New Research Provides Insights into the COVID-19 Cytokine Storm

New Research Provides Insights into the COVID-19 Cytokine Storm

One of the reasons COVID-19 has such a high mortality rate is the cytokine storm it induces in some patients. The cytokine storm is an excessive response by the immune system that, rather than helping the body kill the invading virus, causes more harm than the virus itself.

Cytokines play an important role in the immune response to invading bacteria and viruses. Cytokines stimulate cell pathways and allow for communication between cells; however, if there is an outpouring of cytokines it can cause high levels of inflammation, which can prove fatal. In COVID-19, the cytokine storm is centered in the lungs and can result in patients getting very sick, very quickly, with patients often complaining of fever and extreme shortness of breath. These patients usually require ventilation and the mortality rate is over 40%.

A new study has been conducted on the COVID-19 cytokine storm by immunologists at the Columbia University Vagelos College of Physicians and Surgeons which sheds light on this excessive response to the presence of SARS-CoV-2. This is one of very few studies that has looked at the immune response in the lungs as it unfolds. Most studies focus on the immune response from blood samples, as it is difficult to obtain the necessary samples from the lungs. The researchers found they could obtain samples from the daily saline washes of the endotracheal tubes used to connect patients to a ventilator.

The researchers collected respiratory immune cells from 15 COVID-19 patients with severe symptoms that had been intubated. Each patient spent between 4 and 7 days on the ventilator, with samples taken daily and checked for cytokines.

Studies on the blood found many different cytokines; however, there were much higher numbers in the samples taken from the lungs. The immunologists did not identify any cytokines in the blood that were not present in the samples obtained from the lungs, so they concluded the cytokine storm was driven by immune cells in the lungs releasing cytokines. The researchers found that two cytokines – CCL2 and CCL3 – play a key role in the immune response in the lungs. These cytokines attract immune cells called monocytes to the site of infection to clear the virus.

“Normally, these cells never make it to the airway, but in severe COVID patients, they accumulate throughout the lung and clog up the alveolar spaces,” said Donna Farber, PhD, professor of microbiology & immunology and the George H. Humphreys II Professor of Surgical Sciences in the Department of Surgery, and lead of the study.

The researchers believe targeting these two cytokines with drugs could help calm the immune response and improve survival rates. Cytokine inhibitors have been trialed in COVID-19 patients, but the results have been variable. That could be because they are inhibiting cytokines that are not playing a major role in the overactive immune response and inflammation in the lungs. Drugs that block the immune response to CCL2 are now being studied in clinical trials on patients with severe COVID-19.

The immunologists also found patients that survived (8/15 in the study) had a higher number of antiviral T-cells in the lungs than the patients who died, and a lower proportion of inflammatory macrophages and monocytes. The cell differences could potentially be used as an indicator of who is likely to develop severe COVID-19 symptoms.

“Our next step is to try to find a more accessible biomarker that predicts severe COVID so we can try to give treatments earlier to patients who are most at risk,” said Faber.

You can read more about the study in the paper – Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19 – which was recently published in the journal Immunity. DOI: 10.1016/j.immuni.2021.03.005