Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.

The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection and viral replication. ACE2 is an important enzymatic component of the renin-angiotensin system (RAS) expressed in the lung and other organs. The peptidase regulates the levels of the peptide hormones Ang II and Ang-(1-7), which have distinct and opposing actions to one another, as well as other cardiovascular peptides. A potential consequence of severe acute respiratory syndrome-related coronavirus-2 infection is reduced ACE2 activity by internalization of the viral-ACE2 complex and subsequent activation of the RAS (higher ratio of Ang II:Ang-[1-7]) that may exacerbate the acute inflammatory events in COVID-19 patients and possibly contribute to the effects of long COVID-19. Moreover, COVID-19 patients present with an array of autoantibodies to various components of the RAS including the peptide Ang II, the enzyme ACE2, and the AT1 AT2 and Mas receptors. Greater disease severity is also evident in male COVID-19 patients, which may reflect underlying sex differences in the regulation of the 2 distinct functional arms of the RAS. The current review provides a critical evaluation of the evidence for an activated RAS in COVID-19 subjects and whether this system contributes to the greater severity of severe acute respiratory syndrome-related coronavirus-2 infection in males as compared with females.

The testicular form of angiotensin converting enzyme as a marker for human sperm quality assessment.

INTRODUCTION: Spermatozoa are rapidly changing cellular structures that are highly dependent on their interaction with the environment. These interactions cause fundamental changes in the spermatozoa's cells and membrane.

Nanoluciferase-based cell fusion assay for rapid and high-throughput assessment of SARS-CoV-2-neutralizing antibodies in patient samples.

After more than two years, COVID-19 still represents a global health burden of unprecedented extent and assessing the degree of immunity of individuals against SARS-CoV-2 remains a challenge. Virus neutralization assays represent the gold standard for assessing antibody-mediated protection against SARS-CoV-2 in sera from recovered and/or vaccinated individuals. Neutralizing antibodies block the interaction of viral spike protein with human angiotensin-converting enzyme 2 (ACE2) receptor in vitro and prevent viral entry into host cells. Classical viral neutralization assays using full replication-competent viruses are restricted to specific biosafety level 3-certified laboratories, limiting their utility for routine and large-scale applications. We developed therefore a cell-fusion-based assay building on the interaction between viral spike and ACE2 receptor expressed on two different cell lines, substantially reducing biosafety risks associated with classical viral neutralization assays. This chapter describes this simple, sensitive, safe and cost-effective approach for rapid and high-throughput evaluation of SARS-CoV-2 neutralizing antibodies relying on high-affinity NanoLuc® luciferase complementation technology (HiBiT). When applied to a variety of standards and patient samples, this method yields highly reproducible results in 96-well, as well as in 384-well format. The use of novel NanoLuc® substrates with increased signal stability like Nano-Glo® Endurazine™ furthermore allows for high flexibility in assay set-up and full automatization of all reading processes. Lastly, the assay is suitable to evaluate the neutralizing capacity of sera against the existing spike variants, and potentially variants that will emerge in the future.

Epistatic Variations in the Omicron Receptor Binding Domain Can Enhance Host Recognition: An In Silico Assessment and Prediction.

The hypermutated receptor binding domain (RBD) of the Omicron (B.1.1.529) lineage exhibits a different binding interface with human angiotensin-converting enzyme 2 (ACE2) relative to that of the wild-type Wuhan Hu-1, yet how the altered interaction will affect viral evolution is largely unknown. Here, we used molecular dynamics simulation to characterize the binding features of the Omicron BA.1/hACE2 complex and used free energy perturbation calculations to assess the ongoing and putative variations. The complex reveals a substantial rearrangement of the interfacial hydrogen-bond network: R493 of RBD forms a dynamic electrostatic interaction with both E35 and D38 of hACE2, which prohibits the hydrogen bonds of R498-D38 and Y449-D38. Whereas most circulating mutations minimally affect RBD binding to hACE2, the charge-altering mutation R493Q attenuates the affinity by abolishing the electrostatic interaction. However, the potential variants H505Y or N417K/R493Q could restore and gain even greater binding affinities than BA.1 as a result of their optimized interaction network and epistasis effects.

LC/MS/MS assessment of changes in placental angiotensin I metabolism in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a condition characterized by high blood pressure and significant proteinuria in pregnant women. It affects about 7% pregnancies and can be cause of fetal and maternal morbidity and mortality. During pregnancy, a physiological overexpression of the Renin-Angiotensin System (RAS) components is observed, including increased plasma Ang II level. Dysregulation of RAS in placenta may contribute to preeclampsia and uterine growth retardation. The aim of the study was to evaluate the Ang I metabolism in human preeclamptic placentas and to compare to normal pregnancies condition. METHOD: Fragments of placental tissues were collected right after ceasarian section from PE and physiological pregnancies. Tissues were incubated in Krebs buffer in the presence of Ang I. Evaluation of Ang I metabolites in incubating fluid was performed by LC/MS/MS method. mRNA expression of main RAS components was measured by RT-PCR. RESULTS: Pattern of angiotensin metabolites did not differ between groups. The main products were Ang 1-7 and Ang II. Comparing to control group, more than 3-fold lower production of Ang II and Ang 1-7 in preeclampsia was observed. mRNA expressions of ACE and AT1 were significantly decreased in pre- eclamptic placentas, whereas higher expression of mRNA of ACE2 and MAS receptor were observed. CONCLUSIONS: Production of Ang 1-7 by PE placentas was significantly lower than in control group. Significantly decreased mRNA expression of ACE and AT1 receptor and lower production of Ang II in placentas of PE patients suggest that placental Ang II/ACE/AT1r pathway could be less important than Ang 1-7/ACE-2/MASr pathway in development of preeclampsia, but this requires further investigations.

Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) of SARS-CoV-2 spike infectivity and pathogenicity: A comparative sequence and structural-based computational assessment.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron's receptor-binding domain (RBD) and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterizing in the RBD, we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and negative electrostatic surface potential human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild-type (WT). Negative electrostatic potential of N-terminal domain (NTD) of the spike protein value indicates that the Omicron variant binds receptors less efficiently than the WT. Given that at least one receptor is highly expressed in lung and bronchial cells, the electrostatic potential of NTD negative value could be one of the factors contributing to why the Omicron variant is thought to be less harmful to the lower respiratory tract. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, and R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N.

Dapagliflozina para o tratamento adicional de pacientes adultos com insuficiência cardíaca com fração de ejeção reduzida (FEVE≤40%), NYHA II-IV e sintomáticos apesar do uso de terapia padrão com inibidor da Enzima Conversora de Angiotensina (IECA) ou Antagonista do Receptor da angiotensina II (ARA II), com betabloqueadores, diuréticos e antagonista do receptor de mineralocorticoides / Dapagliflozin for the additional treatment of adult heart failure patients with reduced ejection fraction (LVEF≤40%), NYHA II-IV and symptomatic despite the use of standard Angiotensin Converting Enzyme inhibitor therapy (ACEI) or Angiotensin II Receptor Antagonist (ARA II), with beta-blockers, diuretics and mineralocorticoid receptor antagonists

INTRODUÇÃO: A IC é uma síndrome clínica complexa, na qual o coração é incapaz de bombear sangue de forma a atender às necessidades metabólicas tissulares representando um desafio pelo caráter progressivo da doença, a limitação da qualidade de vida e a alta mortalidade. É a principal causa de re-hospitalização no Brasil, com elevada mortalidade em cinco anos e se constatando que uma em cada cinco pessoas tem chance de desenvolvê-la ao longo da vida. A dapagliflozina age por inibição do cotransportador sódio-glicose 2 (SGLT2) melhorando o controle glicêmico em pacientes com diabetes mellitus e promovendo benefícios cardiovasculares. A inibição do SGLT2 promove redução da absorção de glicose do filtrado glomerular no túbulo renal proximal, com diminuição da reabsorção de sódio, levando à excreção urinária da glicose e diurese osmótica. Desta forma, aumenta a entrega de sódio ao túbulo distal, o qual aumenta a retroalimentação no túbulo glomerular e reduz a pressão intraglomerular. Este efeito combinado com a diurese osmóticaleva a uma redução na sobrecarga de volume, redução na pressão

Assessment of angiotensin converting enzyme gene polymorphism in patients with psoriasis.

Psoriatic patients had diversity of clinical presentations and complications. Psoriasis can have significant interference with the patient's quality of life, recovery, and outcome. Some evidences suggest that the angiotensin converting enzyme (ACE) is present in the skin of psoriatic patients. This study intended to assess the patterns of ACE insertion/deletion (ACE ID) polymorphism and the levels of serum ACE among psoriatic patients in comparison to normal controls. The study included two groups: 20 patients with psoriasis and 20 apparently healthy adults with negative family history of psoriasis as a control group. Psoriasis area and severity index (PASI) was used to measure of severity of psoriasis. In both groups, ACE ID gene polymorphism was assessed by quantitative real-time polymerase reaction and serum ACE levels was evaluated using an enzyme-linked immunosorbent assay. ACE ID genotype was significantly higher among the psoriatic group in comparison to the control group (40.0% versus 15.0%, respectively, p=0.016). D allele was significantly higher among the psoriatic group than the control group (25.0% versus 7.5%, respectively, p=0.034). ACE ID genotype carried significantly higher risk in psoriatic group versus control group (OR=3.8). The D allele carried higher risk in psoriatic group versus control group (OR=4.1). ACE serum levels were significantly higher among the psoriatic group compared to the control group (87.4±7.03 versus 2.3±0.7, respectively; p < 0.001). We concluded that ACE ID gene polymorphism may be considered as a risk factor for developing psoriasis.

Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients.

