Medical Bulletin 22/January/2024

Here are the top medical news of the day:

Evolution of the human immune system in the post-Omicron era

It has been 4 years since the start of the COVID-19 pandemic. SARS-CoV-2 has yet to be eradicated and new variants are continuously emerging. Despite the extensive immunization programs, breakthrough infections (infection after vaccination) by new variants are common. New research suggests that human immune responses are also changing in order to combat the never-ending emergence of new SARS-CoV-2 variants. Specifically, it has been discovered the immune system that encountered breakthrough infection by the Omicron variant acquires enhanced immunity against future versions of the Omicron.

A team of South Korean scientists led by Professor SHIN Eui-Cheol of the Korea Virus Research Institute Center for Viral Immunology within the Institute for Basic Science (IBS) announced that the memory T cells that form during the Omicron breakthrough infection respond to subsequent strains of the virus.

Emerging in late 2021, the SARS-CoV-2 Omicron variant had drastically increased transmissibility in comparison to its predecessors, which quickly allowed it to become the dominant strain in 2022. New strains of Omicron have kept emerging ever since then. Starting with BA.1 and BA2, BA.4/BA.5, BQ.1, XBB strains, and more recently JN.1 strains were among the new strains of the Omicron variant. This has led to widespread breakthrough infection despite vaccination.

After becoming infected or vaccinated, the body creates neutralizing antibodies and memory T cells against the virus. The neutralizing antibody serves to prevent host cells from being infected by the virus. While memory T cells cannot prevent the infection, they can quickly search and destroy infected cells, preventing the viral infection from progressing into a severe disease.

The research team selected patients who suffered then recovered from BA.2 Omicron breakthrough infection in early 2022 as subjects and conducted studies on their memory T cells, specifically in their ability to respond to various Omicron variants such as BA.2, BA.4/BA/5, and others. In order to do so, immune cells were separated from the peripheral blood of the subjects, and the memory T cells' cytokine production and anti-viral activities in response to various spike proteins from different variants were measured.

The results showed that the memory T cells from these patients showed heightened response against not only the BA.2 strain but the later BA.4 and BA.5 strains of Omicron as well. By suffering from breakthrough infection, these patients' immune system was strengthened to combat future strains of the same virus. The research team also discovered the specific part of the spike protein which is the primary cause of the observed enhancement in the memory T cells. These results show that once a person undergoes breakthrough infection by the Omicron infection, it is unlikely for them to ever suffer severe COVID-19 symptoms from the future emerging variants.

Reference: Evolution of the human immune system in the post-Omicron era; Science Immunology;DOI: 10.1126/sciimmunol.adg8691

Bacterial meningitis damages one in three children for life

One in three children who suffer from bacterial meningitis live with permanent neurological disabilities due to the infection. This is according to a new epidemiological study led by Karolinska Institutet and published in leading medical journal JAMA Network Open.

For the first time, researchers have identified the long-term health burden of bacterial meningitis. The bacterial infection can currently be cured with antibiotics, but it often leads to permanent neurological impairment. And since children are often affected, the consequences are significant.

"When children are affected, the whole family is affected. If a three-year-old child has impaired cognition, a motor disability, impaired or lost vision or hearing, it has a major impact. These are lifelong disabilities that become a major burden for both the individual and society, as those affected need health care support for the rest of their lives," says Federico Iovino, associate professor in Medical Microbiology at the Department of Neuroscience, Karolinska Institutet, and one of the authors of the current study.

By analyzing data from the Swedish quality register on bacterial meningitis between 1987 and 2021, the researchers have been able to compare just over 3,500 people who contracted bacterial meningitis as children with just over 32,000 matched controls from the general population. The average follow-up time is over 23 years.

The results show that those diagnosed with bacterial meningitis consistently have a higher prevalence of neurological disabilities such as cognitive impairment, seizures, visual or hearing impairment, motor impairment, behavioral disorders, or structural damage to the head.

The risk was highest for structural head injuries - 26 times the risk, hearing impairment - almost eight times the risk, and motor impairment - almost five times the risk.

About one in three people affected by bacterial meningitis had at least one neurological impairment compared to one in ten among controls.

“We are trying to develop treatments that can protect neurons in the brain during the window of a few days it takes for antibiotics to take full effect. We now have very promising data from human neurons and are just entering a preclinical phase with animal models. Eventually, we hope to present this in the clinic within the next few years," says Federico Iovino.

Reference: Bacterial meningitis damages one in three children for life; JAMA Network Open; DOI: 10.1001/jamanetworkopen.2023.52402

Research into the nature of memory reveals how cells that store information are stabilized over time

Think of a time when you had two different but similar experiences in a short period. Maybe you attended two holiday parties in the same week or gave two presentations at work. Shortly afterward, you may find yourself confusing the two, but as time goes on that confusion recedes and you are better able to differentiate between these different experiences.

New research published in Nature Neuroscience published on January 19, reveals that this process occurs on a cellular level, findings that are critical to the understanding and treatment of memory disorders, such as Alzheimer’s disease.

The research focuses on engrams, which are neuronal cells in the brain that store memory information. “Engrams are the neurons that are reactivated to support memory recall,” says Dheeraj S. Roy, PhD, one of the paper’s senior authors and an assistant professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. “When engrams are disrupted, you get amnesia.”

In the minutes and hours that immediately follow an experience, he explains, the brain needs to consolidate the engram to store it. “We wanted to know: What is happening during this consolidation process? What happens between the time that an engram is formed and when you need to recall that memory later?”

The researchers developed a computational model for learning and memory formation that starts with sensory information, which is the stimulus. Once that information gets to the hippocampus, the part of the brain where memories form, different neurons are activated, some of which are excitatory and others that are inhibitory.

When neurons are activated in the hippocampus, not all are going to be firing at once. As memories form, neurons that happen to be activated closely in time become a part of the engram and strengthen their connectivity to support future recall.

“Activation of engram cells during memory recall is not an all or none process but rather typically needs to reach a threshold (i.e., a percentage of the original engram) for efficient recall,” Roy explains. “Our model is the first to demonstrate that the engram population is not stable: The number of engram cells that are activated during recall decreases with time, meaning they are dynamic in nature, and so the next critical question was whether this had a behavioral consequence.”

Reference: Research into the nature of memory reveals how cells that store information are stabilized over time; Nature Neuroscience