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1.
Am J Respir Crit Care Med ; 209(7): 840-851, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38226855

RESUMO

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Pulmão , Teste para COVID-19 , Replicação Viral
2.
Leuk Lymphoma ; 63(2): 370-376, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34612761

RESUMO

The pathogenesis of plasmablastic lymphoma (PBL) involves the Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), and MYC gene aberrations. We aimed to determine the EBV latent infection pattern and frequency of MYC gene aberrations in PBLs. Immunohistochemistry was performed using antibodies for EBNA1, EBNA2, and LMP1 while fluorescence in situ hybridization was performed using a MYC probe. The patient cohort comprised 49 adult cases (44 were HIV-positive and three were HIV-negative). Forty-one cases were EBV-positive with 11 EBNA1-positive cases, all cases EBNA2-negative, and four LMP1-positive cases. Latency 0 was determined in 29 cases, latency I in eight cases, and latency II in four cases. The MYC gene was rearranged in eight cases, showed copy number alterations in 11 cases and, no rearrangement in 11 cases. This is the largest cohort of PBLs from South Africa to show a predominantly restricted EBV latency pattern with MYC gene aberrations as a common finding.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Plasmablástico , Proteínas Proto-Oncogênicas c-myc , Adulto , Antígenos Nucleares do Vírus Epstein-Barr/genética , Genes myc , Herpesvirus Humano 4/genética , Humanos , Hibridização in Situ Fluorescente , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/genética , Linfoma Plasmablástico/virologia , Proteínas Proto-Oncogênicas c-myc/genética , Latência Viral
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