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1.
Nat Commun ; 14(1): 149, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627290

RESUMO

Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin's lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.


Assuntos
COVID-19 , Linfócitos T Citotóxicos , Humanos , SARS-CoV-2 , Linfócitos T CD8-Positivos , Anticorpos Neutralizantes , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus
2.
Mycoses ; 57 Suppl 3: 91-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25187314

RESUMO

We prospectively observed 36 haematological patients with mucormycosis from nine hospitals of St. Petersburg during 2004-2013. The most frequent underlying diseases were acute leukaemia (64%), and main risk factors were prolonged neutropenia (92%) and lymphocytopenia (86%). In 50% of the patients, mucormycosis was diagnosed 1-65 days after invasive aspergillosis. Main clinical form of mucormycosis was pulmonary (64%), while two or more organ involvement was noted in 50% of the cases. The most frequent aetiological agents of mucormycosis were Rhizopus spp. (48%). Twelve-week survival rate was 50%. Combination therapy (echinocandins + amphotericin B forms) and recovery from the underlying disease significantly improved the survival rate.


Assuntos
Linfopenia/microbiologia , Mucormicose/tratamento farmacológico , Mucormicose/epidemiologia , Neutropenia/microbiologia , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Criança , Combinação de Medicamentos , Equinocandinas/uso terapêutico , Feminino , Humanos , Linfopenia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Estudos Prospectivos , Rhizopus/classificação , Rhizopus/patogenicidade , Fatores de Risco , Federação Russa/epidemiologia , Adulto Jovem
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