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1.
Biosci Rep ; 41(2)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33442728

RESUMO

The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global catastrophe. The elderly and people with comorbidity are facing a serious complication of the disease. The entry and infection strategy of SARS-CoV-2 in a host cell is raised by an amazing way of angiotensin-converting enzyme (ACE) 2 (ACE2) receptor recognition and imbalance of ACE/ACE2 in various organs, especially in the lungs. Here it has been discussed the role of interferon and protease during the receptor recognition (begining of infection) and followed by the impact of cytokine and hypoxia in the context of the balance of ACE/ACE2. It has also very concisely delineated the biochemistry and mechanism of ACE/ACE2 balance in different stages of infection and its role in comorbidity.


Assuntos
/sangue , /etiologia , Peptidil Dipeptidase A/sangue , /patogenicidade , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Comorbidade , Citocinas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Sistema Renina-Angiotensina/fisiologia , Internalização do Vírus
2.
Lancet ; 396(10256): 968-976, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010842

RESUMO

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin-angiotensin hormonal cascade. We assessed whether plasma ACE2 concentrations were associated with greater risk of death or cardiovascular disease events. METHODS: We used data from the Prospective Urban Rural Epidemiology (PURE) prospective study to conduct a case-cohort analysis within a subset of PURE participants (from 14 countries across five continents: Africa, Asia, Europe, North America, and South America). We measured plasma concentrations of ACE2 and assessed potential determinants of plasma ACE2 levels as well as the association of ACE2 with cardiovascular events. FINDINGS: We included 10 753 PURE participants in our study. Increased concentration of plasma ACE2 was associated with increased risk of total deaths (hazard ratio [HR] 1·35 per 1 SD increase [95% CI 1·29-1·43]) with similar increases in cardiovascular and non-cardiovascular deaths. Plasma ACE2 concentration was also associated with higher risk of incident heart failure (HR 1·27 per 1 SD increase [1·10-1·46]), myocardial infarction (HR 1·23 per 1 SD increase [1·13-1·33]), stroke (HR 1·21 per 1 SD increase [1·10-1·32]) and diabetes (HR 1·44 per 1 SD increase [1·36-1·52]). These findings were independent of age, sex, ancestry, and traditional cardiac risk factors. With the exception of incident heart failure events, the independent relationship of ACE2 with the clinical endpoints, including death, remained robust after adjustment for BNP. The highest-ranked determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI). When compared with clinical risk factors (smoking, diabetes, blood pressure, lipids, and BMI), ACE2 was the highest ranked predictor of death, and superseded several risk factors as a predictor of heart failure, stroke, and myocardial infarction. INTERPRETATION: Increased plasma ACE2 concentration was associated with increased risk of major cardiovascular events in a global study. FUNDING: Canadian Institute of Health Research, Heart & Stroke Foundation of Canada, and Bayer.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Peptidil Dipeptidase A/sangue , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
3.
Virus Res ; 289: 198148, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32866536

RESUMO

In late 2019, SARS-CoV-2 started to spread throughout the world causing the COVID-19 that has taken a considerable number of lives. Results obtained from several investigations have explained the virus origin, pathogenicity, and transmission. Similar to SARS coronavirus, the pulmonary angiotensin converting enzyme (ACE) 2 was introduced as the virus receptor for entering the cell. An increased body of epidemiological and clinical evidences has shown modulating effects of vitamin D in lung injuries through several mechanisms. Several clinical symptoms as well as molecular factors have shown to be related to the disease transmission and severity. In this study, vitamin D, ACE concentrations, and neutrophil to lymphocyte ratio (NLR) were measured in patients with confirmed COVID-19 in comparison with control group. Results demonstrated significant alterations in vitamin D and ACE levels as well as NLR in the patients' group. Contribution of those factors with the prognosis and severity of the disease has been shown.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Deficiência de Vitamina D/complicações , Vitamina D/fisiologia , Adolescente , Adulto , Idoso , Infecções por Coronavirus/sangue , Progressão da Doença , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Peptidil Dipeptidase A/sangue , Pneumonia Viral/sangue , Vitamina D/sangue , Adulto Jovem
4.
Ecotoxicol Environ Saf ; 203: 111044, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888613

RESUMO

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.


Assuntos
Poluentes Atmosféricos/toxicidade , Angiotensina I/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Material Particulado/toxicidade , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Acetilglucosaminidase/urina , Angiotensina I/sangue , Animais , Biomarcadores/sangue , Biomarcadores/urina , Hipertensão/urina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , beta-Galactosidase/urina
5.
Hypertension ; 76(5): 1526-1536, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32981365

RESUMO

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.


