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

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Taxonomic anarchy or an inconvenient truth for conservation? Accelerated species discovery reveals evolutionary patterns and heightened extinction threat in Afro-Malagasy small mammals

We respond to recent criticisms of supposed “taxonomic anarchy” which is said to hamper conservation efforts. Using examples from African small mammals, we document recent increases of 13% (rodents) and 18% (bats) over the past three decades in the number of recognized species of Afro-Malagasy rodents and bats. By reference to a number of case studies involving Afro-Malagasy taxa (predominantly from montane habitats), and a suggested four-criterion approach to delimiting species accurately, we show that these increases are a genuine reflection of speciation in cryptic species complexes. Moreover, we show that some of these cryptic species are subject to increased extinction risks due to small population size and anthropogenic changes (habitat degradation and climate change). These changes were captured accurately in a recent Mammal Red List of South Africa, Lesotho and Swaziland, indicating that taxonomists and conservationists can work together to assess the Red List status of cryptic species based on robust taxonomic revisions

Species definitions and conservation: a review and case studies from African mammals

The nature of species, especially as applied to large mammals, is of major concern in conservation. Here, we briefly comment on recent thinking in alpha taxonomy, and assert that species are in essence evolutionary lineages, and that the most effective way of recognising them is by their diagnosability, i.e. the so-called Phylogenetic Species Concept. We further assert that the amount of genetic distance is not a relevant datum for distinguishing species, and that the ability to interbreed is not relevant. We consider a few case studies, especially that of the Northern White Rhinoceros Ceratotherium cottoni, and also species in Loxodonta, Giraffa and Oreotragus

Molecular and morphological evidence for a Pleistocene radiation of laminate-toothed rats (Otomys: Rodentia) across a volcanic archipelago in equatorial Africa

West African Mountains of the Cameroon Volcanic Line harbour two montane-endemic species of laminated-toothed rats (Otomys), which represent the most westerly occurrence of the genus. We explore here through mtDNA sequencing and cranial morphometrics the taxonomic status and phylogenetic relationships of O. burtoni (Mt Cameroon) and O. occidentalis (Mts Oku and Gotel). We conclude that both species are valid and can be discriminated by molecular data, as well as quantitative and qualitative cranial characters. From molecular data, O. occidentalis and O. burtoni are closest neighbours (p-distance = 7.5–8.5%) and weakly associated sister species (suggesting a single West African radiation) and both are sister clades to a well supported clade of central, East and northeast African members of the O. typus s.l. and O. tropicalis s.l. species complexes from mountain ranges comprising the East African ‘Montane Circle’ and Ethiopian Highlands. Re-evaluation of the evolutionary origins of the allopatric Otomys populations in equatorial Africa is undertaken in light of fossil evidence of a southern African origin of the genus. We can conclude that Otomys reached the Cameroon Volcanic Line via corridors of temperate grasslands during the Late Pliocene. Our data support the hypothesis that, following major peripatric speciation events at around 2.3 to 2.03 Ma (from East Africa into West and North Africa respectively), further speciation occurred across neighbouring mountain ranges in West, Central-East and North-East Africa. Estimated molecular dates of speciation events in Otomys reveal close congruence with well-constrained geochronological estimates, pertinently the uplift of the Albertine Rift in the Early Pleistocene. These regional analyses reveal how peripatric speciation events established narrow-range endemics of Otomys on principal stratovolcanoes across the East African plateau and Cameroon