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COVID-19: What Places the Elderly in Danger?

The elderly appear to be more susceptible to COVID-19, and vaccinations protect them less well. Why? Reem Dowery discovers the solution in her doctoral thesis, which she wrote under the supervision of Professor Doron Melamed. She examines the immune system’s aging process and proposes ways to rejuvenate it. The findings have been published in the journal Blood.

Memory B lymphocytes are cells found in the human body that produce effective antibodies over an extended period of time. They develop as a result of the body’s exposure to a novel infection (i.e. virus, microbe, etc.). They recognize and elicit an increased antibody response in response to subsequent exposures to the same pathogen, resulting in a faster and amplified immune response. These cells are extremely long-lived, capable of surviving and retaining immunological memory for an extended period of time. They are what vaccinations seek to induce by exposing the body to what it views as a pathogen for the first time.

It has long been recognized that the aged population’s memory B lymphocyte generation is less effective, putting them at greater risk when exposed to novel viruses such as COVID-19. For the first time, Prof. Doron Melamed’s research group at the Technion’s Ruth and Bruce Rappaport Faculty of Medicine has been able to explain why this is the case. As with many other systems in the body, the group discovered that the immune system maintains a stable state, or homeostasis. It turns out that existing memory B lymphocytes hinder the generation of new ones via hormonal cues. As a result, the human immune system gets more adept at responding to previously encountered diseases but less capable of adjusting to novel threats as it ages. The same process reduces vaccine effectiveness in protecting the elderly.

After establishing an explanation for the phenomena and elucidating the signaling channel via which it occurs, the researchers questioned if it could be able to alter or renew the immune system. Prof. Melamed’s lab cooperated with the departments of haematology and rheumatology at the Sourasky Medical Center and the Rambam Health Care Center, respectively, to address that subject. Patients with certain medical diseases (including lupus, lymphoma, and multiple sclerosis) receive B-cell depletion as part of their treatment. In other words, they lose a considerable number of memory B cells. When the scientists examined elderly individuals who had undergone this therapy, they discovered that their immune systems had been regenerated and their bodies were once again capable of producing new high-potency B cells.

By blocking one of the hormones involved in the signaling pathway that suppresses the formation of new memory B lymphocytes, a comparable impact to B-cell depletion can be achieved. Reem Dowery and Prof. Melamed’s groundbreaking proof-of-concept study paved the path for further investigation into immune system rejuvenation. Its immediate consequences include a better knowledge of the immune response in the elderly and the provision of appropriate disease prevention strategies in light of this new information, particularly in view of the present COVID-19 outbreak.

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