Background Neurological and psychiatric sequelae of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis. Methods For this retrospective cohort study and time-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism. Findings Among 236 379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33·62% (95% CI 33·17–34·07), with 12·84% (12·36–13·33) receiving their first such diagnosis. For patients who had been admitted to an ITU, the estimated incidence of a diagnosis was 46·42% (44·78–48·09) and for a first diagnosis was 25·79% (23·50–28·25). Regarding individual diagnoses of the study outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50–0·63) for intracranial haemorrhage, 2·10% (1·97–2·23) for ischaemic stroke, 0·11% (0·08–0·14) for parkinsonism, 0·67% (0·59–0·75) for dementia, 17·39% (17·04–17·74) for anxiety disorder, and 1·40% (1·30–1·51) for psycho...

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A posthoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5•9 months (IQR 4•9-6•5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity.Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments w...

Apathy is a debilitating syndrome associated with many neurological disorders, including several common neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, and focal lesion syndromes such as stroke. Here, we review neuroimaging studies to identify anatomical correlates of apathy, across brain disorders. Our analysis reveals that apathy is strongly associated with disruption particularly of dorsal anterior cingulate cortex (dACC), ventral striatum (VS) and connected brain regions. Remarkably, these changes are consistent across clinical disorders and imaging modalities.Review of the neuroimaging findings allows us to develop a neurocognitive framework to consider potential mechanisms underlying apathy. According to this perspective, an interconnected group of brain regions – with dACC and VS at its core – plays a crucial role in normal motivated behaviour. Specifically we argue that motivated behaviour requires a willingness to work, to keep working, and to learn what is worth working for. We propose that deficits in any one or more of these processes can lead to the clinical syndrome of apathy, and outline specific approaches to test this hypothesis. A richer neurobiological understanding of the mechanisms underlying apathy should ultimately facilitate development of effective therapies for this disabling condition.

The new diagnostic criteria for apathy provide a clinical and scientific framework to increase the validity of apathy as a clinical construct. This should also help to pave the path for apathy in brain disorders to be an interventional target.

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When rewards are available, people expend more energy, increasing their motivational vigor. In theory, incentives might drive behavior for two distinct reasons: First, they increase expected reward; second, they increase the difference in subjective value between successful and unsuccessful performance, which increases contingency—the degree to which action determines outcome. Previous studies of motivational vigor have never compared these directly. Here, we indexed motivational vigor by measuring the speed of eye movements toward a target after participants heard a cue indicating how outcomes would be determined. Eye movements were faster when the cue indicated that monetary rewards would be contingent on performance than when the cue indicated that rewards would be random. But even when the cue indicated that a reward was guaranteed regardless of speed, movement was still faster than when no reward was available. Motivation by contingent and certain rewards was uncorrelated across individuals, which suggests that there are two separable, independent components of motivation. Contingent motivation generated autonomic arousal, and unlike noncontingent motivation, was effective with penalties as well as rewards.

Background There are concerns about a link between the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines against COVID-19 and cerebral venous thrombosis (CVT) and other thrombotic events. One key missing component of the risk-benefit analysis of using such vaccines is the risk of these severe thrombotic events following COVID-19. Methods Using a retrospective cohort study based on electronic health records primarily in the USA, the absolute risks of CVT and portal vein thrombosis (PVT) in the two weeks following a diagnosis of COVID-19 (made between January 20, 2020 and March 25, 2021) were calculated. The risks were compared to cohorts of patients with influenza (diagnosed within the same period) and people receiving an mRNA vaccine (i.e. not the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines) against COVID-19 (matched for demographics and the main risk factors for CVT and PVT). Findings A total of 537,913 patients with a COVID-19 diagnosis were included. The incidence of CVT in the two weeks after a COVID-19 diagnosis was 42.8 per million people (95% CI 28.5–64.2). This was significantly higher than in a matched cohort of people who received an mRNA vaccine (RR = 6.33, 95% CI 1.87–21.40, P = 0.00014) and patients with influenza (RR = 2.67, 95% CI 1.04–6.81, P = 0.031). The incidence of PVT after COVID-19 diagnosis was 392.3 per million people (95% CI 342.8–448.9). This was significantly higher than in a matched cohort of people who received an mRNA vaccine (RR=4.46, 95% CI 3.12–6.37, P < 0.0001) and patients with influenza (RR=1.43, 95% CI 1.10–1.88, P = 0.0094).