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01 Apr 2021

Repeated exposure to other coronaviruses may explain why elderly respond poorly to COVID-19

Peer reviewed: Nature Communications (10.1038/s41467-021-22236-7)
Funding:  Jack Ma foundation, Emergent Ventures Fast Grants, NHMRC, MRFF, European Union’s Horizon 2020 Marie Skłodowska-Curie Fellowship
This study used human samples

Repeated prior exposure to different coronaviruses could contribute to why the elderly experience a much more severe immune response to COVID-19 compared to children according to new research.

Published today in Nature Communications, scientists looked at blood samples from 89 children, 98 adults, 57 elderly individuals and 50 COVID-19 patients, comparing antibodies to a range of coronaviruses, including SARS-CoV-2, SARS-CoV-1, MERS-CoV, and viruses that cause the common cold.

Lead author, University of Melbourne Dr Amy Chung, a laboratory head at the Peter Doherty Institute for Infection and Immunity (Doherty Institute), said one of the striking observations from the pandemic was the disproportionate disease severity and deaths in the elderly compared to children.

“Before commencing this project, we hypothesised the reason behind the differences in immune responses to COVID-19 were because children were likely to have more recent exposure to seasonal coronaviruses and therefore have some immunity to protect them against COVID-19,” Dr Chung said.

“But it’s the complete opposite. The elderly had more mature antibodies (known as IgA and IgG), which indicates repeated exposure to coronaviruses. Their immune system retains an immunological memory, and likely recognised COVID-19 as a less serious coronavirus and were unable to mount a robust immune response.

“Whereas we found children have less mature antibodies (IgM) and less trained immunity, so were likely to mount a strong, targeted immune response against COVID-19.”

The research team also found that children who were exposed to COVID-19 were able to develop antibodies that were better able to activate surrounding white blood cells to engulf and clear up the virus.

Dr Chung developed a cutting-edge technology, called “systems serology”, executed by postdoctoral fellows Dr Kevin Selva, Dr Carolien van de Sandt and collaborators at the University of Michigan, to examine functional antibodies against a range of coronaviruses, including SARS-CoV-2.

“Systems serology” combines high throughput antibody mapping experiments with computational machine learning analysis, which allowed the researchers to identify immunological patterns or fingerprints that are unique to mild or severe disease.

“Being able to describe such differences in the immune responses in this way provides key insights for COVID-19 vaccination and immunotherapy strategies,” said University of Melbourne Professor Katherine Kedzierska, co-senior author on the paper.

“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.”

This research was done in collaboration with the University of Michigan and the Murdoch Children’s Research Institute.