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1.
Eur Rev Med Pharmacol Sci ; 25(1): 523-526, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33506944

RESUMO

OBJECTIVE: Since the start of the COVID-19 pandemic, millions of people have been infected with thousands of deaths. Few data regarding factors that increase the risk of infection are available. Our study aimed to evaluate all people living in retirement homes (PLRNH) and identify factors that could increase infection risk in a close community. MATERIALS AND METHODS: We conducted a retrospective study enrolling all PLRNH, where at least one SARS-CoV-2 infected person was present. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on the infection. RESULTS: We included 452 PLRNH; 144 (31.7%) were male, with a mean age of 82.2±8.6 years. People with a positive swab for SARS-CoV-2 were 306 (67.4%). A significant difference between SARS-CoV-2 infected and not infected was observed in the percentage of those receiving chronic treatment with Angiotensin II receptor blockers (ARBs) (18.6% vs. 9.5%, p=0.012). On the contrary, there was no difference in the proportion of those receiving ACE inhibitors (ACE-I) (21.2% vs. 23.6%, p=0.562). At multivariate analysis, people with mental illness and cancer had an increased risk of being infected. Furthermore, receiving ARBs as a chronic treatment was an independent predictor of infection risk [OR 1.95 (95% CI 1.03-3.72) p=0.041]. CONCLUSIONS: Our data suggest that, in close communities, such as retirement nursing homes, the receipt of ARBs increased the risk of acquiring SARS-CoV-2 infection. However, before changing an important chronic treatment in a fragile population, such as the elderly living in retirement nursing homes, clinicians should carefully evaluate the risk-benefit ratio.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , /epidemiologia , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Uso de Medicamentos , Feminino , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Humanos , Masculino , Casas de Saúde/estatística & dados numéricos , Pandemias , Estudos Retrospectivos , Medição de Risco
2.
Clin Sci (Lond) ; 135(3): 465-481, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33479758

RESUMO

The key link between renin-angiotensin system (RAS) and COVID-19 is ACE2 (angiotensin-converting enzyme 2), which acts as a double-edged sword, because ACE2 increases the tissue anti-inflammatory response but it is also the entry receptor for the virus. There is an important controversy on several drugs that regulate RAS activity and possibly ACE2, and are widely used, particularly by patients most vulnerable to severe COVID-19. In the lung of healthy rats, we observed that candesartan (an angiotensin type-1, AT1, receptor blocker; ARB) and captopril (an ACE inhibitor; ACEI) up-regulated expression of tissue ACE2 and RAS anti-inflammatory axis receptors (AT2 and Mas receptors). This effect was particularly pronounced in rats with metabolic syndrome (obesity, increased blood pressure and hyperglycemia) and aged rats. Treatment of cultures of human type-II pneumocytes with candesartan or captopril induced up-regulation of ACE2 expression in cells. Treatment with viral spike protein induced a decrease in full-length (i.e. transmembrane) ACE2, an increase in levels of a short intracellular ACE2 polypeptide and an increase in ADAM17 activity in cells, together with an increase in levels of soluble ACE2 and major proinflammatory cytokines in the culture medium. Spike protein-induced changes and levels of spike protein internalization in cells were inhibited by pretreatment with the above-mentioned drugs. The results suggest that these drugs increase ACE2 levels and promote the anti-inflammatory RAS axis in the lung. Furthermore, possible up-regulation of viral entry by the drug-induced increase in expression of transmembrane ACE2 is counteracted by additional mechanisms, particularly by drug-induced inhibition of ADAM17 activity.


Assuntos
Benzimidazóis/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Captopril/administração & dosagem , Tetrazóis/administração & dosagem , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , /genética , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , /metabolismo , Feminino , Humanos , Pulmão/metabolismo , Pulmão/virologia , Masculino , Ratos , Sistema Renina-Angiotensina/efeitos dos fármacos , /fisiologia
3.
Pharmacol Res Perspect ; 9(1): e00691, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33378565

RESUMO

Coronaviruses represent global health threat. In this century, they have already caused two epidemics and one serious pandemic. Although, at present, there are no approved drugs and therapies for the treatment and prevention of human coronaviruses, several agents, FDA-approved, and preclinical, have shown in vitro and/or in vivo antiviral activity. An in-depth analysis of the current situation leads to the identification of several potential drugs that could have an impact on the fight against coronaviruses infections. In this review, we discuss the virology of human coronaviruses highlighting the main biological targets and summarize the current state-of-the-art of possible therapeutic options to inhibit coronaviruses infections. We mostly focus on FDA-approved and preclinical drugs targeting viral conserved elements.


