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.
Patients with cancer have higher mortality rates from coronavirus disease 2019 (COVID-19), 1-4 particularly those with lung cancer. 5 Therefore, efforts are ongoing to limit exposure of these patients to the health care system. As a result, the COVID-19 pandemic has changed cancer care provision, but the extent and type of these changes are unknown. The goal of this study was to evaluate the changes in lung cancer treatment during the COVID-19 pandemic. Methods | We prospectively assessed the treatment plan of all patients seen in the thoracic oncology clinic at the McGill University Health Centre (MUHC) between March 2 and May 30, 2020. Inclusion criteria were a diagnosis of either non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Those who had a diagnosis of COVID-19 were excluded. Primary end points were to describe the extent of changes in the treatment plan and qualify the types of changes observed as a direct result of the COVID-19 pandemic. Definition of change as a direct result of the pandemic was classified as such according to the patient's medical record and not inferred. The study was determined to be exempt by the MUHC research ethics board and was conducted according to the declaration of Helsinki.
Proliferation of arterial smooth muscle cells is regarded as an important event in atherogenesis, which according to in vitro culture studies is influenced by diabetes and insulin. To assess whether this holds true in vivo, we studied the cellular kinetics of thoracic aorta in normal and streptozocin-induced diabetic rats with and without insulin treatment. We measured the incorporation of [3H]thymidine into intima-media, as well as its DNA content, 2 and 14 days after endothelial denudation. We found that the mitotic response of an injured artery is not modified by diabetes but is depressed by insulin treatment in nondiabetic rats, probably due to hypoglycemia. Our data in insulin-treated diabetic rats support but do not definitely settle the view that insulin is mitogenic as long as the treatment does not cause sustained hypoglycemia.
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