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1.
Rev Soc Bras Med Trop ; 55: e06152021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35894403

RESUMO

BACKGROUND: Coronavirus disease-2019 (COVID-19) results in acute lung injury. This study examined the usefulness of serum transforming growth factor-beta 1 (TGF-ß1) and connective tissue growth factor (CTGF) levels in predicting disease severity in COVID-19 patients with pulmonary involvement. METHODS: Fifty patients with confirmed COVID-19 and pulmonary involvement between September 2020, and February 2021 (Group 1) and 45 healthy controls (Group 2) were classified into three subgroups based on clinical severity: moderate, severe, and critical pneumonia. Serum TGF-ß1 and CTGF concentrations were measured on days 1 and 7 of admission in Group 1 using an enzyme-linked immunosorbent assay. These concentrations were also measured in control cases. The mean serum TGF-ß1 and CTGF levels were then compared among COVID-19 patients, based on clinical severity. RESULTS: Significantly higher mean serum TGF-ß1 and CTGF levels were observed on both days in Group 1 than in the control group. The mean serum TGF-ß1 and CTGF levels on day 7 were also significantly higher than those on day 1 in Group 1. The critical patient group had the highest serum TGF-ß1 and CTGF levels on both days, and the difference between this group and the moderate and severe pneumonia groups was significant. Cutoff values of 5.36 ng/mL for TGF-ß1 and 626.2 pg/mL for CTGF emerged as predictors of COVID-19 with pulmonary involvement in receiver-operating characteristic curve analysis. CONCLUSIONS: TGF-ß1 and CTGF are potential markers that can distinguish COVID-19 patients with pulmonary involvement and indicate disease severity. These findings may be useful for initiating treatment for early-stage COVID-19.


Assuntos
COVID-19 , Fator de Crescimento do Tecido Conjuntivo , Pneumopatias , Fator de Crescimento Transformador beta1 , COVID-19/complicações , Estudos de Coortes , Fator de Crescimento do Tecido Conjuntivo/sangue , Humanos , Pneumopatias/virologia , Estudos Prospectivos , Fator de Crescimento Transformador beta1/sangue
2.
Radiology ; 304(1): 185-192, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35289657

RESUMO

Background The long-term effects of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized. Purpose To test whether SARS-CoV-2 infection leads to small airways disease in patients with persistent symptoms. Materials and Methods In this single-center study at a university teaching hospital, adults with confirmed COVID-19 who remained symptomatic more than 30 days following diagnosis were prospectively enrolled from June to December 2020 and compared with healthy participants (controls) prospectively enrolled from March to August 2018. Participants with post-acute sequelae of COVID-19 (PASC) were classified as ambulatory, hospitalized, or having required the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests, and chest CT images were collected. Quantitative CT analysis was performed using supervised machine learning to measure regional ground-glass opacity (GGO) and using inspiratory and expiratory image-matching to measure regional air trapping. Univariable analyses and multivariable linear regression were used to compare groups. Results Overall, 100 participants with PASC (median age, 48 years; 66 women) were evaluated and compared with 106 matched healthy controls; 67% (67 of 100) of the participants with PASC were classified as ambulatory, 17% (17 of 100) were hospitalized, and 16% (16 of 100) required the ICU. In the hospitalized and ICU groups, the mean percentage of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than that in the ambulatory group (3.7%, P < .001 for both comparisons). The mean percentage of total lung affected by air trapping was 25.4%, 34.6%, and 27.3% in the ambulatory, hospitalized, and ICU groups, respectively, and 7.2% in healthy controls (P < .001). Air trapping correlated with the residual volume-to-total lung capacity ratio (ρ = 0.6, P < .001). Conclusion In survivors of COVID-19, small airways disease occurred independently of initial infection severity. The long-term consequences are unknown. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Elicker in this issue.


Assuntos
COVID-19/complicações , Pneumopatias , COVID-19/diagnóstico por imagem , Feminino , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/virologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos
3.
Respir Res ; 23(1): 65, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313890

RESUMO

BACKGROUND: Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge. METHODS: In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected. RESULTS: Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the "oxygen only" and "IMV" group (53% and 49% of patients, respectively), compared to 29% in the "CPAP" group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the "oxygen only", "CPAP" and "IMV" group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up. CONCLUSION: DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed.


