Risks of neurological and psychiatric sequelae 2 years after hospitalisation or intensive care admission with COVID-19 compared to admissions for other causes.

The association between COVID-19 and subsequent neurological and psychiatric disorders is well established. However, two important questions remain unanswered. First, what are the risks in those admitted to intensive care unit (ICU) with COVID-19? Admission to ICU is itself associated with neurological and psychiatric sequelae and it is not clear whether COVID-19 further increases those risks or changes their profile. Second, what are the trajectories of neurological and psychiatric risks in patients admitted to hospital or ICU with COVID-19, and when do the risks subside? We sought to answer these two questions using a retrospective cohort study based on electronic health records (EHR) data from the TriNetX Analytics Network (covering 89 million patients, mostly in the USA). Cohorts of patients admitted to hospital or ICU with COVID-19 were propensity score-matched (for 82 covariates capturing risk factors for COVID-19 and more severe COVID-19 illness) to patients admitted to hospital or ICU (respectively) for any other reason. Matched cohorts were followed for up to two years and the risk of 14 neurological and psychiatric outcomes were compared. A total of 280,173 patients admitted to hospital and 46,573 patients admitted to ICU with COVID-19 were successfully matched to an equal number of patients admitted to hospital or ICU for any other reason. Those hospitalised with COVID-19 were found to be at a greater risk of a range of neurological and psychiatric outcomes including seizure/epilepsy, encephalitis, myoneural junction/muscle disease, Guillain-Barré syndrome (GBS), dementia, cognitive deficits, psychotic disorder, mood and anxiety disorders, but not ischaemic stroke or intracranial haemorrhage. When risks were elevated after COVID-19, most remained so for the whole two years of follow-up (except for mood and anxiety disorders). Risk profiles and trajectories were substantially different among those admitted to ICU: compared to those admitted for any other reasons, those admitted with COVID-19 were at a greater risk of myoneural junction/muscle disease, GBS, cognitive deficits and anxiety disorder, but at a significantly lower risk of ischaemic stroke, intracranial haemorrhage, encephalitis, and mood disorder. When elevated, the risks in those admitted to ICU with COVID-19 were mostly short-lived. In summary, risks of neurological and psychiatric sequelae in patients hospitalised with COVID-19 are wide ranging and long standing whereas those in patients admitted to ICU with COVID-19 are similar to, or lower than, the risks observed post-ICU admission for any other cause. These contrasting risk trajectories are relevant for researchers, clinicians, patients, and policymakers.

Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study.

BACKGROUND: The relationship between COVID-19 and epilepsy is uncertain. We studied the potential association between COVID-19 and seizures or epilepsy in the six months after infection. METHODS: We applied validated methods to an electronic health records network (TriNetX Analytics) of 81 million people. We closely matched people with COVID-19 infections to those with influenza. In each cohort, we measured the incidence and hazard ratios (HRs) of seizures and of epilepsy. We stratified data by age and by whether the person was hospitalized during the acute infection. We then explored time-varying HRs to assess temporal patterns of seizure or epilepsy diagnoses. RESULTS: We analyzed 860,934 electronic health records. After matching, this yielded two cohorts each of 152,754 patients. COVID-19 was associated with an increased risk of seizures and epilepsy compared to influenza. The incidence of seizures within 6 months of COVID-19 was 0.81% (95% CI, 0.75-0.88; HR compared to influenza 1.55 (1.39-1.74)). The incidence of epilepsy was 0.30% (0.26-0.34; HR compared to influenza 1.87 (1.54-2.28)). The HR of epilepsy after COVID-19 compared to influenza was greater in people who had not been hospitalized and in individuals aged under 16 years. The time of peak HR after infection differed by age and hospitalization status. CONCLUSIONS: The incidence of new seizures or epilepsy diagnoses in the six months following COVID-19 was low overall, but higher than in matched patients with influenza. This difference was more marked in people who were not hospitalized, highlighting the risk of epilepsy and seizures even in those with less severe infection. Children appear at particular risk of seizures and epilepsy after COVID-19 providing another motivation to prevent COVID-19 infection in pediatric populations. That the varying time of peak risk related to hospitalization and age may provide clues as to the underlying mechanisms of COVID-associated seizures and epilepsy.

