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1.
Molecules ; 25(20)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066442

RESUMO

The activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and/or its components is associated with the physio-pathogenesis of many respiratory diseases including asthma, COPD (chronic obstructive pulmonary disease), SARS Cov-2 (severe acute respiratory syndrome coronavirus 2), and in several autoimmune diseases. Hibiscus noldeae Baker f. has been widely reported to be traditionally used in the treatment of different ailments, some of which are of inflammatory background such as asthma, wounds, headache, etc. However, the claims have not been supported by evidence at the molecular and functional levels. Here, we report on the bio-guided fractionation of H. noldeae and assessment of the inhibitory properties of some fractions and purified compounds on NLRP3 inflammasome and Interleukin 6 (IL-6). The activation of the NLRP3 inflammasome was determined by detecting the activity of caspase-1 and the production of Interleukin 1ß (IL-1ß) in Lipopolysaccharide (LPS) and ATP-stimulated Tamm-Horsfall Protein 1 (THP-1) macrophages, while the production of IL-6 was studied in LPS-stimulated RAW264.7 mouse macrophages. It was observed that hexane and ethyl acetate fractions of the crude extract of the aerial parts of H. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1ß and IL-6 production. The ER2.4 and ER2.7 fractions downregulated the production of IL-1ß and IL-6, in a similar range as the caspase-1 inhibitor AC-YVAD-CHO and the drug Dexamethasone, both used as controls, respectively. Overall, our work does provide the very first scientific based evidence for Hibiscus noldeae anti-inflammatory effects and widespread use by traditional healers in Rwanda for a variety of ailments.


Assuntos
Anti-Inflamatórios/farmacologia , Hibiscus/química , Inflamassomos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Extratos Vegetais/farmacologia , Animais , Inflamassomos/imunologia , Inflamassomos/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células RAW 264.7
2.
In Vivo ; 34(5): 3027-3028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871847
3.
Eur Cytokine Netw ; 31(2): 44-49, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933891

RESUMO

BACKGROUND: Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020. RESULTS: Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups. CONCLUSIONS: Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Pneumonia Viral/tratamento farmacológico , Idoso , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Feminino , Expressão Gênica , Humanos , Unidades de Terapia Intensiva , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/imunologia , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
4.
Front Immunol ; 11: 2094, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973818

RESUMO

The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there is a need for medical options to mitigate this current epidemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract. A number of current studies on COVID-19 have demonstrated the substantial increase in pro-inflammatory factors in the lungs during infection. The virus is also documented in the central nervous system and, particularly in the brainstem, which plays a key role in respiratory and cardiovascular function. Currently, there are few antiviral approaches, and several alternative drugs are under investigation. Two of these are Idelalisib and Ebastine, already proposed as preventive strategies in airways and allergic diseases. The interesting and evolving potential of phosphoinositide 3-kinase δ (PI3Kδ) inhibitors, together with Ebastine, lies in their ability to suppress the release of pro-inflammatory cytokines, such as IL-1ß, IL-8, IL-6, and TNF-α, by T cells. This may represent an optional therapeutic choice for COVID-19 to reduce inflammatory reactions and mortality, enabling patients to recover faster. This concise communication aims to provide new potential therapeutic targets capable of mitigating and alleviating SARS-CoV-2 pandemic infection.


Assuntos
Betacoronavirus , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Terapia de Alvo Molecular/métodos , Pneumonia Viral/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Butirofenonas/farmacologia , Butirofenonas/uso terapêutico , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Infecções por Coronavirus/virologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Pandemias , Peptidil Dipeptidase A/metabolismo , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pneumonia Viral/virologia , Purinas/farmacologia , Purinas/uso terapêutico , Quinazolinonas/farmacologia , Quinazolinonas/uso terapêutico
5.
Rev Bras Ter Intensiva ; 32(3): 337-347, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32965395