Assuntos
Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Progressão da Doença , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/fisiopatologia , Peptidil Dipeptidase A/sangue , Pneumonia Viral/epidemiologia , Centros Médicos Acadêmicos , Análise de Variância , Biomarcadores/metabolismo , Estudos de Coortes , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Prognóstico , Modelos de Riscos Proporcionais , Proteômica/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estados Unidos
6.
Eur Heart J ; 41(41): 4037-4046, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32984892

RESUMO

AIMS: The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability. METHODS AND RESULTS: Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level. CONCLUSIONS: Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.


Assuntos
Fibrilação Atrial/sangue , Betacoronavirus , Infecções por Coronavirus/sangue , Peptidil Dipeptidase A/sangue , Pneumonia Viral/sangue , Idoso , Antitrombinas/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Biomarcadores/sangue , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Dabigatrana/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico
8.
Am J Med Sci ; 360(4): 338-341, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32736832

RESUMO

Severe Acute Respiratory Distress Syndrome caused by a novel human coronavirus SARS-CoV-2 named COVID-19 and declared as a pandemic. This paper reviews the possibility of repurposing angiotensin type 1 receptor (AT1R) antagonists and vitamin D to treat COVID-19. ACE2 protein found on the cell membranes is the target of SARS-CoV-2 for entering into the host cells. Viral spike protein-binding with ACE2 down-regulates it. As ACE2 is known to protect the lung from injuries, SARS-CoV-2-induced ACE2 deficiency may expose patients to lung damage. AT1R antagonists and vitamin D increase the expression of ACE2 independently. Besides, vitamin D suppresses the compensatory increase in renin levels following the inhibition of the renin-angiotensin system by AT1R antagonists. Therefore, a combination of AT1R antagonists and vitamin D may offer protection against COVID-19 induced lung injury.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Peptidil Dipeptidase A/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Sistema Renina-Angiotensina/efeitos dos fármacos , Síndrome Respiratória Aguda Grave/virologia , Internalização do Vírus , Vitamina D/farmacologia , Vitaminas/farmacologia
9.
Medicine (Baltimore) ; 99(31): e21492, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756181

RESUMO

Activation of the renin angiotensin system and renal oxidative stress (OS) are critical contributors in the progression of chronic kidney disease(CKD). Recent studies have confirmed that the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas(ACE2/Ang(1-7)/Mas) axis, the important components of renin angiotensin system, protected kidneys against damage by antagonizing angiotensin II and attenuating OS in rats with several nephropathy models, but its effect needs to be further evaluated in clinic. In this study, we aimed to detected serum ACE2/Ang (1-7)/Mas axis, OS conditions and described its clinical associations in patients with CKD at different stages.A total of 48 patients with CKD and 6 healthy controls (CT) were enrolled, and serum angiotensin converting enzyme (ACE), ACE2, Ang (1-7), 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined by ELISA. Serum extracellular glutathione peroxidase(eGSH-Px) activity and renal functions were determined by the biochemical method.Serum ACE and ACE2 levels in CKD stages 3 to 5 and serum Ang(1-7) levels in CKD stages 4 to 5 without Ang II receptor blockers treatment significantly increased compared to those in the CT group. However, ACE2 was decreased and Ang(1-7) level increased in early CKD stage with Ang II receptor blockers treatment. Higher serum 8-OHdG levels and lower eGSH-Px activity were noted in CKD stages 4 to 5. Serum 8-OHdG level was correlated with serum ACE2, Ang(1-7) expression. Estimated glomerular filtration rate (eGFR) was correlated with serum ACE, ACE2, Ang(1-7), 8-OHdG, Hcy levels and serum eGSH-Px activity. Multiple-regression analysis eGFR was predicted by ACE, Hcy, eGSH-Px, and also can be predicted by ACE2, Ang(1-7), Hcy in CT subgroup.The ACE2/Ang(1-7)/Mas axis is associated with OS, and both them were associated with eGFR in the progression of CKD. Activation of ACE2/Ang(1-7)/Mas axis may have renoprotective effect and can be a potential therapeutic target in patients with early CKD stages.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Insuficiência Renal Crônica/sangue , 8-Hidroxi-2'-Desoxiguanosina/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistema Renina-Angiotensina/fisiologia
13.
Ann Biol Clin (Paris) ; 78(4): 454-460, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32616472

