Research Roundup: Explaining Rare Immune Response in Children with COVID-19 and More

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

Explaining Rare Immune Response in Children Infected with COVID-19

Children generally have fewer symptoms than adults with COVID-19, and are typically less prone to infection. One of the rare symptoms in children is multi-system inflammatory response (MIS-C), which occurs in about one in 1,000 children infected with COVID-19. This is usually observed four to six weeks after confirmed SARS-CoV-2 infection, and is marked by a range of symptoms, including fever, abdominal pain with vomiting and/or diarrhea, rash, and cardiovascular and neurological issues. When diagnosed early, it is easily treated with steroids or other immune suppressants. If untreated, it can be deadly.

Researchers at Yale University published new research in the journal Immunity describing what is happening in children with MIS-C. They analyzed blood samples from children with MIS-C, adults with severe COVID-19, and healthy children and adults. In the children with MIS-C, they identified immune system biomarkers, specifically high levels of alarmins. These molecules are part of the innate immune system that is stimulated quickly to respond to all infections. They were also found to have an increased amount of specific adaptive immune responses that usually are associated with the development of immunological memory. But instead of being protective, they seem to behave like an autoimmune disease and attack host tissues.

“Innate immunity may be more active in children who are infected with virus,” said Carrie Lucas, an assistant professor of immunobiology at Yale and corresponding author of the study. “But on the flip side, in rare cases it may get too revved up and contribute to this inflammatory disease.”

Whole New Set of Proteins Associated with Dementia and Alzheimer’s Risk

Scientists at Johns Hopkins University Bloomberg School of Public Health identified dozens of proteins that appeared in the blood at abnormal levels up to five years before people demonstrated symptoms of dementia and Alzheimer’s. The researchers analyzed blood samples from more than 10,000 middle-aged and elderly individuals, samples that were stored from large-scale studies for several decades. They linked abnormal blood levels of 38 proteins to people at higher risk of developing Alzheimer’s within five years. Of those 38, 16 seem to predict Alzheimer’s risk two decades ahead. One in particular, SVEP1, appears to be a likely contributor to the disease process. They published their research in the journal Nature Aging.

“This is the most comprehensive analysis of its kind to date, and it sheds light on multiple biological pathways that are connected to Alzheimer’s,” said Josef Coresh, senior author, and the George W. Comstock Professor in the Department of Epidemiology at the Bloomberg School. “Some of these proteins we uncovered are just indicators that disease might occur, but a subset may be causally relevant, which is exciting because it raises the possibility of targeting these proteins with future treatments.”

Possible Link Between Migraine with Aura and Blood Clot Factors

Investigators with Brigham and Women's Hospital identified four blood coagulation measures that appeared linked to susceptibility to migraine with aura. However, there did not appear to be a relationship between the blood coagulation factors and migraine without aura. The factors are coagulation factor VIII, von Willebrand factor, phosphorylated fibrinopeptide A, and genetically decreased levels of fibrinogen. It is still unknown if the factors are causative—which is to say, which comes first, the migraine with aura or the increased levels of those coagulation factors?

New Insights into Tau Proteins in Alzheimer’s Disease

Tau is one of two proteins that abnormally accumulate in in the brains of Alzheimer’s victims (the other is beta-amyloid). It has been known for some time that an inhaled anesthetic, sevoflurane, promotes the brain changes of Alzheimer’s disease. A study by Massachusetts General Hospital found that in mice, sevoflurane caused tau to leave neurons and enter microglia, a type of immune cell found in the brain. This shift led to inflammation and cognitive impairment. They found the mechanisms for this, which involves phosphorylation of the tau protein. They hope that this will lead to new approaches to dealing with phosphorylated tau and its spread.

New Immunotherapy Appears Highly Effective Against Hepatitis B

Researchers at University College London (UCL) identified a new immunotherapy against hepatitis B virus (HBV). They isolated immune cells directly from the patient’s liver and tumor tissue and demonstrated that targeting acyl-CoA: cholesterol acyltransferase (ACAT), was highly effective at boosting immune responses. ACAT is an enzyme that is involved in managing cellular cholesterol levels. They found that blocking the activity of ACAT with ACAT inhibitors increased the specific immune cells that battle the virus and associated cancerous tumors. It also slowed down HBV’s replication, acting as a direct antiviral.

Retinal Blood Vessel Deterioration Possible Early Indicator of Alzheimer’s Disease

Investigators at UCSF Weill Institute for Neurosciences believe that retinal scans can identify key changes in blood vessels that might be early signs of Alzheimer’s. One of the key genetic risk factors for Alzheimer’s is the APOE4 gene variant, although it is not understood exactly what its role is in the disease. The researchers were studying the effect of APOE4 on capillaries in the brain of mice. But since there is no technology to study brain capillaries in humans, they looked at retinas of the eye in people. They found that APOE4-associated capillary changes can be detected in humans via an easy, painless eye scan. In retina scans, they found reduced capillary density in APOE4 carriers, an effected that increased with participant age. They then compared the abnormalities seen in OCTA scans of retinal capillaries to measurements of the flow of blood through the brain measured by way of MRI. They found that patients with higher retinal capillary density had greater blood flow in the brain.

“This is the first time that we have demonstrated in living, asymptomatic humans that the smallest blood vessels are affected in APOE4 gene carriers,” said Fanny Elahi, lead author, an assistant professor of neurology and member of the UCSF Memory and Aging Center (MAC). This suggests that increased risk of brain degeneration and Alzheimer’s disease in APOE4 carriers may be because of its effect on blood vessels. “This is just the beginning. But the implications for early detection and possible intervention can be significant in combating Alzheimer’s disease and other neurodegenerative disorders. It’s much harder to regenerate neurons than to stop their degeneration from happening in the first place. Similar to cancer, early detection can save lives.”