Abstract
Management of COVID-19 patients experiencing persisting respiratory failure despite corticosteroids remains challenging. Data on high-dose intravenous anakinra (HD-ANK) in this context are lacking. We aimed to investigate the impact of HD-ANK on mortality in COVID-19 patients progressing to non-invasive ventilation (NIV) while receiving corticosteroids. We retrospectively analyzed the impact of HD-ANK on 28-day mortality in individuals hospitalized with COVID-19 necessitating NIV after corticosteroid initiation. A total of 256 patients were identified: 146 received standard-of-care only (SOC), and 110 received HD-ANK+SOC. The groups were well-balanced at baseline. In-hospital mortality at 28 days did not differ between the two groups. HD-ANK is not beneficial in patients with severe COVID-19 deteriorating despite corticosteroids.
This is a preview of subscription content, log in via an institution to check access.
Data availability
The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
References
Lamers MM, Haagmans BL (2022) SARS-CoV-2 pathogenesis. Nat Rev Microbiol 20:270–284. https://doi.org/10.1038/s41579-022-00713-0
van de Veerdonk FL, Giamarellos-Bourboulis E, Pickkers P, Derde L, Leavis H, van Crevel R et al (2022) A guide to immunotherapy for COVID-19. Nat Med 28:39–50. https://doi.org/10.1038/s41591-021-01643-9
Kyriazopoulou E, Poulakou G, Milionis H, Metallidis S, Adamis G, Tsiakos K et al (2021) Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nat Med 27:1752–1760. https://doi.org/10.1038/s41591-021-01499-z
Barkas F, Filippas-Ntekouan S, Kosmidou M, Liberopoulos E, Liontos A, Milionis H (2021) Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a systematic review and meta-analysis. Rheumatology 60(12):5527–5537. https://doi.org/10.1093/rheumatology/keab447
Kyriazopoulou E, Huet T, Cavalli G, Gori A, Kyprianou M, Pickkers P et al (2021) Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. Lancet Rheumatol 3(10):e690–e697. https://doi.org/10.1016/S2665-9913(21)00216-2
The REMAP-CAP Investigators, Lennie P.G. Derde et al. (2021) Effectiveness of tocilizumab, sarilumab, and anakinra for critically ill patients with COVID-19. The REMAP-CAP COVID-19 Immune Modulation Therapy Domain Randomized Clinical Trial medRxiv 06.18.21259133. https://doi.org/10.1101/2021.06.18.21259133
Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS (2020) Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Lancet Rheumatol 2:e358–e367. https://doi.org/10.1016/S2665-9913(20)30096-5
Diorio C, Vatsayan A, Talleur AC, Annesley C, Jaroscak JJ, Shalabi H et al (2022) Anakinra utilization in refractory pediatric CAR T-cell associated toxicities. Blood Adv 6(11):3398–3403. https://doi.org/10.1182/bloodadvances.2022006983
Sartini C, Tresoldi M, Scarpellini P, Tettamanti A, Carcò F, Landoni G et al (2020) Respiratory parameters in patients with COVID-19 after using noninvasive ventilation in the prone position outside the intensive care unit. JAMA 232:2338–2340. https://doi.org/10.1001/jama.2020.7861
Cavalli G, Luca GD, Campochiaro C, Della-Torre E, Ripa M, Canetti D et al (2020) Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol 2:e325–e331. https://doi.org/10.1016/S2665-9913(20)30127-2
Acknowledgements
We are deeply grateful to all healthcare professionals who contributed to the management of the COVID-19 pandemic and to the realization of this study.
Funding
This study was supported by IRCCS San Raffaele Hospital Program Project COVID-19 funds.
Author information
Authors and Affiliations
Contributions
AM and MR conceived the study, analyzed and interpreted the data, and drafted the final version of the manuscript. RM contributed to the study design, analyzed and interpreted the data, and critically discussed the manuscript. LG performed statistical analysis and interpreted the data. AT, CTD, DC, EM, MG, AD, CC, GC, GM, PC, PS, GL, FC, LD, and AC enrolled patients, analyzed and interpreted the data, and critically discussed the manuscript. AM and RM contributed equally as first authors.
Corresponding author
Ethics declarations
Ethics approval
The study protocol was approved by the San Raffaele Hospital Ethics Committee, and all patients signed informed consent.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
ESM 1
(DOCX 18.3 kb)
Rights and permissions
About this article
Cite this article
Mastrangelo, A., Monardo, R., Galli, L. et al. High-dose anakinra in addition to standard of care including corticosteroids in patients with severe COVID-19 treated with non-invasive ventilation. Eur J Clin Microbiol Infect Dis 42, 1383–1387 (2023). https://doi.org/10.1007/s10096-023-04661-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-023-04661-2