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Focus on Cytokine Storm Syndrome May Be COVID-19 Silver Lining

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September 15, 2020

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Cron RQ. COVID-19 Cytokine Storm Syndrome. Presentation: Clinical Rheumatology Society-Eastern Annual Symposium. September 10-13, 2020 (virtual conference).

Disclosure: Cron reports on Novartis and Sironax consulting, Pfizer’s participation in clinical trials, and remarks and participation in Sobi’s advisory board.

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Increased attention to deaths from COVID-19 Cytokine Storm Syndrome According to a presenter from the Eastern Society of Clinical Rheumatoid Arthritis in 2020, attention will be focused on these immune events, which may ultimately benefit both patients with the virus and patients with certain rheumatic diseases.

“People are afraid to treat cytokine storms, and of course.” Randy Q. Cron, MD, PhD, Officials from the University of Alabama Children’s Hospital and the University of Alabama in Birmingham pointed out in his presentation that the event could occur unexpectedly and often be fatal.

Doctor-held test tube reading COVID-19
Increasing attention to mortality from cytokine storm syndrome in the COVID-19 setting has drawn attention to these immune events. Source: Adobe Stock

Rheumatoidologists may be familiar with cytokine storm syndrome. Because they are many rheumatoid and immune-mediated diseases, especially Systemic juvenile idiopathic arthritis (SJIA)..

Storms often come in the form of Macrophage Activation Syndrome (MAS) or secondary forms Hemophagocytic lymphohistiocytosis (HLH). However, according to Cron, there are other potential causes, from malignant tumors and metabolic dysregulation to herpes and hemorrhagic fever viruses.

Randy Q. Coulomb

A concern for so many clinicians in the face of a cytokine storm is that “it is the immune response that kills the host, not the virus or infection,” Cron said. The immune system has “long-term involvement and crosstalk” that can cause damage to the multi-organ system.

Despite these challenges, Cron sees a silver lining on COVID-19. “One of the consequences of this horrific pandemic is that we are beginning to pay more attention to cytokine storms,” ​​he said.

Attention is producing results. Researchers have gained a better understanding of the genetic factors that are acting. The protein RAB27A has been linked to as well UNC13D variant. “If the expression of this mutant is low, it may be associated with MAS,” Cron said.

According to Cron, the protein STXBP2, which is involved in the fusion of cytolytic granules, may be a genetic predictor of mortality in the event of a cytokine storm. in addition Dock 8 The gene has been reported in the context of HLH.

All this information COVID-19 Forefront of Battle.. Cron believes that the experience of these storms can make many rheumatologists a valuable contribution to the fight.

For example, Cron, like many colleagues in his field of expertise, heard early reports of deaths from China, lymphopenia, lymphopenia, elevated C-reactive protein (CRP), IL-6 and I have identified D-dimer and so on. I immediately recognized it as Cytokine Storm Syndrome.

Many of these patients have a flu-like illness for several days and then appear to be recovering. “They hit this inflection point,” Cron said.

At this point, therapeutic intervention is needed. Time is the most important. “Initially, the use of IL-6 was reported outside of clinical trials,” Cron said. “It seemed to improve survival.”

Cron acknowledged that although the IL-6 approach did not work well in clinical trials, their failure may be due to patient selection and timing of treatment.

Since then, according to Cron, IL-1 inhibition has become a viable option. “It’s better to start Anakinra (Kinelet, Sobi) early,” Cron said. He suggested that the drug have a “huge treatment window” that can balance excess IL-1. “It’s pretty easy.”

In addition to IL-1, Janus kinase (JAK) / signal transducer and transcriptional activator (STAT) Pathways, and interferon (IFN) -γ-targeted emaparmab (Gamifant, Sobi). “HLH’s emaparmab is a new option for us,” Cron said.

A closer look at the equipment suggests that previous experience suggests that corticosteroids are contraindicated in the coronavirus. “Some people say it’s profitable, others say it’s not,” Cron said. The data is still evolving.

Ultimately, Cron, a combination of antiviral therapy and biological intervention along IL-1, IL-6, JAK / STAT or other pathways, most effectively reduces COVID-19 mortality. It is said that it will be a cocktail for. As those therapeutic paradigms emerge, rheumatoid arthritis patients will definitely benefit.

“Cytokine storm syndrome is a comprehensive term that includes MAS, HLH, malignancies, cytokine release, and a large Ben-figure bubble of infectious diseases such as influenza and Epstein Valley syndrome,” he said. “Now you can include SARS-CoV2 and COVID-19.”

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