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.

Viral shedding dynamics reveals sputum as a reliable and cost-saving specimen for SARS-CoV-2 diagnosis within the first 10 days since symptom onset: A prospective cohort study

BackgroundCoronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome virus (SARS-CoV-2) is challenging global public health, due to an increasing demand for testing and the shortage of diagnostic supplies. Nasopharyngeal swab (NPS) is considered the optimal sample for SARS-CoV2 diagnosis and sputum (SPT) has been proposed as an economic alternative. However, the temporal concordance of diagnosis in NPS and SPT has not been addressed. MethodsThrough a longitudinal study we compared the shedding dynamics of SARS-CoV-2 RNA evaluated by RT-qPCR in serially collected SPT and NPS obtained from 82 ambulatory and hospitalized patients during acute infection and convalescence. The concordance during the follow-up and cost analysis between both collected specimens was evaluated. FindingsWe analyzed 379 samples, 177 NPS and 202 SPT. The highest proportion of positive samples was detected within the first 15 days after the symptoms onset. The median time of positivity was higher for NPS (median= 25 days) than SPT (median= 21 days). There was no significant difference in the median RT-qPCR CT values between both sample types. The temporal categorization of matched-paired samples indicated substantial correlation (r=0{middle dot}6023) and substantial agreement (87{middle dot}23%) during the first ten days since symptoms onset (kappa = 0{middle dot}697). A cost analysis demonstrated a significant saving when the SPT specimen was used. InterpretationSputum is a feasible and cost-saving alternative to NPS, providing an equivalent value for the detection and follow-up of SARS-CoV-2 RNA. FundingAgencia Nacional de Investigacion y Desarrollo (ANID) of Chile, NIH-NIAID USA.

Three essential conditions to cultivate physician scientists / 医学教育

1) We conducted a workshop to discuss the definition of the term "physician scientist", what thought processes and competencies are expected, and how to better help physician scientists develop through medical schools.2) The definition of a physician-scientist is a physician who both provides patient care and approaches unsolved questions in understanding the mechanisms of diseases and developing new treatments.3) Essential conditions for a medical school to cultivate physician scientists include providing good role models for physician scientists, making efforts to stimulate students' motivation, and supporting collaboration among physicians and scientists on the faculty.