RESUMO

Blood angiotensin-converting enzyme (ACE) assay is now realized by the determination of enzyme activity on synthetic substrate, mostly furylacryloyl-phenylalanyl-L-glycyl-L-glycine (FAPGG). The matrix can be serum or heparin-plasma, with or without a separator; the assay developed on serum or plasma is not adapted to other matrix such as cerebrospinal fluid where the ACE activity is much lower. This assay has been adapted on a number of automated biochemistry analyzers with the specifications of the supplier of reagents, sometimes with modification of volumes or times for analysis. Samples can be stored at +4̊C for at least for one week, freezing at -20̊C is possible but refreezing is not advised. The assay is linear from 10 to 200 UI/L. Fidelity is excellent after calibration of the assay. Accuracy can be calculated from IQA and EQA results, and the analytical uncertainty is between 2% and 5% in function of the serum ACE value. Usual values will be soon available from studies on age brackets and sex, because ACE activity seems to be more elevated in boys during adolescence. At signature, it is interesting to have medical information on the diagnosis of sarcoidosis or its treatment including ACE inhibitors as a proof of intake; we can give a commentary on elevation of serum ACE activity from other causes than sarcoidosis and the causes for low activities.


Assuntos
Análise Química do Sangue/métodos , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/sangue , Biomarcadores/análise , Biomarcadores/sangue , Análise Química do Sangue/normas , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Granuloma/sangue , Granuloma/diagnóstico , Granuloma/terapia , Humanos , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Fase Pré-Analítica , Reprodutibilidade dos Testes , Sarcoidose/sangue , Sarcoidose/diagnóstico , Sarcoidose/terapia , Sensibilidade e Especificidade , Estudos de Validação como Assunto
14.
Prev Chronic Dis ; 17: E63, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678061

RESUMO

Data suggest that more men than women are dying of coronavirus disease 2019 (COVID-19) worldwide, but it is unclear why. A biopsychosocial approach is critical for understanding the disproportionate death rate among men. Biological, psychological, behavioral, and social factors may put men at disproportionate risk of death. We propose a stepwise approach to clinical, public health, and policy interventions to reduce COVID-19-associated morbidity and mortality among men. We also review what health professionals and policy makers can do, and are doing, to address the unique COVID-19-associated needs of men.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/psicologia , Política de Saúde , Pneumonia Viral/mortalidade , Pneumonia Viral/psicologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Feminino , Promoção da Saúde , Humanos , Masculino , Pandemias , Educação de Pacientes como Assunto/métodos , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Medicina Preventiva , Saúde Pública , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologia
15.
JAMA Netw Open ; 3(6): e2011122, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525548

RESUMO

Importance: Severe acute respiratory syndrome coronavirus 2 has caused a global outbreak of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 binds angiotensin-converting enzyme 2 of the rennin-angiotensin system, resulting in hypokalemia. Objective: To investigate the prevalence, causes, and clinical implications of hypokalemia, including its possible association with treatment outcomes, among patients with COVID-19. Design, Setting, and Participants: This cohort study was conducted at Wenzhou Central Hospital and Sixth People's Hospital of Wenzhou, Wenzhou, China, from January 11, 2020, to February 15, 2020. Participants included patients who received a diagnosis of COVID-19 according to the criteria issued by the Chinese Health Bureau and were admitted to the hospital. The patients were classified as having severe hypokalemia (plasma potassium <3 mmol/L), hypokalemia (plasma potassium 3-3.5 mmol/L), and normokalemia (plasma potassium >3.5 mmol/L). The clinical features, therapy, and outcomes were compared between the 3 groups. Data analysis was conducted in March 2020. Interventions: The patients were given general support and antiviral therapy. Their epidemiological and clinical features were collected. Main Outcomes and Measures: The prevalence of hypokalemia and response to treatment with potassium supplements were measured by analyzing plasma and urine potassium levels. Results: One hundred seventy-five patients (87 female patients [50%]; mean [SD] age, 45 [14] years) were classified as having severe hypokalemia (31 patients [18%]), hypokalemia (64 patients [37%]), and normokalemia (80 patients [46%]). Patients with severe hypokalemia had statistically significantly higher body temperature (mean [SD], 37.6 °C [0.9 °C]) than the patients with hypokalemia (mean [SD], 37.2 °C [0.7 °C]; difference, 0.4 °C; 95% CI, 0.2-0.6 °C; P = .02) and the patients with normokalemia (mean [SD], 37.1 °C [0.8 °C]; difference, 0.5 °C; 95% CI, 0.3-0.7 °C; P = .005). Patients with higher levels of hypokalemia also had higher creatine kinase levels (severe hypokalemia, mean [SD], 200 [257] U/L [median, 113 U/L; interquartile range {IQR}, 61-242 U/L]; hypokalemia, mean [SD], 97 [85] U/L; and normokalemia, mean [SD], 82 [57] U/L), higher creatine kinase-MB fraction (severe hypokalemia, mean [SD], 32 [39] U/L [median, 14 U/L; IQR, 11-36 U/L]; hypokalemia, mean [SD], 18 [15] U/L; and normokalemia, mean [SD], 15 [8] U/L), higher lactate dehydrogenase levels (mean [SD], severe hypokalemia, 256 [88] U/L; hypokalemia, 212 [59] U/L; and normokalemia, 199 [61] U/L), and higher C-reactive protein levels (severe hypokalemia, mean [SD], 29 [23] mg/L; hypokalemia, mean [SD], 18 [20] mg/L [median, 12, mg/L; IQR, 4-25 mg/L]; and normokalemia, mean [SD], 15 [18] mg/L [median, 6 U/L; IQR, 3-17 U/L]). Of 40 severely and critically ill patients, 34 (85%) had hypokalemia. Patients with severe hypokalemia were given potassium at a dose of 40 mEq per day, for a total mean (SD) of 453 (53) mEq potassium chloride, during the hospital stay. The patients responded well to potassium supplements as they recovered. Conclusions and Relevance: The correction of hypokalemia is challenging because of continuous renal potassium loss resulting from the degradation of angiotensin-converting enzyme 2. The high prevalence of hypokalemia among patients with COVID-19 suggests the presence of disordered rennin-angiotensin system activity, which increases as a result of reduced counteractivity of angiotensin-converting enzyme 2, which is bound by severe acute respiratory syndrome coronavirus 2.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Hipopotassemia/sangue , Hipopotassemia/virologia , Pneumonia Viral/complicações , Adulto , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Feminino , Humanos , Hipopotassemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/sangue , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Potássio/sangue , Prevalência
17.
Vascul Pharmacol ; 130: 106680, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32423553

