How the aging immune system makes older people vulnerable to COVID-19

Health activists administer the flu and pneumonia vaccine to 78-year-old Sonia Olita as part of their community immunization campaign on August 12, 2020 in Makati City, Barangay Pembo. George Cavallo, ABS-CBN News

Patients with COVID-19 who are 80 or older are hundreds of times more likely to die under 40 years of age.

This is partly because they are more likely to have underlying conditions – such as diabetes and lung disease – that make the body more sensitive to COVID-19.

But some scientists suggest another possibility, if disregarded, as the driver of this risk: the aging immune system.

The changes that occur through our network of immune cells as decades pass are complex, resulting in redundancy here, a delayed response there and, overall, a strangely altered landscape of immunity.

Scientists studying the immune system of aging say that understanding it may not only help to understand how old the disease is, but also COVID-19 is a better strategy for vaccines and treatments.

“I felt like I was yelling at people, ‘What’s going on!” But no one was listening, ”said Arne Akbar, a professor of immunology at University College London, who recently published an article in the journal Science detailing the state of research on aging immune systems.

When a virus infiltrates the body, the cells in the first line of defense act rapidly and violently – sending alerts and instructions to other cells, and begin to reduce the virus to inflame inflammation.

The “innate” immune system, as it is called, is also responsible for cleaning damaged cells, misfolded proteins and other detritus in the body, even when there is no infection to fight.

In older people, such waste overtakes the ability to cleanse the immune system, said Dr. Dr. Chief Executive of the Buck Institute for Research on Aging in Novato, California. Eric Verdin said. The innate immune system becomes heavy, and slides into a constant state of warning and inflammation.

At the same time, elderly cells in tissues throughout the body are believed to change with age, releasing their own inflammatory substances.

Akbar said, “They are not just gentle like old good grandparents.” “They are very dangerous indeed.”

As a result, even fully healthy 65-year-old children typically have high levels of immune proteins such as cytokines. This increased state of chronic inflammation, sometimes referred to as “inflammatory”, is associated with cruelty – older adults with higher levels may be more fragile and less mobile.

It also means that fighting pathogens becomes more complex: this inflammatory chaos in an aging body makes it harder for the innate immune system to reach the messages sent to its targets.

On top of that, there is a danger that the innate immune system may die.

“We think this is one of the reasons that older individuals react poorly to COVID-19,” Verdin said.

Verdin and other experts said the aging immune system may be linked to reports of severe COVID-19 in the cytokine storm, a response that causes high numbers of immune messengers to flood the body and organs. May cause failure.

Why this inflammation may be part of the vaccine, whose effectiveness depends on a strong immune system response, also does not work in older people – an effect that is likely to spread to COVID-19 vaccines. Akbar and his colleagues have found that people with high levels of inflammation have a weak immune response to the chickenpox virus, for example. And when he took an anti-inflammatory drug for four days before injecting, his immune response improved.

one second

Several days after the innate immune response begins, the body begins a second wave of attacks against the viral attacker. This adaptive immune system response is more targeted than before, destroying the cells infected by this specific virus.

But in older bodies, the adaptive response not only takes longer to get into gear, it comes to finding a scene of the inflammatory epidemic, said Amber Mueller, a postdoctoral researcher at Harvard Medical School, who spoke about COVID in May. Wrote a paper published. 19 and aging. Think of firefighters coming to extinguish a house fire, she said.

He said, “You have a whole locality of pedestrians or people living nearby who are just walking around, ripping their heads, causing chaos.” “To the point that it makes it harder for firefighters to find the infection – to find the infection – and then flush it out effectively.”

These delays mean that by the time the adaptive immune system works and regains a foothold that may not be available in a younger person, the pathogen has already made several copies. Additionally, older people have fewer fresh T cells, which are important players in the adaptive response trained to prey on cells infected with a specific pathogen. When everything is working correctly, successful T cells make copies of themselves so that at the height of infection, the body is moving around with them. Later, only a few remain to prime us against withdrawal attacks from the virus.

The supply of T cells that have not diminished the pathogen for decades already. Those who remain are not as good at copying themselves. And they may have trouble making the transition to patrol the body against future attacks, Dr. Professor of Epidemiology and Public Health at the University of Maryland School of Medicine. Shabnam Salimi said she had recently written a letter about the conversation between aging and COVID. 19.

“All of these together make the immune system less functional during aging,” Salimi said.

Drug potential

Research examining COVID-19 therapies needs to take into account the specific cells and substances that degrade upon the aging of the immune system, and screening drugs to fight aging may be useful against coronoviruses, Write Salmi and his colleague John Hamlin in your article. .

For the treatment of COVID-19, so far, little has been straightforward. As it became clear that the virus sometimes provoked an out-of-control immune response, researchers tested whether it could help reduce inflammation. Drugs that reduce cytokine levels, such as those used to treat rheumatism and other autoimmune diseases, have not shown success in fighting the virus. What’s more, chloroquine, which can help prevent aging of cells, led to increased mortality in COVID-19 clinical trials.

But the steroid dexamethasone, a potent anti-inflammatory, has been shown to reduce virus deaths. According to a study published in June, it accounted for one-third of the deaths on ventilators and one-fifth in those on oxygen. (However, the drug may also be ineffective or harmful to patients in the early stages of the disease.)

At this point, it is important to design studies that take into account the particular immune status of the aging population. Understanding these immune changes can help to find treatments that work for older COVID-19 patients, but, Salimi said, it can also help younger people who have similar problems. Those without knowing.

It is not just older people who have an abnormally high level of inflammation, or have a shingle in their immune shield. It can also happen to younger people.

In a recent study, for example, researchers found that young men with severe COVID-19 had mutations in the gene for a certain cell receptor. This receptor, some researchers suspect, increases the scarlet as we age.

This seems to be particularly associated with immune changes as to why, in this case, the virus caused serious illness in young people with no acute condition and apparently not in good health.

“Younger people may also experience the same pattern of serious illness,” said Salimi.

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