Table 1 Ten urging questions about glucocorticosteroids (GCs) in critical care and proposed studies needed to answer them

Q1: Why are GCs effective in COVID-19 but not in bacterial sepsis nor severe influenza?

1. Molecular characterization of the systemic vs local response to corticotherapy in COVID-19, influenza, sepsis

2. Longitudinal study of inflammatory response in presence/absence of steroids

Q2: Is refractory vasoplegia the only viable target for GCs treatment in septic shock?

1. Efficacy of corticotherapy in specific endotypes of sepsis

2. Retrospective analysis of clinical and laboratory effects of corticotherapy in COVID-19

Q3: Are the currently recommended doses of dexamethasone in COVID-19 immunomodulatory?

1. Influence of GCs on the IFN antiviral response

2. Single-cell resolution and local immunity focused studies on the effects of GCs in sepsis

Q4: How can we identify responders versus non-responders?

1. Development of rapid and point-of care available biomarkers of corticotherapy resistance/responsiveness

Q5: When is the patient benefitting the most from corticotherapy?

1. Initiation time of the corticotherapy on the clinical effect

2. Optimization of dose-tapering in various patient cohorts

Q6: Can a positive response to GCs be boosted in septic and COVID-19 patients?

1. Clinical studies of corticotherapy combined with other immunomodulators in sepsis (similarly to COVID-19)

2. Identification of drugs increasing sensitivity to GCs

Q7: What are the molecular and spatial dependencies that modulate effects of GCs in various cells and tissues?

1. Organ-and cell-specific distribution of the GC receptor complexes

2. Non-genomic effects of GCs in sepsis

Q8: Can we make the GCs action more specific?

1. Evaluation of context-specific action of GCs in septic patients

2. Identification of the relevant cell target in sepsis to test specific antibody-GC conjugate

Q9: Does the GCs type matter for sepsis and COVID-19 outcomes?

1. Comparison of the biological effect of different GC preparations in septic shock and COVID-19

2. Pharmacokinetic studies of GCs in septic shock

Q10: How to effectively utilize novel- generation GCs?

1. Evaluation of the novel short-acting GC receptor agonists and liposomal formulations in severe infections

2. Comparison of parental versus inhaled corticotherapy in pulmonary infections