Anakinra for patients with COVID-19
Authors: Xavier Valette, Damien du Cheyron
Journal: The Lancet Rheumatology (2020)

We read with interest the Article by Giulio Cavalli and colleagues1Cavalli G De Luca G Campochiaro C et al.Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study.Lancet Rheumatol. 2020; 2: 325-331Summary Full Text Full Text PDF PubMed Scopus (769) Google Scholar in The Lancet Rheumatology about the use of anakinra for patients with acute respiratory distress syndrome (ARDS) related to COVID-19. Although the study by Cavalli and colleagues was not performed in intensive care units (ICUs), the semantics used by the authors derive from critical care practice and need some precision. First, the definition of ARDS necessitates a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2:FiO2) of less than 200 mm Hg for a diagnosis of moderate ARDS and of less than 100 mm Hg for severe ARDS, assessed on invasive mechanical ventilation with a positive end-expiratory pressure of more than 5 cm H2O.2Ranieri VM Rubenfeld GD et al.ARDS Definition Task ForceAcute respiratory distress syndrome: the Berlin definition.JAMA. 2012; 307: 2526-2533Crossref PubMed Scopus (7705) Google Scholar Individuals included in this study benefited from non-invasive ventilation, which defines the patients as having mild ARDS. Thus, the patients in the study by Cavalli and colleagues had mild ARDS, irrespective of the PaO2:FiO2 ratio (provided that PaO2:FiO2 is <300 mm Hg), and the authors are incorrect to classify the patients as having moderate-to-severe ARDS. Second, non-invasive ventilation can be used outside the ICU, but only in specific patients, in specialised units with adequate monitoring and skilled and experienced physicians and nurses,3Nava S Hill N Non-invasive ventilation in acute respiratory failure.Lancet. 2009; 374: 250-259Summary Full Text Full Text PDF PubMed Scopus (599) Google Scholar which seems to differ from the care reported by Cavalli and colleagues.1Cavalli G De Luca G Campochiaro C et al.Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study.Lancet Rheumatol. 2020; 2: 325-331Summary Full Text Full Text PDF PubMed Scopus (769) Google Scholar Consequently, the COVID-19 pandemic context, with a shortage of ICU resources, and the patient severity raise questions about the use of non-invasive ventilation in general wards, and subsequently about the patient outcomes that were compared. Third, the evolution of PaO2:FiO2 ratio was assessed with a derivative formula based on oxygen saturation.4Rice TW Wheeler AP Bernard GR et al.Comparison of the SpO2/FiO2 ratio and the PaO2/FiO2 ratio in patients with acute lung injury or ARDS.Chest. 2007; 132: 410-417Summary Full Text Full Text PDF PubMed Scopus (546) Google Scholar This formula, which is neither recommended nor used in clinical practice, showed a satisfactory ability to assess a range of PaO2:FiO2 ratios with the transcutaneous oxygen saturation, but this cannot be used as a surrogate for the PaO2:FiO2 ratio. Finally, despite a high rate of bacteraemia, the authors conclude that anakinra has a remarkable safety profile that makes it especially suitable for use in critically ill patients. This assertion remains questionable without additional data focusing on ICU patients, especially those undergoing invasive mechanical ventilation with moderate-to-severe ARDS. Such patients are at increased risk of nosocomial infections, notably ventilator-associated pneumonia,5Vincent J-L Sakr Y Singer M et al.Prevalence and outcomes of infection among patients in intensive care units in 2017.JAMA. 2020; 323: 1478-1487Crossref Scopus (383) Google Scholar the diagnosis of which could be more difficult in a patient treated with anakinra due to the drug's immunosuppressive effect. Indeed, decreases in fever and leucocyte count could delay treatment and have important effects on the attributable mortality of such hospital-acquired infections. In conclusion, further studies are necessary to establish the safety and efficacy profile of the recombinant interleukin-1 receptor antagonist anakinra in patients with ARDS who are hospitalised in the ICU setting. We declare no competing interests. Anakinra for patients with COVID-19The Article published by Giulio Cavalli and colleagues in The Lancet Rheumatology,1 in combination with our case series of nine patients,2 supports the targeting of the IL-1 pathway as a safe and promising approach in the various types of lung involvement in patients with COVID-19. These complementary studies that cover the entire spectrum of severity of lung involvement in hospitalised patients with COVID-19, provide the first efficacy and safety data for anakinra, depending on the doses used and the stage of lung injury. Full-Text PDF Anakinra for patients with COVID-19In The Lancet Rheumatology, Giulio Cavalli and colleagues1 report potential beneficial effects of the IL-1 receptor antagonist anakinra in patients with COVID-19, acute respiratory distress syndrome (ARDS), and hyperinflammation. In the study protocol, anakinra was given in combination with a 4-aminoquinoline and, although promising, we suggest that this combination cannot be fully synergistic in the presence of cytokine release syndrome. Full-Text PDF Anakinra for patients with COVID-19 – Authors' replyWe thank Xavier Valette and Damien du Cheyron, Nicolas Martin-Silva and colleagues, and Omar Maoujoud and colleagues for their interest in our Article on treatment of patients with COVID-19 and acute respiratory distress syndrome (ARDS) with the IL-1 receptor antagonist anakinra, published in The Lancet Rheumatology.1 Full-Text PDF Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort studyIn this retrospective cohort study of patients with COVID-19 and ARDS managed with non-invasive ventilation outside of the ICU, treatment with high-dose anakinra was safe and associated with clinical improvement in 72% of patients. Confirmation of efficacy will require controlled trials. Full-Text PDF