Research Roundup: Why COVID-19 Is More Severe in the Elderly and Men and More
Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.
Studies Suggest Why COVID-19 is Deadlier in the Elderly and Men
COVID-19 tends to be much more severe in the elderly and in males. Why is not completely understood. Researchers at the University of Washington, Nicole Lieberman and Alexander Greninger, suggest that the response may depend on viral load and the time-course of infection. The research team isolated and sequenced viral RNA from swabs collected from 430 positive COVID-19 patients and 54 negative controls. They then analyzed the patients’ antiviral and immune responses across infection status, viral load, age and sex. The research was published in PLOS Biology.
They found that immune cell responses were not activated until about three days after the onset of infection. They also found that immune cell composition and function varied depending on viral loads in a way that suggested a dysfunctional antiviral response in males and the elderly. The authors note that older people have decreased expression of the Th1 chemokines CXCL9/10/11 and their cognate receptor CXCR3, in addition to CD8A and granzyme B. This suggest deficiencies in tracking and/or function of cytotoxic T-cells and natural killer (NK) cells. And males, compared to females, have reduced B-cell-specific and NK cell-specific transcripts and an increase in inhibitors of nuclear factor kappa-B (NF-kB) signaling, which may inappropriately “throttle” antiviral responses.
The authors wrote, “Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time with observed differences due to age and sex that may contribute to disease severity.”
One problem with the study is the swabs were taken from the nasopharynx. The authors point out this is not a sensitive anatomic location for accurately examining markers of systemic inflammation.
Protein Injection Induces Remission of Type 2 Diabetes in Rodents
Scientists at the University of Washington Health Sciences/UW Medicine experimented with a single surgical injection of a protein called fibroblast growth factor 1 into the rats with type 2 diabetes. The injection appeared to restore blood sugar levels to normal, but why is not well understood. In two studies, it appears that cellular responses seem to safeguard brain-signaling pathways needed to keep blood sugar under control. A second study found that extracellular matrix assemblies called perineuronal nets that enmesh neurons are involved in blood sugar control. The fibroblast growth factor 1 appears in perineuronal nets that have been damaged by diabetes.
Investigational Drug Halts Toxic Proteins Linked to Neurodegenerative Diseases
Researchers at the University of Pennsylvania School of Medicine found that an investigational drug that targets an instigator of the TDP-43 protein, associated with ALS and frontotemporal dementia (FTD), decreased the buildup of the protein and neurological decline associated with the disorders. The preclinical research was conducted by scientists at Penn Medicine and Mayo Clinic. The study showed how toxic poly(GR)(glycine-arginine repeat) proteins produced by the mutated C9orf72 gene stimulate the clumping of TDP-43 found in ALS and FTD. Using an antisense oligonucleotide (ASO) pipeline drug, c9ASO, it decreased the levels of poly(GR), TDP-43 clumps and the neurodegeneration induced by it.
Researchers Develop Algorithm to Predict the Risk of Esophageal Cancer
Investigators with the European Molecular Biology Laboratory – European Bioinformatics Institute developed a statistical model that analyzes genomic data to predict a patient’s risk of developing esophageal cancer. The scientists sequenced genomes from biopsies routinely collected from patients with Barrett’s esophagus, who are routinely monitored for early signs of esophageal cancer. They developed their model based on each patient’s individual risk. They found that in genomic data from 88 patients with Barrett’s esophagus, half who were diagnosed with esophageal cancer were “high risk” more than eight years before diagnosis. The figure went up to 70% two years before diagnosis. The model also accurately predicted patients who were at very low risk of developing cancer.
Lack of Oxygen Promotes Tumor Metastasis
Researchers at the University of Basel, Switzerland, identified lack of oxygen as a trigger for tumor metastasis. Typically, recovery is much worse after cancer spreads. Earlier research demonstrated that metastases are formed by clusters of cancer cells that separate from the primary tumor and move through the bloodstream to new tissue. The researchers’ study indicates that lack of oxygen is the cause of the CTC clusters separating from the tumor. Different parts of a tumor are supplied with different levels of oxygen—those with a lack of oxygen were found wherever the tumor had fewer blood vessels. They found that the group that separated from the tumor had suffered from a lack of oxygen, “as though too many people are crowded together in a small space,” said Nicola Aceto, who led the research. “A few will go outside to find some fresh air.”
This may lead to new therapeutic approaches. The experiments showed that the CTC clusters with lower oxygen levels are especially dangerous. Compared to clusters with normal oxygen content, they metastasized faster and decreased the laboratory animals’ survival time. They believe that stimulating blood vessel formation might be a treatment approach—at odds with therapies that work by starving blood vessel growth. The research was published in the journal Cell Reports.
“This is a provocative result,” Aceto said. “If we give the tumor enough oxygen, the cancer cells have no reason to leave the tumor and metastasize. On the other hand, this accelerates the growth of the primary tumor. But we speculate that substances that improve oxygen supply to the tumor can inhibit the formation of metastases in breast cancer, alone or in combination with other agents.”