Almost immediately at the start of the pandemic, it was clear that age was a substantial risk factor for experiencing severe COVID-19. But how aging impacts our immune function has been a difficult puzzle to solve.

To answer this question, researchers designed a new study to analyze genetic data from over 700,000 people identified from five biobanks in the United States, United Kingdom, Northern Europe, and Japan in a genome-wide association study. They focused specifically on age-related mosaic chromosomal alterations (mCAs), which are large DNA rearrangements including mutations like deletions or duplications of parts of the DNA, in white blood cells. These mCAs accumulate in our blood as we age and have been previously established as risk factors for blood cancers.

In this Nature Medicine study, the researchers found that mCAs were associated with a 170 percent higher risk of sepsis and a 40 percent increase in risk of respiratory infections. This increased risk was even higher among individuals who had previously been diagnosed with cancer.

The fact that mCAs were associated with higher numbers of infections makes sense: mutations that alter large parts of white blood cells' DNA limit the ability of these immune system warriors to fight against foreign pathogens that cause sepsis, the flu, and even COVID-19. And in an additional analysis of 871 people who had COVID-19 during the first wave of the pandemic in New York, the researchers found that 17 percent of severe cases had mCAs, compared to just six percent of mild cases.

This research highlights one of likely many links between age and infection-related risks. Identifying individuals with these genetic markers could prevent the severe disease outcomes that are likely in this group.