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A look within cytokine storms

Monitoring the host immune response could be key to treating patients suffering with COVID-19 and a number of other infectious or autoimmune diseases.

As with many autoimmune and infectious diseases, COVID-19, which is caused by the SARS-CoV-2 virus (shown), can trigger vicious inflammatory responses.Credit: Smirkdingo/iStock/Getty

Since the virus SARS-CoV-2 was identified as the cause of the COVID-19 pandemic, scientists have focused on finding drugs and vaccines to treat and prevent disease.

No targeted therapeutics against SARS-CoV-2 presently exist. While previously approved antivirals are being trialled in infected patients, promising results are emerging from drugs that modulate the host’s immune response.

One of the most severe manifestations of COVID-19 is Acute Respiratory Distress Syndrome (ARDS), a life-threatening condition in which the lungs can’t provide enough oxygen to the body’s vital organs. A subgroup of COVID-19 patients sustain a dangerous inflammatory response known as a ‘cytokine storm’ that causes ARDS and damage to other organs.

“Cytokine storms likely contribute to a substantial portion of those infected who require hospitalization for respiratory distress, and certainly those with multi-organ dysfunction,” says Randy Cron, a rheumatologist at the University of Alabama at Birmingham, USA.

Cytokine storms can be brought on by infectious and autoimmune diseases, such as lupus and arthritis. Regardless of their trigger, they are characterized by high levels of pro-inflammatory molecules that cause the immune system to damage normal tissues.

Suppressing the storm

Clinicians can adopt various strategies to reduce these storms — using glucocorticoids for broad immunosuppression, for example. Dexamethasone has improved survival rates in hospitalized COVID-19 patients. More targeted anti-cytokine approaches, using monoclonal antibodies against the cytokines Interleukin-1 (IL-1) or Interleukin 6 (IL-6), approved for the treatment of rheumatoid arthritis, are also showing promise.

The race to find new treatments for COVID-19, has also brought cell therapy to the forefront. “Recent trials hinted that the anti-inflammatory effects of mesenchymal stem cell injection might reduce lung injury and mortality in non-viral induced ARDS,” says Maroun Khoury, a cell biologist at the Universidad de los Andes, Chile. “It is too early to say whether this approach will work in COVID-19 patients, but the increasing number of registered cell therapy-based trials highlights the growing interest in exploring stem cells as a potential therapy,” he adds.

However, the decision to pharmacologically immunosuppress a critically unwell patient with COVID-19 remains a difficult one. The possible beneficial effects of reducing inflammation need to be carefully weighed against the potential promotion of further infection, which would complicate the course of disease.

A clear view of inflammation

Monitoring a patient’s immune response is crucial to determine whether to start, continue or stop immunomodulating therapies. “Both clinical parameters and lab results can be used to monitor patient response, but some markers are hard to measure in blood” says Cron.

Fortunately, many key circulating protein biomarkers of hyperinflammation, such as IL-2, IL-6, G-CSF, IFN-γ, IP-10, MCP-1, TNF-α, and others, can be detected by proteomic techniques, including antibody arrays, cytometric bead assays, and mass spectrometry. Multiplex immunoassays in particular are increasingly relied upon to monitor disease status and drug efficacy.

RayBiotech’s multiplex cytokine immunoassays allow researchers and clinicians to accurately measure the expression levels of multiple cytokines in serum and other liquid samples, aiding the discovery of key factors mediating disease mechanisms and biomarkers related to cytokine signalling.

“One of our strengths is our large array-validated antibody pool, which contains the widest variety of cytokines and immune modulators on the market. This gives the researcher flexibility to see a small select panel of inflammatory mediators, or over 2,000 proteins simultaneously,” says Ruo-Pan Huang, founder and CEO of RayBiotech.

Longitudinal studies to examine changes in cytokine levels over the course of infection in both symptomatic and asymptomatic carriers, may help optimize treatments and identify biomarkers that help predict disease severity.

To learn more about how to measure the expression of multiple cytokines, visit RayBiotech.