Research Roundup: Timing the Immune Response of COVID-19 and More

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

Timing the Immune Response of COVID-19

A study from the Keck School of Medicine at USC suggests that temporarily suppressing the immune system during the early stages of COVID-19 can avoid severe symptoms. This is related to research showing an interaction between the body’s two primary lines of defense may be overstimulating the patients’ immune system. The research was published in the Journal of Medical Virology.

“Some COVID-19 patients may experience a resurgence of the disease after an apparent easing of symptoms,” said Sean Du, adjunct researcher and lead author of the study. “It’s possible that the combined effect of the adaptive and the innate immune responses may reduce the virus to a low level temporarily. However, if the virus is not completely cleared, and the target cells regenerate, the virus can take hold again and reach another peak.”

As a result of what they call a “counterintuitive idea,” they are proposing a short regimen of an appropriate immunosuppressant drug applied early in the disease. Du said, “With the right suppressive agent, we may be able to delay the adaptive immune response and prevent it from interfering with the innate immune response, which enables faster elimination of the virus and the infected cells.”

The body’s innate immune response begins right after infection. The second line of defense is the adaptive immune response, which doesn’t start for several days if any virus remains. It uses what it has learned about the virus to marshal a variety of T-cells and B-cells to attack the remaining virus. COVID-19, which targets surface cells throughout the respiratory system, has an average incubation of six days and a slower disease progression than, for example, the flu. The adaptive immune response, they believe, may start before the target cells are depleted, which slows down the infection and interferes with the innate immune response’s ability to kill off most of the virus.

High Blood Pressure Medications Safe for COVID-19 Patients

One of the clear comorbidities for COVID-19 is high blood pressure. NYU Langone Health/NYU School of Medicine studied 12,594 patients to determine if common high blood pressure drugs increased the risk of contracting the disease or of developing severe disease. The study found no links between treatment with four drug classes: angiotensin-converting enzyme (ACE) inhibitors; angiotensin receptor blockers (ARBs); beta blockers; or calcium channel blockers. They also did not find an increased likelihood of a positive test for COVID-19 in people taking these medications.

Researchers ID Protein Linked to Lyme Disease Arthritis

Investigators at Washington State University identified a surface protein called VIsE that prevents the immune system from fighting Lyme disease. In particular, the study looked at how VIsE protects one of the primary protein’s response for persistent arthritis in the disease. This is one step closer to being able to develop a vaccine against Lyme.

Korean Researchers ID 2 Already Approved Drugs that Show Promise Against COVID-19

Korean investigators screened 48 FDA-approved drugs against SARS-CoV-2 and identified two that showed promise. One is niclosamide, marketed by Bayer under the name Niclocide, as well as by others, and is used to treat tapeworm infections. The drug generally has slow absorption, which would likely diminish its effectiveness for COVID-19. The second is ciclesonide, an inhaled corticosteroid used to treat asthma and allergic rhinitis.

Activating an Estrogen Receptor Shows Promise for Halting Pancreatic Cancer

Scientists at the University of Pennsylvania School of Medicine found that activating the G protein-coupled estrogen receptor (GPER), found on the surface of many normal and cancer tissues, appears to stop pancreatic cancer from growing. It also appears to make the cancer cells more visible to the immune system, meaning it should improve immunotherapy. It has generally been noted that women have better outcomes than men for most cancer types. But, the concept that cancers in non-reproductive tissues may also be influenced by sex steroid hormones is a fairly recent concept.

Key Insight into Prion Diseases

An infectious prion is a protein without nucleic acid, linked to mad cow disease and similar disease in humans, Creutzfeldt-Jakob disease, as well as fatal familial insomnia and kuru. These diseases are always fatal and very poorly understood how prions actually cause disease. Tricia Serio, dean of the College of Natural Sciences and professor of biochemistry and molecular biology at University of Massachusetts Amherst, identified a key piece of the puzzle. It has been known that prion protein (PrP) misfolding is part of the disease process. In mammals, the protein quality control system responds to folding mistakes with “chaperone” molecules that search for misfolds and attempt to correct the mistakes. Prions misfold so fat chaperones can’t keep up. The new finding was that prion aggregates come in different sizes—for the same protein—and it turns out that the seed complex has to double in size for the disease to persist. The minimum size of the prion determines whether the chaperone can win.

Genetic Complexity and Redundancy Complicates Precision Medicine

Precision medicine is the concept that each person’s genetic makeup uniquely affects their response to drugs. Mapping of the human genome, completed in 2003, opened up the field. Researchers with McMaster University, noting that precision and personalized medicine hasn’t quite lived up to its promise, undertook a massive review of decades of research in the field, which they published in Genomic Medicine.

Their review found that “unnecessary” complexity in evolutionary pathways need to be further understood, right down to the level of genomic variations between individual cells in the same person, before personalized medicine can be leveraged effectively.

“Our bodies have an immense ability to change and to cope with issues that arise,” said Bhagwati Gupta, who conducted the research with fellow evolutionary biologist Rama Singh. “Context matters in our genome. Even a simple mutation can have a profound effect on the body, when acting in combination with others.”

The authors note that individual genes don’t determine sickness or health on their own. They interact with groups of other genes and the environment in ways that are only starting to be understood.

“The idea has long been that individual genetic mutations could be classified as good, bad or neutral,” Singh says. “Genes, though, do not work alone, and so no single gene can be considered to be good, bad or neutral in all contexts.”