Background Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain. Methods During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.

SummaryBackgroundWhole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life.MethodsThe Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061.FindingsBetween March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to receive either OSC plus WBRT (269) or OSC alone (269). Baseline characteristics were balanced between groups, and the median age of participants was 66 years (range 38–85). Significantly more episodes of drowsiness, hair loss, nausea, and dry or itchy scalp were reported while patients were receiving WBRT, although there was no evidence of a difference in the rate of serious adverse events between the two groups. There was no evidence of a difference in overall survival (hazard ratio 1·06, 95% CI 0·90–1·26), overall quality of life, or dexamethasone use between the two groups. The difference between the mean QALYs was 4·7 days (46·4 QALY days for the OSC plus WBRT group vs 41·7 QALY days for the OSC group), with two-sided 90% CI of −12·7 to 3·3.InterpretationAlthough the primary outcome measure result includes the prespecified non-inferiority margin, the combination of the small difference in QALYs and the absence of a difference in survival and quality of life between the two groups suggests that WBRT provides little additional ...

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