RESUMO

INTRODUCTION: Pro-inflammatory markers play a significant role in the disease severity of patients with COVID-19. Thus, anti-inflammatory therapies are attractive agents for potentially combating the uncontrolled inflammatory cascade in these patients. We designed a trial testing tocilizumab versus standard of care intending to improve the outcomes by inhibiting interleukin-6, an important inflammatory mediator in COVID-19. METHODS AND ANALYSIS: This open-label multicentre randomized controlled trial will compare clinical outcomes of tocilizumab plus standard of care versus standard of care alone in patients with moderate to severe COVID-19. Two of the following four criteria are required for protocol enrolment: D-dimer > 1,000ng/mL; C reactive protein > 5mg/dL, ferritin > 300mg/dL, and lactate dehydrogenase > upper limit of normal. The primary objective will be to compare the clinical status on day 15, as measured by a 7-point ordinal scale applied in COVID-19 trials worldwide. The primary endpoint will be assessed by an ordinal logistic regression assuming proportional odds ratios adjusted for stratification variables (age and sex). ETHICS AND DISSEMINATION: The TOCIBRAS protocol was approved by local and central (national) ethical committees in Brazil following current national and international guidelines/directives. Each participating center had the study protocol approved by their institutional review boards before initiating protocol enrolment. The data derived from this trial will be published regardless of the results. If proven active, this strategy could alleviate the consequences of the inflammatory response in COVID-19 patients and improve their clinical outcomes.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Brasil , Infecções por Coronavirus/fisiopatologia , Humanos , Interleucina-6/antagonistas & inibidores , Pandemias , Pneumonia Viral/fisiopatologia , Índice de Gravidade de Doença
6.
Front Immunol ; 11: 1648, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754159

RESUMO

Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult). Understanding the pathogenesis of cytokine storm will help unravel not only risk factors for the condition but also therapeutic strategies to modulate the immune response and deliver improved outcomes in COVID-19 patients at high risk for severe disease. In this article, we present an overview of the cytokine storm and its implications in COVID-19 settings and identify potential pathways or biomarkers that could be targeted for therapy. Leveraging expert opinion, emerging evidence, and a case-based approach, this position paper provides critical insights on cytokine storm from both a prognostic and therapeutic standpoint.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Cuidados Críticos/métodos , Citocinas/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Tomada de Decisão Clínica/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Estado Terminal , Células Endoteliais/metabolismo , Feminino , Humanos , Hospedeiro Imunocomprometido , Interleucina-6/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Masculino , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Fatores Sexuais , Trombose
8.
Front Immunol ; 11: 1708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754163

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the "cytokine storm" may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Interleucina-6/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Corticosteroides/uso terapêutico , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antimaláricos/uso terapêutico , Artesunato/uso terapêutico , Infecções por Coronavirus/virologia , Hemoperfusão/métodos , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Interleucina-6/antagonistas & inibidores , Camundongos , Pandemias , Pneumonia Viral/virologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores
10.
PLoS One ; 15(8): e0237693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790733

RESUMO

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antimaláricos/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Azitromicina/uso terapêutico , Criança , Pré-Escolar , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Feminino , Seguimentos , Hospitalização , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Interleucina-6/antagonistas & inibidores , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
PLoS One ; 15(8): e0237903, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817689

RESUMO

AIM: To identify investigated interventions for COVID-19 prevention or treatment via trial registry entries on planned or ongoing randomised clinical trials. To assess these registry entries for recruitment status, planned trial size, blinding and reporting of mortality. METHODS: We identified trial registry entries systematically via the WHO International Clinical Trials Registry Platform and 33 trial registries up to June 23, 2020. We included relevant trial registry entries for randomized clinical trials investigating medical preventive, adjunct or supportive therapies and therapeutics for treatment of COVID-19. Studies with non-random and single-arm design were excluded. Trial registry entries were screened by two authors independently and data were systematically extracted. RESULTS: We included 1303 trial registry entries from 71 countries investigating 381 different single interventions. Blinding was planned in 47% of trials. Sample size was >200 participants in 40% of trials and a total of 611,364 participants were planned for inclusion. Mortality was listed as an outcome in 57% of trials. Recruitment was ongoing in 54% of trials and completed in 8%. Thirty-five percent were multicenter trials. The five most frequent investigational categories were immune modulating drugs (266 trials (20%)), unconventional medicine (167 trials (13%)), antimalarial drugs (118 trials (9%)), antiviral drugs (100 trials (8%)) and respiratory adjuncts (78 trials (6%)). The five most frequently tested uni-modal interventions were: chloroquine/hydroxychloroquine (113 trials with 199,841 participants); convalescent plasma (64 trials with 11,840 participants); stem cells (51 trials with 3,370 participants); tocilizumab (19 trials with 4,139 participants) and favipiravir (19 trials with 3,210 participants). CONCLUSION: An extraordinary number of randomized clinical trials investigating COVID-19 management have been initiated with a multitude of medical preventive, adjunctive and treatment modalities. Blinding will be used in only 47% of trials, which may have influence on future reported treatment effects. Fifty-seven percent of all trials will assess mortality as an outcome facilitating future meta-analyses.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Humanos , Hidroxicloroquina/uso terapêutico , Interleucina-6/antagonistas & inibidores , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Resultado do Tratamento
13.
Sci Rep ; 10(1): 13689, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792492

