic regression, risk factors associated with SBP drops were identified. RESULTS: Patients were admitted with a median Hunt & Hess score of 3 (2-5; IV 3 [2-5], PO 1 [1-2], p < 0.001) and were 58 (49-69) years of age. Initiation of IV nimodipine was associated with a > 10% SBP drop in 30% (81/271) of patients, with a maximum effect after 15 min. A start or increase in noradrenaline was necessary in 136/271 (50%) patients, and colloids were administered in 25/271 (9%) patients within 1 h after IV nimodipine initiation. SBP drops > 10% occurred after 53/601 (9%) PO nimodipine intakes, with a maximum effect after 30-45 min in 28/49 (57%) patients. Noradrenaline application was uncommon (3% before and 4% after nimodipine PO intake). Hypotensive episodes to an SBP < 90 mm Hg were not observed after IV or PO nimodipine application. In multivariable analysis, only a higher SBP at baseline was associated with a > 10% drop in SBP after IV (p < 0.001) or PO (p = 0.001) nimodipine application, after adjusting for the Hunt & Hess score on admission, age, sex, mechanical ventilation, days after intensive care unit admission, and delayed cerebral ischemia. CONCLUSIONS: Significant drops in SBP occur in one third of patients after the start of IV nimodipine and after every tenth PO intake. Early recognition and counteracting with vasopressors or fluids seems necessary to prevent hypotensive episodes.

The Loss of Temporal Muscle Volume is Associated with Poor Outcome in Patients with Subarachnoid Hemorrhage: An Observational Cohort Study.

BACKGROUND: Intensive care unit (ICU) acquired weakness is a major contributor to poor functional outcome of ICU patients. Quantification of temporal muscle volume assessed on routine computed tomography (CT) scans may serve as a biomarker for muscle wasting in patients suffering from acute brain injury. METHODS: This is a retrospective analysis of prospectively collected data. Temporal muscle volume was assessed on head CT scans of consecutive patients with spontaneous subarachnoid hemorrhage within prespecified time frames (on admission, then weekly ± 2 days). Whenever possible, temporal muscle volume was assessed bilaterally and averaged for the analysis. Poor functional outcome was defined as a 3-month modified Rankin Scale Score ≥ 3. Statistical analysis was performed using generalized estimating equations to handle repeated measurements within individuals. RESULTS: The analysis comprised 110 patients with a median Hunt & Hess score of 4 (interquartile range 3-5). Median age was 61 (50-70) years, 73 patients (66%) were women. Baseline temporal muscle volume was 18.5 ± 0.78 cm3 and significantly decreased over time (p < 0.001) by a mean of 7.9% per week. Higher disease severity (p = 0.002), hydrocephalus (p = 0.020), pneumonia (p = 0.032), and bloodstream infection (p = 0.015) were associated with more pronounced muscle volume loss. Patients with poor functional outcome had smaller muscle volumes 2 and 3 weeks after subarachnoid hemorrhage compared with those with good outcome (p = 0.025). The maximum muscle volume loss during ICU stay was greater in patients with poor functional outcome (- 32.2% ± 2.5% vs. - 22.7% ± 2.5%, p = 0.008). The hazard ratio for poor functional outcome was 1.027 (95% confidence interval 1.003-1.051) per percent of maximum muscle volume loss. CONCLUSIONS: Temporal muscle volume, which is easily assessable on routine head CT scans, progressively decreases during the ICU stay after spontaneous subarachnoid hemorrhage. Because of its association with disease severity and functional outcome, it may serve as a biomarker for muscle wasting and outcome prognostication.

