Anakinra: a silver lining in COVID-19?

Dear Editor,

In the recent review article Blocking IL-1 to prevent respiratory failure in COVID-19 by Dr. Veerdonk and Dr. Netea [1], they have implicated the importance IL-1 signaling in severe COVID-19 pathogenesis and proposed anakinra as a therapeutic intervention. I would like to humbly add some views to it; in severe COVID-19 pathology, higher amounts of microthrombi deposition can lead to the blockage in the capillaries and arteries culminating in hypoxic condition and ensuing necrosis-like events. In fact, autopsy studies have reported necrotic events of lung pneumocytes in severe COVID-19 patients [2]. Also, high serum levels of receptor-interacting protein kinase 3 (RIPK-3) in severe patients corroborate necroptosis too [3].

The damage-associated molecular pattern IL-1α (alarmin) liberated by necrotizing lung epithelial cells could be one of the initial cytokine produced during COVID-19 pathogenesis [4]. IL-1α by further engagement to IL-1R lead to the production of an array of chemokines and cytokines [4]. IL-1β, IL-6, TNF-α, GM-CSF, IL-17, CXC chemokines, CCL chemokines, etc. are some of the few upregulated cytokines/chemokines in severe COVID-19 responsible for exacerbating the lung pathophysiology by fueling up infiltration of macrophages/neutrophils, hypercoagulability, and fibrosis phenomena [1]. Interestingly, IL-17, IL-6, GM-CSF, HIF-α, and CXC chemokines are regulated by IL-1β. The hypercoagulability with thromboembolic indications in severe patients is attributed to platelet activation and platelet monocyte aggregation, leading to the induction of tissue factor (TF) [5]. Also, IL-1β is known to positively regulate TF expression. Taming the cytokine storm can be an effective management strategy and IL-1 signaling might play a crucial role in the pathogenesis of the disease. It could be initial necrosis liberating IL-1α, which drives amplifying inflammation loop eventually leading to inflammasome-dependent pyroptosis determining the severity of the disease. Anakinra (IL-1α and IL-1β blocker) has shown greatly reduced mortality, need for invasive mechanical ventilation, and bettering oxygenation status in severe COVID-19 patients in smaller clinical studies [1]. Hence, anakinra might be effective in managing the severe pandemic state; more so, it is a well-tolerated molecule with no adverse effects. Larger controlled clinical trials with anakinra are much warranted to test the efficacy unequivocally.

Author’s contributions

Rahul did the literature survey and wrote the manuscript. The author read and approved the final manuscript.

Funding

The study has not received any funding as yet.

Availability of data and materials

Literature survey

Ethics approval and consent to participate

Not applicable

Consent for publication

Yes.

Competing interests

I do not have any competing interests.