A new study unveiled the paralysis of the immune system when dealing with COVID-19. Researchers found in some cases that innate immunity performed sluggishly than it should be.
The immune-system paralysis during the SARS-CoV-2 invasion was revealed by researchers at Stanford University, a US private research university. Instead of acting immediately, the innate side of the immune system would act slowly to contain the infection. They linked this flaw to the ancient mechanics of innate immunity, which could fail to recognize the novel coronavirus. They published their findings in the journal Science.
The Innate Immune System
The human immune system is a complex network of defenders that use numerous chemical signals and weaponry to fight pathogens. But the network can be divided into two main aspects: innate and adaptive. The two aspects describe the role of immune cells and related chemicals based on situations. Innate immunity triggers during the first stages of infection while adaptive immunity activates when the situation goes out of control. White blood cells called neutrophils are first responders in innate immunity, and white blood cells called B cells release antibodies once adaptive immunity is in full strength.
According to the University of Arizona, a US public research university, innate immunity refers to nonspecific response to infection. It can activate immediately or within hours of invasion. Defensive mechanisms in innate immune include physical barriers like the skin, macrophages and neutrophils, and inflammatory signals. Whenever an antigen is detected inside the body, an innate immune response takes place to contain the pathogen, regardless of its strain or type.
Meanwhile, adaptive immunity refers to specific immune responses. It can only respond to a specific antigen that innate immunity must provide. During innate immune responses, immune cells gather information about pathogens encountered. Dendritic cells gather information and send it to the adaptive immune system. Once processed, adaptive immune cells will know exactly what they must eliminate, including infected cells. B cells require that information to release the correct antibodies.
Because adaptive immunity is more complex than innate immunity, it can take time to fully kick in. In real life, it can take days before a person develops the antibodies for virus. But its potential in conquering infections is significantly greater. The only problem is the risk of complications and severe symptoms during the priming process.
Paralyzed Innate Immunity
Scientists around the world learn as they go in treating COVID-19. While addressing patient symptoms, clinicians gather data to find useful patterns and potential targets for treatments. Fortunately, there has been some progress like the emergency authorization to use remdesivir in severe or critically-ill COVID-19 patients. The same progress pushed numerous vaccine models to clinical trials.
At Stanford, researchers investigated why SARS-CoV-2 is highly capable of causing severe symptoms and complications. This represented the diversity in symptoms and outcomes of COVID-19 patients. Some would recover as if nothing happened. But others would recover with long-lasting damage to their organs, particularly the lungs. There were even cases linked to excessive blood clotting.
In the study, the data of 76 people diagnosed with COVID-19 and 69 healthy people were analyzed. Out of 76 patients, 36 were from Hong Kong and 40 were from Atlanta, US. Out of 69 healthy controls, 45 were in Hong Kong and 24 were in Atlanta. About 58% of patients in Hong Kong and 55% in Atlanta were males. While 58% of controls in Hong Kong and 42% in Atlanta were males.
Based on symptoms, 75% of Hong Kong patients and 18% of Atlanta patients had mild to moderate COVID-19. Around 14% of Hong Kong patients and 60% Atlanta patients had severe symptoms but not admitted to intensive care. About 11% of Hong Kong patients and 18% of Atlanta patients were admitted to intensive care. Approximately 20% of Hong Kong patients were given interferon, 19% were given corticosteroids, and 61% were given antivirals as intervention to their symptoms.
Using mass cytometry and other tests, they examined the immune response among these individuals. The tests helped enhance the molecules involved in blood inflammation among COVID-19 patients. Results highlighted three molecules with significant correlation to lung inflammation in other illnesses. These three were not found before in COVID-19 cases.
Next, results highlighted the elevated levels of bacterial debris, such as bacterial DNA and materials from bacterial cell walls, among COVID-19 patients with severe symptoms. The greater the debris, the sicker patients were. They also exhibited higher pro-inflammatory chemicals in their blood, compared to those with milder symptoms. Researchers interpreted these results as bacterial debris reaching the bloodstream, which triggered inflammation in the circulatory system.
But what surprised researchers had been the bizarre activity of certain immune cells. Results unveiled the sluggish performance of some innate immune cells. Normally, these cells should have been highly active and rapid in fighting SARS-CoV-2. The cells among COVID-19 patients were determined inactive or quiet, as if paralyzed. This led a question to their minds: what released the inflammatory signals in the bloodstream if the immune cells were less vigilant?
Typical sources of inflammation signals are immune cells to alarm nearby healthy cells. The signals will cause healthy cells to pass the message to other friendly cells. This ensures the call for reinforcement to effectively contain the situation. Other blood cells do not release these chemicals because they lack the capability. So, where do these signals originated?
Researchers suggested in the site of infection: the lungs. Although inflammatory signals are exclusive to immune cells, other cells can utilize several means to call for help. They can produce danger signals to stimulate inflammation and notify an infection. The cells in the lung may do this to alert the immune system. But if the innate immune cells acted slowly, the inflammation within the lungs will be extended without benefit.
The inflammation will eventually damage the organs because the immune cells are too slow to respond. And since there is a problem, cells in the lungs have no choice but go on until responders arrive. This may explain why some COVID-19 patients suffer from inflammatory-related complications. The chemicals just damage the organs as the coronavirus continue its onslaught.
“These findings reveal how the immune system goes awry during coronavirus infections, leading to severe disease, and point to potential therapeutic targets,” said Dr. Bali Pulendran, the senior author of the study and professor of pathology and of microbiology and immunology at Stanford.
The study findings pointed out the lapses of innate immunity, especially against novel pathogens. These lapses may be potential targets for new therapies.