Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Toxicity of legume seeds to rhizobia: Selective marker for strain identification and selection of toxin-free seeds

Seeds of legume species Argyrolobium flaccidum, Desmodium elegans, D. tortuosum, Indigofera gangetica, Lespedeza stenocarpa and Sesbania sesban have been evaluated for the toxicity to rhizobia for the first time. Legume species differ in quantity and quality of released seed toxins to which the symbiotic bacteria respond differentially. Therefore, seed toxicity may be used as a selectable taxonomic marker for the strainal identification of rhizobia. Seed toxins are located in seed coat and are thermolabile to some extent. The seed genotypes, within the species, differ in toxicity and such polymorphism can be used in the selection of toxin-free seeds. Seed surface-disinfection procedures involving subsequent soaking and washing with water are the most useful methods for reducing the seed toxins. The seed toxins from I. gangetica inhibited the growth of its homologous strain but did not affect nodulation and symbiotic parameters. Various seed-toxin-producing legume species did not affect nodulation and symbiotic efficiency and effectiveness.