Assuntos
COVID-19/complicações , Pneumopatias/diagnóstico , Pneumopatias/virologia , Idoso , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Seguimentos , Hospitalização , Humanos , Pneumopatias/terapia , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Estudos Prospectivos , Respiração Artificial , Testes de Função Respiratória , Fatores de Tempo
4.
PLoS One ; 17(2): e0263834, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35143571

RESUMO

Disease associated with Nipah virus infection causes a devastating and often fatal spectrum of syndromes predominated by both respiratory and neurologic conditions. Additionally, neurologic sequelae may manifest months to years later after virus exposure or apparent recovery. In the two decades since this disease emerged, much work has been completed in an attempt to understand the pathogenesis and facilitate development of medical countermeasures. Here we provide detailed organ system-specific pathologic findings following exposure of four African green monkeys to 2.41×105 pfu of the Malaysian strain of Nipah virus. Our results further substantiate the African green monkey as a model of human Nipah virus disease, by demonstrating both the respiratory and neurologic components of disease. Additionally, we demonstrate that a chronic phase of disease exists in this model, that may provide an important opportunity to study the enigmatic late onset and relapse encephalitis as it is described in human disease.


Assuntos
Encefalite Viral/patologia , Infecções por Henipavirus/patologia , Pneumopatias/virologia , Vírus Nipah/patogenicidade , Animais , Chlorocebus aethiops , Modelos Animais de Doenças , Pneumopatias/patologia , Malásia , Masculino , Vírus Nipah/classificação
7.
Sci Rep ; 11(1): 23205, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853380

RESUMO

The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , COVID-19/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Pneumopatias/patologia , Metaloproteinase 9 da Matriz/metabolismo , SARS-CoV-2/efeitos dos fármacos , Carga Viral , Monofosfato de Adenosina/efeitos adversos , Idoso , Alanina/efeitos adversos , Formação de Anticorpos , Antimaláricos/efeitos adversos , Antivirais/efeitos adversos , Antivirais/uso terapêutico , COVID-19/virologia , Feminino , Hospitalização , Humanos , Pneumopatias/induzido quimicamente , Pneumopatias/enzimologia , Pneumopatias/virologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
8.
J Clin Invest ; 131(23)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34609969

RESUMO

The capacity of respiratory viruses to undergo evolution within the respiratory tract raises the possibility of evolution under the selective pressure of the host environment or drug treatment. Long-term infections in immunocompromised hosts are potential drivers of viral evolution and development of infectious variants. We showed that intrahost evolution in chronic human parainfluenza virus 3 (HPIV3) infection in immunocompromised individuals elicited mutations that favored viral entry and persistence, suggesting that similar processes may operate across enveloped respiratory viruses. We profiled longitudinal HPIV3 infections from 2 immunocompromised individuals that persisted for 278 and 98 days. Mutations accrued in the HPIV3 attachment protein hemagglutinin-neuraminidase (HN), including the first in vivo mutation in HN's receptor binding site responsible for activating the viral fusion process. Fixation of this mutation was associated with exposure to a drug that cleaves host-cell sialic acid moieties. Longitudinal adaptation of HN was associated with features that promote viral entry and persistence in cells, including greater avidity for sialic acid and more active fusion activity in vitro, but not with antibody escape. Long-term infection thus led to mutations promoting viral persistence, suggesting that host-directed therapeutics may support the evolution of viruses that alter their biophysical characteristics to persist in the face of these agents in vivo.


Assuntos
Hospedeiro Imunocomprometido , Pneumopatias/virologia , Pulmão/virologia , Vírus da Parainfluenza 3 Humana/metabolismo , Infecções por Paramyxoviridae/virologia , Adulto , Sítios de Ligação , Análise Mutacional de DNA , Feminino , Frequência do Gene , Doença Enxerto-Hospedeiro/tratamento farmacológico , Células HEK293 , Humanos , Leucemia Mieloide Aguda , Mutação , Ácido Micofenólico/administração & dosagem , Ácido N-Acetilneuramínico/química , Vírus da Parainfluenza 3 Humana/genética , Infecções por Paramyxoviridae/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Receptores Virais/metabolismo , Sirolimo/administração & dosagem , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/metabolismo , Internalização do Vírus , Adulto Jovem
9.
Virology ; 563: 88-97, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34500147

RESUMO

Two experimental challenge studies were conducted to evaluate the pathogenesis of a porcine parainfluenza virus type 1 (PPIV-1) isolate. Four-week-old conventional (CON) pigs were challenged in Study 1 and six-week-old caesarean derived/colostrum deprived (CDCD) pigs were challenged in Study 2. Results indicate that PPIV-1 shedding and replication occur in the upper and lower respiratory tracts of CON and CDCD pigs as detected by RT-qPCR and immunohistochemistry. Mild macroscopic lung lesions were observed in CON pigs but not in CDCD pigs. Microscopic lung lesions were mild and consisted of peribronchiolar lymphocytic cuffing and epithelial proliferation in CON and CDCD pigs. Serum neutralizing antibodies were detected in the CON and CDCD pigs by 14 and 7 days post inoculation, respectively. This study provides evidence that in spite of PPIV-1 infection and replication in challenged swine, significant clinical respiratory disease was not observed.


