The group led by Sunil Ahuja of the University of Texas Health Sciences Center gathered a large number of human and animal studies in the journal “Nature Communications” to develop their concept of immune resilience. With just two parameters, she was able to explain the health history of nearly 50,000 people.
The uneven course of infection, among other things with HIV/AIDS, has long puzzled medicine, Ahuja told science.ORF.at: “If HIV-positive women had children before antiretroviral therapies were available, the children would be infected – but only ten to 30 percent of children. The same applies to people with hemophilia: unfortunately, many initially received HIV-contaminated products, but most of them did not become infected. And even after HIV infection, the disease progressed in a very different way: some were doing very well, while others died very quickly without treatment. With Covid-19 it is the same thing.”
Age is not enough as an explanation
Statistically speaking, advanced age means a greater risk of severe Covid courses, but there have also been many cases of very old people surviving the disease quite well, while young people died with no recognizable risk factors.
These atypical courses cannot be explained only by age or genetics, says the professor of medicine, microbiology, immunology and biochemistry, who researches mainly HIV/AIDS, allergies, autoimmune diseases and aging phenomena. Ultimately, the team created a combination of two factors.
Factor 1: CD4/CD8 ratio
The first of the two metrics is not new. Until now, it has been used, among other things, to measure how the immune system develops over time in HIV-infected people. It is the ratio of two types of immune cells: CD4+ helper T cells (T lymphocytes) and CD8+ cytotoxic T cells (formerly killer T cells). According to Ahuja’s group, a certain minimum number of CD4+ cells and a relative excess of CD8+ cells in comparison results in the ideal immune state.
Factor 2: Gene activity patterns
In the Covid-19 pandemic, certain patterns of activity of genes and the proteins they produce have been identified: some are dominant in people who recover quickly or who do not get sick; others were found in large numbers in those who had severe strokes, and some died. According to Ahuja, those who have a lot of the first and little of the second can better deal with infections and inflammation and also have a better chance of living a long life.
An immune resilience scale
As a result, the team developed four levels of immune health: Immune Health Grades IHG-I through -IV. According to Ahuja, these values are universal. They can be measured in all humans, in non-human primates, and also in mice. Average immune health is worse in populations chronically exposed to infections; for example, in developing countries where schistosomiasis is very common. That’s why HIV can do more damage in parts of Africa than in Europe, says Ahuja.
constitution can change
If you get sick, it initially means your immune resilience has dropped, says Ahuja. However, people who previously had good stats tend to recover their immunity quickly. However, some recover from symptoms, for example after the flu, but levels of immune resilience do not return to previous levels. “When you look at them six months later, some people still have a small deficit. If these people get it a second time, they are more susceptible to a more serious infection.”
exercise and enough sleep
Ajuha’s team recommends monitoring immune resilience. At his institute, this is already being done for patients at risk and in suspected cases. According to Ahuja, a test costs about $100. If immune resilience is low, you can look for the cause and take countermeasures.
Ahuja has yet to conduct a systematic study of what measures can improve immune health. However, some of the datasets examined show that daily exercise in particular has a positive effect on values. It has already been confirmed that immune cells benefit from getting enough sleep, most recently in a study at the Icahn School of Medicine at Mount Sinai in New York. One of the studies analyzed by Ahuja also showed that positive gene signatures became more pronounced during REM sleep.
Infection – risk or opportunity?
“I don’t know if I’m resilient if I’m never attacked,” says Ahuja in an interview with science.ORF.at. Whether an infection is helpful or harmful to long-term immune health depends on how adequately the immune system can respond to it: “It needs the right amount in the right place at the right time and the right kind.”
Why do women live longer?
Incidentally, health-promoting gene signatures have been increasingly found in women and are also associated with longevity. So the concept of immune resilience could also explain why women statistically live longer than men, says Ahuja. He suspects an evolutionary biological reason behind this: good immune resistance in women during pregnancy promotes the health of the fetus and therefore the preservation of the species. Current results make it less likely that the hormonal difference between the sexes is solely responsible for women’s longevity, says Ahuja; because better immunity levels last until menopause.
The group does not rule out that other factors may influence the course of immune resilience throughout life. Among other things, the involution of the thymus and the decrease in stem cell production are questioned for them.