New Delhi: The ability of the immune system to combat Covid-19, like any infection, largely depends on the system's ability to replicate the immune cells effective at destroying SARS-CoV-2. However, the cloned immune cells cannot be infinitely created. According to a new study, the body's ability to create these cloned cells decreases significantly in old age.


The study, led by researchers at University of Washington, Seattle, was recently published in the The Lancet EBioMedicine. 


University of Washington research professor James Anderson, the lead author of the paper, created a model as part of the study. According to the model, the genetically predetermined limit on the immune system may be the explanation behind the devastating effect of Covid-19 on the elderly. In the paper, the researchers have detailed the modelled link between ageing, Covid-19, and mortality. 


What Happens To Telomeres Every Time Cells Divide?


In a statement issued by University of Washington, Anderson said that when DNA is split in cell division, the end cap, called a telomere, gets a little shorter with each division. He added that after a series of replications of a cell, it gets too short and stops further division. Not all cells or all animals have this limit, but immune cells in humans have this cell life, Anderson explained.


The immune system of an average person functions pretty well despite this limit until about 50 years old. Once a person crosses 50 years of age, the core immune cells, called T cells, have shortened telomeres and cannot quickly clone themselves through cellular division in large enough numbers to attack and clear the Covid-19 virus. 


Impact Of Covid-19 Virus On Immune Cells


The trait of SARS-CoV-2 is to sharply reduce immune cell numbers, Anderson said. Telomere lengths are inherited by people from their parents, he added. Therefore, there are some differences in these lengths between people at every age. Also, there are differences in how old people become before these lengths are mostly used up. 


The key difference between this understanding of ageing, which has a threshold for when the immune system has run out of collective telomere length, and the idea that all people age consistently over time is the "most exciting" discovery of the research, Anderson said.


Depending on a person's parents, and very little on how the person lives, the longevity and the response to Covid-19 is a function of who the person was at the time of birth, Anderson said. This is "kind of a big deal", he asserted.


How Was The Study Conducted


The researchers used publicly available data on Covid-19 mortality from the Centers for Disease Control and Prevention and US Census Bureau and studies on telomeres, in order to build this model. Many of the studies were published by the co-authors over the past two decades. 


Anderson said that assembling telomere length information about a person or specific demographic could help doctors know who was less susceptible. Depending on which populations and individuals may be more susceptible to Covid-19, the doctors could allocate resources, such as booster shots.


Anderson said that he is a modeller and that he sees things through mathematical equations that he is interpreting by working with biologists, but the biologists need to look at the information through the model to guide their research questions. He cautioned that the model might explain too much. 


According to Anderson, there is a lot of data supporting every parameter of the model, and there is a nice logical train of thought for how one gets from the data to the model. He said the model is so simple and intuitively appealing that people should be suspicious of it too. 


Anderson added that as a scientist, his hope is that researchers begin to further understand the immune system and population responses as part of natural selection.


Significance Of The Research


The study found that severe Covid-19 T-cell lymphopenia is more common among older adults, and entails poor prognosis, which is the likely course of a disease or ailment. Lymphopenia is a disorder in which the blood does not have enough white blood cells called lymphocytes, which help protect the body from infection, according to the US National Institutes of Health (NIH). The disorder is also called lymphocytopenia, and occurs when the lymphocyte count in the bloodstream is lower than normal. Counterbalancing the decline in T-cell count during Covid-19 demands fast and massive T-cell clonal expansion, which is dependent on the telomere length (TL).


According to the study, the model shows that an individual with average hematopoietic cell TL (HCTL) at twenty years of age maintains maximal T-cell clonal expansion capacity until the sixth decade of life. Hematopoietic cells are immature cells that can develop into all types of blood cells, including white blood cells, red blood cells, and platelets, and are also called blood stem cells. 


After the sixth decade of one's life, the capacity rapidly declines by more than 90 per cent over the next ten years. The collapse in the T-cell clonal expansion capacity coincides with the steep increase in Covid-19 mortality with age, the authors noted in the study.


Short hematopoietic cell telomere length might increase vulnerability of many older adults, and some younger individuals with inherently short hematopoietic cell telomere length, to Covid-19 T-cell lymphopenia and severe disease, the authors interpreted.