Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

Collective dosimetry to distinguish occupational exposure to natural uranium from alimentary uranium background in bioassay measurements.

PURPOSE: To assess occupational exposure from uranium bioassay results which are low and impacted by dietary intakes. MATERIAL AND METHODS: First, the bioassay results of a group of workers exposed to UO2 were compiled along with results of a control group. A Bayesian approach was developed to account for dietary intakes in the calculation of the committed effective dose from occupational exposure of a group of workers. RESULTS: Significant differences in uranium bioassay between the exposed and control groups were found establishing an occupational contamination of the exposed group of workers. Because uranium alimentary excretion estimated from the control group is very variable leading to unreliable individual dose assessment, a collective dosimetric approach was chosen. Applying the Bayesian method, all annual committed effective doses for the exposed group were estimated to be below 0.5 mSv with 95% confidence. CONCLUSIONS: The Bayesian method presented here is well designed to derive best estimate and dose distribution for a group of workers when a contamination is difficult to discriminate from a natural background or alimentary excretion.