Why do some people become extremely ill with COVID-19, while others have angry symptoms? Three key molecules seem to play a crucial role, new research opened this week.
These important indicators, all found in the bloodstream of critically ill patients, can be characterized as specific cytokines, as hormonal molecules produced by the immune cells in the body that can regulate immune response. During overproduction, cytokines accelerate the inflammation and can produce serious results.
Their scientific names may not mean much to the average reader – EN-RAGE, TNFSF14 and oncostatin-M – but researchers at Stanford University School of Medicine, in consultation with others in Atlanta and Hong Kong, believe that these specific molecules could help to accurately to alleviate what happens in the body’s immune system when fighting COVID-19.
“One of the great mysteries of COVID-19 infections was that some people develop serious illness while others seem to recover,” said Bali Pulendran, senior author of the study and Stanford professor of pathology, microbiology and immunology. “Now we have some insight into why that happens.”
Researchers found higher levels of these molecules in the blood of very sick patients. The scientists are now working to block the activity of these molecules as potential therapy for the disease, and hope to help very sick patients whose immune system overreacts to the virus.
The study, published in the journal Science on Tuesday, looked at the responses of the immune system of 76 COVID-19 patients and 69 non-infected people from Princess Margaret Hospital at Hong Kong University and the Hope Clinic at Emory University. in Atlanta.
When an infection like COVID-19 strikes, the body’s infected immune system produces cytokines, which help the body fight the virus. If too many cytokines are produced, it causes the immune system to malfunction and start attacking the body, which can create life-threatening symptoms.
The three specific molecules found in high levels in the most ill patients were not previously identified in COVID-19 patients, the Stanford study shows. Researchers are now testing therapeutic drugs that target these molecules as potential treatments. One medication that is expected to reduce the activity of the TNFSF14 molecule, also called LIGHT, will reduce inflammation. It is similar to the anti-inflammatory steroid dexamethasone, mentioned for improving outcomes for extremely ill coronavirus patients, but is more targeted and could be more effective against one of the most produced molecules in those patients.
Pulendran and other Stanford researchers are conducting a study in September to test the drug on hamsters. If successful, they will test it on nonhuman primates, then humans.
The study also found high levels of bacterial puncture in the blood of extremely ill COVID-19 patients. The authors of the study believe that these traveled from the lungs or intestines to the bloodstream, causing the far-reaching effects of the infection. The scientists think that waste contributes to the overproduction of the molecules found in very sick patients. They hope that another study of the progression of the disease will reveal more.
The authors of the study found something else surprising: Even though there was restless inflammation in the lungs of very ill patients, the domestic immune system was suppressed in their blood. Researchers want to study what this means for recovering COVID-19 patients, for example, whether they may be vulnerable to influence in blood.
While researchers now know more about what happens in the body’s immune system when someone becomes seriously ill with COVID-19, it’s not yet clear what causes that response. People with health conditions, such as diabetes, are more susceptible to worse outcomes, but how those risk factors affect the state of someone’s immune system has not been scientifically studied, Pulendran said. This study did not have a broad enough sample to evaluate the impact, he added.
Pulendran and colleagues, in collaboration with Emory researchers, are now enrolling hundreds of frontline health workers without COVID-19 in a baseline study to collect blood samples every two weeks. If only participants become infected, researchers will investigate if there was anything else in those patients’ immune systems that may have made them afraid of more serious illness.
The study helps alleviate the sometimes baffling experiences of tens of thousands in the Bay Area infected with the virus. That includes a Sunnyvale family that all got COVID-19, with a hodgepodge of symptoms.
Connie Lares Ruspini, a medical interpreter at Lucile Packard Children’s Hospital Stanford, spent her birthday on April 7 on her family’s temperature and oxygen levels and listening to her lungs. Her daughter Natalia, 16, felt tired, considered her body, and she was having trouble breathing. Her husband Diego was coughing, feverish and vomiting. Ruspini herself had joint pain, a mild fever and lost her appetite. The couple both had diarrhea. Her son Santiago, 12, had no symptoms – except eating three times what he would normally.
Nanny of the family, who had pre-existing conditions, including obesity, high blood pressure and diabetes, dropped to dangerously low oxygen levels and spent about 10 days in intensive care. Diego, who has asthma, also spent a week on oxygen at the hospital.
The whole family tested negative the first week of May. The uncle was given six weeks to return home after her stay in the hospital and remains having some difficulty breathing, Ruspini said. Sometimes Diego is still tired and has tightness in his chest. In contrast, Ruspini, fully recovered, walked Mount Whitney on August 3rd.
“It was a huge shock in this family,” Ruspini said. ‘I would hope people take this seriously … because it can be devastating. We are happy, despite having a household business and sick, everyone made it through. ”
Mallory Moench is a staff writer at San Francisco Chronicle. Email: [email protected] Twitter: @mallorymoench
