Rod-Shaped Particles Might Distract Neutrophils and Halt Cytokine Storm in COVID-19: Study
Fri, December 9, 2022

Rod-Shaped Particles Might Distract Neutrophils and Halt Cytokine Storm in COVID-19: Study



A new study showed the cell type with a significant role in a complication of COVID-19, but researchers determined that the same cell type could be diverted by a particle shape, which might prevent the complication or improve its symptoms.

The white blood cell that could be distracted in COVID-19-associated acute respiratory distress syndrome (ARDS) was unveiled by researchers at the University of Michigan (U-M), a public research university in the US. Their findings suggested that the overreaction of neutrophils during an immune response to the novel diseases could lead to acute and deadly inflammation. But the overreaction might be mitigated by rod-shaped particles, which would stop the cells from damaging the lungs. The results were published in the journal Science Advances.



Neutrophils and Acute Respiratory Distress Syndrome

According to Britannica, an English-language general-knowledge encyclopedia, neutrophils are immune cells that can be found in infection sites. These are one of the first responders when foreign particles and pathogens entered the human body. Approximately 50% to 80% of the entire human white blood cell population is composed of neutrophils. When unfriendly particles are detected, neutrophils perform phagocytosis to devour the intruders and kill them before damage can be done to healthy tissue.

However, an increased number of neutrophils circulating the bloodstream can result in a condition called neutrophilia. Its most common cause is a bacterial infection, which must be addressed before an adverse outcome hit. That outcome is called acute inflammation and its extended duration may lead to tissue damage.



Meanwhile, ARDS is a respiratory condition characterized by liquid filling up the tiny sacs in the lungs called alveoli, according to the Mayo Clinic, an American not-for-profit medical center. The liquid makes it difficult for the person to breathe because they are essentially drowning. If left untreated, they are at risk of untimely death as organs are denied of oxygen supply, but ARDS normally occurs in patients with major injuries or in critical condition.

There are several known causes of ARDS, including sepsis, severe pneumonia, excessive inhalation of toxic substances, major physical trauma, internal inflammation, and COVID-19. Due to the complexity of ARDS, the patient is prone to other health conditions. Some of the complications of ARDS are blood clots, lung collapse, and pulmonary fibrosis - the scarring of the lungs.



Rod-Shaped Particles Might Lessen or Prevent ARDS in COVID-19 Patients

At U-M, researchers identified rod-shaped particles that could reduce ARDS in patients of COVID-19. These particles could distract certain white blood cells from the infection site, which might lower inflammation. They identified that sphere-shaped particles might work as well, but rod-shaped particles were preferred by those cells. They interpreted that the cells specifically disliked rods more than other particle shapes.



In the study, researchers conducted lab experiments to examine the immune response of several types of white blood cells called phagocytes, such as neutrophils, monocytes, and macrophages. These cells were recognized for their phagocytosis at the beginning and later stages of an infection. Because the disease in focus was COVID-19, they analyzed what external force could influence phagocytosis and what it would do in the respiratory system.

The experiments were designed to investigate the effect of the aspect ratio of white blood cells, in association with various polymeric particle shapes, meaning the experiments sought the number of each white blood cell type that responded to a specific particle. Then, results were compared to highlight which of the cell type was more aggressive to a certain shape. These experiments were done in vivo, thanks to human blood donors, and ex vivo, which involved mice models.

Experiments showed that the most abundant white blood cell – neutrophils – could be distracted by rod-shaped particles. While the shape of a particle could activate phagocytosis, there was no known exact reason why neutrophils disliked it more than other shapes. When neutrophils detected rod-shaped particles, the majority would leave an infection site to put more effort into eliminating those particles. This phenomenon was observed in in vivo and ex vivo experiments. The cells' unusual preference was apparent compared to monocytes and macrophages, which could also devour particles.

"They're like the Coast Guard - their main job is to make sure your boundaries aren't breached. We asked, do neutrophils also have a disdain for eating rods? We found the complete opposite. They actually have a preference for eating rods," said Lola Eniola-Adefeso, the lead author of the study and professor of chemical engineering at U-M.

In real-life settings, researchers pinpointed the main trait of neutrophils in an immune response. Unlike B and T cells, members of the adaptive immunity, neutrophils were a part of innate immunity or an old evolutionary immune defense system among many organisms. As a member of that system, neutrophils could easily attack a variety of unfriendly or foreign matter inside the body. But in exchange, they lack specialization that influenced their ability to stop.

Without specialization, neutrophils might start a cycle of ever-flowing cytokine in the blood. A neutrophil could produce cytokine to signal others of a pathogen. Another neutrophil would respond to that and generate its own cytokine. Eventually, numerous neutrophils would do the same to alert nearby cells and other immune cells to respond immediately. In this episode, there would be a chance that neutrophils could not stop attacking because of the high expression of cytokine in the blood. In the lungs, these cells would break down lung tissue and cause liquid to build up, leading to ARDS, if uncontrolled.

A therapy based on rod-shaped particles may distract neutrophils and leave other phagocytes to fight invaders. The experiments in the study show that up to 80% of neutrophils devoured rods while only 5% to 10% of other phagocytes did the same. Such a therapy may be administered to patients with acute inflammation and ARDS.



In a different study published in the journal JAMA Internal Medicine, authors investigated the risk factors of ARDS in COVID-19 patients. Out of 201 cohort patients with COVID-19 pneumonia, 41.8% developed ARDS and of those sufferers, 52.4% died from the complication. Among sufferers of ARDS, 59.5% of them presented signs of dyspnea or shortness of breath, compared to only 25.6% of patients who did not develop ARDS. Also, comorbidities were confirmed as risk factors of ARDS. Among ARDS patients with COVID-19, 27.4% had hypertension and 19% had diabetes.

If a therapy based on particle shape is possible for patients, it may help those who are at risk of acute inflammation. It can be given to patients with COVID-19, with major injuries, and with other illnesses. Alone, the theoretical therapy can lower the cases of death from ARDS and its complications.