Research Roundup: Why COVID-19 Variants Evade Immunity and More

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SARS-CoV-2, the virus that causes COVID-19, has been particularly adept at mutating and creating variants that, if not more deadly, appear to be better at evading immunity from antibody treatments and the immune system after previous infections and vaccines. New research tells us what’s going on. For that and more research stories, continue reading.

Why New COVID-19 Variants Evade Antibody Treatments

It has been noted that the most recent variants of the COVID-19 virus, SARS-CoV-2, aren’t more lethal but are better at evading immunity from vaccines and antibody therapies. In particular, the subvariants of the Omicron variant appear to be much more efficient at this, partly responsible for a new surge of cases this summer. Researchers at the University of Colorado Anschutz Medical Campus published research in the journal Biochemistry analyzing the specific mutations accountable for this evasive ability.

"Earlier studies, including ours, have focused on explaining the effect of single mutations and not the mechanism underlying the co-evolution of mutations,” Krishna Mallela, Ph.D., corresponding author and professor in the department of pharmaceutical sciences at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, said. “Our study helps explain the concept of convergent evolution by balancing positive and negative selection pressures. Understanding the mechanisms underlying the antibody escape and the location of mutations in the spike protein will help in developing new antibody therapeutics that will work against new variants by targeting epitopes with minimal mutations or developing broad neutralizing antibodies that target multiple epitopes.”

They discovered that specific mutations repeatedly occur in emerging variants. One example is at three amino acid positions K417, E484 and N501, in the spike protein’s receptor binding domain (RBD). About 2.14 million variant sequences out of 4.3 million found in the GISAID database that contains these three mutations have them occurring together. Individual mutations are both beneficial and deleterious, but when they come together, they cancel each other out, which leads to improved selection of the mutations together. 

The three RBD mutations have specific and distinct roles that improve viral fitness, even when the individual mutations hurt the virus. For example, K417T escapes Class 1 antibodies and has increased stability and expression but decreases ACE2 receptor binding. E484 escapes Class 2 antibodies but decreases receptor binding, stability and expression. N501Y increases receptor binding but decreases stability and expression. When combined, the deleterious effects are canceled out. The variant with all three mutations has increased ACE2 receptor binding, escapes both Class 1 and 2 antibodies and has stability and expression similar to the wild-type virus.

Transplanting Islet Cells in Type 1 Diabetes Patients

Imagine Pharma showcased its Type 1 Diabetes Activated Islet Progenitor Cells (T1D AIPCs). T1D AIPCs are a novel cell population created from isolated type 1 diabetes human islets or from pancreas biopsies using a simple culture protocol. These T1D AIPCs secrete insulin in response to compounds that cause cells to secrete. The company’s research generated T1D AIPCs from eight different tissue/cell preparations from patients 27 to 58 years of age who had T1D for more than 15 years. The T1D AIPCs were created in large enough amounts to support autologous transplantation. They appear to be commercially viable, and because they utilize a patient’s own cells, they minimize the need for immunosuppressants. As such, this approach has the potential to develop insulin independence in type 1 diabetic patients.

Study: COVID-19 Kills More Republicans Than Democrats

A study by the University of Maryland and the University of California compared the number of COVID-19 deaths through October 2021 to counties’ voting behavior in the 2020 presidential election. The analysis considered other characteristics likely to influence COVID-19 transmission and mortality, such as age, race/ethnicity, chronic disease and access to health care. The bottom line? Counties where 70% or more voted Republican had 73 more COVID-19 deaths per 100,000 people compared to Democratic counties (where less than 30% voted Republican). The researchers found that the disparities were largely due to structural, policy and behavioral differences in the more conservative counties.

Senior author Dylan Roby, Ph.D., associate professor of health, society and behavior in the UC Irvine Program in Public Health, said, “Voting behaviors at the county level are likely to represent the compliance or lack of compliance with mask mandates, vaccine uptake and use of other protective policies to mitigate the impacts of the pandemic.”

Is Schizophrenia an Autoimmune Disease?

Tokyo Medical and Dental University research found that some people with schizophrenia have autoantibodies against NCAM1. This is a protein essential for communication between brain cells. Researchers then tested these autoantibodies in mice and noted they appeared to cause schizophrenia-related behaviors in the laboratory animals. NCAM1, or neural cell adhesion molecule, appears to help cells in the brain communicate with one another via synapses. It was previously thought that this autoantibody might be associated with schizophrenia. In their study, they searched for autoantibodies against NCAM1 in about 200 healthy controls and in 200 patients with schizophrenia. They found the autoantibodies in 12 schizophrenia patients, which they suggest might mean it is associated with a small subset of schizophrenia cases. The further tests in laboratory mice did indicate an actual effect, with very little exposure to the autoantibodies leading to changes in behavior and synapses similar to what was observed in schizophrenic humans.

In 2020, COVID-19 Made Up 62% of Duty-Related Law Enforcement Deaths

In 2020, 295 law enforcement officers in the United States lost their lives related to their duties. And according to the National Law Enforcement Officer Memorial Fund database and the University at Buffalo, 62% of those deaths were COVID-19-related. The study published in Policing: An International Journal found that COVID-19 made up 82% of deaths among Black law enforcement members and 77% of deaths among Latinx officers; it was only 48% among white police officers.

“The study’s finding that the majority of law enforcement deaths in 2020 were from COVID-19 reveals the added danger that law enforcement face during this pandemic,” John Violanti, Ph.D., the study’s first author and research professor of epidemiology and environmental health in UB’s School of Public Health and Health Professions said. He is also a retired New York State Trooper and an expert in police stress. “Law enforcement were continuously exposed to the disease and were mandated to assist others in prevention and cure. The study should prompt police and other organizations to make informed decisions about preparation or any future disease outbreaks.”

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