RESUMO
Background: Although the human adenovirus infection is common, adenovirus infection with liver dysfunction is rare. Methods: To retrospectively analyze and compare the clinical characteristics and outcomes of pediatric patients diagnosed with severe adenovirus pneumonia with and without liver dysfunction, who were admitted to the pediatric intensive care unit of Hunan Childrens Hospital (South China University) between January 2018 and June 2022. Results: Of the 330 severe adenovirus pneumonia cases analyzed (mean age, 19.88 ± 18.26 months), 102 were girls and 228 were boys. They were divided into two groups: those with liver dysfunction (n = 54) and without liver dysfunction (n = 276). Comparison analysis showed no significant between-group differences in body mass index and levels of white blood cells, neutrophils, platelets, albumin, total bilirubin, direct bilirubin, indirect bilirubin, creatine kinase, procalcitonin, creatinine, and urea nitrogen. However, the levels of alanine aminotransferase (175.99 U/L vs 30.55 U/L) and aspartate transaminase (215.96 U/L vs 74.30 U/L) were significantly higher in patients with liver dysfunction compared to those without liver dysfunction. Further analysis showed that pediatric patients with liver dysfunction had a significantly lower percentage of natural killer (NK) cells (6.93% vs 8.71%) and higher mortality rate (22% vs 9%) than those without liver dysfunction. Conclusion: A decrease in serum NK cell levels in pediatric patients with severe adenovirus pneumonia could serve as a marker for monitoring the onset or progression of hepatic damage (AU)
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Infecções por Adenoviridae/imunologia , Pneumonia Viral/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Fígado/fisiopatologia , Índice de Gravidade de Doença , Unidades de Terapia Intensiva PediátricaRESUMO
Interferon (IFN) regulatory factor 3 (IRF3) is a transcription factor activated by phosphorylation in the cytoplasm of a virus-infected cell; by translocating to the nucleus, it induces transcription of IFN-ß and other antiviral genes. We have previously reported IRF3 can also be activated, as a proapoptotic factor, by its linear polyubiquitination mediated by the RIG-I pathway. Both transcriptional and apoptotic functions of IRF3 contribute to its antiviral effect. Here, we report a nontranscriptional function of IRF3, namely, the repression of IRF3-mediated NF-κB activity (RIKA), which attenuated viral activation of NF-κB and the resultant inflammatory gene induction. In Irf3-/- mice, consequently, Sendai virus infection caused enhanced inflammation in the lungs. Mechanistically, RIKA was mediated by the direct binding of IRF3 to the p65 subunit of NF-κB in the cytoplasm, which prevented its nuclear import. A mutant IRF3 defective in both the transcriptional and the apoptotic activities was active in RIKA and inhibited virus replication. Our results demonstrated IRF3 deployed a three-pronged attack on virus replication and the accompanying inflammation.
Assuntos
Imunidade Inata , Fator Regulador 3 de Interferon , NF-kappa B , Pneumonia Viral , Transporte Ativo do Núcleo Celular , Animais , Núcleo Celular/metabolismo , Expressão Gênica , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/genética , Camundongos , NF-kappa B/metabolismo , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Vírus SendaiRESUMO
BACKGROUND: Pneumonia is a common complication of influenza and closely related to mortality in influenza patients. The present study examines cytokines as predictors of the prognosis of influenza-associated pneumonia. METHODS: This study included 101 inpatients with influenza (64 pneumonia and 37 non-pneumonia patients). 48 cytokines were detected in the serum samples of the patients and the clinical characteristics were analyzed. The correlation between them was analyzed to identify predictive biomarkers for the prognosis of influenza-associated pneumonia. RESULTS: Seventeen patients had poor prognosis and developed pneumonia. Among patients with influenza-associated pneumonia, the levels of 8 cytokines were significantly higher in those who had a poor prognosis: interleukin-6 (IL-6), interferon-γ (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-3, Interleukin-2 receptor subunit alpha and Hepatocyte growth factor. Correlation analysis showed that the IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had positive correlations with the severity of pneumonia. IL-6 and G-CSF showed a strong and positive correlation with poor prognosis in influenza-associated pneumonia patients. The combined effect of the two cytokines resulted in the largest area (0.926) under the receiver-operating characteristic curve. CONCLUSION: The results indicate that the probability of poor prognosis in influenza patients with pneumonia is significantly increased. IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had a positive correlation with the severity of pneumonia. Importantly, IL-6 and G-CSF were identified as significant predictors of the severity of influenza-associated pneumonia.
