Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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 light climate of Loch Leven, a shallow Scottish lake, in relation to primary production of phytoplankton

Seasonal changes in incident irradiance and underwater light penetration at Loch Leven from 1968 to 1971 are discussed in relation to the photosynthetic behaviour and crop density of phytoplankton. Light extinction was highest in the blue and lowest in the orange spectral regions, a pattern typical of other turbid waters. Euphotic depth varied between 1·2 and 7·4 m and was on average c. three times the Secchi disc transparency. Underwater light extinction depended chiefly on phytoplankton crop density (estimated as chlorophyll a). Despite the shallowness and wind-exposed situation of the loch there was no evidence of appreciable light extinction due to sediment disturbance. Possible causes of variability in the relationship between the minimum vertical extinction coefficient (k min) and the concentration of chlorophyll a are discussed. The value of ks, the increment in kmin per unit increment in algal concentration, was estimated from field data as 0·0086 In units per mg chl a/m2 and from laboratory spectroradiometer data as 0·0079 In units per mg chl a/m2. These ks values imply theoretical upper limits for the amount of chlorophyll a in the euphotic zone (Σn max) of 430 and 468 mg chl a/m2, respectively. Observed euphotic chlorophyll a contents (Σn) were sometimes close to these upper limits. Typical photosynthesis/depth profiles are described. Profile area is shown to be related to the logarithm of the ratio between surface-penetrating irradiance (Io') and the irradiance (Ik) defining the onset of light-saturation of photosynthesis. Standardized profiles, plotted on a common scale of 'optical depth', are used to illustrate the relatively minor influence of variations in Io' and Ik on hourly rates of photosynthesis per unit area. The saturation parameter (Ik) generally increased as photosynthetic capacity (Pmax) increased; the temperature-dependence of Ik is explained by the temperature-dependence of the enzyme-controlled (dark) reactions of photosynthesis, which control Pmax. A spring peak in the ratio between surface penetrating irradiance (Io') and Ik is interpreted as a result of a lag in the seasonal increase in water temperature with increase in surface irradiance. The gradient (K') of the linear light-limited region of the photosynthesis-irradiance curve showed little variation and had an average value of 0·31 mg O2/mg chl a.h per 1 W/m2 (PAR). Interactions between mixed depth, underwater light extinction and phytoplankton productivity are discussed; comparisons are made with other shallow, optically deep lakes