Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to ...discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country.
COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369).
180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 95% CI -18·23 to 11·19; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study.
Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies.
Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.
The potential of canopy reflectance distributions in the hotspot region for characterizing leaf geometry (leaf size and shape) of grass and crop canopies is explored with computer simulations. In ...this article, a computer graphics method—Lindenmayer-systems (L-systems)—is used to render a series of leaf (grass) and architecturally realistic row-planted crop (corn-like) canopies that have a variety of geometrical structures. A radiosity–graphics combined model is then employed to calculate the radiation regime in a canopy, including canopy directional reflectance. An effectiveness ratio (
E ratio) is proposed, which is able to evaluate the performance of a given measure or index in estimation of the parameter of interest under the influence of a number of “noise” factors (other geometric and optical parameters of the canopy) at various noise levels. This
E ratio is then applied to evaluate reflectance and normalized reflectance in the hotspot region for leaf geometry characterization. The result from simulated hotspot reflectance demonstrates that for both canopies, leaf geometry is estimable by using normalized reflectance within ±4–8° (or ±2–4°) around the hotspot direction in the principal cone (or principal plane). However, the center position and angular width of the optimal sampling region are affected by the number of noise factors such as leaf area index, leaf angle distribution for leaf canopies, plus row structure for row-plant crop canopies and their variation ranges. In most cases, normalized spectral reflectance in the near-infrared at a high solar zenith angle in the PC produces the most reliable results. The reason for better estimation of leaf geometry for grass and crop canopies than forests from hotspot observations is also discussed in this article.
Background & objectives: India has been reporting the cases of coronavirus disease 2019 (COVID-19) since January 30, 2020. The Indian Council of Medical Research (ICMR) formulated and established ...laboratory surveillance for COVID-19. In this study, an analysis of the surveillance data was done to describe the testing performance and descriptive epidemiology of COVID-19 cases by time, place and person.
Methods: The data were extracted from January 22 to April 30, 2020. The frequencies of testing performance were described over time and by place. We described cases by time (epidemic curve by date of specimen collection; seven-day moving average), place (area map) and person (attack rate by age, sex and contact status), and trends were represented along with public health measures and events.
Results: Between January 22 and April 30, 2020, a total of 1,021,518 individuals were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Testing increased from about 250 individuals per day in the beginning of March to 50,000 specimens per day by the end of April 2020. Overall, 40,184 (3.9%) tests were reported positive. The proportion of positive cases was highest among symptomatic and asymptomatic contacts, 2-3-fold higher than among those with severe acute respiratory infection, or those with an international travel history or healthcare workers. The attack rate (per million) by age was highest among those aged 50-69 yr (63.3) and was lowest among those under 10 yr (6.1). The attack rate was higher among males (41.6) than females (24.3). The secondary attack rate was 6.0 per cent. Overall, 99.0 per cent of 736 districts reported testing and 71.1 per cent reported COVID-19 cases.
Interpretation & conclusions: The coverage and frequency of ICMR's laboratory surveillance for SARS-CoV-2 improved over time. COVID-19 was reported from most parts of India, and the attack rate was more among men and the elderly and common among close contacts. Analysis of the data indicates that for further insight, additional surveillance tools and strategies at the national and sub-national levels are needed.
Various canopy reflectance models are reviewed, with emphasis on their attractive features and shortcomings. A universal model for the radiation regime in kilometer level scenes is described which ...can emulate these models. Areas for future research are outlined.
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