RESUMO

Angiotensin-converting enzyme (ACE) and its homologue, ACE2, have been mostly associated with hypertensive disorder. However, recent pandemia of SARS-CoV-2 has put these proteins at the center of attention, as this virus has been shown to exploit ACE2 protein to enter cells. Clear difference in the response of affected patients to this virus has urged researchers to find the molecular basis and pathophysiology of the cell response to this virus. Different levels of expression and function of ACE proteins, underlying disorders, consumption of certain medications and the existence of certain genomic variants within ACE genes are possible explanations for the observed difference in the response of individuals to the SARS-CoV-2 infection. In the current review, we discuss the putative mechanisms for this observation.


Assuntos
Infecções por Coronavirus/enzimologia , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral/enzimologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Humanos , Pandemias , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Pneumonia Viral/patologia
19.
Eur J Clin Invest ; 50(9): e13276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32406522

RESUMO

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.


Assuntos
Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/estatística & dados numéricos , Gastroenteropatias/epidemiologia , Pandemias/estatística & dados numéricos , Peptidil Dipeptidase A/sangue , Pneumonia Viral/epidemiologia , /epidemiologia , Biomarcadores/sangue , Comorbidade , Infecções por Coronavirus/fisiopatologia , Transmissão de Doença Infecciosa/prevenção & controle , Feminino , Gastroenteropatias/fisiopatologia , Humanos , Masculino , Pneumonia Viral/fisiopatologia , Prognóstico , Medição de Risco
20.
Transfus Apher Sci ; 59(3): 102804, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32387238

RESUMO

Covid-19 is characterized by weak symptoms in most affected patients whilst severe clinical complications, with frequent fatal issues, occur in others. Disease severity is associated with age and comorbidities. Understanding of viral infectious mechanisms, and antibody immune response, can help to better control disease progression. SARS-CoV-2 has a major impact on the Renin Angiotensin Aldosterone System (RAAS), through its binding to the membrane cellular glycoprotein, Angiotensin Converting Enzyme-2 (ACE-2), then infecting cells for replication. This report hypothesizes the possible implication of an autoimmune response, induced by generation of allo- or autoantibodies to ACE-2, or to its complexes with viral spike protein. This could contribute to some delayed severe complications occurring in affected patients. We also propose a strategy for investigating this eventuality.


Assuntos
Anticorpos Antivirais/imunologia , Autoanticorpos/imunologia , Autoimunidade , Betacoronavirus/imunologia , Coagulação Sanguínea , Infecções por Coronavirus/sangue , Isoanticorpos/imunologia , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/sangue , Sistema Renina-Angiotensina/fisiologia , Trombofilia/etiologia , Especificidade de Anticorpos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Progressão da Doença , Coagulação Intravascular Disseminada/etiologia , Humanos , Pandemias , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Serina Endopeptidases/fisiologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Trombofilia/sangue , Trombofilia/imunologia , Fatores de Tempo
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