Assuntos
Fator Estimulador de Colônias de Granulócitos , Influenza Humana , Interleucina-6 , Pneumonia Viral , Citocinas/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Influenza Humana/complicações , Influenza Humana/imunologia , Interleucina-6/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , PrognósticoRESUMO
The host immunity of patients with adenovirus pneumonia in different severity of illness is unclear. This study compared the routine laboratory tests and the host immunity of human adenovirus (HAdV) patients with different severity of illness. A co-cultured cell model in vitro was established to verify the T cell response in vitro. Among 140 patients with confirmed HAdV of varying severity, the number of lymphocytes in the severe patients was significantly reduced to 1.91 × 109/L compared with the healthy control (3.92 × 109/L) and the mild patients (4.27 × 109/L). The levels of IL-6, IL-10, and IFN-γ in patients with adenovirus pneumonia were significantly elevated with the severity of the disease. Compared with the healthy control (20.82%) and the stable patients (33.96%), the percentage of CD8+ T cells that produced IFN-γ increased to 56.27% in the progressing patients. Adenovirus infection increased the percentage of CD8+ T and CD4+ T cells that produce IFN-γ in the co-culture system. The hyperfunction of IFN-γ+ CD8+ T cells might be related to the severity of adenovirus infection. The in vitro co-culture cell model could also provide a usable cellular model for subsequent experiments.
Assuntos
Infecções por Adenovirus Humanos/imunologia , Adenovírus Humanos/fisiologia , Linfócitos T CD8-Positivos/microbiologia , Interferon gama/imunologia , Pneumonia Viral/imunologia , Infecções por Adenovirus Humanos/genética , Infecções por Adenovirus Humanos/patologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Interferon gama/genética , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Contagem de Linfócitos , Masculino , Gravidade do Paciente , Pneumonia Viral/genética , Pneumonia Viral/patologia , Pneumonia Viral/virologiaRESUMO
Adenovirus (Ad) is a major causal agent of acute respiratory infections. However, they are a powerful delivery system for gene therapy and vaccines. Some Ad serotypes antagonize the immune system leading to meningitis, conjunctivitis, gastroenteritis, and/or acute hemorrhagic cystitis. Studies have shown that the release of small, membrane-derived extracellular vesicles (EVs) may offer a mechanism by which viruses can enter cells via receptor-independent entry and how they influence disease pathogenesis and/or host protection considering their existence in almost all bodily fluids. We proposed that Ad3 could alter EV biogenesis, composition, and trafficking and may stimulate various immune responses in vitro. In the present study, we evaluated the impact of in vitro infection with Ad3 vector on EV biogenesis and composition in the human adenocarcinoma lung epithelial cell line A549. Cells were infected in an exosome-free media at different multiplicity of infections (MOIs) and time points. The cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and fluorometric calcein-AM. EVs were isolated via ultracentrifugation. Isolated EV proteins were quantified and evaluated via nanoparticle tracking, transmission electron microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting assays. The cell viability significantly decreased with an increase in MOI and incubation time. A significant increase in particle mean sizes, concentrations, and total EV protein content was detected at higher MOIs when compared to uninfected cells (control group). A549 cell-derived EVs revealed the presence of TSG101, tetraspanins CD9 and CD63, and heat shock proteins 70 and 100 with significantly elevated levels of Rab5, 7, and 35 at higher MOIs (300, 750, and 1500) when compared to the controls. Our findings suggested Ad3 could modulate EV biogenesis, composition, and trafficking which could impact infection pathogenesis and disease progression. This study might suggest EVs could be diagnostic and therapeutic advancement to Ad infections and other related viral infections. However, further investigation is warranted to explore the underlying mechanism(s).
