A new review from the British Society for Immunology summarises what we do not know about how the immune systems of older people respond to COVID-19, and what the immunology research priorities should be for scientists working in this area The information in this review was put together by our expert group, led by Professor Deborah Dunn-Walters.
COVID-19 and SARS-CoV-2, the virus that causes it, affect different people in different ways. Age is probably the most important factor affecting the chances of becoming severely ill or dying from the disease.
Here’s what we know so far about how our immune systems change with age, how this influences the risks from coronavirus, and what it means for preventing and treating COVID-19 in older people.
How does age affect the immune system and immune responses to COVID-19?
The immune system is a complex collection of cells and molecules that work together to protect us from infections, help us recover from illness or injury and get rid of abnormal cells, such as cancer cells.
Most parts of the immune system change as we get older, particularly after the age of around 55, making it harder to produce an effective immune response to infection.
For example, the immune cells that normally respond to infections or produce protective antibodies become slower and less efficient with age. Older people also make fewer cells that can recognise and deal with new infections, such as SARS-CoV-2, or provide protection in response to vaccines. Ageing also affects the ability of cells in the airways to fight off infections.
At the same time, ageing is associated with an increase in general background immune activity throughout the body, known as inflammation. Widespread low-level (systemic) inflammation has a negative impact on overall health and interferes with specific immune responses to illness, infections and vaccines.
This might explain why older people become more seriously ill with COVID-19 than those who are younger. But we don’t yet know exactly how baseline levels of inflammation before catching the virus are related to the harmful overactive immune responses and inflammation seen in older people with severe COVID-19.
Are older people more at risk of catching or passing on the SARS-CoV-2 coronavirus?
It is difficult to know for sure whether older people are more at risk of being infected with SARS-CoV-2, because different age groups in the population have different living circumstances and behaviours.
Younger people are also more likely not to have any symptoms from the virus (asymptomatic) compared with those who are older, so won’t be picked up if testing is restricted to people showing signs of the disease.
Random testing across the whole population shows that the rates of infection are similar across all age groups from 5 years upwards, suggesting that older people aren’t at greater risk of catching the virus in the first place.
It also appears that the amount of virus produced and shed by infected people is similar across all age groups, despite having such striking differences in how ill it makes them.
This could be because children and younger adults can tolerate larger doses of the virus compared with older people – possibly due to the fact that older people have higher levels of a molecule called ACE-2 on the cells in their airways, which acts as a ‘gateway’ for coronavirus to get into cells and infect them. Or it may be that the virus tends to infect cells deeper in the airways in older people, where it is harder to detect and measure.
Why do older people become more ill with COVID-19?
There is a strong correlation between age and falling seriously ill with COVID-19. This is not necessarily related to how fit and healthy you feel, although older people who are frail or have multiple underlying health conditions are more at risk.
Older people are more likely to end up in hospital with COVID-19, and the chances of dying from it go up significantly with age: people aged 60-69 are around five times more likely to die from the disease compared with those under 50, while people aged 70-79 are at 8.5 times the risk.
Older people also appear to suffer from different symptoms compared with younger people. For example, older people who are hospitalised with COVID-19 are more likely to have confusion (delirium), cough, shortness of breath and fever than younger people.
What impact do other health conditions have on COVID-19 risk?
Older people are more likely to have other underlying health conditions that also increase the risks posed by COVID-19.
By the age of 70, three quarters of adults have two or more long-term health conditions - a situation known as multimorbidity. A number of studies have shown that people with two or more conditions - including type 2 diabetes, dementia, lung disease, kidney disease, high blood pressure and certain heart conditions - are at greater risk of becoming seriously ill or dying from COVID-19.
Most research on age and COVID-19 has focused on how old people are according to the calendar (chronological age). But their underlying biological age – calculated by measuring a range of molecular markers in their blood and tissue - is probably more important.
A recent study of more than 340,000 participants in the UK Biobank showed that people whose biological age was 10-14 years older than their chronological age had a significantly higher risk of catching COVID-19 and dying from the disease.
Do other infections have an impact on SARS-CoV-2 and COVID-19?
It is not unusual for people to be infected with different things at the same time – this is particularly true in older people. Because SARS-CoV-2 is so new, we know little about how it interacts with other viral, bacterial and fungal infections, and much more research needs to be done.
Viral infections such as colds, influenza (flu) and pneumonia can be more serious in older people, and there are concerns that the combination of flu and COVID-19 during the winter months may bring additional risks.
Animal studies suggest that catching the flu virus followed by SARS-CoV-2 leads to serious breathing problems, weight loss and death compared with infection by either virus alone, but much more research needs to be done. Ironically, social distancing measures appear to have reduced the spread of flu, making it harder to study the impact of combined infection in human populations.