Assuntos
/metabolismo , Infecções por Coronavirus/metabolismo , Coronavirus/metabolismo , Dipeptidil Peptidase 4/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , /antagonistas & inibidores , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/metabolismo , Antivirais/administração & dosagem , Antivirais/metabolismo , Azóis/administração & dosagem , Azóis/metabolismo , Coronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/metabolismo , Humanos , Naftoquinonas/administração & dosagem , Naftoquinonas/metabolismo , Compostos Organosselênicos/administração & dosagem , Compostos Organosselênicos/metabolismo , Síndrome Respiratória Aguda Grave/tratamento farmacológico
4.
Med. clín (Ed. impr.) ; 155(11): 488-490, dic. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-190829

RESUMO

INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2


INTRODUCCIÓN: Existe controversia respecto al uso de los inhibidores de la enzima convertidora de angiotensina (IECA) o los bloqueadores de los receptores tipo I de la angiotensina II (ARA-II) para el tratamiento de la hipertensión arterial en COVID-19. Se ha sugerido que estos fármacos podrían tanto aumentar como reducir el riesgo de COVID-19 grave. PACIENTES Y MÉTODO: Estudio de cohortes retrospectivo de pacientes consecutivos de un área sanitaria, con hipertensión e infección por SARS-CoV-2. Variable de resultados: ingreso hospitalario por COVID-19 grave. RESULTADOS: Fueron diagnosticados 539 sujetos por infección por SARS-CoV-2. De estos, 157 (29,1%) eran hipertensos y se incluyeron en el estudio. Se ingresaron 69 (43,9%) pacientes por COVID-19 grave. En el análisis multivariante, la edad más elevada, la diabetes y la miocardiopatía hipertensiva se relacionaron con el riesgo de ingreso hospitalario. El tratamiento con ARA-II se asoció con un riesgo significativamente más bajo de ingreso (HR: 0,29, IC 95%: 0,10-0,88). Una tendencia similar, aunque no significativa, se encontró para los IECA. CONCLUSIÓN: el tratamiento con ARA-II o IECA no se asoció con una peor evolución clínica en pacientes hipertensos consecutivos infectados por SARS-CoV-2


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/complicações , Hipertensão/complicações , Pandemias , Pneumonia Viral/complicações , Estudos de Coortes , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Índice de Gravidade de Doença , Estudos Retrospectivos , Hospitalização , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Modelos Logísticos
5.
High Blood Press Cardiovasc Prev ; 27(6): 597-599, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33006010

RESUMO

Systemic sclerosis (SSc) is a rare autoimmune disease that causes fibrosis in the skin and subcutaneous tissue, involving other organs such as the heart, lungs, kidneys, and gastrointestinal tract. Additionally, it can cause pulmonary arterial hypertension. Scleroderma renal crisis (SRC) is one of the most dreadful complications of SSc. SRC is a medical emergency that can present as a clinical picture of hypertensive encephalopathy. The pathophysiology involves an abrupt onset of moderate to severe hypertension that ranges from days to weeks; it is associated with an increase in plasma renin activity and acute kidney injury. It is known that by introducing angiotensin-converting enzyme inhibitors, the mortality decreases significantly in SRC. The renal biopsy plays an important role on the diagnosis and opportune treatment. We present a clinical case of SRC with a typical presentation of hypertensive emergency and acute kidney injury.