Lower initial red blood cell count in cerebrospinal fluid predicts good functional outcome in patients with spontaneous subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: Red blood cell (RBC) degradation after subarachnoid haemorrhage (SAH) negatively affects functional outcome. Although the detection of RBCs in the cerebrospinal fluid (CSF) is a widely available part of neurological routine diagnostics, the prognostic value as a biomarker remains unclear. This study was undertaken to investigate whether CSF RBC count correlates with established radiological markers of SAH volume and whether the CSF RBC count can predict functional outcome in SAH patients. METHODS: A total of 121 consecutive spontaneous SAH patients were retrospectively analyzed. CSF was collected from external ventricular drain as part of routine diagnostic procedures. We used multivariable binary logistic regression to investigate associations between CSF RBC counts and functional outcome 3 months after SAH or hospital survival. Good functional outcome was defined as modified Rankin Scale ≤ 2. RESULTS: Patients' age was 60 ± 14 years, and the median admission Hunt & Hess grade (H&H) was 4. CSF samples were collected 2 days after intensive care unit admission. High CSF RBC counts positively correlated with radiological measurements for SAH volume, for example, modified Fisher score (p = 0.002) and Hijdra ventricle score (p = 0.016). Multivariable regression analysis adjusted for age, H&H grade, modified Fisher and Hijdra scores showed that low CSF RBC counts predicted hospital survival (per 100,000 CSF RBCs: adjusted odds ratio [adjOR] = 0.74, 95% confidence interval [CI] = 0.61-0.89, p = 0.001) and good functional outcome after 3 months (per 100,000 CSF RBC: adjOR = 0.76, 95% CI = 0.60-0.96, p = 0.020). CONCLUSIONS: CSF RBC counts correlate with radiographic scores quantifying SAH volume and may serve as an early independent biomarker for hospital survival and good functional 3-month outcome in patients requiring ventriculostomy after SAH.

Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage.

Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcomes in poor-grade subarachnoid haemorrhage patients. We recruited 55 consecutive non-traumatic subarachnoid haemorrhage patients who underwent multimodal neuromonitoring, including cerebral microdialysis. Mitochondrial dysfunction was defined as lactate-to-pyruvate ratio >30 together with pyruvate >70 mmol/L and metabolic distress as lactate-to-pyruvate ratio >40. The multidimensional 12-month outcome was assessed by means of the modified Rankin scale (poor outcome: modified Rankin scale ≥4) and a standardized neuropsychological test battery. We used multivariable generalized estimating equation models to assess associations between total microdialysate-tau levels of the first 10 days after admission and hospital complications and outcomes. Patients were 56 ± 12 years old and presented with a median Hunt & Hess score of 5 (interquartile range: 3-5). Overall mean total microdialysate-tau concentrations were highest within the first 24 h (5585 ± 6291 pg/mL), decreased to a minimum of 2347 ± 4175 pg/mL on Day 4 (P < 0.001) and remained stable thereafter (P = 0.613). Higher total microdialysate-tau levels were associated with the occurrence of delayed cerebral ischaemia (P = 0.001), episodes of metabolic distress (P = 0.002) and mitochondrial dysfunction (P = 0.034). Patients with higher tau levels had higher odds for a poor 12-month functional outcome (adjusted odds ratio: 2.61; 95% confidence interval: 1.32-5.17; P = 0.006) and impaired results in the trail making test-B (adjusted odds ratio: 3.35; 95% confidence interval: 1.16-9.68; P = 0.026) indicative of cognitive flexibility. Total microdialysate-tau levels significantly decreased over the first 10 days (P < 0.05) in patients without delayed cerebral ischaemia or good functional outcomes and remained high in those with delayed cerebral ischaemia and poor 12-month outcomes, respectively. Dynamic changes of total tau in the cerebral microdialysate may be a useful biomarker for axonal damage associated with functional and neurocognitive recovery in poor-grade subarachnoid haemorrhage patients. In contrast, ongoing axonal damage beyond Day 3 after bleeding indicates a higher risk for delayed cerebral ischaemia as well as a poor functional outcome.

Cognitive dysfunction 1 year after COVID-19: evidence from eye tracking.

Increasing evidence suggests persistent cognitive dysfunction after COVID-19. In this cross-sectional study, frontal lobe function was assessed 12 months after the acute phase of the disease, using tailored eye tracking assessments. Individuals who recovered from COVID-19 made significantly more errors in all eye tracking tasks compared to age/sex-matched healthy controls. Furthermore, patients who were treated as inpatients performed worse compared to outpatients and controls. Our results show impaired inhibitory cortical control in individuals who recovered from COVID-19. The association between disease severity and its sequelae may contribute to a better understanding of post-COVID-19 cognitive function.

Neurological outcomes 1 year after COVID-19 diagnosis: A prospective longitudinal cohort study.