We still don’t know much about the impact of chronic infections on COVID-19. Around 85% of older people in the UK have cytomegalovirus (CMV) - a common infection that rarely causes problems in healthy people. CMV is thought to accelerate ageing of the immune system, but it is unknown whether it has an impact on COVID-19. Long-term human immunodeficiency virus (HIV) infection may also have an effect, and the average age of HIV-positive COVID-19 patients is 55, compared with 74 for people without HIV. Chronic liver damage (cirrhosis) caused by infection with the hepatitis B or C viruses also significantly increases the risk of dying from COVID-19.
Does age affect immunity against SARS-CoV-2?
People become immune to viruses either through catching them or through vaccination. We still don’t really understand how immunity to SARS-CoV-2 is generated for people of any age or how long it might last, although catching the virus twice appears to be very rare.
Different components of viral immunity are affected by age and may have an impact on the effectiveness of any COVID-19 vaccines.
Immune B cells produce antibodies, which recognise and neutralise the virus. Antibodies are hard to measure and can disappear after a few months. Although research on other infections shows that older people can produce good antibody responses, this takes longer than it does for younger people. Long lasting B cells can hold the memory of the infection and produce antibodies later, but these are difficult to measure.
We also have long-lasting memory T cells that ‘remember’ previous infections so we can respond swiftly if we encounter them again. Although research into other viruses and vaccines shows that immune memory lasts as long in the old as it does in the young, the quality and strength of the immune response seems to be lower in older people when they are exposed again.
Will COVID-19 vaccines be effective in older people?
The ability to respond to infections goes down in older people. This is primarily due to a decline in the body’s ability to mount effective immune responses. This means that it can be harder to develop vaccines that can induce immunity in older people.
There are many different vaccines against SARS-CoV-2 currently being developed and tested around the world. Given the risks posed to older people by COVID-19, the elderly are a priority as soon as a suitable vaccine is available. But right now, we have only limited data about the effectiveness of any SARS-CoV-2 vaccines in older people.
The reduced effectiveness of the immune system in older people might mean that vaccination against SARS-CoV-2 is less effective or doesn’t last as long as in younger groups. It may also be the case that older people need multiple doses, different vaccine formulations or alternative vaccination schedules.
We also know that older people are less able to produce an immune response to infections they have never encountered before, which would impact the effectiveness of a vaccine against SARS-CoV-2 for those who have not already been infected.
How can we treat older people with COVID-19 better?
As well as preventing COVID-19 through public health measures and vaccines, it is also important to continue to find better ways to treat the disease in older people, especially if vaccination is less effective for this group.
There are many clinical trials underway around the world testing treatments for COVID-19, including anti-viral drugs, antibodies and therapies that alter the immune response. Most of these approaches have been tested in the most seriously ill patients who have been hospitalised, who tend to be older. There are also trials going on to test treatments for older people with milder COVID-19 who don’t need to go to hospital.
One of the most significant findings so far has been the result from the UK RECOVERY trial, which showed that the cheap steroid drug dexamethasone cuts deaths by a third in people hospitalised with COVID-19. There are promising results coming through from clinical trials of antibody-based therapies, but several large trials suggests that other anti-viral drugs, such as remdesivir, appear to have only limited benefits.
What do we still need to find out?
We urgently need to find ways of measuring the strength and duration of immunity to COVID-19 and the effectiveness of vaccines across all age groups, as well as those who are infected but have no symptoms. This should capture all aspects of the immune response, including antibodies and T cells.
It is essential that vaccine researchers include older people in clinical trials for new COVID-19 vaccines in large enough numbers to get robust data, and also optimise vaccines and dosing schedules for older age groups.
We still need to know more about the symptoms, progression and treatment of COVID-19 in older people, whether living at home or in care facilities. This will identify those most at risk of becoming infected, in order to target prevention. It will also help doctors and carers to spot the critical signs that indicate someone is becoming severely ill, and aid decisions about the best treatments for people at different ages.
There’s a lot we still don’t know about the interaction between COVID-19 and the immune system, or how this is affected by age. Immune responses play a big part in the symptoms and severity of the disease, and overactive immune responses can even be fatal. At the same time, the immune system plays a vital role in fighting off infection.
Understanding more about all the components of the immune system and how they work together at different stages of the disease could reveal ways to target overactive immune responses while still fighting the infection. More research is also needed looking at the effect of other infections on top of SARS-CoV-2, and the impact of vaccination against other diseases such as flu or tuberculosis.
Written by Kat Arney, First Create The Media