Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Ecosystem responses to differing ratios of reduced and oxidised nitrogen inputs

While it is well established that ecosystems display strong responses to elevated nitrogen deposition, the importance of the ratio between the dominant forms of deposited nitrogen (NHx and NOy) in determining ecosystem response is poorly understood. As large changes in the ratio of oxidised and reduced nitrogen inputs are occurring, this oversight requires attention. One reason for this knowledge gap is that plants experience a different NHx:NOy ratio in soil to that seen in atmospheric deposits because atmospheric inputs are modified by soil transformations, mediated by soil pH. Consequently species of neutral and alkaline habitats are less likely to encounter high NH4+ concentrations than species from acid soils. We suggest that the response of vascular plant species to changing ratios of NHx:NOy deposits will be driven primarily by a combination of soil pH and nitrification rates. Testing this hypothesis requires a combination of experimental and survey work in a range of systems

Differential effects of oxidised and reduced nitrogen on vegetation and soil chemistry of species-rich acidic grasslands

Emissions and deposition of ammonia and nitrogen oxides have strongly increased since the 1950s. This has led to significant changes in the nitrogen (N) cycle, vegetation composition and plant diversity in many ecosystems of high conservation value in Europe. As a consequence of different regional pollution levels and of the increased importance of reduced N in the near future, determining the effect of different forms of N is an important task for understanding the consequences of atmospheric N inputs. We have initiated three replicated N addition experiments in species-rich, acidic grasslands spanning a climatic gradient in the Atlantic biogeographic region of Europe in Norway, Wales and France at sites with low levels of pollution. N was added in two doses (0 and 70 kg N ha−1 year−1 above background) and in three forms (oxidised N, reduced N and a 50–50 combination). After 2.5 years of N additions, the effects of these treatments on plant biomass, plant nutritional status, soil pH and soil nutrient availability were determined. Impacts of the N additions were observed within the 2.5-year research period. In some cases, the first signs of differential effects of N form could also be demonstrated. In the French site, for example, grass biomass was significantly increased by the oxidised N treatments but decreased by the reduced N treatments. In the Norwegian site, the reduced N treatments significantly reduced soil pH, whereas oxidised N did not. Effects on nutrient availability were also observed. These experiments will be continued to elucidate the longer term impacts of N deposition on these grasslands