Assuntos
Cesárea , Colostro/imunologia , Infecções por Paramyxoviridae/veterinária , Paramyxoviridae/classificação , Doenças dos Suínos/virologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Pneumopatias/veterinária , Pneumopatias/virologia , Infecções por Paramyxoviridae/transmissão , Infecções por Paramyxoviridae/virologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/transmissão , Replicação Viral
10.
Respiration ; 100(11): 1078-1087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515212

RESUMO

BACKGROUND: Long-term pulmonary sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia are not yet confirmed; however, preliminary observations suggest a possible relevant clinical, functional, and radiological impairment. OBJECTIVES: The aim of this study was to identify and characterize pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. METHODS: In this multicentre, prospective, observational cohort study, patients hospitalized for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only," "continuous positive airway pressure," and "invasive mechanical ventilation") and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6-min walking test, chest X-ray, physical examination, and modified Medical Research Council (mMRC) dyspnoea score were collected. RESULTS: Between March and June 2020, 312 patients were enrolled (83, 27% women; median interquartile range age 61.1 [53.4, 69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥1, or showed restrictive ventilatory defects (9%). In the logistic regression model, having asthma as a comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalization appeared as a protective factor. The need for invasive ventilatory support during hospitalization was associated with chest imaging abnormalities. CONCLUSIONS: DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with the coronavirus disease 2019 (COVID-19) during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.


Assuntos
COVID-19/complicações , Pneumopatias/epidemiologia , Pneumopatias/virologia , Respiração Artificial , Idoso , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Seguimentos , Hospitalização , Humanos , Modelos Logísticos , Pneumopatias/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Testes de Função Respiratória , Fatores de Tempo
11.
J Clin Invest ; 131(15)2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338230

RESUMO

The healthy lung was long thought of as sterile, but recent advances using molecular sequencing approaches have detected bacteria at low levels. Healthy lung bacteria largely reflect communities present in the upper respiratory tract that enter the lung via microaspiration, which is balanced by mechanical and immune clearance and likely involves limited local replication. The nature and dynamics of the lung microbiome, therefore, differ from those of ecological niches with robust self-sustaining microbial communities. Aberrant populations (dysbiosis) have been demonstrated in many pulmonary diseases not traditionally considered microbial in origin, and potential pathways of microbe-host crosstalk are emerging. The question now is whether and how dysbiotic microbiota contribute to initiation or perpetuation of injury. The fungal microbiome and virome are less well studied. This Review highlights features of the lung microbiome, unique considerations in studying it, examples of dysbiosis in selected disease, emerging concepts in lung microbiome-host interactions, and critical areas for investigation.


Assuntos
Pneumopatias , Pulmão , Micobioma , Viroma , Animais , Humanos , Pulmão/microbiologia , Pulmão/virologia , Pneumopatias/microbiologia , Pneumopatias/virologia
12.
Zool Res ; 42(5): 633-636, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34423606

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression. In the present study, we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-CoV-2. Results revealed that SARS-CoV-2 replication was delayed in hypertensive mouse lungs. In contrast, SARS-CoV-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-CoV-2-infected normotensive mice. Furthermore, antihypertensive treatment alleviated lung inflammation induced by SARS-CoV-2 replication (interleukin (IL)-1ß up-regulation and increased immune cell infiltration). No differences in lung inflammation were observed between the SARS-CoV-2-infected normotensive mice and hypertensive mice. Our findings suggest that captopril treatment may alleviate COVID-19 progression but not affect viral replication.


