Clonal hematopoiesis is associated with risk of severe Covid-19

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.1-4 These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH.2,5,6 A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19.7,8 Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of Clostridium Difficile (HR=2.0, 95% CI: 1.2-3.3, p=6x10-3) and Streptococcus/Enterococcus infections (HR=1.5, 95% CI=1.1-2.1, p=5x10-3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

Fractional SIR Epidemiological Models

The purpose of this work is to make a case for epidemiological models with fractional exponent in the contribution of sub-populations to the transmission rate. More specifically, we question the standard assumption in the literature on epidemiological models, where the transmission rate dictating propagation of infections is taken to be proportional to the product between the infected and susceptible sub-populations; a model that relies on strong mixing between the two groups and widespread contact between members of the groups. We content, that contact between infected and susceptible individuals, especially during the early phases of an epidemic, takes place over a (possibly diffused) boundary between the respective sub-populations. As a result, the rate of transmission depends on the product of fractional powers instead. The intuition relies on the fact that infection grows in geographically concentrated cells, in contrast to the standard product model that relies on complete mixing of the susceptible to infected sub-populations. We validate the hypothesis of fractional exponents i) by numerical simulation for disease propagation in graphs imposing a local structure to allowed disease transmissions and ii) by fitting the model to a COVID-19 data set provided by John Hopkins University (JHUCSSE) for the period Jan-31-20 to Mar-24-20, for the countries of Italy, Germany, Iran, and France.