RESUMO

To describe the epidemiological and clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) in Beijing. To analyze the application of corticosteroids in patients with severe pneumonia. We collected information on demographic characteristics, exposure history, clinical characteristics, corticosteroids use, and outcomes of the 65 confirmed cases of COVID-19 at Fifth Medical Center of PLA General Hospital from Jan 20 to Feb 23, 2020. The final follow-up date observed was April 15th, 2020. The number of patients with mild, general, severe, and critical type were 10 (15.38%), 32 (49.23%), 8 (12.31%), and 15 (23.08%), respectively. The median incubation period was 6 days. Notable outliers were 1 patient at 16 days and 1 patient at 21 days. In lymphocyte subgroup analysis, decreases in total, T, CD4, and CD8 lymphocytes were more common as the disease worsened (All P < 0.05). Methylprednisolone (mPSL) was applied to 31 (47.69%) patients with pneumonia, including 10 (31.25%) general, 8 (100%) severe, and 13 (86.67%) critical patients, respectively. Corticosteroids inhibited Interleukin-6(IL-6) production (P = 0.0215) but did not affect T lymphocyte (P = 0.0796). There was no significant difference between patients using lower dose (≤ 2 mg/kg day) and higher dose (> 2 mg/kg day) mPSL in inhibiting IL-6 production (P = 0.5856). Thirty of 31 patients (96.77%) had stopped mPSL due to improvement of pneumonia. Virus RNA clearance time lengthened with disease progression (P = 0.0001). In general type, there was no significant difference in virus clearance time between patients with (15, 12-19 days) and without (14.5, 11-18 days) (P = 0.7372) mPSL use. Lymphocyte, especially T lymphocyte, in severe and critical patients showed a dramatic decrease. Application of lower dose corticosteroids (≤ 2 mg/kg day) could inhibit IL-6 production (a representative of cytokines) as effectively as a higher dose. Proper use corticosteroids in general type patients did not delay virus clearance.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Glucocorticoides/uso terapêutico , Metilprednisolona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Pequim/epidemiologia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Criança , Pré-Escolar , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacologia , Humanos , Interleucina-6/antagonistas & inibidores , Contagem de Linfócitos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/farmacologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , RNA Viral/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
14.
Food Chem Toxicol ; 145: 111694, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32822775

RESUMO

We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 µm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. CLINICAL TRIAL REGISTRATION: url: https://www.clinicaltrials.gov. Unique identifier: NCT03288584.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Endotélio/efeitos dos fármacos , Glicocálix/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Idoso , Betacoronavirus , Permeabilidade Capilar/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Feminino , Coração/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Análise de Onda de Pulso
15.
Nat Rev Immunol ; 20(10): 585-586, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788708
16.
Mediators Inflamm ; 2020: 7527953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724296

RESUMO

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.


Assuntos
Alarminas/imunologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Armadilhas Extracelulares/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Alarminas/antagonistas & inibidores , Autofagia/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Armadilhas Extracelulares/efeitos dos fármacos , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Pulmão/imunologia , Pulmão/patologia , Pandemias , Pneumonia Viral/patologia
19.
Front Immunol ; 11: 1446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612617

RESUMO

COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called "cytokine storm" induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório do Adulto/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/sangue , Humanos , Interleucina-6/antagonistas & inibidores , Pandemias , Pneumonia Viral/imunologia , Receptores de Interleucina-6/antagonistas & inibidores , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/patologia
20.
Front Immunol ; 11: 1439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655577

RESUMO

In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, we feel a duty to share our experience and our knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.


Assuntos
Betacoronavirus/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Imunidade Adaptativa/efeitos dos fármacos , Adulto , Anticoagulantes/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Hidroxicloroquina/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Interleucina-1/antagonistas & inibidores , Interleucina-6/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/etiologia
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