Clonal Hematopoiesis and Critical Illness

Clonal hematopoiesis (CH) is a condition in which somatic mutations in a single blood stem cell lineage lead to the overproduction of mature blood cell 'clones'. It is well-established that CH increases in prevalence with age and confers substantially greater risks of blood cancer and mortality. A relationship has been uncovered between CH and altered inflammatory immune function, which suggests that it may play a role in the development or progression of other non-cancerous, non-blood-related diseases. There is a considerable amount of evidence showing that several common CH mutations increase the risk of cardiovascular disease, for example. Although CH has not been well-studied in relation to critical illness, there are striking similarities between these two disease categories. Prevalent infections such as COVID-19 and C. difficile also tend to be more severe in older individuals and have similarly been associated with excessive inflammation and genetic influences. Recent evidence suggests that these and other critical illnesses are more severe among patients with existing CH; however, there is a need to replicate these results on larger and more diverse scales. This research will use targeted next-generation sequencing and whole-genome analysis to identify CH mutations associated with critical illness. These findings will then be used to inform investigation of cellular and molecular interactions occurring when both conditions are present, which may increase the severity of infection experienced by the patient. In an age when mortality rates from COVID-19 are continuously growing, this research holds the potential to significantly improve the prevention, management and outcomes of critical illness in the Intensive Care Unit setting.