CAMBRIDGE, UK — COVID-19 cases range dramatically from severity, from asymptomatic to self-limited influenza-like illness to severe respiratory failure or even death.
The worst cases often involve cardiovascular events, coagulopathy, thrombosis and high mortality. International researchers, including participation from the Uniformed Services University of the Health Sciences in Bethesda, MD, pointed out that risk factors for severe disease have been identified, including age, sex, ethnicity, genetic variation and a range of comorbidities, those don’t fully predict disease therapy.
The article in Blood suggested that additional determinants remain to be identified. One of those might be clonal hematopoiesis (CH), according to the researchers.1
They explained that CH is “the disproportionate expansion of a hematopoietic stem cell (HSC) and its progeny, in association with leukemia-associated somatic mutations, most commonly affecting the genes for epigenetic regulators DNMT3A, TET2 and ASXL1. 8,9 The prevalence and size of such clones rise with age, in association with changes in the driver gene landscape.”1
Patients with CH have an increased risk of hematologic malignancies, as well as cardiovascular disease (CVD), independently of other known CVD risk factors, the study advised
The interest in CH’s possible link to severe COVID-19 cases is that the heightened CVD risk has been linked to hyperinflammatory positive feedback loops driven by increased cytokine release from clonal myeloid cells, especially interleukin IL-6 and IL-1β.
“The close association of CH with advancing age and chronic inflammation led us to hypothesize that it may be another factor associated with increased risk of severe Covid-19 disease, through hyperactivation of abnormal, clonally-derived, myeloid cells, including monocytes and macrophages, following SARS-CoV-2 infection,” researchers wrote.
The authors sought to determine whether an association between CH and COVID-19 disease severity actually existed. To do that, they focused on 568 patients 50-90 years old (median age 64), including 120 non-hospitalized individuals with asymptomatic or mild disease, 241 hospitalized patients not requiring intensive care unit (ICU) support, and 207 critically ill patients who required ICU admission, mechanical ventilation or who died.
All patients had laboratory-confirmed SARS-CoV-2 infection during the first six months of 2020.
“In summary, our study found no evidence that CH is associated with COVID-19 disease severity, even after adjusting for covariates known to affect the risk of severe disease,” researchers concluded. “Previous studies examining the association between COVID-19 disease severity and clonal hematopoiesis CH have produced conflicting results.
Pointing out that their study attempted to mitigate limitations in prior research by including the largest number of patients to date, directly comparing relevant patient groups (asymptomatic/mild, hospitalized, critically ill), incorporating covariates from well-characterized additional risk factors, as well as performing sequencing and mutation calling using the same platforms.
“Overall, we found no evidence of an association between CH and COVID-19 severity, resolving much of the uncertainty surrounding this question,” the researchers wrote. “Whilst it is never possible to rule out an association with absolute certainty, our study indicates that the clinical impact of any theoretical association is unlikely to be substantial.”
- Zhou Y, Shalhoub RN, Rogers SN, Yu S, et. al. Clonal Hematopoiesis Is Not Significantly Associated with Covid-19 Disease Severity. Blood. 2022 Jul 15:blood.2022015721. doi: 10.1182/blood.2022015721. Epub ahead of print. PMID: 35839449; PMCID: PMC9293387.