Assuntos
Infecções por Adenovirus Humanos/imunologia , Adenovírus Humanos/imunologia , Vesículas Extracelulares/imunologia , Pulmão/patologia , Pneumonia Viral/imunologia , Células A549 , Infecções por Adenovirus Humanos/patologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/genética , Sobrevivência Celular/imunologia , Vesículas Extracelulares/metabolismo , Humanos , Pulmão/citologia , Pulmão/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , SorogrupoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a historic pandemic of respiratory disease (coronavirus disease 2019 [COVID-19]), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2 signaling restricts the viral burden in the lung. We find that a recently developed mouse-adapted SARS-CoV-2 (MA-SARS-CoV-2) strain as well as the emerging B.1.351 variant trigger an inflammatory response in the lung characterized by the expression of proinflammatory cytokines and interferon-stimulated genes. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45+ cells into the lung parenchyma that is dominated by monocyte-derived cells. Single-cell RNA sequencing (scRNA-Seq) analysis of lung homogenates identified a hyperinflammatory monocyte profile. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes the infiltration of classical monocytes into the lung and the expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a potential CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection. IMPORTANCE SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts the viral burden in the lung. We find that SARS-CoV-2 triggers an inflammatory response in the lung characterized by the expression of proinflammatory cytokines and interferon-stimulated genes. Using RNA sequencing and flow cytometry approaches, we demonstrate that SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45+ cells into the lung parenchyma that is dominated by monocyte-derived cells. Mechanistically, CCR2 signaling promoted the infiltration of classical monocytes into the lung and the expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified that the CCR2 pathway is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.
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Pulmão/imunologia , Pneumonia Viral/prevenção & controle , Receptores CCR2/imunologia , SARS-CoV-2/imunologia , Transdução de Sinais/imunologia , Animais , COVID-19 , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunidade Inata , Inflamação , Pulmão/citologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores CCR2/genética , Receptores CCR2/metabolismo , SARS-CoV-2/genética , Carga Viral , Replicação Viral/imunologiaRESUMO
INTRODUCTION: Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. AREAS COVERED: This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. EXPERT OPINION: Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.
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COVID-19/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Sistema Imunitário/imunologia , Pneumonia Viral/imunologia , Humanos , SARS-CoV-2RESUMO
It focused on the antiviral immune regulation of biofilm-localized protein kinase Dbf2p-related kinase 1 (NDR1) in viral pneumonia. Mouse alveolar monocyte RAW264.7 was used as blank control, and viral pneumonia cell model was prepared by infecting cells with respiratory syncytial virus (RSV). NDR1 overexpression vector and siRNA interference sequences were synthesized, and overexpression/silence NDR1 cell model was fabricated. About 50 ng/mL interleukin 17 (IL-17) was given to stimulate. Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription PCR (RT-qRCR), and Western blot were performed to detect cytokines and chemokines, mRNA of inflammatory factors, and signal molecule protein expression. Notably, RSV infection increased RSV-F mRNA in RAW264.7 cells and reduced NDR1 mRNA and protein. Secretion levels of IL-6, interferon ß (IFN-ß), chemokine (C-X-C motif) ligand 2 (CXCL2), and chemokine (C-C motif) ligand 2 (CCL20) increased in the model group versus blank control (P< 0.05). IL-6, IFN-ß, tumor necrosis factor α (TNF-α), and toll-like receptor 3 (TLR3) mRNA were up-regulated (P < 0.05). Extracellular signal-regulated kinase (ERK1/2), p38 protein phosphorylation, human recombinant 1 (TBK1), and nuclear factor kappa-B (NF-κB) protein levels increased (P < 0.05). After overexpression of NDR1, the secretion levels of cytokines and chemokines, inflammatory factors mRNA, and signal molecule protein increased significantly. After NDR1 was silenced, cytokines and chemokines, inflammatory factors mRNA, and signal molecule protein were not significantly different versus blank control group (P > 0.05). In short, NDR1 regulated innate immune response to viral pneumonia induced by IL-17, which can be used as a new target for the treatment of IL-17-induced inflammatory response and autoimmune diseases.
Assuntos
Biofilmes/crescimento & desenvolvimento , Imunidade Inata , Interleucina-17/metabolismo , Pneumonia Viral/enzimologia , Pneumonia Viral/imunologia , Animais , Proliferação de Células , Quimiocinas/metabolismo , Inflamação/patologia , Camundongos , Proteínas Serina-Treonina Quinases , Células RAW 264.7 , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/fisiologia , Transdução de SinaisRESUMO
The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein-pseudotyped (Spp) lentivirus with the proper tropism of the SARS-CoV-2 spike protein on the surface and determined the distribution of the Spp lentivirus in wild-type C57BL/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV-G) or with a deletion of the receptor-binding domain (RBD) in the spike protein [Spp (∆RBD)] were used as controls. Two hours postinfection (hpi), there were 27-75 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3-5 times more viral burden from Spp lentivirus than from VSV-G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC+ and LDLR+ pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR-γ were quickly upregulated in response to infection in the lungs as well as in macrophage-like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS-CoV-2 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2-independent viral entry pathway may be recruited in the heart and aorta.
