A team from Lawson Health Research Institute and Western University has made significant steps in understanding COVID-19 through two back-to-back studies published in Critical Care Explorations. In one study, the team identified six molecules that can be used as biomarkers to predict how severely ill a patient will become. In the other study, they revealed for the first time a new mechanism causing blood clots in COVID-19 patients and potential ways to treat them.
The studies were conducted by analyzing blood samples from critically ill patients at London Health Sciences Centre (LHSC). They build on a growing body of work from the team that was first to profile the body’s immune response to the virus by revealing six molecules that could act as potential targets to treat hyperinflammation in critically ill patients.
Dr Douglas Fraser, lead researcher from Lawson and Western’s Schulich School of Medicine & Dentistry, and a critical care physician at LHSC, clarifies that the findings need to be validated with larger groups of patients, but they could have important implications for treating and studying this disease.
Predicting which COVID-19 patients will get worse
When patients are admitted to ICU, care providers wait to see if they are going to get worse before considering risky interventions. Dr Fraser explains that to improve outcomes they need new therapies but also a way to predict which patients are going to get worse.
The researchers identified six molecules of importance (CLM-1, IL12RB1, CD83, FAM3B, IGFR1R, and OPTC). They found that these molecules were elevated in COVID-19 patients who would become even more severely ill, and when measured on a COVID-19 patient’s first day of ICU admission, the molecules could be used to predict which patients will survive following standard ICU treatment.
The team measured 1161 plasma proteins from the blood of 30 participants: 10 COVID-19 patients, 10 patients with other infections admitted to LHSC’s ICU, and 10 healthy control participants. Blood was drawn on set days of ICU admission, processed in a lab, and then analyzed using statistical methods and artificial intelligence.
The team notes that predicting a patient’s disease severity can help by allowing medical teams to have important conversations with family members, and setting goals of care based on the patient’s health and personal wishes. Medical teams could use the knowledge to mobilize resources more quickly. If they know a patient is at higher risk of death, they may consider intervening sooner despite associated risks. The team also hopes the findings can be used to better design COVID-19 clinical trials by grouping patients based on their risk. This could allow for stronger results when examining potential treatments for the disease.
Understanding why blood clots occur and how to treat them
A major complication occurring in most critically ill COVID-19 patients is clotting in the small blood vessels of the lungs, which leads to low oxygen levels in the body. The reason for this clotting has been unclear. The team further analyzed the blood samples from their 30 participants and found evidence to suggest that the inner linings of small blood vessels become damaged and inflamed, making them a welcoming environment for platelets to stick.
They discovered that COVID-19 patients had elevated levels of three molecules (hyaluronic acid, syndecan-1, and P-selectin.) The first two molecules are products broken down from the glycocalyx that lines the inside of the blood vessels. Their presence suggests the glycocalyx is being damaged with its breakdown products sent into the bloodstream. The presence of P-selectin is also significant as this molecule helps to make platelets and the inner lining of blood vessels adhere to one another. The team suggests that two therapies may hold promise for treating blood clots in COVID-19 patients: platelet inhibitors to stop platelets from sticking and molecules to protect and restore the inner lining of blood vessels.
The two articles are “Novel outcome biomarkers identified with targeted proteomic analyses of plasma from critically ill coronavirus disease 2019 patients” (doi: 10.1097/CCE.0000000000000189) and “Endothelial injury and glycocalyx degradation in critically ill coronavirus disease 2019 patients: Implications for microvascular platelet aggregation” (doi: 10.1097/CCE.0000000000000194).
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