Assuntos
Anti-Hipertensivos/uso terapêutico , COVID-19/complicações , Captopril/uso terapêutico , Hipertensão/complicações , Pneumopatias/tratamento farmacológico , SARS-CoV-2 , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/complicações , Inflamação/tratamento farmacológico , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Pneumopatias/etiologia , Pneumopatias/virologia , Camundongos , Replicação Viral/efeitos dos fármacos
13.
Pathol Oncol Res ; 27: 1609900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421396

RESUMO

Background: Autopsies on COVID-19 deceased patients have many limitations due to necessary epidemiologic and preventative measures. The ongoing pandemic has caused a significant strain on healthcare systems and is being extensively studied around the world. Clinical data does not always corelate with post-mortem findings. The goal of our study was to find pathognomonic factors associated with COVID-19 mortality in 100 post-mortem full body autopsies. Materials and Methods: Following necessary safety protocol, we performed 100 autopsies on patients who were diagnosed with COVID-19 related death. The macroscopic and microscopic pathologies were evaluated along with clinical and laboratory findings. Results: Extensive coagulopathic changes are seen throughout the bodies of diseased patients. Diffuse alveolar damage is pathognomonic of COVID-19 viral pneumonia, and is the leading cause of lethal outcome in younger patients. Extrapulmonary pathology is predominantly seen in the liver and spleen. Intravascular thrombosis is often widespread and signs of septic shock are often present. Conclusion: The described pathological manifestations of COVID-19 in deceased patients are an insight into the main mechanisms of SARS-CoV-2 associated lethal outcome. The disease bears no obvious bias in severity, but seems to be more severe in some patients, hinting at genetic or epigenetic factors at play.


Assuntos
COVID-19/patologia , Laboratórios/estatística & dados numéricos , Pneumopatias/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , COVID-19/complicações , COVID-19/virologia , Estudos de Coortes , Feminino , Humanos , Pneumopatias/complicações , Pneumopatias/virologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
14.
BMJ Open Respir Res ; 8(1)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34385149

RESUMO

BACKGROUND: The majority of patients with SARS-CoV-2 infection are diagnosed and managed as outpatients; however, little is known about the burden of pulmonary disease in this setting. Lung ultrasound (LUS) is a convenient tool for detection of COVID-19 pneumonia. Identifying SARS-CoV-2 infected outpatients with pulmonary disease may be important for early risk stratification. OBJECTIVES: To investigate the prevalence, natural history and clinical significance of pulmonary disease in outpatients with SARS-CoV-2. METHODS: SARS-CoV-2 PCR positive outpatients (CV(+)) were assessed with LUS to identify the presence of interstitial pneumonia. Studies were considered positive based on the presence of B-lines, pleural irregularity and consolidations. A subset of patients underwent longitudinal examinations. Correlations between LUS findings and patient symptoms, demographics, comorbidities and clinical outcomes over 8 weeks were evaluated. RESULTS: 102 CV(+) patients underwent LUS with 42 (41%) demonstrating pulmonary involvement. Baseline LUS severity scores correlated with shortness of breath on multivariate analysis. Of the CV(+) patients followed longitudinally, a majority showed improvement or resolution in LUS findings after 1-2 weeks. Only one patient in the CV(+) cohort was briefly hospitalised, and no patient died or required mechanical ventilation. CONCLUSION: We found a high prevalence of LUS findings in outpatients with SARS-CoV-2 infection. Given the pervasiveness of pulmonary disease across a broad spectrum of LUS severity scores and lack of adverse outcomes, our findings suggest that LUS may not be a useful as a risk stratification tool in SARS-CoV-2 in the general outpatient population.


Assuntos
COVID-19 , Pneumopatias/diagnóstico por imagem , COVID-19/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/virologia , Pacientes Ambulatoriais , Prevalência , Ultrassonografia
15.
Medwave ; 21(6): e8224, 2021 Jul 07.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-34292923

RESUMO

OBJECTIVE: This living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the role of pulmonary rehabilitation in the treatment of patients with COVID-19. DESIGN: This is the protocol of a living systematic review. DATA SOURCES: We will conduct searches in the L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that maps PICO questions to a repository maintained through regular searches in electronic databases, preprint servers, trial registries and other resources relevant to COVID-19. No date or language restrictions will be applied. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomized trials evaluating the effect of pulmonary rehabilitation as monotherapy or in combination with other interventions-versus sham or no treatment in patients with COVID-19. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the certainty of the evidence for each outcome. ETHICS AND DISSEMINATION: No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.


