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1.
J Infect ; 89(3): 106217, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38969238

ABSTRACT

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. METHODS: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. RESULTS: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.


Subject(s)
COVID-19 Drug Treatment , COVID-19 , Hospitalization , Imatinib Mesylate , Quality of Life , SARS-CoV-2 , Humans , Imatinib Mesylate/therapeutic use , Female , Male , Middle Aged , COVID-19/mortality , Hospitalization/statistics & numerical data , Aged , Treatment Outcome , Adult
2.
J Bacteriol ; 186(16): 5342-54, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15292135

ABSTRACT

The icosahedral bacteriophage PM2 has a circular double-stranded DNA (dsDNA) genome and an internal lipid membrane. It is the only representative of the Corticoviridae family. How the circular supercoiled genome residing inside the viral membrane is translocated into the gram-negative marine Pseudoalteromonas host has been an intriguing question. Here we demonstrate that after binding of the virus to an abundant cell surface receptor, the protein coat is most probably dissociated. During the infection process, the host cell outer membrane becomes transiently permeable to lipophilic gramicidin D molecules proposing fusion with the viral membrane. One of the components of the internal viral lipid core particle is the integral membrane protein P7, with muralytic activity that apparently aids the process of peptidoglycan penetration. Entry of the virion also causes a limited depolarization of the cytoplasmic membrane. These phenomena differ considerably from those observed in the entry process of bacteriophage PRD1, a dsDNA virus, which uses its internal membrane to make a cell envelope-penetrating tubular structure.


Subject(s)
Corticoviridae/physiology , Pseudoalteromonas/virology , Bacteriophage PRD1/growth & development , Bacteriophage PRD1/physiology , Capsid Proteins/metabolism , Cell Membrane/chemistry , Corticoviridae/growth & development , DNA/metabolism , DNA, Viral/metabolism , Gramicidin/metabolism , Membrane Proteins/metabolism , Microscopy, Electron , Peptidoglycan/metabolism , Permeability , Receptors, Virus/physiology , Viral Matrix Proteins/metabolism
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