Improved survival in intensive care unit in severe COVID-19 associated with amantadine use - retrospective study

OBJECTIVES: Possible immunomodulatory effect of amantadine in patients treated in intensive care unit (ICU), mostly among patients with brain injuries or vascular diseases was observed in several studies. The potential antiviral effect of amantadine against SARS-CoV-2 was discarded in clinical trials; however, immunomodulatory potential was not studied. The aim of the study was to investigate the effect of immunomodulatory amantadine therapy on mortality in patients with respiratory insufficiency due to COVID-19 requiring mechanical ventilation in ICU. METHODS: Retrospective analysis of 241 cases of 141 (58.5%) receiving intravenous amantadine sulfate vs 100 (41.5%) controls on standard of care only was performed. RESULTS: Overall mortality was 72.6%, being notably lower among amantadine treated patients (59.5%, n = 84) compared with controls (91%, n = 91), P-value = 0.001. In multivariate models administration of amantadine was independently associated with lower mortality rate (hazard ratio: 0.220, CI: 0.146-0.333 P-value = 0.001). Furthermore, survival was improved in patients who received amantadine; late administration of amantadine after 5th day was independently associated with lower mortality (hazard ratio: 0.560, CI: 0.313-0.999, P-value = 0.050). CONCLUSION: In patients treated in ICU with severe respiratory failure, administration of amantadine is associated with lower mortality, which may be associated with the potential anti-inflammatory and immunomodulatory effects of this agent.