6 April 2021

The COVID-19 age curve explained

Clinical COVID-19

Anyone who’s seen a child use Blu Tack to replace a missing bathplug or the family dog to dry wet hands on knows having “fresh eyes” can lead to some innovative problem-solving.

It turns out their fresh immune systems might be similarly better at solving novel problems, such as SARS-CoV2 infection.

It’s been a notable feature of the COVID-19 pandemic that morbidity and mortality have varied with age, with old people suffering the worst and children hardly at all.

Now, Australian-led research suggests elderly people’s history of exposure to similar-looking coronaviruses is “distracting” their immune response when they’re introduced to SARS-CoV-2 by causing them to focus on producing antibodies targeting regions of the virus they have seen in the past.

But children generate a broader range of solutions.  

Immunologist Dr Amy Chung co-led a team of researchers from around Australia, the Netherlands, and the US on the research, recently published in Nature Communications.

“We started the study with a completely different hypothesis [to what we found],” Dr Chung, an infectious diseases researcher at the University of Melbourne and laboratory head at the Doherty Institute, told TMR.

Because children are reported to experience seasonal colds more frequently than the elderly, which are caused by other human coronaviruses that look similar to SARS-CoV-2, the researchers thought children might already have antibodies help protect them against COVID-19.

They assessed antibodies to SARS-CoV-2 in 244 healthy people, including 89 children (aged 1.5 to 19 years old), 98 adults (aged 22 to 63) and 57 elderly people (aged 65 to 92).

They also assessed antibodies in 43 SARS-CoV-2-infected patients aged 1 to 76 from two sites, who ranged from “very mild” symptoms to those admitted to the ICU.

“When we looked at the antibody responses from healthy children in comparison to healthy elderly, they were actually the complete opposite results to what we expected: the elderly had much more ‘mature’ antibodies,” Dr Chung said.

“The elderly have lived long lives and been repeatedly exposed to human coronaviruses, and upon each exposure, they’re developing an immunological memory.

“[The results suggest that] when they see SARS-CoV-2 – because there are parts that are similar to other human coronaviruses – they have a similar response, rather than specifically targeting regions that need to be used to combat COVID-19 infection.”

“It’s like [the antibodies] become distracted because they have this pre-existing understanding of what they think they’re seeing.”

But children had less of an immunological memory.

“When they see COVID-19 for the first time, it’s a brand new immune response, and they go in and develop fresh, unique antibodies that target the regions that are really important,” Dr Chung said.

Another key finding, which the team is conducting further research on, was that the immune response in children involved higher levels of phagocytosis.  

“In children, the antibodies don’t just neutralise the virus, they’re actually able to activate surrounding white blood cells to come in and clear the virus up much better than the elderly.”

Dr Chung said their findings may help explain why immunisation is working well.

“The vaccine is putting in the regions that their immune systems should be focussing on, it’s like giving a magnifying glass to the elderly and showing them what to zoom in on without the distractions of the other regions.”

Dr Chung also helped to develop a machine learning approach to spot immunological patterns unique to mild or severe disease.

Co-author Professor Katherine Kedzierska of the University of Melbourne said the ability to describe these differences in immune response would help progress immunotherapy approaches.

“These findings take us several steps closer to understanding why the elderly are more susceptible to severe COVID-19 and provide insights into why some people experience mild-to-moderate symptoms and others get extremely sick,” she said in a statement.

Nature Communications 2021, 1 April

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