Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

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To estimate the frequency of headache in patients with confirmed COVID-19 and characterize the phenotype of headache attributed to COVID-19, comparing patients depending on the need of hospitalization and sex, an observational study was done. We systematically screened all eligible patients from a reference population of 261,431 between March 8 (first case) and April 11, 2020. A physician administered a survey assessing demographic and clinical data and the phenotype of the headache. During the study period, 2194 patients out of the population at risk were diagnosed with COVID-19. Headache was described by 514/2194 patients (23.4%, 95% CI 21.7–25.3%), including 383/1614 (23.7%) outpatients and 131/580 (22.6%) inpatients. The headache phenotype was studied in detail in 458 patients (mean age, 51 years; 72% female; prior history of headache, 49%). Headache was the most frequent first symptom of COVID-19. Median headache onset was within 24 h, median duration was 7 days and persisted after 1 month in 13% of patients. Pain was bilateral (80%), predominantly frontal (71%), with pressing quality (75%), of severe intensity. Systemic symptoms were present in 98% of patients. Headache frequency and phenotype was similar in patients with and without need for hospitalization and when comparing male and female patients, being more intense in females.Trial registration: This study was supported by the Institute of Health Carlos III (ISCIII), code 07.04.467804.74011 and Regional Health Administration, Gerencia Regional de Salud, Castilla y Leon (GRS: 2289/A/2020).