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BackgroundClozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics.AimsTo investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation and intensive care treatment, and death, among patients taking antipsychotics with schizophrenia-spectrum disorders.MethodUsing data from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics at the time of the COVID-19 pandemic in the UK, and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores.ResultsIn the 157 individuals who developed COVID while on antipsychotics, there were 44 COVID-related hospitalisations, 13 COVID-related intensive care treatments and 13 deaths of any cause during the follow-up period. In the unadjusted analysis, there was no significant association between clozapine and any of the outcomes and there remained no associations following adjusting for the confounding variables.ConclusionsIn our sample of patients with COVID-19 and schizophrenia-spectrum disorders, we found no evidence that clozapine treatment puts patients at increased risk of hospitalisation, intensive care treatment or death, compared to any other antipsychotic treatment. However, further research should be considered in larger samples to confirm this.Conflict of interestRDH has received research funding from Roche, Pfizer, Janssen, and Lundbeck. DFF has received research funding from Janssen and Lundbeck. JHM has received research funding from Lundbeck. JTT has received research funding from Bristol-Meyers-Squibb. RS declares research support in the last 36 months from Janssen, GSK and Takeda.Ethics statementThe research was conducted under ethical approval reference 18/SC/0372 from Oxfordshire Research Ethics Committee C.

INTRODUCTIONSpatial navigation is emerging as a critical factor in identifying pre-symptomatic Alzheimer pathophysiology, with the impact of sex and APOE status on spatial navigation yet to be established.METHODSWe estimate the effects of sex on navigation performance in 27,308 individuals (50-70 years [benchmark population]) by employing a novel game-based approach to cognitive assessment using Sea Hero Quest. The effects of APOE genotype and sex on game performance was further examined in a smaller lab-based cohort (n = 44).RESULTSBenchmark data showed an effect of sex on wayfinding distance, duration and path integration. Importantly in the lab cohort, performance on allocentric wayfinding levels was reduced in ε4 carriers compared to ε3 carriers, and effect of sex became negligible when APOE status was controlled for. To demonstrate the robustness of this effect and to ensure the quality of data obtained through unmonitored at-home use of the Sea Hero Quest game, post-hoc analysis was carried out to compare performance by the benchmark population to the monitored lab-cohort.DISCUSSIONAPOE ε4 midlife carriers exhibit changes in navigation pattern before any symptom onset. This supports the move towards spatial navigation as an early cognitive marker and demonstrates for the first time how the utility of large-scale digital cognitive assessment may hold future promise for the early detection of Alzheimer’s disease. Finally, benchmark findings suggest that gender differences may need to be considered when determining the classification criteria for spatial navigational deficits in midlife adults.