OBJETIVO: Proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el papel de la rehabilitación pulmonar en el tratamiento de los pacientes con COVID-19. DISEÑO: Es el protocolo de una revisión sistemática viva. FUENTE DE DATOS: Realizaremos búsquedas en la plataforma L·OVE (Living OVerview of Evidence) para COVID-19, un sistema que mapea los componentes de las preguntas de investigación (PICO) en un repositorio mantenido a través de búsquedas regulares en bases de datos electrónicas, servidores de pre-impresión, registros de ensayos y otros recursos relevantes para COVID-19. No se aplicarán restricciones de fecha ni de idioma. CRITERIOS DE ELEGIBILIDAD PARA LA SELECCIÓN DE ESTUDIOS Y MÉTODOS: Se adaptó un protocolo común ya publicado para revisiones sistemáticas paralelas múltiples a las especificidades de la pregunta. Se incluirán ensayos aleatorios que evalúen el efecto de la rehabilitación pulmonar como monoterapia o en combinación con otras intervenciones frente a un tratamiento simulado o ningún tratamiento en pacientes con COVID-19. Dos revisores examinarán de forma independiente cada estudio para determinar su elegibilidad, extraerán los datos y evaluarán el riesgo de sesgo. Se agruparán los resultados mediante un metaanálisis y se aplicará el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE) para evaluar la certeza de las pruebas para cada resultado. ÉTICA Y DIFUSIÓN: No se considera necesaria la aprobación ética. Los resultados de esta revisión se difundirán ampliamente a través de publicaciones revisadas por pares, redes sociales y medios de comunicación tradicionales.


Assuntos
COVID-19/reabilitação , Pneumopatias/reabilitação , COVID-19/complicações , Bases de Dados Factuais , Humanos , Pneumopatias/virologia , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
16.
Cell Rep ; 36(3): 109401, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34289371

RESUMO

Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. The lack of a licensed RSV vaccine calls for the development of vaccines with other targets and vaccination strategies. Here, we construct a recombinant protein, designated P-KFD1, comprising RSV phosphoprotein (P) and the E.-coli-K12-strain-derived flagellin variant KFD1. Intranasal immunization with P-KFD1 inhibits RSV replication in the upper and lower respiratory tract and protects mice against lung disease without vaccine-enhanced disease (VED). The P-specific CD4+ T cells provoked by P-KFD1 intranasal (i.n.) immunization either reside in or migrate to the respiratory tract and mediate protection against RSV infection. Single-cell RNA sequencing (scRNA-seq) and carboxyfluorescein succinimidyl ester (CFSE)-labeled cell transfer further characterize the Th1 and Th17 responses induced by P-KFD1. Finally, we find that anti-viral protection depends on either interferon-γ (IFN-γ) or interleukin-17A (IL-17A). Collectively, P-KFD1 is a promising safe and effective mucosal vaccine candidate for the prevention of RSV infection.


Assuntos
Flagelina/genética , Imunidade nas Mucosas/imunologia , Mutação/genética , Fosfoproteínas/metabolismo , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Animais , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Células Clonais , Citotoxicidade Imunológica/genética , Feminino , Humanos , Imunidade , Imunização , Interferon gama/metabolismo , Interleucina-17/metabolismo , Pneumopatias/patologia , Pneumopatias/virologia , Ativação Linfocitária/imunologia , Camundongos Endogâmicos BALB C , Fosforilação , Proteínas Recombinantes/imunologia , Análise de Célula Única , Células Th1/imunologia , Células Th17/imunologia
17.
Medwave ; 21(6): e8223, jul. 2021.
Artigo em Inglês | LILACS | ID: biblio-1284251

RESUMO

Objective This living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the role of pulmonary rehabilitation in the treatment of patients with COVID-19. Design This is the protocol of a living systematic review. Data sources We will conduct searches in the L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that maps PICO questions to a repository maintained through regular searches in electronic databases, preprint servers, trial registries and other resources relevant to COVID-19. No date or language restrictions will be applied. Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomized trials evaluating the effect of pulmonary rehabilitation as monotherapy or in combination with other interventions-versus sham or no treatment in patients with COVID-19. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will pool the results using meta-analysis and will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the certainty of the evidence for each outcome. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.


Assuntos
Humanos , COVID-19/reabilitação , Pneumopatias/reabilitação , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como Assunto , Metanálise como Assunto , Bases de Dados Factuais , Recuperação de Função Fisiológica , Revisões Sistemáticas como Assunto , COVID-19/complicações , Pneumopatias/virologia
18.
J Heart Lung Transplant ; 40(9): 936-947, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34172387

