Research Roundup: COVID-19 Cognitive Impairment Equal to 20 Years of Aging
By now, the complexity of COVID-19 is well known, if not well understood. One of the mysteries is so-called “brain fog,” or cognitive issues such as confusion or forgetfulness that occur as a result of Long Covid. New research is quantifying this. Here’s a look at that story and other research news.
COVID-19 Cognitive Impairment Equal to 20 Years of Aging
A study from the University of Cambridge and Imperial College London found that cognitive impairment caused by severe COVID-19 is similar to that sustained between 50 and 70 years of age. Another way of putting it is that it was equal to losing 10 IQ points. The research came out of the NIHR COVID-19 BioResource and found the effects were still detectable more than six months after acute illness, and recovery is — at best — gradual. The research was published in The Lancet's publication eClinicalMedicine.
“Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw — the cognitive ‘fingerprint’ of COVID-19 — was distinct from all of these,” said Dr. David Menon, M.D. from the Division of Anaesthesia at the University of Cambridge, the study’s senior author. “We followed some patients up as late as ten months after their acute infections, and were able to see a very slow improvement. While this was not statistically significant, it is at least heading in the right direction, but it is very possible that some of these individuals will never fully recover.”
The reason behind the cognitive deficits seen with COVID-19 is not well understood. One theory is that direct viral infection may be to blame, but scientists don’t believe it is a major cause. They think it is more likely that a combination of factors is involved, including poor oxygen and blood supply to the brain, blockage of large or small blood vessels from clotting and microscopic bleeds. Emerging evidence suggests the most significant factor may be damage from the body’s own inflammatory and immune response.
Repairing Tendons with Silk Proteins
Tendon injuries take a long time and often don’t heal completely. Some of this is related to the relative lack of blood flow to the tendons and the fact they are soft tissues connected to stiff bones. Damage often changes the connective tissue from a linear to a kinked formation.
Investigators with the Terasaki Institute for Biomedical Innovation tested the use of biomaterial scaffolds to generate new tendon tissue. They started with silk fibroin, a silk protein generated by the Bombyx mori silkworm. It is used in silk fabrics and optical and electrical devices, and in several biomedical applications, including sutures and bioengineered ligaments, bone and corneal tissue.
They paired silk fibroin with GelMA, a gelatin-based, water-retaining gel. The mixtures were seeded with mesenchymal stem cells. They found that cell viability and proliferation and MSC gene activity were significantly increased, showing more than an 80% attachment rate. They also tested them on live rats with injured Achilles tendons, and the new technology accelerated healing with reduced injury sites and the formation of well-aligned, densely packed tendon fibers and remodeled muscle components.
Decreased Sedentary Time Mitigates Risk of Type 2 Diabetes & CV Disease
Research from the University of Turku in Finland found that decreasing the amount of time you’re sedentary can mitigate the risk of type 2 diabetes and cardiovascular diseases. This is a slightly different lens than the association of exercise with decreased risk of diabetes and CV disease in that it looked at reducing the intervention group’s time sitting by one hour per day by increasing standing and light-intensity physical activity.
The control group was to keep their typical habits and sedentary lifestyle. The groups were measured by wearing accelerometers for the entire three-month period. The intervention group decreased sedentary time by 50 minutes per day on average, typically by increasing the amount of light- and moderate-intensity physical activity. The study observed benefits in health outcomes associated with blood sugar regulation, insulin sensitivity and liver health.
Nanotechnology Visualizes RNA Structure at Near-Atomic Resolution
Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School developed a new approach, ROCK, that uses an RNA nanotechnological technique to visualize RNA structure at near-atomic resolution. ROCK stands for “RNA oligomerization-enabled cryo-EM via installing kissing loops.” It allows for assembly of identical RNA molecules into a highly organized structure. This decreases the individual RNA molecules’ flexibility and increases their molecular weight.
It allows for structural analysis of the contained RNA subunits using the cryo-electron microscopy (cryo-EM) technique. For proof-of-principle, they focused on a large intron RNA from Tetrahymena, a single-celled organism, and a small intron RNA from Azoarcus, a nitrogen-fixing bacterium in addition to the FMN riboswitch.
Autism-Linked Mutation Reversed in Brain Organoids with Gene Therapy
A study out of the University of California San Diego School of Medicine utilized human brain organoids to test a gene therapy. A number of neurological and neuropsychiatric diseases, including autism spectrum disorders (ASD) and schizophrenia, are linked to Transcription Factor 4 (TCF4) mutations. TCF4 is an essential gene in brain development. The researchers focused on Pitt-Hopkins Syndrome, an ASD caused by mutations in TCF4.
Existing mouse models of the syndrome don’t accurately mimic patients’ neural characteristics. As a result, the research team created a human research model of the disorder using stem cells to convert patients’ skin cells to develop into three-dimensional brain organoids. They found that the TCF4 mutation led to downstream dysregulation of SOX genes and the Wnt pathway. These molecular signals guide embryonic cells to multiply, mature into neurons, and migrate to the appropriate brain location.
They then tested two different gene therapies for recovering the functional gene in brain tissue. Both effectively increased TCF4 levels and corrected Pitt-Hopkins Syndrome characteristics at molecular, cellular and electrophysiological levels.
“The fact that we can correct this one gene and the entire neural system reestablishes itself, even at a functional level, is amazing,” Alysson R. Muotri, Ph.D. said, professor at UC San Diego School of Medicine, director of the UC San Diego Stem Cell Program and member of the Sanford Consortium for Regenerative Medicine.
The work took place at a prenatal stage of brain development. Children diagnosed with this syndrome do so typically several years later in the clinic. Clinical trials would be required to confirm if a later intervention would be safe and effective. The research group is currently optimizing its licensed gene therapy tools for a trial, which would use spinal injections of the genetic vector in hopes of recovering TCF4 brain function.