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.
The clinical picture in severe cases of pandemic (H1N1) 2009 influenza is markedly different from the disease pattern seen during epidemics of seasonal influenza, in that many of those affected were previously healthy young people. Current predictions estimate that, during a pandemic wave, 12-30% of the population will develop clinical influenza (compared with 5-15% for seasonal influenza) with 4% of those patients requiring hospital admissions and one in five requiring critical care. This review covers the background, clinical presentation, diagnosis, and treatment. The role of immunization and antiviral drugs is discussed. Experience from the first wave of pandemic (H1N1) 2009 influenza suggests that a number of infected patients become critically ill and require intensive care admission. These patients rapidly develop severe progressive respiratory failure which is often associated with failure of other organs, or marked worsening of underlying airways disease. The critical care management of these patients and the implications for resources is reviewed. Guidance from a range of bodies has been produced in a relatively short period of time in response to pandemic (H1N1) 2009 influenza. Disease severity has the potential to change, especially if there is virus mutation. Clinicians must be prepared for the unexpected and continue to share their experiences to maximize patient outcomes.
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