RESUMO

BACKGROUND: There are limited data on management strategies and outcomes among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). We implemented management protocols based on the best available evidence and consensus among multidisciplinary teams. The current study reports our experience and outcomes using this protocol-based management strategy. METHODS: We included single or bilateral LT patients who tested positive for SARS-CoV-2 on nasopharyngeal swab between March 1, 2020, to December 15, 2020 (n = 25; median age: 60, range 20-73 years; M: F 17:8). A group of patients with Respiratory Syncytial Virus (RSV) infection during 2016-18 were included to serve as a comparator group (n = 36). RESULTS: As compared to RSV, patients with COVID-19 were more likely to present with constitutional symptoms, spirometric decline, pulmonary opacities, new or worsening respiratory failure, and need for ventilator support. Patients with SARS-CoV-2 infection were less likely to receive a multimodality treatment strategy, and they experienced worse post-infection lung function loss, functional decline, and three-month survival. A significant proportion of patients with COVID-19 needed readmission for worsening allograft function (36.4%), and chronic kidney disease at initial presentation was associated with this complication. Lower pre-morbid FEV1 appeared to increase the risk of new or worsening respiratory failure, which was associated with worse outcomes. Overall hospital survival was 88% (n = 22). Follow-up data was available for all discharged patients (median: 43.5 days, range 15-287 days). A majority had persistent radiological opacities (19/22, 86.4%), with nearly half of the patients with available post-COVID-19 spirometry showing > 10% loss in lung function (6/13, median loss: 14.5%, range 10%-31%). CONCLUSIONS: Despite similar demographic characteristics and predispositions, LT patients with COVID-19 are sicker and experience worse outcomes as compared to RSV. Despite the availability of newer therapeutic agents, COVID-19 continues to be associated with significant morbidity and mortality.


Assuntos
COVID-19/epidemiologia , COVID-19/terapia , Pneumopatias/cirurgia , Transplante de Pulmão , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Adulto , Idoso , COVID-19/diagnóstico , Estudos de Casos e Controles , Protocolos Clínicos , Feminino , Hospitalização , Humanos , Pneumopatias/mortalidade , Pneumopatias/virologia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Respiração Artificial , Insuficiência Respiratória/mortalidade , Espirometria , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
19.
Pediatr Pulmonol ; 56(8): 2489-2494, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33983678

RESUMO

BACKGROUND: Studies investigating clinical and imaging findings of coronavirus disease 2019 (COVID-19) pneumonia and predictors for lung injury mostly focus on adults. In this study, we aimed to evaluate the role of laboratory findings in predicting lung involvement in children with COVID-19. METHODS: Children with COVID-19 confirmed by reverse-transcription polymerase chain reaction or COVID-19 IgM and who underwent chest computed tomography (CT) scans were reviewed retrospectively. Admission absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC/ALC ratio, platelet count, D-dimer, fibrinogen, ferritin, procalcitonin, C-reactive protein (CRP), and lactate dehydrogenase levels were compared in patients with normal and abnormal CT scans. RESULTS: A total of 101 children were included. Among the patients, 68 (67.3%) had normal CT scans, and 33 (32.7%) had pulmonary involvement. The median CRP, ferritin, and fibrinogen levels were significantly higher in children with abnormal CT findings. The model of binary logistic regression based on the presence of cough, shortness of breath, fibrinogen, ferritin, and CRP levels showed that the possibility of having abnormal CT was 1.021 times more likely for every one unit increase in fibrinogen levels. CONCLUSION: Fibrinogen might be useful to predict pulmonary involvement of COVID-19 in children. Restricting radiological imaging to patients with significant symptoms and high fibrinogen levels might be helpful in children with COVID-19 infections.


Assuntos
COVID-19 , Laboratórios , Pneumopatias , Adulto , COVID-19/complicações , Criança , Feminino , Humanos , Pneumopatias/virologia , Contagem de Linfócitos , Masculino , Estudos Retrospectivos , SARS-CoV-2
20.
Front Immunol ; 12: 656362, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936084

RESUMO

Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/prevenção & controle , Doenças do Sistema Imunitário/virologia , Vacinação/métodos , Diabetes Mellitus/imunologia , Diabetes Mellitus/virologia , Europa (Continente) , Prova Pericial , Glomerulonefrite/complicações , Glomerulonefrite/imunologia , Glomerulonefrite/virologia , Humanos , Inflamação/imunologia , Inflamação/virologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/virologia , Pneumopatias/complicações , Pneumopatias/imunologia , Pneumopatias/virologia , Pandemias/prevenção & controle , Doenças Reumáticas/complicações , Doenças Reumáticas/imunologia , Doenças Reumáticas/virologia , Dermatopatias/complicações , Dermatopatias/imunologia , Dermatopatias/virologia , Uveíte/complicações , Uveíte/imunologia , Uveíte/virologia
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