BACKGROUND AND PURPOSE: Neurological sequelae from coronavirus disease 2019 (COVID-19) may persist after recovery from acute infection. Here, the aim was to describe the natural history of neurological manifestations over 1 year after COVID-19. METHODS: A prospective, multicentre, longitudinal cohort study in COVID-19 survivors was performed. At a 3-month and 1-year follow-up, patients were assessed for neurological impairments by a neurological examination and a standardized test battery including the assessment of hyposmia (16-item Sniffin' Sticks test), cognitive deficits (Montreal Cognitive Assessment < 26) and mental health (Hospital Anxiety and Depression Scale and Post-traumatic Stress Disorder Checklist 5). RESULTS: Eighty-one patients were evaluated 1 year after COVID-19, out of which 76 (94%) patients completed a 3-month and 1-year follow-up. Patients were 54 (47-64) years old and 59% were male. New and persistent neurological disorders were found in 15% (3 months) and 12% (10/81; 1 year). Symptoms at 1-year follow-up were reported by 48/81 (59%) patients, including fatigue (38%), concentration difficulties (25%), forgetfulness (25%), sleep disturbances (22%), myalgia (17%), limb weakness (17%), headache (16%), impaired sensation (16%) and hyposmia (15%). Neurological examination revealed findings in 52/81 (64%) patients without improvement over time (3 months, 61%, p = 0.230) including objective hyposmia (Sniffin' Sticks test <13; 51%). Cognitive deficits were apparent in 18%, whereas signs of depression, anxiety and post-traumatic stress disorders were found in 6%, 29% and 10% respectively 1 year after infection. These mental and cognitive disorders had not improved after the 3-month follow-up (all p > 0.05). CONCLUSION: Our data indicate that a significant patient number still suffer from neurological sequelae including neuropsychiatric symptoms 1 year after COVID-19 calling for interdisciplinary management of these patients.

The effect of the volemic and cardiac status on brain oxygenation in patients with subarachnoid hemorrhage: a bi-center cohort study.

BACKGROUND: Fluid management in patients after subarachnoid hemorrhage (SAH) aims at the optimization of cerebral blood flow and brain oxygenation. In this study, we investigated the effects of hemodynamic management on brain oxygenation by integrating advanced hemodynamic and invasive neuromonitoring. METHODS: This observational cohort bi-center study included data of consecutive poor-grade SAH patients who underwent pulse contour cardiac output (PiCCO) monitoring and invasive neuromonitoring. Fluid management was guided by the transpulmonary thermodilution system and aimed at euvolemia (cardiac index, CI ≥ 3.0 L/min/m2; global end-diastolic index, GEDI 680-800 mL/m2; stroke volume variation, SVV < 10%). Patients were managed using a brain tissue oxygenation (PbtO2) targeted protocol to prevent brain tissue hypoxia (BTH, PbtO2 < 20 mmHg). To assess the association between CI and PbtO2 and the effect of fluid challenges on CI and PbtO2, we used generalized estimating equations to account for repeated measurements. RESULTS: Among a total of 60 included patients (median age 56 [IQRs 47-65] years), BTH occurred in 23% of  the monitoring time during the first 10 days since admission. Overall, mean CI was within normal ranges (ranging from 3.1 ± 1.3 on day 0 to 4.1 ± 1.1 L/min/m2 on day 4). Higher CI levels were associated with higher PbtO2 levels (Wald = 14.2; p < 0.001). Neither daily fluid input nor fluid balance was associated with absolute PbtO2 levels (p = 0.94 and p = 0.85, respectively) or the occurrence of BTH (p = 0.68 and p = 0.71, respectively). PbtO2 levels were not significantly different in preload dependent patients compared to episodes of euvolemia. PbtO2 increased as a response to fluid boluses only if BTH was present at baseline (from 13 ± 6 to 16 ± 11 mmHg, OR = 13.3 [95% CI 2.6-67.4], p = 0.002), but not when all boluses were considered (p = 0.154). CONCLUSIONS: In this study a moderate association between increased cardiac output and brain oxygenation was observed. Fluid challenges may improve PbtO2 only in the presence of baseline BTH. Individualized hemodynamic management requires advanced cardiac and brain monitoring in critically ill SAH patients.