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4.
Front Immunol ; 11: 2167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013911

RESUMO

The inflammatory response to and the subsequent development of Adult Respiratory Distress Syndrome (ARDS) is considered to underpin COVID-19 pathogenesis. With a developing world catastrophe, we need to examine our known therapeutic stocks, to assess suitability for prevention and/or treatment of this pro-inflammatory virus. Analyzing commonly available and inexpensive immunomodulatory and anti-inflammatory medications to assess their possible effectiveness in improving the host response to COVID-19, this paper recommends the following: (1) optimize current health-cease (reduce) smoking, ensure adequate hypertension and diabetes control, continue exercising; (2) start on an HMG CoA reductase inhibitor "statin" for its immunomodulatory and anti-inflammatory properties, which may reduce the mortality associated with ARDS; and (3) consider using Diclofenac (or other COX-2 inhibition medications) for its anti-inflammatory and virus toxicity properties. For purposes of effectiveness, this needs to be in the early course of the disease (post infection and/or symptom presentation) and given in a high dose. The downsides to these recommended interventions are considered manageable at this stage of the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Diclofenaco/efeitos adversos , Diclofenaco/uso terapêutico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/prevenção & controle , Síndrome do Desconforto Respiratório do Adulto/virologia , Internalização do Vírus/efeitos dos fármacos
7.
Clin Immunol ; 220: 108598, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32961333

RESUMO

Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. Deregulated complement activation may fuel cytokine-driven hyper-inflammation, thrombotic microangiopathy and NET-driven immunothrombosis, thereby leading to multi-organ failure. Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2 infection. Whether blockade of terminal complement effectors (C5, C5a, or C5aR1) may elicit similar outcomes to upstream intervention at the level of C3 remains debated. Here we compare the efficacy of the C5-targeting monoclonal antibody eculizumab with that of the compstatin-based C3-targeted drug candidate AMY-101 in small independent cohorts of severe COVID-19 patients. Our exploratory study indicates that therapeutic complement inhibition abrogates COVID-19 hyper-inflammation. Both C3 and C5 inhibitors elicit a robust anti-inflammatory response, reflected by a steep decline in C-reactive protein and IL-6 levels, marked lung function improvement, and resolution of SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). C3 inhibition afforded broader therapeutic control in COVID-19 patients by attenuating both C3a and sC5b-9 generation and preventing FB consumption. This broader inhibitory profile was associated with a more robust decline of neutrophil counts, attenuated neutrophil extracellular trap (NET) release, faster serum LDH decline, and more prominent lymphocyte recovery. These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials.


Assuntos
Betacoronavirus/patogenicidade , Complemento C3/antagonistas & inibidores , Complemento C5/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Coortes , Ativação do Complemento/efeitos dos fármacos , Complemento C3/genética , Complemento C3/imunologia , Complemento C5/genética , Complemento C5/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Armadilhas Extracelulares/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/virologia , Pandemias , Peptídeos Cíclicos/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/virologia , Índice de Gravidade de Doença
10.
Medicine (Baltimore) ; 99(38): e22311, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957394

RESUMO

Diabetes mellitus results in an attenuated inflammatory response, reduces pulmonary microvascular permeability, and may decrease the risk of developing acute respiratory distress syndrome (ARDS). Studies have shown that patients with ARDS are better managed by a conservative as compared to liberal fluid management strategy. However, it is not known if the same fluid management principles hold true for patients with comorbid diabetes mellitus and ARDS.As diabetes mellitus results in reduced pulmonary microvascular permeability and an attenuated inflammatory response, we hypothesize that in the setting of ARDS, diabetic patients will be able to tolerate a positive fluid balance better than patients without diabetes.The Fluid and Catheter Treatment Trial (FACTT) randomized patients with ARDS to conservative versus liberal fluid management strategies. In a secondary analysis of this trial, we calculated the interaction of diabetic status and differing fluid strategies on outcomes. Propensity score subclassification matching was used to control for the differing baseline characteristics between patients with and without diabetes.Nine hundred fifty-six patients were analyzed. In a propensity score matched analysis, the difference in the effect of a conservative as compared to liberal fluid management strategy on ventilator free days was 2.23 days (95% CI: -0.97 to 5.43 days) in diabetic patients, and 2.37 days (95% CI: -0.21 to 4.95 days) in non-diabetic patients. The difference in the effect of a conservative as compared to liberal fluid management on 60 day mortality was 2% (95% CI: -11.8% to 15.8%) in diabetic patients, and -7.9% (95% CI: -21.7% to 5.9%) in non-diabetic patients.When comparing a conservative fluid management strategy to a liberal fluid management strategy, diabetic patients with ARDS did not have a statistically significant difference in outcomes than non-diabetic patients.


