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New Drugs Show Promise For Treating Cytokine Storm in COVID-19, and Beyond

Posted on 15 February 2021

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Two drugs currently being developed in Israel have shown promising results in clinical trials for the treatment of cytokine storm, a life-threatening event that can occur in COVID-19 patients.

What Is A Cytokine Storm?

When the immune system first detects the presence of a pathogen such as the Sars-CoV-2 virus, immune cells called macrophages and dendritic cells release a group of chemicals called cytokines. Cytokines are chemical signals that fulfil a variety of functions, such as causing inflammation and alerting other cells of the immune system (such as T cells) to the presence of a threat, rousing them to action and attracting them to the site of infection.

Cytokine production exists in a delicate balance, however, as the resulting inflammation also damages the body’s own cells. In a cytokine storm, also known as cytokine release syndrome, this balance is disturbed either because of a failure of regulation or excessive stimulation of the immune system. This causes an excessive production of cytokines and leads to systemic inflammation – cytokines are able to leave the site of infection and enter the blood, causing inflammatory responses throughout the body. This can cause multiple organ failure and is frequently fatal.

How are cytokine storms prevented?

In the past, cytokine storms were treated with immunosuppressants like steroids. Steroids would help to lower the immune response but this treatment comes with many side effects including high blood pressure and osteoporosis. Yet two novel drugs are showing promise in clinical trials for lowering the levels of cytokine storm by utilizing and amplifying the natural mechanisms used by the immune system to squelch cytokine production.


Allocetra is a treatment in development by Enlivex Therapeutics that recently completed phase II clinical trials. It aims to treat COVID-19 induced cytokine storm by administering dying T cells called early-apoptotic T cells.

Out of 9 severe and 7 critical patients in the phase II trial, most having risk factors for death from COVID-19 such as obesity and hypertension, 14 recovered and were discharged after an average of 5.3 days.


EXO-CD24 is an inhaled medication developed at Tel Aviv Sourasky Medical Center. The treatment uses exosomes, tiny membrane packages roughly the size of a virus that are released by cells to deliver signals to their neighbours. EXO-CD24 uses exosomes packed with CD24, a cell surface protein that plays a role in regulating the immune system and can suppress cytokine release. Since the medication is inhaled, it only suppresses cytokines in the lungs and thereby avoids causing side effects in other organs.

Image result for exosome size
Exosome size comparison (not to scale).
Analysis of the microRNA profile and origin of exosomes in plasma of melanoma patients and healthy individuals

The treatment has been used in 30 severe COVID-19 patients in phase I clinical trials so far. Of those, 29 saw their condition improve within two to three days, and most were discharged within five days. The 30th patient also recovered, but after a longer time.

These two novel drugs illustrate that the future is bright for patients suffering from cytokine storm.

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