ImportanceSome individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).ObjectiveTo estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.Design, Setting, and ParticipantsBayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.ExposuresSymptomatic SARS-CoV-2 infection.Main Outcomes and MeasuresProportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.ResultsA total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.Conclusions and RelevanceThis study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

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Purpose of Review Over the last years, the focus of clinical and animal research in subarachnoid hemorrhage (SAH) shifted towards the early phase after the bleeding based on the association of the early injury pattern (first 72 h) with secondary complications and poor outcome. This phase is commonly referenced as early brain injury (EBI). In this clinical review, we intended to overview commonly used definitions of EBI, underlying mechanisms, and potential treatment implications. Recent Findings We found a large heterogeneity in the definition used for EBI comprising clinical symptoms, neuroimaging parameters, and advanced neuromonitoring techniques. Although specific treatments are currently not available, therapeutic interventions are aimed at ameliorating EBI by improving the energy/supply mismatch in the early phase after SAH. Summary Future research integrating brain-derived biomarkers is warranted to improve our pathophysiologic understanding of EBI in order to ameliorate early injury patterns and improve patients’ outcomes.

ObjectiveTo review the published literature on the clinical application of cerebral microdialysis (CMD) in aneurysmal subarachnoid hemorrhage (SAH) patients and to summarize the evidence relating cerebral metabolism to pathophysiology, secondary brain injury, and outcome.MethodsStudy selection: Two reviewers identified all manuscripts reporting on the clinical use of CMD in aneurysmal SAH patients from MEDLINE. All identified studies were grouped according to their focus on brain metabolic changes during the early and subacute phase after SAH, their association with mechanisms of secondary brain injury and outcome.ResultsThe review demonstrated: (1) limited literature is available in the very early phase before the aneurysm is secured. (2) Brain metabolic changes related to early and delayed secondary injury mechanisms may be used in addition to other neuromonitoring parameters in the critical care management of SAH patients. (3) CMD markers of ischemia may detect delayed cerebral ischemia early (up to 16 h before onset), underlining the importance of trend analysis. (4) Various CMD-derived parameters may be associated with patient outcome at 3–12 months, including CMD-lactate-to-pyruvate-ratio, CMD-glucose, and CMD-glutamate.ConclusionThe clinical use of CMD is an emerging area in the literature of aneurysmal SAH patients. Larger prospective multi-center studies on interventions based on CMD findings are needed.

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.

Purpose of review Delayed cerebral ischaemia (DCI) complicates the clinical course of patients with subarachnoid haemorrhage (SAH) in 20--30% and substantially worsens outcome. In this review, we describe a multimodal diagnostic approach based on underlying mechanisms of DCI and provide treatment options with a special focus on the most recently published literature. Recent findings Symptomatic vasospasm refers to clinical deterioration in the presence of vasospasm whereas DCI constitutes multiple causes. Pathophysiologic mechanisms underlying DCI range beyond large vessel vasospasm from neuroinflammation, to microthromboembolism, impaired cerebral autoregulation, cortical spreading depolarizations and many others. The current definition of DCI can be challenged by these mechanisms. We propose a pragmatic approach using a combination of clinical examination, cerebral ultrasonography, neuroimaging modalities and multimodal neuromonitoring to trigger therapeutic interventions in the presence of DCI. In addition to prophylactic nimodipine and management principles to improve oxygen delivery and decrease the brain metabolic demand, other specific interventions include permissive hypertension, intra-arterial application of calcium channel blockers and in selected patients angioplasty. Summary The complex pathophysiology underlying DCI urges for a multimodal diagnostic approach triggering targeted interventions. Novel treatment concepts still have to be proven in large trials.

BACKGROUND Long COVID, defined as presence of COVID-19 symptoms 28 days or more after clinical onset, is an emerging challenge to healthcare systems. The objective of this study was to explore recovery phenotypes in non-hospitalized COVID-19 individuals. METHODS A dual cohort, online survey study was conducted between September 2020 and July 2021 in the neighboring European regions Tyrol (TY, Austria, n = 1157) and South Tyrol (STY, Italy, n = 893). Data on demographics, comorbidities, COVID-19 symptoms and recovery adult outpatients were collected. Phenotypes of acute COVID-19, post-acute sequelae and risk of protracted recovery were explored by semi-supervised clustering and multi-parameter LASSO modeling. RESULTS Working age subjects (TY: 43 yrs (IQR: 31 – 53), STY: 45 yrs (IQR: 35 – 55)) and females (TY: 65.1%, STY: 68.3%) predominated the study cohorts. Nearly half of the participants (TY: 47.6%, STY: 49.3%) reported symptom persistence beyond 28 days. Two acute COVID-19 phenotypes were discerned: the non-specific infection phenotype and the multi-organ phenotype (MOP). Acute MOP symptoms encompassing multiple neurological, cardiopulmonary, gastrointestinal and dermatological complaints were linked to elevated risk of protracted recovery. The major subset of long COVID individuals (TY: 49.3%, STY: 55.6%) displayed no persistent hyposmia or hypogeusia but high counts of post-acute MOP symptoms and poor self-reported physical recovery. CONCLUSION The results of our two-cohort analysis delineated phenotypic diversity of acute and post-acute COVID-19 manifestations in home-isolated patients which needs to be considered for predicting protracted convalescence and allocation of medical resources.

High initial pressure reactivity index, presumably reflecting early brain injury, but not oxygen reactivity index, was associated with delayed cerebral ischemia and worse clinical outcome in poor-grade subarachnoid hemorrhage patients. Our data indicate that autoregulation indices should be interpreted cautiously when used in these patients and that timing is crucial when autoregulation indices are evaluated as predictor for delayed cerebral ischemia and outcome.