COVID-19 Data Shows the Importance of Thymic Atrophy in Aging

The decline of the immune system is of great importance in aging. Vulnerability to infection, a decreased surveillance of senescent cells and cancerous cells, and growing chronic inflammation all take their toll. A sizable fraction of this problem stems from the diminished supply of new T cells of the adaptive immune system. T cells begin life as thymocytes in the bone marrow, then migrate to the thymus where they mature. Unfortunately, the thymus atrophies with age, a process known as thymic involution, in which active tissue is replaced by fat. The T cell supply falters, and as a result the existing T cell population becomes ever more damaged and dysfunctional. Researchers have shown that raised cancer risk over time maps very well to the pace of thymic involution, and here more data is deployed to point out the same correlation for vulnerability to infectious disease.

Here we report that COVID-19 hospitalisation rates follow an exponential relationship with age, increasing by 4.5% per year of life. This mirrors the exponential decline of thymus volume and T-cell production (decreasing by 4.5% per year). COVID-19 can therefore be added to the list of other diseases with this property, including those caused by MRSA, West Nile virus, Streptococcus Pneumonia, and certain cancers, such as chronic myeloid leukemia and brain cancers. In addition, incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. For under 20s, COVID-19 incidence is remarkably low.

A Bayesian analysis of daily hospitalisations, accounting for contact-based and environmental transmission, indicates that non-adults are the only age group to deviate significantly from the exponential relationship. Our model fitting suggests under 20s have 53-77% additional immune protection beyond that predicted by strong thymus function alone. We found no evidence for differences between age groups in susceptibility to overall infection, or, relative infectiousness to others. The simple inverse relationship between risk and thymus size we report here suggests that therapies based on T-cell mechanisms may be a promising target.

Link: https://doi.org/10.1101/2020.08.25.20181487

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