Assuntos
Macrófagos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Glicoproteína da Espícula de Coronavírus/imunologia , Doença Aguda , Células Epiteliais Alveolares/virologia , Animais , Antígeno B7-1 , Linhagem Celular , Mediadores da Inflamação , Interleucina-10 , Interleucina-6 , Lentivirus/genética , Lentivirus/isolamento & purificação , Lentivirus/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos/virologia , Masculino , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama , Células RAW 264.7 , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Proteínas do Envelope ViralRESUMO
Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10-correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.
Assuntos
COVID-19/imunologia , Vírus da Influenza A/fisiologia , Pneumonia Viral/imunologia , Sistema Respiratório/imunologia , SARS-CoV-2/fisiologia , Adulto , Idoso , Proteínas Sanguíneas/metabolismo , Líquido da Lavagem Broncoalveolar/imunologia , COVID-19/diagnóstico , Quimiocina CXCL10/metabolismo , Estudos de Coortes , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Respiratória , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients. METHODS: We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1-6, 7-10, and 11-15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated. RESULTS: Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P < 0.01). CD19+ B cells were the only significantly elevated immune cells, especially among patients under 1 year old (cell proportion: n = 12, 30.0%, P < 0.001; cell count: n = 13, 32.5%, P < 0.001). While, low levels of immune related makers, such as immunoglobulin (Ig) G (P < 0.001), IgA (P < 0.001), IgM (P < 0.001) and serum complement C3c (P < 0.001), were also mostly found among patients under 1 year old, together with elevated levels of inflammation related markers, such as tumor necrosis factor γ (P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P < 0.001), and procalcitonin (P = 0.007). CONCLUSION: The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.
Assuntos
COVID-19/imunologia , Pneumonia Viral/imunologia , SARS-CoV-2/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Adolescente , Biomarcadores/sangue , COVID-19/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Citocinas/imunologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Subpopulações de Linfócitos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/epidemiologiaRESUMO
OBJECTIVE: Respiratory failure is the leading cause of mortality in COVID-19 patients, characterized by a generalized disbalance of inflammation. The aim of this study was to investigate the relationship between immune-inflammatory index and mortality in PSI IV-V patients with COVID-19. METHODS: We retrospectively reviewed the medical records of COVID-19 patients from Feb. to Apr. 2020 in the Zhongfa Xincheng Branch of Tongji Hospital, Wuhan, China. Patients who presented high severity of COVID-19-related pneumonia were enrolled for further analysis according to the Pneumonia Severity Index (PSI) tool. RESULTS: A total of 101 patients diagnosed with COVID-19 were identified at initial research. The survival analysis revealed that mortality of the PSI IV-V cohort was significantly higher than the PSI I-III group (p = 0.0003). The overall mortality in PSI IV-V patients was 32.1% (9/28). The fatal cases of the PSI IV-V group had a higher level of procalcitonin (p = 0.022) and neutrophil-to-lymphocyte ratio (p = 0.033) compared with the survivors. Procalcitonin was the most sensitive predictor of mortality for the severe COVID-19 population with area under receiver operating characteristic curve of 0.78, higher than the neutrophil-to-lymphocyte ratio (0.75) and total lymphocyte (0.68) and neutrophil (0.67) counts. CONCLUSION: Procalcitonin and neutrophil-to-lymphocyte ratio may potentially be effective predictors for mortality in PSI IV-V patients with COVID-19. Increased procalcitonin and neutrophil-to-lymphocyte ratio were associated with greater risk of mortality.
