Corticosteroid Therapy in Severe Respiratory Viral Infections

Severe respiratory viral infections, including those caused by influenza and coronaviruses, frequently trigger an excessive inflammatory response in the lungs. Corticosteroids represent a class of anti-inflammatory agents that modulate immune activation and cytokine production. By dampening the host immune response, they can reduce pulmonary oedema and improve oxygenation, yet the balance between therapeutic benefit and risks such as delayed viral clearance or secondary infection remains delicate. Optimal outcomes depend on precise dosing, timing and selection of specific corticosteroids. In acute respiratory distress syndrome (ARDS) precipitated by viral pathogens, low-dose regimens of agents such as dexamethasone have demonstrated mortality reduction in patients requiring oxygen or ventilation, while higher doses or prolonged courses may increase adverse events. Beyond COVID-19, meta-analyses in influenza pneumonitis have raised concerns about increased mortality and nosocomial complications. Contemporary research seeks to delineate the biological heterogeneity among patients, refine immunomodulatory strategies for different viral aetiologies and identify biomarkers that predict response. Integrating mechanistic insights from immunogenomics with clinical trial data is enabling personalised approaches to corticosteroid therapy, with the aim of maximising benefit, minimising harm and informing global treatment guidelines during outbreaks.

Research from Nature Portfolio

Recent work has elucidated the compartment-specific immunological effects of dexamethasone in critically ill COVID-19 patients. By combining bulk and single-cell RNA sequencing of pulmonary and blood samples with cytokine profiling, investigators characterised how standard-dose dexamethasone suppresses T cell activation pathways systemically while leaving interferon signalling in the respiratory tract relatively unaltered. This dual profiling revealed downregulation of antigen-presenting machinery and cell-adhesion molecules in blood, suggesting mechanisms for reduced systemic inflammation. Simultaneously, the persistence of interferon responses in the lung raises the possibility of adjunctive therapies to target steroid-resistant pathways. These findings provide mechanistic validation for dexamethasone use in viral ARDS and point towards future targeted interventions to improve clinical outcomes.

Corticosteroid Therapy in Severe Respiratory Viral Infections publication trend

The graph below shows the total number of articles in corticosteroid therapy in severe respiratory viral infections across all publications each year (not limited to Nature Index journals).

Technical terms

Corticosteroids: Synthetic analogues of adrenal hormones that suppress inflammation and modulate immune responses.

Acute respiratory distress syndrome (ARDS): A life-threatening condition characterised by widespread inflammation in the lungs leading to impaired gas exchange.

Hyperinflammation: An excessive immune response marked by elevated cytokine levels and tissue damage.

Single-cell RNA sequencing: A technique to profile gene expression at the individual cell level, revealing cellular heterogeneity.

Viral clearance: Elimination of replicating virus from the host, often measured by absence of detectable viral RNA.

References

1. Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19. Nature Communications (2024).
2. Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial. The Lancet (2023).
3. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Critical Care (2019).
4. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19. JAMA (2020).