Clonal hematopoiesis is associated with risk of severe Covid-19

Abstract

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15–2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15–3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22–3.30, p = 6×10−3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15–2.13, p = 5×10−3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

Role of Myeloid Tet Methylcytosine Dioxygenase 2 in Pulmonary and Peritoneal Inflammation Induced by Lipopolysaccharide and Peritonitis Induced by Escherichia coli

“…As global Tet2 knockout increases, the myeloid cells that play the most important roles in antibacterial defense in mice, indicating that the antibacterial capacity per cell in Tet2 knockout host is decreased. Somatic TET2 mutations are among the most frequent reported mutations in human clonal hematopoiesis, which recently has been reported as an increased risk of certain infections caused by both virus and bacteria [ 60 , 61 , 62 ]. At present, the mechanism by which Tet2 mediates this effect is unknown and is an interesting subject for future investigations.…”

Clonal Hematopoiesis and Myeloid Neoplasms in the Context of Telomere Biology Disorders

“…Depending on whether the mutation is accompanied or not by persistent cytopenias, CH can be further classified as CH of indeterminate potential (CHIP, where the variant allele fraction is ≥ 2%) or clonal cytopenia of unclear significance (CCUS), respectively [ 16 , 17 ]. The interest of CH and CCUS in clinical practice has increased over the years not only due to the fact that carriers present higher risk of evolving to hematological neoplasms (about 1% per year risk, hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), but also because more recently, CH presence has been associated with increased risk of all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), largely due to cardiovascular diseases [ 15 ], inflammation, immune deregulation, type 2 diabetes [ 18 ], or response to infection with SARS-CoV-2 [ 19 ], among others. The role of CH in non-TBD individuals has been discussed elsewhere in both the hematological [ 20 ] and non-hematological [ 21 ] contexts.…”

Clonal Hematopoiesis and Liquid Biopsy in Gastrointestinal Cancers

“…CH has been related to a number of negative health outcomes, with inflammation emerging as a significant mediator (40). Dharan et al (41) suggested that chronic HIV infection, might be an etiology for CH, whereas Bolton et al (42) established the relationship of CH with a wide spectrum of infections, including infection with SARS-CoV. Inflammation and clonal growth are reinforcing one other in a self-perpetuating circle.…”