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1.
bioRxiv ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36789445

RESUMO

Lung inflammation, pneumonia, is an acute respiratory disease of varying etiology that has recently drawn much attention during the COVID-19 pandemic as lungs are among the main targets for SARS-CoV-2. Multiple other etiological agents are associated with pneumonias. Here, we describe a newly-recognized pathology, namely abnormal lipid depositions in the lungs of patients who died from COVID-19 as well as from non-COVID-19 pneumonias. Our analysis of both semi-thin and Sudan III-stained lung specimens revealed extracellular and intracellular lipid depositions irrespective of the pneumonia etiology. Most notably, lipid depositions were located within vessels adjacent to inflamed regions, where they apparently interfere with the blood flow. Structurally, the lipid droplets in the inflamed lung tissue were homogeneous and lacked outer membranes as assessed by electron microscopy. Morphometric analysis of lipid droplet deposition area allowed us to distinguish the non-pneumonia control lung specimens from the macroscopically intact area of the pneumonia lung and from the inflamed area of the pneumonia lung. Our measurements revealed a gradient of lipid deposition towards the inflamed region. The pattern of lipid distribution proved universal for all pneumonias. Finally, lipid metabolism in the lung tissue was assessed by the fatty acid analysis and by expression of genes involved in lipid turnover. Chromato-mass spectrometry revealed that unsaturated fatty acid content was elevated at inflammation sites compared to that in control non-inflamed lung tissue from the same individual. The expression of genes involved in lipid metabolism was altered in pneumonia, as shown by qPCR and in silico RNA-seq analysis. Thus, pneumonias of various etiologies are associated with specific lipid abnormalities; therefore, lipid metabolism can be considered to be a target for new therapeutic strategies.

2.
Leuk Lymphoma ; 63(7): 1607-1616, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35156528

RESUMO

We describe a retrospective cohort, 156 patients with chronic lymphocytic leukemia (CLL) diagnosed with COVID-19, analyze factors associated with a severe disease course and the effects of various treatment regimens. Anti-SARS-CoV-2 IgG and IgM levels are significantly lower. Patients with CLL are more likely to have a severe course of COVID-19, with IL-6 levels acting as a consistent biomarker of disease severity. Ten patients had recurrent episodes, fatality rate of 20%. Overall survival did not differ between patients receiving ibrutinib monotherapy and anti-CD20 antibodies ± chemotherapy. It seems that the immunodeficiency inherent to CLL influences outcomes to a larger degree than does the treatment. Glucocorticoids are not associated with significant OS improvement whereas anti-cytokine compounds usage seemed to be beneficial in patients with mild pulmonary involvement. Our data attest to the necessity of reorganizing health care for patients with CLL. Early administration of effective antiviral compounds and tailored vaccination protocols are warranted.


Assuntos
COVID-19 , Leucemia Linfocítica Crônica de Células B , COVID-19/epidemiologia , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/epidemiologia , Moscou , Estudos Retrospectivos
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