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

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

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. 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. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Factors leading to sub-surface pan silcrete formation in north-central Botswana

New evidence was sought for sub-pan silcrete formation along the southern margin of Ntwetwe Pan in the Botswana Makgadikgadi basin. This was achieved by integrating drillhole and surface sample descriptions with element and isocon analysis. The silcrete deposit which lies ~1.0 m below the pan surface, comprises Ntane sandstone fragments and detrital infill, cemented by amorphous silica. The deposit probably evolved during sequential periods of palaeo-lake infilling and drying since at least the Mid-Pleistocene. Changes in basin water pH brought about during fresher water infill interspersed with brine evapo-concentration and later evaporative pumping, induced the mobilisation and precipitation of the silica cement immediately below the pan floor

Microclimates mitigate against hot temperatures in dryland ecosystems: termite mounds as an example

Termite mounds have recently been shown to protect against drought by providing refuges for plants and foci for revegetation, but whether mounds modulate temperature remains untested. Organisms tend to experience climate at finer scales than those captured by models predicting how distributions alter with global change, so microclimates represent important “climate refuges.” Using data we collected from African savanna sites, generalized linear mixed-effects models and linear quantile regression analysis confirm for the first time that the woody species associated with large termite mounds establish microclimates that are significantly cooler than surrounding savannas, a cooling effect that is even greater at warmer extremes. As air temperatures approached 40°C, a cooling effect of up to 4°C occurred, representing a doubling from that observed at 34°C. African savannas encompass 10 million km2, and much of this harbors evenly dispersed termitaria. The temperature-modulating effect of mounds facilitates agricultural and conservation decision-making as global change begins to impact the integrity of both human well-being and ecological processes

Use of the geochemical and biological sedimentary record in establishing palaeo-environments and climate change in the Lake Ngami basin, NW Botswana

Sediment samples from a continuous 4.6 m profile in the dry bed of Lake Ngami in NW Botswana were analysed for geochemistry and dated using both 14C and TL methods. Certain units in the profile were found to be diatom rich and these, with the geochemical results, were used as indicators of high and low lake levels within the basin. The Lake Ngami sediments contain a high proportion of SiO2 (51–92.5 wt%, avg. 72.4 wt%) and variable levels of Al2O3 (2.04–17.2 wt%, avg. 8.88 wt%). Based on elevated Al2O3 and organic matter (LOIorgC ) results, lacustrine conditions occurred at ca. 42 ka until 40 ka and diatom results suggest that relatively deep but brackish conditions prevailed. At 40 ka, the lacustrine sedimentary record was terminated abruptly, possibly by tectonic activity. At ca. 19 ka, shallow, aerobic, turbulent conditions were prevalent, but lake levels were at this time increasing to deeper water conditions up until ca. 17 ka. This period coincides with the Late Glacial Maximum, a period of increased aridity in the central southern Africa region. Generally, increasing Sr/Ca ratios and decreasing LOIorgC and Al2O3, from ca. 16 to 5 ka, suggest decreasing inflow into the basin and declining lake levels. Based on the enrichment of LREE results, slightly alkaline conditions prevailed at ca. 12 ka. Diatom results also support shallow alkaline conditions around this time. These lake conditions were maintained primarily by local rainfall input as the region experienced a warmer, wetter phase between 16 and 11 ka. Lake levels rose rapidly by 4 ka, probably in response to enhanced rainfall in the Angolan catchment. These results indicate that lake levels in the Lake Ngami basin are responding to rainfall changes in the Angolan catchment area and local rainfall. The results confirm that the present-day anti-phase rainfall relationship between southern Africa and regions of equatorial Africa was extant during the late Quaternary over the Angolan highlands and NW Botswana

Assessing local scale impacts of Opuntia stricta (Cactaceae) invasion on beetle and spider diversity in Kruger National Park, South Africa

There is a paucity of studies examining direct impacts of introduced alien species on biodiversity, a key need for motivating for alien species control in conservation areas. The introduced prickly pear (Opuntia stricta) has invaded some 35 000 ha of Kruger National Park. We investigated the effect of O. stricta on beetle and spider species assemblages in the Skukuza region of Kruger National Park. We used unbaited pitfall traps over a 12-month period in four treatments of varying O. stricta density. Species richness, species density and abundance of beetles and spiders were compared. A total of 72 beetle and 128 spider species were collected. Species richness and species density for beetles and spiders did not differ significantly across the four treatments. Assemblages for spiders did not differ across treatments but beetle assemblages were significantly different from uninvaded control sites. This study suggests that the current density of O. stricta does not significantly affect spider species richness, density or assemblages but that beetle assemblages are significantly affected.DST-NRF Centre for Invasion Biology and the University of Pretoria. Ditsong National Museum of Natural Histor