Assuntos
Lesão Renal Aguda/etiologia , Pressão Sanguínea , Hipertensão/etiologia , Escleroderma Sistêmico/complicações , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Administração Intravenosa , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Emergências , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Diálise Renal , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Resultado do Tratamento , Vasodilatadores/administração & dosagem
6.
Bol Med Hosp Infant Mex ; 77(5): 274-281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064690

RESUMO

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with hypertension and other cardiovascular comorbidities develop more severe coronavirus disease (COVID)-19 and are at high risk of death, a controversy arose about the use of antihypertensives as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Such drugs might increase the expression of the fundamental receptor of this new infectious agent: the angiotensin-converting enzyme 2 (ACE2). Preclinical observations indicate that the increase of ACE2 expression or the activity by ACEis and ARBs leads to a greater transformation of angiotensin (Ang)-II to Ang-(1-7), which is associated with positive effects on cardiovascular and pulmonary pathophysiology. This association has been demonstrated in observational studies in patients with cardiovascular pathology and pneumonia. It has not been possible to confirm whether users of ACEis or ARBs are more infected by the new coronavirus, due to methodological issues in studies with patients infected with SARS-CoV-2. However, the use of such antihypertensive treatments in both children and adults might reduce the virulence of infection. Therefore, changes in the antihypertensive therapy of patients at risk of contracting COVID-19 are not recommended.


Assuntos
Anti-Hipertensivos/administração & dosagem , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Adulto , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Criança , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Humanos , Hipertensão/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco
7.
Med. clín (Ed. impr.) ; 155(7): 295-298, oct. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-193238

RESUMO

INTRODUCTION AND OBJECTIVE: A recent outbreak of coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin–angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with hypertension. PATIENTS AND METHOD: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. RESULTS: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. CONCLUSIONS: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanism


INTRODUCCIÓN Y OBJETIVO: Un reciente brote de la enfermedad coronavirus 2019 (COVID-19) se produce en todo el mundo. La enzima convertidora de angiotensina 2 (ACE2) puede mediar la entrada del coronavirus en las células huésped. Por lo tanto, se sospechaba que los inhibidores del sistema renina-angiotensina (SRA) contribuían al aumento de la infección por coronavirus. Nos propusimos analizar los efectos de los SRA en los pacientes COVID-19 con hipertensión. PACIENTES Y MÉTODO: En este estudio retrospectivo, de un solo centro, se analizaron 27 pacientes de COVID-19 con hipertensión, que fueron admitidos en el Centro Clínico de Salud Pública de Shangai desde el 25 de enero de 2020 hasta el 31 de enero de 2020, para determinar las características clínicas, los parámetros de laboratorio, los medicamentos y la duración de la estancia. A todos los pacientes se les administró un tratamiento antiviral y antihipertensivo, de los cuales 14 pacientes fueron tratados con SRA y 13 sin SRA. RESULTADOS: Comparando los dos grupos, no encontramos diferencias estadísticamente significativas en los síntomas clínicos y las pruebas de laboratorio. Además, la tos no se agravó. CONCLUSIONES: A través del análisis de esta pequeña muestra, el SRA podría considerarse seguro y eficaz para controlar la presión arterial alta de los pacientes con COVID-19. Es necesario realizar más análisis con una muestra de mayor tamaño para explorar los mecanismos subyacentes


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina , Betacoronavirus , Proteína C-Reativa/análise , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Hipertensão/complicações , Hipertensão/virologia , Carga Viral
8.
Hypertension ; 76(5): 1563-1571, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32869673

RESUMO

The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme) 2 cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization database of COVID-19 publications, and ClinicalTrials.gov through June 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the Grading of Recommendations Assessment, Development and Evaluation approach. After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACE inhibitors (adjusted odds ratio, 0.95 [95% CI, 0.86-1.05]) or ARBs (adjusted odds ratio, 1.05 [95% CI, 0.97-1.14]). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, -0.006 [95% CI, -0.016 to 0.004]), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 years old). The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Síndrome Respiratória Aguda Grave/induzido quimicamente , Síndrome Respiratória Aguda Grave/epidemiologia , Idoso , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Causas de Morte , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Medição de Risco , Análise de Sobrevida
9.
Inflammopharmacology ; 28(6): 1477-1480, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32920716

RESUMO

During the COVID-19 pandemic, a correspondence, published at the Lancet Respiratory Medicine, that linked angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and ibuprofen to a higher risk of SARS CoV-2 infection and complications, has influenced, when adopted by official health authorities, the practical management of COVID-19 with regard to non-steroidal anti-inflammatory drugs that were avoided in all COVID-19 management protocols all over the world. This manuscript discusses, from a pharmacological point of view, the points of weakness in the mentioned correspondence and it also lists some important contradictory review articles as well as clinical results that refuted its claims. The author chose to argue against each claim represented in the mentioned correspondence to confirm that ACEIs, ARBs and NSAIDs including ibuprofen should not be considered hazardous to be administered for COVID-19 patients and to warn against any future adoption of such unproved claims.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Infecções por Coronavirus/epidemiologia , Ibuprofeno/efeitos adversos , Pneumonia Viral/epidemiologia , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Ibuprofeno/administração & dosagem , Pandemias
10.
J Endocrinol ; 247(2): R45-R62, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32966970

