RESUMO
Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Formação de Anticorpos , Glicoproteína da Espícula de Coronavírus/genética , Proteínas do Envelope Viral/genética , Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , COVID-19/prevenção & controle , Citocinas , RNA MensageiroRESUMO
Integrase inhibitor is uniquely available as single tablet regimen (STR) in Korea. In this study, the durability until 96 weeks was compared between dolutegravir/abacavir/lamivudine (D/A/L) and elvitegravir/cobicistat/tenofovir/emtricitabine (E/T/E) in treatment naïve human immunodeficiency virus 1 (HIV-1) infected individuals. From 2014 to 2017, 153 and 234 subjects started D/A/L and E/T/E, respectively. During 96 weeks, 73 discontinued initial STR and the reason of discontinuation was typable in 44. The frequency of drug adverse event related discontinuation (AEDC) was higher in D/A/L (13.1% vs. 6.4%, P = 0.023) while most non-AE related discontinuations occurred in E/T/E (8/9), such as drug-drug interaction, meal requirement and virologic failure. AEDC occurred usually within 24 weeks (20/35) and D/A/L to E/T/E AEDC incidence rate ratio was 3.71 (95% confidence interval, 1.36-10.10) in this period. Regarding the durability, D/A/L and E/T/E revealed no significant difference at week 96 (P = 0.138) while durability of D/A/L was worse in the aspect of AEDC (P = 0.013).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por HIV/tratamento farmacológico , Comprimidos/química , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças do Sistema Nervoso Central/etiologia , Cobicistat/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , Esquema de Medicação , Emtricitabina/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Oxazinas/administração & dosagem , Piperazinas/administração & dosagem , Piridonas/administração & dosagem , Quinolonas/administração & dosagem , Tenofovir/administração & dosagem , Recusa do Paciente ao TratamentoRESUMO
Penicillium marneffei may cause life-threatening systemic fungal infection in immune-compromised patients and it is endemic in Southeast Asia. A 39-yr-old HIV-infected male, living in Laos, presented with fever, cough, and facial vesiculopapular lesions, which had been apparent for two weeks. CT scans showed bilateral micronodules on both lungs; Pneumocystis jirovecii was identified by bronchoscopic biopsy. Despite trimethoprim-sulfamethoxazole and anti-tuberculosis medications, the lung lesions progressed and the facial lesions revealed central umbilications. Biopsy of the skin lesions confirmed disseminated penicilliosis, with the culture showing P. marneffei hyphae and spores. The P. marneffei was identified by rRNA PCR. A review of the bronchoscopic biopsy indicated penicilliosis. The patient completely recovered after being prescribed amphotericin-B and receiving antiretroviral therapy. This is the first case of penicilliosis in a Korean HIV-infected patient. It is necessary to consider P. marneffei when immunocompromised patients, with a history of visits to endemic areas, reveal respiratory disease.
Assuntos
Infecções por HIV/diagnóstico , Pneumopatias/microbiologia , Penicillium/isolamento & purificação , Adulto , Anfotericina B/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Antifúngicos/uso terapêutico , Broncoscopia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Dermatomicoses/patologia , Infecções por HIV/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Laos , Pneumopatias/tratamento farmacológico , Masculino , Penicillium/genética , Pneumocystis carinii/isolamento & purificação , Tomografia Computadorizada por Raios XRESUMO
Mycobacteruim kansasii occasionally causes disseminated infection with poor outcome in immunocompromised patients. We report the first case of disseminated M. kansasii infection associated with multiple skin lesions in a 48-yr-old male with myelodysplastic syndrome. The patient continuously had taken glucocorticoid during 21 months and had multiple skin lesions developed before 9 months without complete resolution until admission. Skin and mediastinoscopic paratracheal lymph node (LN) biopsies showed necrotizing granuloma with many acid-fast bacilli. M. kansasii was cultured from skin, sputum, and paratracheal LNs. The patient had been treated successfully with isoniazid, rifampin, ethmabutol, and clarithromycin, but died due to small bowel obstruction. Our case emphasizes that chronic skin lesions can lead to severe, disseminated M. kansasii infection in an immunocompromised patient. All available cases of disseminated M. kansasii infection in non HIV-infected patients reported since 1953 are comprehensively reviewed.
Assuntos
Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium kansasii , Dermatopatias Bacterianas/diagnóstico , Antituberculosos/uso terapêutico , Claritromicina/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/imunologia , Mycobacterium kansasii/isolamento & purificação , Síndromes Mielodisplásicas/tratamento farmacológico , Rifampina/uso terapêutico , Dermatopatias Bacterianas/imunologia , Dermatopatias Bacterianas/patologia , Escarro/microbiologia , Síndrome de Sweet/diagnósticoRESUMO
Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. Recent studies have shown that the VEGF levels increase in several cell types, for example, macrophages and smooth muscle cells after LPS stimulation, suggesting that it is important in the initiation and development of sepsis. In particular, LPS-regulated contractility in lung pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during sepsis. This study investigated the production of VEGF by rat lung pericytes in response to LPS. LPS was found to enhance VEGF mRNA expression in a concentration-dependent manner peaking 2 h after stimulation in pericytes. Vascular endothelial growth factor protein levels in conditioned medium and in cell lysate also increased on increasing LPS and peaked after 24 to 48 h. LPS also significantly augmented iNOS expression in lung pericytes within 6 h. However, iNOS mRNA induction occurred later than LPS-induced VEGF mRNA increases. Interestingly, attempted inhibition with nuclear factor-kappaB or tyrosine kinase did not suppress LPS-induced augmented VEGF mRNA expression in lung pericytes, although both inhibitors markedly inhibited LPS-induced iNOS mRNA expression. SB203580, a p38 MAP kinase inhibitor, repressed LPS-induced VEGF mRNA expression. Furthermore, LPS stimulated a rapid and sustained phosphorylation of p38 MAP kinase. These results show that pericytes produce VEGF in response to LPS stimulation, and that this may be partly mediated by the p38 MAP kinase pathway. More research should be done to establish the regulation of capillary hemodynamics and identify mechanisms of their regulation.