Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Oct:111:109075.
doi: 10.1016/j.intimp.2022.109075. Epub 2022 Jul 20.

Current evidence on the use of anakinra in COVID-19

Elnaz Khani  1 , Marzieh Shahrabi  2 , Haleh Rezaei  1 , Fariba Pourkarim  1 , Hoda Afsharirad  1 , Mohammad Solduzian  3
Affiliations
Review

Current evidence on the use of anakinra in COVID-19

Elnaz Khani et al. Int Immunopharmacol. 2022 Oct.

Abstract

Despite the progressing knowledge in COVID-19 management, remdesivir is the only agent that got approval to inhibit viral replication. However, there are limited data about effective immunomodulatory agents to prevent cytokine release in COVID-19. Cytokine release syndrome in COVID-19 resembles secondary hemophagocytic lymphohistiocytosis, in which interleukin-1 (IL-1) plays a key role. Anakinra is the first recombinant IL-1 receptor antagonist studied for off-label use in COVID-19 treatment. This study reviews the current clinical evidence on the role of interleukin-1 in COVID-19-related cytokine storm, therapeutic effects, significant clinical concerns, and pros and cons of anakinra administration in the management of COVID-19 patients. In this review, four items are shown to be important for achieving the optimal therapeutic effects of anakinra in COVID-19 patients. These items include duration of treatment ≥ 10 days, doses ≥ 100 mg, intravenous administration, and early initiation of therapy. Also, anakinra might be more beneficial in the early stages of the disease when higher levels of cytokines are yet to be observed, which could prevent progression to severe illness and mechanical ventilation. Further studies are required to address the SARS-CoV-2 induced cytokine release syndrome and the role of anakinra in identifying ideal treatment approaches for COVID-19 patients based on their clinical status.

Keywords: Acute respiratory distress syndrome; Anakinra; COVID-19; Cytokine release syndrome; Interleukin-1; Multiple organ failure.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
The effects and blockade of interleukin-1 (IL-1) signaling by anakinra. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the epithelial cells of the lungs and destruction of cells leads to IL-1α release, which in turn recruits neutrophils and monocytes and promotes IL-1β release from monocytes/macrophages. Furthermore, SARS-CoV-2 directly leads to IL-1β release from monocytes/macrophages and neutrophils. Both IL-1α and IL-1β bind to IL-1 receptors. Accordingly, MyD88, IL-1 receptor-associated kinase 4 (IRAK4), and nuclear factor kappa B (NFκB) are phosphorylated. NFκB stimulates the transcription of pro-inflammatory genes. Anakinra blocks IL-1 receptors and inhibits the binding of IL-1α and IL-1β, thus preventing the signaling pathway. DIC, disseminated intravascular coagulation; MOF, multiple organ failure.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. WHO Coronavirus (COVID-19) Dashboard, World Heal. Organ. (n.d.). https://covid19.who.int.
    1. Symptoms of COVID-19, 2021, Centers Dis. Control Prev. (n.d.). https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html.
    1. Hasan S.S., Capstick T., Ahmed R., Kow C.S., Mazhar F., Merchant H.a., Zaidi S.T.R. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Expert Rev. Respir. Med. 2020;14(11):1149–1163. doi: 10.1080/17476348.2020.1804365. - DOI - PMC - PubMed
    1. de la Calle C., López-Medrano F., Pablos J.L., Lora-Tamayo J., Maestro-de la Calle G., Sánchez-Fernández M., Fernández-Ruiz M., Pérez-Jacoiste Asín M.A., Caro-Teller J.M., García-García R., Catalán M., Martínez-López J., Sevillano Á., Origüen J., Ripoll M., Juan R.S., Lalueza A., de Miguel B., Carretero O., Aguilar F., Gómez C., Paz-Artal E., Bueno H., Lumbreras C., Aguado J.M. Effectiveness of anakinra for tocilizumab-refractory severe COVID-19: a single-centre retrospective comparative study. Int. J. Infect. Dis. 2021;105:319–325. doi: 10.1016/j.ijid.2021.02.041. - DOI - PMC - PubMed
    1. EMA recommends approval for use of Kineret in adults with COVID-19, Eur. Med. Agency. (n.d.).
-