RESUMO

Coronavirus disease (COVID-19) is caused by a new strain of coronavirus, the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. At the time of writing, SARS-CoV-2 has infected over 5 million people worldwide. A key step in understanding the pathobiology of the SARS-CoV-2 was the identification of -converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 to gain entry into host cells. ACE2 is an established component of the 'protective arm' of the renin-angiotensin-aldosterone-system (RAAS) that opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions. Identification of ACE2 as the entry point for SARS-CoV-2 into cells quickly focused attention on the use of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA) in patients with hypertension and cardiovascular disease given that these pharmacological agents upregulate ACE2 expression in target cells. ACE2 is cleaved from the cells by metalloproteases ADAM10 and ADAM17. Steroid hormone receptors regulate multiple components of the RAAS and may contribute to the observed variation in the incidence of severe COVID-19 between men and women, and in patients with pre-existing endocrine-related disease. Moreover, glucocorticoids play a critical role in the acute and chronic management of inflammatory disease, independent of any effect on RAAS activity. Dexamethasone, a synthetic glucocorticoid, has emerged as a life-saving treatment in severe COVID-19. This review will examine the endocrine mechanisms that control ACE2 and discusses the impact of therapies targeting the RAAS, glucocorticoid and other endocrine systems for their relevance to the impact of SARS-CoV-2 infection and the treatment and recovery from COVID-19-related critical illness.


Assuntos
Aldosterona/metabolismo , Betacoronavirus/fisiologia , Infecções por Coronavirus/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/enzimologia , Sistema Renina-Angiotensina , Esteroides/metabolismo , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Betacoronavirus/genética , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Humanos , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo
12.
Hypertension ; 76(5): 1339-1349, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32851855

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 originated from Wuhan, China, in December 2019 and rapidly spread to other areas worldwide. Since then, coronavirus disease 2019 (COVID-19) has reached pandemic proportions with >570 000 deaths globally by mid-July 2020. The magnitude of the outbreak and the potentially severe clinical course of COVID-19 has led to a burst of scientific research on this novel coronavirus and its host receptor ACE (angiotensin-converting enzyme)-2. ACE2 is a homolog of the ACE that acts on several substrates in the renin-Ang (angiotensin) system. With unprecedented speed, scientific research has solved the structure of SARS-CoV-2 and imaged its binding with the ACE2 receptor. In SARS-CoV-2 infection, the viral S (spike) protein receptor-binding domain binds to ACE2 to enter the host cell. ACE2 expression in the lungs is relatively low, but it is present in type II pneumocytes-a cell type also endowed with TMPRSS2 (transmembrane protease serine 2). This protease is critical for priming the SARS-CoV-2 S protein to complex with ACE2 and enter the cells. Herein, we review the current understanding of the interaction of SARS-CoV-2 with ACE2 as it has rapidly unfolded over the last months. While it should not be assumed that we have a complete picture of SARS-CoV-2 mechanism of infection and its interaction with ACE2, much has been learned with clear therapeutic implications. Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Betacoronavirus/metabolismo , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Ligação Proteica/genética , China , Infecções por Coronavirus/metabolismo , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/metabolismo , RNA Viral/genética
15.
Isr Med Assoc J ; 7(22): 375-379, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692500

RESUMO

BACKGROUND: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs). OBJECTIVES: To determine factors associated with attaining upper-range doses in patients with HFrEF. METHODS: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines. RESULTS: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65-78) and LVEF of 30% (IQR 25-35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05-1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m2/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34-5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13-0.90, P = 0.031). CONCLUSIONS: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Benchmarking , Índice de Massa Corporal , Diabetes Mellitus/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos
16.
Hypertension ; 76(3): 732-741, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32654555

RESUMO

Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8+ cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20-2.70]; matched cohort [2.24, 1.36-3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4+ cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.


Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Infecções por Coronavirus , Hipertensão Essencial , Pandemias , Pneumonia Viral , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Betacoronavirus , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/tratamento farmacológico , Hipertensão Essencial/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Prognóstico , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos , Medição de Risco
17.
Hypertension ; 76(3): 742-749, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32654557

RESUMO

The severe acute respiratory syndrome coronavirus 2 is known to infect host cells by interacting with ACE2 (angiotensin-converting enzyme 2) expressed in the respiratory epithelium. There have been concerns on whether alterations of ACE2 expression by renin-angiotensin-aldosterone system (RAAS) inhibitors would contribute to the infectivity and severity of coronavirus disease 2019 (COVID-19). We performed a case-control study to investigate the association between RAAS inhibitors and risk and severity of COVID-19 infection in South Korea using the population-based data provided by the Korean National Health Insurance System. Of 16 281 subjects with hypertension, there were 950 (5.8%) confirmed COVID-19 cases. After case-control matching, multivariable-adjusted conditional logistic regression analysis was performed. The adjusted odds ratio and 95% CIs for COVID-19 infection and long-term hospitalization comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors was 1.161 (0.958-1.407) and 0.863 (0.533-1.397), respectively. When comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors for intensive care unit admission, high-flow oxygen therapy, and death, the adjusted odds ratios (95% CIs) were 1.515 (0.402-5.701), 0.663 (0.272-1.619), and 1.363 (0.513-3.662), respectively. In all analyses, P values were not significant (P>0.05). The present study demonstrates the absence of an identifiable association between the exposure to RAAS inhibitors and risk and severity of COVID-19 infection, supporting the current medical guidelines and recommendations that patients should not discontinue RAAS inhibitors out of a concern that they are at increased risk for infection or severe illness of COVID-19.


Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Infecções por Coronavirus , Hipertensão , Pandemias , Pneumonia Viral , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Betacoronavirus , Estudos de Casos e Controles , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Prognóstico , Sistema Renina-Angiotensina/efeitos dos fármacos , República da Coreia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença
18.
J Physiol Pharmacol ; 71(2)2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32633235

RESUMO

COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Humanos , Hipertensão/tratamento farmacológico , Pandemias , Pneumonia Viral/virologia , Sistema Renina-Angiotensina/efeitos dos fármacos
19.
J Am Med Dir Assoc ; 21(7): 909-914.e2, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32674818

RESUMO

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and HMG-CoA reductase inhibitors ("statins") have been hypothesized to affect COVID-19 severity. However, up to now, no studies investigating this association have been conducted in the most vulnerable and affected population groups (ie, older adults residing in nursing homes). The objective of this study was to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19-infected older adults residing in nursing homes. DESIGN: We undertook a retrospective multicenter cohort study to analyze the association between ACEi/ARB and/or statin use with clinical outcome of COVID-19. The outcomes were (1) serious COVID-19 defined as long-stay hospital admission or death within 14 days of disease onset, and (2) asymptomatic (ie, no disease symptoms in the whole study period while still being diagnosed by polymerase chain reaction). SETTING AND PARTICIPANTS: A total of 154 COVID-19-positive subjects were identified, residing in 1 of 2 Belgian nursing homes that experienced similar COVID-19 outbreaks. MEASURES: Logistic regression models were applied with age, sex, functional status, diabetes, and hypertension as covariates. RESULTS: We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 (odds ratio [OR] 2.91; confidence interval [CI] 1.27-6.71), which remained statistically significant after adjusting for covariates (OR 2.65; CI 1.13-6.68). Although the effects of statin intake on serious clinical outcome were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.24-1.87). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 2.72; CI 0.59-25.1) or serious clinical outcome (OR 0.48; CI 0.10-1.97). CONCLUSIONS AND IMPLICATIONS: Our data indicate that statin intake in older, frail adults could be associated with a considerable beneficial effect on COVID-19 clinical symptoms. The role of statins and renin-angiotensin system drugs needs to be further explored in larger observational studies as well as randomized clinical trials.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Causas de Morte , Estudos de Coortes , Feminino , Avaliação Geriátrica , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Casas de Saúde/estatística & dados numéricos , Razão de Chances , Pandemias/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
20.
Cardiol Young ; 30(9): 1339-1342, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32522307
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