Neuropsychiatric disorders following SARS-CoV-2 infection.

Several large-scale electronic health records studies have reported increased diagnostic rates for neuropsychiatric disorders following Coronavirus disease 2019 [COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection)], but many questions remain. To highlight the issues, we selectively review this literature, focusing on mood disorder, anxiety disorder, psychotic disorder, and cognitive impairment ('brain fog'). Eight key questions are addressed, comprising: (i) the nature and magnitude of the risks; (ii) their association with severity of infection; (iii) their duration; (iv) whether the risks differ between adults and children, or between men and women; (v) whether prior vaccination protects against them; (vi) the risk profile associated with different SARS-CoV-2 strains; (vii) what the underlying mechanisms might be; and (viii) whether the sequelae can be predicted. We consider the major unknowns, the limitations of electronic health records for research in this area, and the use of additional approaches to help characterize and understand the neuropsychiatric burden of COVID-19.

Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study.

Post-COVID cognitive deficits (often referred to as 'brain fog') are common and have large impacts on patients' level of functioning. No specific intervention exists to mitigate this burden. This study tested the hypothesis, inspired by recent experimental research, that post-COVID cognitive deficits can be prevented by inhibiting receptor-interacting protein kinase. Using electronic health record data, we compared the cognitive outcomes of propensity score-matched cohorts of patients with epilepsy taking phenytoin (a commonly used receptor-interacting protein kinase inhibitor) versus valproate or levetiracetam at the time of COVID-19 diagnosis. Patients taking phenytoin at the time of COVID-19 were at a significantly lower risk of cognitive deficits in the 6 months after COVID-19 infection than a matched cohort of patients receiving levetiracetam (hazard ratio 0.78, 95% confidence interval 0.63-0.97, P = 0.024) or valproate (hazard ratio 0.73, 95% confidence interval 0.58-0.93, P = 0.011). In secondary analyses, results were robust when controlling for subtype of epilepsy, and showed specificity to cognitive deficits in that similar associations were not seen with other 'long-COVID' outcomes such as persistent breathlessness or pain. These findings provide pharmacoepidemiological support for the hypothesis that receptor-interacting protein kinase signaling is involved in post-COVID cognitive deficits. These results should prompt empirical investigations of receptor-interacting protein kinase inhibitors in the prevention of post-COVID cognitive deficits.

Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients.

BACKGROUND: COVID-19 is associated with increased risks of neurological and psychiatric sequelae in the weeks and months thereafter. How long these risks remain, whether they affect children and adults similarly, and whether SARS-CoV-2 variants differ in their risk profiles remains unclear. METHODS: In this analysis of 2-year retrospective cohort studies, we extracted data from the TriNetX electronic health records network, an international network of de-identified data from health-care records of approximately 89 million patients collected from hospital, primary care, and specialist providers (mostly from the USA, but also from Australia, the UK, Spain, Bulgaria, India, Malaysia, and Taiwan). A cohort of patients of any age with COVID-19 diagnosed between Jan 20, 2020, and April 13, 2022, was identified and propensity-score matched (1:1) to a contemporaneous cohort of patients with any other respiratory infection. Matching was done on the basis of demographic factors, risk factors for COVID-19 and severe COVID-19 illness, and vaccination status. Analyses were stratified by age group (age <18 years [children], 18-64 years [adults], and ≥65 years [older adults]) and date of diagnosis. We assessed the risks of 14 neurological and psychiatric diagnoses after SARS-CoV-2 infection and compared these risks with the matched comparator cohort. The 2-year risk trajectories were represented by time-varying hazard ratios (HRs) and summarised using the 6-month constant HRs (representing the risks in the earlier phase of follow-up, which have not yet been well characterised in children), the risk horizon for each outcome (ie, the time at which the HR returns to 1), and the time to equal incidence in the two cohorts. We also estimated how many people died after a neurological or psychiatric diagnosis during follow-up in each age group. Finally, we compared matched cohorts of patients diagnosed with COVID-19 directly before and after the emergence of the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529) variants. FINDINGS: We identified 1 487 712 patients with a recorded diagnosis of COVID-19 during the study period, of whom 1 284 437 (185 748 children, 856 588 adults, and 242 101 older adults; overall mean age 42·5 years [SD 21·9]; 741 806 [57·8%] were female and 542 192 [42·2%] were male) were adequately matched with an equal number of patients with another respiratory infection. The risk trajectories of outcomes after SARS-CoV-2 infection in the whole cohort differed substantially. While most outcomes had HRs significantly greater than 1 after 6 months (with the exception of encephalitis; Guillain-Barré syndrome; nerve, nerve root, and plexus disorder; and parkinsonism), their risk horizons and time to equal incidence varied greatly. Risks of the common psychiatric disorders returned to baseline after 1-2 months (mood disorders at 43 days, anxiety disorders at 58 days) and subsequently reached an equal overall incidence to the matched comparison group (mood disorders at 457 days, anxiety disorders at 417 days). By contrast, risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period. Post-COVID-19 risk trajectories differed in children compared with adults: in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02 [95% CI 0·94-1·10) or anxiety (1·00 [0·94-1·06]) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 [1·09-1·33] to 2·16 [1·46-3·19]). Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days). A sizeable proportion of older adults who received a neurological or psychiatric diagnosis, in either cohort, subsequently died, especially those diagnosed with dementia or epilepsy or seizures. Risk profiles were similar just before versus just after the emergence of the alpha variant (n=47 675 in each cohort). Just after (vs just before) the emergence of the delta variant (n=44 835 in each cohort), increased risks of ischaemic stroke, epilepsy or seizures, cognitive deficit, insomnia, and anxiety disorders were observed, compounded by an increased death rate. With omicron (n=39 845 in each cohort), there was a lower death rate than just before emergence of the variant, but the risks of neurological and psychiatric outcomes remained similar. INTERPRETATION: This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them. FUNDING: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, The Wolfson Foundation, and MQ Mental Health Research.

Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study

Post-COVID cognitive deficits (often referred to as ‘brain fog’) are common and have large impacts on patients’ level of functioning. No specific intervention exists to mitigate this burden. This study tested the hypothesis, inspired by recent experimental research, that post-COVID cognitive deficits can be prevented by inhibiting receptor-interacting protein kinase (RIPK). Using electronic health record data, we compared the cognitive outcomes of propensity score-matched cohorts of patients with epilepsy taking phenytoin (a commonly used RIPK inhibitor) vs. valproate or levetiracetam at the time of COVID-19 diagnosis. Patients taking phenytoin at the time of COVID-19 were at a significantly lower risk of cognitive deficits in the six months after COVID-19 infection than a matched cohort of patients receiving levetiracetam (hazard ratio 0.78, 95% CI 0.63-0.97, p = 0.024) or valproate (hazard ratio 0.73, 95% CI 0.58-0.93, p = 0.011). In secondary analyses, results were robust when controlling for subtype of epilepsy, and showed specificity to cognitive deficits in that similar associations were not seen with other ‘long-COVID’ outcomes such as persistent breathlessness or pain. These findings provide pharmacoepidemiological support for the hypothesis that RIPK signaling is involved in post-COVID cognitive deficits. These results should prompt empirical investigations of RIPK inhibitors in the prevention of post-COVID cognitive deficits. Graphical Graphical

Impact of the COVID-19 Pandemic on the Global Delivery of Mental Health Services and Telemental Health: Systematic Review.

