Introduction Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

In this exploratory study we apply Granger Causality (GC) to investigate the brain-brain and brain-heart interactions during wakefulness and sleep. Our analysis includes electroencephalogram (EEG) and electrocardiogram (ECG) data during all-night polysomnographic recordings from volunteers with apnea, available from the Massachusetts General Hospital’s Computational Clinical Neurophysiology Laboratory and the Clinical Data Animation Laboratory. The data is manually annotated by clinical staff at the MGH in 30 second contiguous intervals (wakefulness and sleep stages 1, 2, 3, and rapid eye movement (REM). We applied GC to 4-s non-overlapping segments of available EEG and ECG across all-night recordings of 50 randomly chosen patients. To identify differences in GC between the different sleep stages, the GC for each sleep stage was subtracted from the GC during wakefulness. Positive (negative) differences indicated that GC was greater (lower) during wakefulness compared to the specific sleep stage. The application of GC to study brain-brain and brain-heart bidirectional connections during wakefulness and sleep confirmed the importance of fronto-posterior connectivity during these two states, but has also revealed differences in ipsilateral and contralateral mechanisms of these connections. It has also confirmed the existence of bidirectional brain-heart connections that are more prominent in the direction from brain to heart. Our exploratory study has shown that GC can be successfully applied to sleep data analysis and captures the varying physiological mechanisms that are related to wakefulness and different sleep stages.