Blocking IL-1 to Prevent Respiratory Failure in COVID-19

Frank L. van de Veerdonk; Mihai G. Netea


Crit Care. 2020;24(445) 

In This Article

Abstract and Introduction


COVID-19 is an emerging disease that can manifest itself as asymptomatic or mild respiratory tract infection in the majority of individuals, but in some, it can progress into severe pneumonia and acute respiratory distress syndrome (ARDS). Inflammation is known to play a crucial role in the pathogenesis of severe infections and ARDS and evidence is emerging that the IL-1/IL-6 pathway is highly upregulated in patients with severe disease. These findings open new avenues for host-directed therapies in patients with symptomatic SARS-CoV-2 infection and might in addition to antiviral treatment be enough to curb the currently unacceptably high morbidity and mortality associated with COVID-19.


Although the majority of patients with COVID-19 are asymptomatic or have mild SARS-CoV-2 infections, many patients have been hospitalized and admitted to intensive cares (ICUs) and mortality is significant. Understanding this outbreak, including the effectiveness of supportive, immune-modulatory, and antiviral treatments, is essential. An important aspect of severe COVID-19 is a hyperinflammatory status, and immunomodulatory therapy might therefore be an important aspect in the treatment of COVID-19. Although ICU patients have been treated with glucocorticoids, some experts have even argued, based on studies in Middle-Eastern respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome (SARS), influenza, and respiratory syncytial virus (RSV), that they are likely to do more harm than good.[1,2] However, a more recent study showed that early short-course corticosteroids during admission were associated with fewer ICU admissions,[3] and a yet to be published study on dexamethasone argues that it can save lives especially in mechanically ventilated patients. Other immune modulatory treatments of interest include blocking the IL-1 or IL-6 pathway, the use of interferon-β, and many others. There are currently only small observational trials that contribute to the evidence for the benefit or harm of these interventions in COVID-19. In addition to the lack of available treatments known to be effective, insight into the pathophysiology of this coronavirus needs to be urgently addressed. This is essential in the pathway towards developing new, or repurposing existing, therapies that can be used in the treatment of patients with SARS-CoV-2.