Assuntos
COVID-19/imunologia , COVID-19/fisiopatologia , Pandemias , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/mortalidade , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Inflamação/imunologia , Inflamação/fisiopatologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Pró-Calcitonina/sangue , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
Elevated ambient temperatures and extreme weather events have increased the incidence of wildfires world-wide resulting in increased wood smoke particle (WSP). Epidemiologic data suggests that WSP exposure associates with exacerbations of respiratory diseases, and with increased respiratory viral infections. To assess the impact of WSP exposure on host response to viral pneumonia, we performed WSP exposures in rodents followed by infection with mouse adapted influenza (HINI-PR8). C57BL/6 male mice aged 6-8 weeks were challenged with WSP or PBS by oropharyngeal aspiration in acute (single dose) or sub-acute exposures (day 1, 3, 5, 7 and 10). Additional groups underwent sub-acute exposure followed by infection by influenza or heat-inactivated (HI) virus. Following exposures/infection, bronchoalveolar lavage (BAL) was performed to assess for total cell counts/differentials, total protein, protein carbonyls and hyaluronan. Lung tissue was assessed for viral counts by real time PCR. When compared to PBS, acute WSP exposure associated with an increase in airspace macrophages. Alternatively, sub-acute exposure resulted in a dose dependent increase in airspace neutrophils. Sub-acute WSP exposure followed by influenza infection was associated with improved respiratory viral outcomes including reduced weight loss and increased blood oxygen saturation, and decreased protein carbonyls and viral titers. Flow cytometry demonstrated dynamic changes in pulmonary macrophage and T cell subsets based on challenge with WSP and influenza. This data suggests that sub-acute WSP exposure can improve host response to acute influenza infection.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Pneumonia Viral , Fumaça , Incêndios Florestais , Administração por Inalação , Animais , Vírus da Influenza A Subtipo H1N1/fisiologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/virologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Transcriptoma , Replicação Viral , MadeiraRESUMO
The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.
Assuntos
COVID-19/etiologia , Pneumonia Viral/etiologia , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/fisiologia , Autopsia , COVID-19/epidemiologia , COVID-19/patologia , Citocinas/biossíntese , Humanos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/virologia , Modelos Biológicos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/patologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de DoençaRESUMO
O estudo liderado pela pesquisadora do Instituto de Ciências Biológicas da UFJF, Rossana Melo, foi selecionado entre sete projetos brasileiros que serão financiados pelo Fundo de Pesquisa Lemann Harvard Brazil 2021. O objetivo da proposta contemplada é investigar os papéis desempenhados pelos eosinófilos no combate à infecção causada pela Covid-19 no corpo humano. Os eosinófilos são um tipo de leucócito, células responsáveis pela defesa do sistema imunológico humano que agem diretamente contra os mais diversos agentes infecciosos. Como os processos agressivos da doença provocada pela Covid-19 ainda são desconhecidos pela ciência, a pesquisa explora se os eosinófilos têm papel principal no combate à replicação do vírus no corpo.
Assuntos
Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Eosinófilos/imunologia , Pesquisa em Sistemas de Saúde PúblicaRESUMO
RATIONALE: Viruses are the most common pathogens that can cause infection-related non-recurrent death after transplantation, occurring mostly from the early stages of hematopoietic stem cell transplantation (HSCT) to within 1âyear after transplantation. Human coronavirus (HCoV)-NL63 is a coronavirus that could cause mortality among patients with underlying disease complications. Serological tests are of limited diagnostic value in immunocompromised hosts and cases of latent infection reactivation. In contrast, macro-genomic high-throughput (DNA and RNA) sequencing allows for rapid and accurate diagnosis of infecting pathogens for targeted treatment. PATIENT CONCERNS: In this report, we describe a patient who exhibited acute B-lymphocytic leukemia and developed complicated pulmonary HCoV-NL63 infection after a second allogeneic HSCT (allo-HSCT). Six months after the second allo-HSCT, he developed sudden-onset hyperthermia and cough with decreased oxygen saturation. Chest computed tomography (CT) suggested bilateral multiple rounded ground-glass opacities with the pulmonary lobules as units. DIAGNOSES: HCoV-NL63 was detected by metagenomic next-generation sequencing (NGS), and HCoV-NL63 viral pneumonia was diagnosed. INTERVENTIONS: The treatment was mainly based on the use of antiviral therapy, hormone administration, and gamma-globulin. OUTCOMES: After the therapy, the body temperature returned to normal, the chest CT findings had improved on review, and the viral copy number eventually became negative. LESSONS: The latest NGS is an effective method for early infection diagnosis. The HCoV-NL63 virus can cause inflammatory factor storm and alter the neutrophil-to-lymphocyte ratio (NLR). This case suggests that the patient's NLR and cytokine levels could be monitored during the clinical treatment to assess the disease and its treatment outcome in a timely manner.
