Before talking about this new EXO-CD24, let’s first look at why there is no specific drug for COVID up to now. According to the research of more than 70,000 pneumonia patients in conducted by China CDC in March 2020, the proportion of mild-severe-critical cases of COVID-19 is about 81%-14%-5%. In the later stage, with the expansion of screening scale, the proportion of severe and critical patients decreased, while the proportion of mild and asymptomatic infected persons increased greatly. It seems that the proportion of severe and critical patients is not particularly high, the mortality rate of these patients in COVID-19 is not low at present. It should be pointed out that COVID-19 does not have a specific therapeutic drug at present, unlike SARS, when Tamiflu was available for treatment.

Cytokine storm, Hormones and Tozumab

The emergence of cytokine storm is one of the key factors for the transition from mild to severe/critical illness, then greatly increasing the mortality rate of COVID-19. In general, cytokine storm is a very complex immune phenomenon in human body. Simply, the immune system, which was originally used to resist pathogens, overreacted and lost control, and then attacked normal cells and organs of human body, resulting in complications such as hypotension, coagulation disorder and multiple organ failure, which eventually led to the death of the patient. For many critical patients, cytokine storm is far more terrible killer than SARS-CoV-2 itself, which is also an important reason why many antiviral drugs fail in the face of COVID-19 pneumonia.

Cytokine storm in the lung following severe influenza infection
Cytokine storm in the lung following severe influenza infection. From Cellular & Molecular Immunology volume 13, pages3–10(2016).

To suppress the excessive immune response of cytokine storm, we used hormones, such as Glucocorticoid etc. Last year, the Lancet published an article discussing the possibility of treating severe pneumonia patients in COVID-19 with Tozumab. And this idea was initially confirmed by the retrospective study in Bologna and other places in Italy at Jun. 2020.In a Italian study, 544 critical patients were included in the study. After adjusting for gender, age, hospital and other factors, it was found that either intravenous or subcutaneous injection of Tozumab can significantly reduce the risk of invasive mechanical ventilation or death in critically ill patients. Neither hormone nor torzumab has antiviral effect, but they can pull the critically ill patients back from the death line, mainly inhibiting excessive immune response. However, high-dose hormone pulse had caused serious femoral head necrosis. Yet, Moderate amount hormone is the only drug that WHO thinks can effectively reduce the mortality rate of COVID-19. Note that “the only one”. This result has been proved by many clinical studies over the past year.

EXO-CD24

According to the information released by the Israeli Embassy in China, in the Phase I clinical trial of this drug in Izirov Hospital in Tel Aviv-Yafo, patients only need to inhale this drug once a day, each time for five minutes. All 30 patients with moderate to severe COVID-19 recovered, and 29 patients recovered within 3 to 5 days after taking the drug. (https://clinicaltrials.gov/ct2/show/NCT04747574) These amazing results bring great hope to people.

A patient is administered Prof. Nadir Arber’s EXO-CD24 COVID-19 treatment
(photo credit: ICHILOV SPOKESPERSON’S OFFICE)

In fact, the EXO-CD24 is an exosome that wraps CD24 (Cluster of Differentiation 24). Exosomes are tiny membrane vesicles secreted by cells, which are widely distributed in various body fluids. Exosomes can carry a variety of information such as proteins, lipids, DNA and RNA, forming a signal transmission between cells. In fact, the process of nasal inhalation mentioned above is to transfer CD24 to the lungs, and exert its efficacy through the inhibition of cytokine storm by CD24. CD24 (Cluster of Differentiation 24) is a highly glycosylated glycosyl phosphatidylinositol anchoring surface protein, and it can inhibit the immune response.

By nasal administration, the drug can reach the lung and cytokine storm center of COVID-19 directly, and reduce the dosage of hormone, avoiding excessive immune response, which is extremely important. Therefore, EXO-CD24 is a potential drug, and we should do more research on this kind of drug.

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