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.
<abstract><p><italic>Monkeypox</italic> 2022, a new re-emerging disease, is caused by the <italic>Monkeypox</italic> virus. Structurally, this virus is related to the smallpox virus and infects the host in a similar way; however, the symptoms of <italic>Monkeypox</italic> are more severe. In this research work, a mathematical model for understanding the dynamics of <italic>Monkeypox</italic> 2022 is suggested that takes into account two modes of transmission: horizontal human dissemination and cross-infection between animals and humans. Due to lack of substantial knowledge about the virus diffusion and the effect of external perturbations, the model is extended to the probabilistic formulation with Lévy jumps. The proposed model is a two block compartmental system that requires the form of Itô-Lévy stochastic differential equations. Based on some assumptions and nonstandard analytical techniques, two principal asymptotic properties are proved: the eradication and continuation in the mean of <italic>Monkeypox</italic> 2022. The outcomes of the study reveals that the dynamical behavior of the proposed <italic>Monkeypox</italic> 2022 system is chiefly governed by some parameters that are precisely correlated with the noise intensities. To support the obtained theoretical finding, examples based on numerical simulations and real data are presented at the end of the study. The numerical simulations also exhibit the impact of the innovative adopted mathematical techniques on the findings of this work.</p></abstract>
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