Assuntos
Diabetes Mellitus/terapia , Hidratação/métodos , Síndrome do Desconforto Respiratório do Adulto/terapia , Adulto , Idoso , Cateteres , Tratamento Conservador , Diabetes Mellitus/congênito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Síndrome do Desconforto Respiratório do Adulto/complicações
11.
Eur Rev Med Pharmacol Sci ; 24(17): 9154-9160, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32965007

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. An association between increased venous thromboembolism in patients with pneumonia-related to COVID-19 has not yet been well described. PATIENTS AND METHODS: We aimed to illustrate cases of pulmonary thromboembolism in patients with acute respiratory distress syndrome related to COVID-19 treated in our intensive care unit. The medical records of patients affected by COVID-19 with acute respiratory distress syndrome in our institute from 1/3/2020 to 31/3/2020 were retrospectively reviewed. RESULTS: Our center registered a high prevalence of thromboembolic events among 62 patients affected by acute respiratory distress syndrome related to COVID-19 despite a regular antithrombotic prophylaxis. Out of these, 32 patients were transferred to other hospitals, and 30 were treated in our center. Venous thromboembolism was registered in 12 (19.3%) cases. In particular, 11 diagnoses of pulmonary embolism and 1 diagnosis of deep vein thrombosis were formulated. We described a case series of venous thromboembolism in nine patients treated in our Intensive Care Unit (ICU). Main pulmonary arteries were always involved in these patients. None of them died. CONCLUSIONS: In conclusion, critically ill patients with ARDS related to COVID-19 may have an increased risk of VTE that could be a leading cause of mortality. These patients require a high index of clinical suspicion and an accurate diagnostic approach, in order to immediately start an appropriate anticoagulant treatment.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Síndrome do Desconforto Respiratório do Adulto/complicações , Tromboembolia Venosa/diagnóstico , Idoso , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Itália , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Tromboembolia Venosa/complicações , Trombose Venosa/complicações , Trombose Venosa/diagnóstico
12.
Am J Cardiol ; 132: 147-149, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32762961

RESUMO

The cardiac involvement in Coronavirus disease (COVID-19) is still under evaluation, especially in severe COVID-19-related Acute Respiratory Distress Syndrome (ARDS). The cardiac involvement was assessed by serial troponin levels and echocardiograms in 28 consecutive patients with COVID-19 ARDS consecutively admitted to our Intensive Care Unit from March 1 to March 31. Twenty-eight COVID-19 patients (aged 61.7 ± 10 years, males 79%). The majority was mechanically ventilated (86%) and 4 patients (14%) required veno-venous extracorporeal membrane oxygenation. As of March 31, the Intensive Care Unit mortality rate was 7%, whereas 7 patients were discharged (25%) with a length of stay of 8.2 ±5 days. At echocardiographic assessment on admission, acute core pulmonale was detected in 2 patients who required extracorporeal membrane oxygenation support. Increased systolic arterial pressure was detected in all patients. Increased Troponin T levels were detectable in 11 patients (39%) on admission. At linear regression analysis, troponin T showed a direct relationship with C-reactive Protein (R square: 0.082, F: 5.95, p = 0.017). In conclusions, in COVID-19-related ARDS, increased in Tn levels was common but not associated with alterations in wall motion kinesis, thus suggesting that troponin T elevation is likely to be multifactorial, mainly linked to disease severely (as inferred by the relation between Tn and C-reactive Protein). The increase in systolic pulmonary arterial pressures observed in all patients may be related to hypoxic vasoconstriction. Further studies are needed to confirm our findings in larger cohorts.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Miocardite/etiologia , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/complicações , Biomarcadores/sangue , Infecções por Coronavirus/epidemiologia , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/sangue , Miocardite/diagnóstico , Pandemias , Pneumonia Viral/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/sangue , Troponina I/sangue
17.
RMD Open ; 6(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32763956

RESUMO

Reactive arthritis (ReA) is typically preceded by sexually transmitted disease or gastrointestinal infection. An association has also been reported with bacterial and viral respiratory infections. Herein, we report the first case of ReA after the he severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This male patient is in his 50s who was admitted with COVID-19 pneumonia. On the second day of admission, SARS-CoV-2 PCR was positive from nasopharyngeal swab specimen. Despite starting standard dose of favipiravir, his respiratory condition deteriorated during hospitalisation. On the fourth hospital day, he developed acute respiratory distress syndrome and was intubated. On day 11, he was successfully extubated, subsequently completing a 14-day course of favipiravir. On day 21, 1 day after starting physical therapy, he developed acute bilateral arthritis in his ankles, with mild enthesitis in his right Achilles tendon, without rash, conjunctivitis, or preceding diarrhoea or urethritis. Arthrocentesis of his left ankle revealed mild inflammatory fluid without monosodium urate or calcium pyrophosphate crystals. Culture of synovial fluid was negative. Plain X-rays of his ankles and feet showed no erosive changes or enthesophytes. Tests for syphilis, HIV, anti-streptolysin O (ASO), Mycoplasma, Chlamydia pneumoniae, antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide antibody and Human Leukocyte Antigen-B27 (HLA-B27) were negative. Gonococcal and Chlamydia trachomatis urine PCR were also negative. He was diagnosed with ReA. Nonsteroidal Anti-Inflammatory Drug (NSAID)s and intra-articular corticosteroid injection resulted in moderate improvement.


Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Artrite Reativa/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/terapia , Corticosteroides/uso terapêutico , Amidas/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/uso terapêutico , Artrite Reativa/tratamento farmacológico , Artrite Reativa/etiologia , Artrocentese , Betacoronavirus , Infecções por Coronavirus/complicações , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pirazinas/uso terapêutico , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/complicações
18.
J Investig Med ; 68(6): 1199-1202, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641351

RESUMO

Predictive factors for adverse outcomes in patients with COVID-19 are urgently needed. Data related to the applicability of the Clinical Frailty Scale (CFS) for risk stratification in patients with COVID-19 are currently lacking. We investigated the ability of CFS to predict need for mechanical ventilation and the duration of hospital stays in European patients with COVID-19. In total, 42 patients with confirmed COVID-19 infection admitted to the University Medical Center Mainz between March 3 and April 15 2020 were included into this validation study and data were retrospectively analyzed. CFS was assessed at admission in all patients. Patients were followed for need for mechanical ventilation and time to hospital discharge. At admission, the median CFS was 3 (range: 1-7) and 14 (33.3%) patients were considered as at least pre-frail (CFS >3). 24 (57.1%) patients were discharged from hospital after a median time of 7 days (IQR 4-8). 12 (28.6%) patients developed acute respiratory distress syndrome and required mechanical ventilation. In multivariable Cox regression analyses, higher CFS scores (HR 1.659, 95% CI 1.090 to 2.525, p=0.018) were an independent predictor for a higher risk of mechanical ventilation after adjusting for age, Charlson Comorbidity Index and quick sepsis-related organ failure score. Additionally, lower CFS scores (HR 0.554, 95% CI 0.312 to 0.983, p=0.043) were associated with earlier discharge from hospital. In conclusion, this report demonstrates the usefulness of the CFS for risk stratification at hospital admission in patients with COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Fragilidade , Pneumonia Viral/diagnóstico , Medição de Risco/métodos , Índice de Gravidade de Doença , Fatores Etários , Idoso , Betacoronavirus , Feminino , Alemanha , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Alta do Paciente , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/complicações , Estudos Retrospectivos , Fatores de Tempo
19.
J Coll Physicians Surg Pak ; 30(6): 46-47, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32723449

RESUMO

Hypoxemia is the most common cause for hospitalization in COVID-19 patients. Acute hypoxemic respiratory failure or acute respiratory distress syndrome (ARDS) is the most common complication in COVID-19 patients. Close monitoring of respiratory decompensation is essential. Supplemental oxygen, high flow nasal canula, non-invasive ventilation and endotracheal intubation are the most commonly suggested methods to improve oxygenation. Early intubation with pre-oxygenation, modified rapid sequence intubation and intubation using a video laryngoscope has been advised as a strategy including lung protective ventilation, prone position ventilation, adequate sedation and extracorporeal membrane oxygenation. Strict personal precautions and challenges related to airway management has been currently studied. The authors summarize here the issues of mechanical ventilation and some strategies to resolve them. Key Words: Mechanical ventilation, COVID-19, Hypoxemia.


Assuntos
Infecções por Coronavirus/complicações , Oxigenação por Membrana Extracorpórea/métodos , Hipóxia/terapia , Oxigenoterapia/métodos , Pneumonia Viral/complicações , Respiração Artificial/efeitos adversos , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/terapia , Insuficiência Respiratória/terapia , Betacoronavirus , Humanos , Hipóxia/complicações , Pandemias , Síndrome do Desconforto Respiratório do Adulto/etiologia , Insuficiência Respiratória/complicações , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle
20.
PLoS One ; 15(7): e0235437, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645025

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe complication of malaria that remains largely unstudied. We aim to describe the development of ARDS associated with severe P. falciparum malaria, its management and impact on clinical outcome. METHODS: Retrospective observational study of adult patients admitted with severe P. falciparum malaria in an Intensive Care Unit (ICU) of a tertiary care hospital from Portugal from 2008 to 2018. A multivariate logistic regression analysis was used to identify factors associated with the development of ARDS, defined according to Berlin Criteria. Prognosis was assessed by case-fatality ratio, nosocomial infection and length of stay. RESULTS: 98 patients were enrolled, of which 32 (33%) developed ARDS, a median of 2 days after starting antimalarial medication (IQR 0-4, range 0-6). Length of stay in ICU and in hospital were significantly longer in patients who developed ARDS: 13 days (IQR 10-18) vs 3 days (IQR 2-5) and 21 days (IQR 15-30.5) vs 7 days (IQR 6-10), respectively. Overall case-fatality ratio in ICU was 4.1% and did not differ between groups. The risk of ARDS development is difficult to establish. CONCLUSION: ARDS is a hard to predict late complication of severe malaria. A low threshold for ICU admission and monitoring should be used. Ideally patients should be managed in a centre with experience and access to advanced techniques.


Assuntos
Malária Falciparum/complicações , Malária Falciparum/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Resultado do Tratamento , Adulto Jovem
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