BACKGROUND: The COVID-19 pandemic required mental health services around the world to adapt quickly to the new restrictions and regulations put in place to reduce the risk of transmission. As face-to-face contact became difficult, virtual methods were implemented to continue to safely provide mental health care. However, it is unclear to what extent service provision transitioned to telemental health worldwide. OBJECTIVE: We aimed to systematically review the global research literature on how mental health service provision adapted during the first year of the pandemic. METHODS: We searched systematically for quantitative papers focusing on the impact of the COVID-19 pandemic on mental health services published until April 13, 2021, in the PubMed, Embase, medRxiv, and bioXriv electronic bibliographic databases, using the COVID-19 Open Access Project online platform. The screening process and data extraction were independently completed by at least two authors, and any disagreement was resolved by discussion with a senior member of the team. The findings were summarized narratively in the context of each country's COVID-19 Stringency Index, which reflects the stringency of a government's response to COVID-19 restrictions at a specific time. RESULTS: Of the identified 24,339 records, 101 papers were included after the screening process. Reports on general services (n=72) showed that several countries' face-to-face services reduced their activities at the start of the pandemic, with reductions in the total number of delivered visits and with some services forced to close. In contrast, telemental health use rapidly increased in many countries across the world at the beginning of the pandemic (n=55), with almost complete virtualization of general and specialistic care services by the end of the first year. Considering the reported COVID-19 Stringency Index values, the increased use of virtual means seems to correspond to periods when the Stringency Index values were at their highest in several countries. However, due to specific care requirements, telemental health could not be used in certain subgroups of patients, such as those on clozapine or depot treatments and those who continued to need face-to-face visits. CONCLUSIONS: During the pandemic, mental health services had to adapt quickly in the short term, implementing or increasing the use of telemental health services across the globe. Limited access to digital means, poor digital skills, and patients' preferences and individual needs may have contributed to differences in implementing and accessing telemental health services during the pandemic. In the long term, a blended approach, combining in-person and virtual modalities, that takes into consideration the needs, preferences, and digital skills of patients may better support the future development of mental health services. It will be required to improve confidence with digital device use, training, and experience in all modalities for both clinicians and service users.

Six-month sequelae of post-vaccination SARS-CoV-2 infection: A retrospective cohort study of 10,024 breakthrough infections.

Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021, i.e. before the emergence of the Omicron variant). Associations with the number of vaccine doses (1 vs. 2) and age (<60 vs. ≥ 60 years-old) were assessed. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p < 0.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those <60 years-old, whereas no robust associations were observed in those ≥60 years-old. In summary, COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae.

Association between serum lithium level and incidence of COVID-19 infection.

An antiviral effect of lithium has been proposed, but never investigated for coronavirus disease 2019 (COVID-19). Using electronic health records of 26 554 patients with documented serum lithium levels during the pandemic, we show that the 6-month COVID-19 infection incidence was lower among matched patients with 'therapeutic' (0.50-1.00) versus 'subtherapeutic' (0.05-0.50) lithium levels (hazard ratio (HR) = 0.82, 95% CI 0.69-0.97, P = 0.017) and among patients with 'therapeutic' lithium levels versus matched patients using valproate (HR = 0.79, 95% CI 0.67-0.92, P = 0.0023). Lower rates of infection were observed for both new COVID-19 diagnoses and positive polymerase chain reaction tests, regardless of underlying psychiatric diagnosis and vaccination status.

Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19.

BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records

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-Barre 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 psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2.66% (2.24-3.16) for intracranial haemorrhage, 6.92% (6.17-7.76) for ischaemic stroke, 0.26% (0.15-0.45) for parkinsonism, 1.74% (1.31-2.30) for dementia, 19.15% (17.90-20.48) for anxiety disorder, and 2.77% (2.31-3.33) for psychotic disorder. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio [HR] 1.44, 95% CI 1.40-1.47, for any diagnosis;1.78, 1.68-1.89, for any first diagnosis) and those who had other respiratory tract infections (1.16, 1.14-1.17, for any diagnosis;1.32, 1.27-1.36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not . . . (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Incidence and outcomes of eating disorders during the COVID-19 pandemic.

There are concerns that eating disorders have become commoner during the coronavirus disease 2019 (COVID-19) pandemic. Using the electronic health records of 5.2 million people aged under 30, mostly in the USA, we show that the diagnostic incidence was 15.3% higher in 2020 overall compared with previous years (relative risk 1.15, 95% CI 1.12-1.19). The relative risk increased steadily from March 2020 onwards, exceeding 1.5 by the end of the year. The increase occurred solely in females, and primarily related to teenagers and anorexia nervosa. A higher proportion of patients with eating disorders in 2020 had suicidal ideation (hazard ratio HR = 1.30, 1.16-1.47) or attempted suicide (HR = 1.69, 1.21-2.35).

Cerebral venous thrombosis and portal vein thrombosis: A retrospective cohort study of 537,913 COVID-19 cases.

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).

Why is COVID-19 associated with mental illness?

The COVID-19 pandemic has taken a toll on people's mental health. Besides the indirect impact of the pandemic, a diagnosis of COVID-19 is itself associated with a greater risk of subsequent mental illness. Conversely, people with an existing psychiatric diagnosis are at an increased risk of getting COVID-19. Here, we discuss why this is the case.

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.