Contribution of the renin-angiotensinogen system in the risk of COVID-19 and related complications have been assessed by several groups. However, the results are not consistent. We examined levels of ACE1 and ACE2 in the circulation of two groups of COVID-19 patients (ICU-admitted and general ward-admitted patients) compared with healthy controls. We also genotyped two polymorphisms in ACE1 gene (the ACE1-I/D polymorphism rs1799752 and rs4359) to appraise their association with expression levels of ACE1 and ACE2. Expression level of ACE1 was significantly higher in ICU patients compared with non-ICU patients (P value = 0.02). However, its expression was not significantly different between total COVID-19 patients and total controls (P value = 0.34). ACE2 expression was not different ether between two groups of COVID-19 patients (P value = 0.12) or between total COVID-19 patients and total controls (P value = 0.79). While distribution of rs1799752 and rs4359 alleles was similar between study groups, genotype frequencies of rs1799752 were differently distributed among total COVID-19 patients and controls (P value = 0.00001). Moreover, genotypes of the other polymorphism tended to be distinctively distributed among these two groups (P value = 0.06). In the total population of patients and controls, different ACE1 mRNA levels were observed among carriers of different rs1799752 genotypes; of note, ID genotype carriers showed a higher expression of ACE1 compared with II genotype carriers (P = 0.01). ACE1 polymorphisms might affect risk of COVID-19 and expression of ACE transcripts.

A Systematic Review of the Assessment of the Presence of SARS-CoV-2 in Human Semen.

Theoretically, human testes are highly expressive organs for angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. This study aimed to investigate whether the causative agent of COVID-19 is found in semen. The databases of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were searched using a combination of related keywords. All studies with original data, involving detection of SARS-CoV-2 in semen of male patients with COVID-19 or in those who have recovered from it, were included in the study. Six articles, including 136 samples, entered the systematic review. Most of the studies were performed in the recovery phase of COVID-19. In four articles, SARS-CoV-2 was not detected in semen, while in the other two articles semen testing showed the presence of the virus in some samples. Testicular discomfort, testicular cell damage, and spermogram disruption were also reported in some studies. We conclude that the study question cannot be answered with this number of studies. Since most of the samples were mild to moderate forms of COVID-19, it is not yet clear what the presence of the virus in semen will be in severe cases. The long-term effects are also vague. More original articles with better design and in different phases of the disease are needed to draw robust conclusions.

The assessment of serum ACE activity in COVID-19 and its association with clinical features and severity of the disease.

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.

Assessment of angiotensin converting enzyme gene polymorphism in preeclampsia mothers of Bangladesh.

The study aimed to assess the association of ACE insertion/deletion (I/D) polymorphisms with the susceptibility for preeclampsia in Bangladesh. It was a case-control study involving 220 subjects (100 preeclamptic and 120 normal pregnant women). The ACE (I/D) genotyping was done using the conventional PCR method. Overall, the frequency of ACE II genotypes was significantly (p<.05) higher in normal pregnant women than the preeclamptic women. The pregnant mother with DD genotype was at 3.43-fold higher risk (OR = 3.43; p<.01) of developing preeclampsia while pregnant mother with ID genotype was at lower risk (OR = 1.32; p>.05). On the other hand, patients having either DD or ID genotypes showed 1.9 fold (OR = 1.90; p>.05) increased risk of developing preeclampsia compared to the control group but not statistically significant. This study suggested that ACE (DD) genotypes may have strong associations with the occurrence of preeclampsia.Impact StatementWhat is already known on this subject? The study was conducted among 100 preeclamptic and 120 normal pregnant women. The preeclamptic patients were diagnosed by protein in urine and high blood pressure. The normal pregnant women were selected with no known complications.What the results of this study add? Overall, the pregnant mothers with DD genotype were at 3.43-fold higher risk of developing preeclampsia while pregnant mothers with ID or II genotypes were at a lower risk.What the implications are of these findings for clinical practice and/or further research? ACE (I/D) gene would be a biomarker of early diagnosis of preeclampsia and also be helpful to intervene in personalised medicine and gene therapy as a novel treatment of preeclampsia.

A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a newly emerging human infectious disease. Because no specific antiviral drugs or vaccines are available to treat COVID-19, early diagnostics, isolation, and prevention are crucial for containing the outbreak. Molecular diagnostics using reverse transcription polymerase chain reaction (RT-PCR) are the current gold standard for detection. However, viral RNAs are much less stable during transport and storage than proteins such as antigens and antibodies. Consequently, false-negative RT-PCR results can occur due to inadequate collection of clinical specimens or poor handling of a specimen during testing. Although antigen immunoassays are stable diagnostics for detection of past infection, infection progress, and transmission dynamics, no matched antibody pair for immunoassay of SARS-CoV-2 antigens has yet been reported. In this study, we designed and developed a novel rapid detection method for SARS-CoV-2 spike 1 (S1) protein using the SARS-CoV-2 receptor ACE2, which can form matched pairs with commercially available antibodies. ACE2 and S1-mAb were paired with each other for capture and detection in a lateral flow immunoassay (LFIA) that did not cross-react with SARS-CoV Spike 1 or MERS-CoV Spike 1 protein. The SARS-CoV-2 S1 (<5 ng of recombinant proteins/reaction) was detected by the ACE2-based LFIA. The limit of detection of our ACE2-LFIA was 1.86 × 105 copies/mL in the clinical specimen of COVID-19 Patients without no cross-reactivity for nasal swabs from healthy subjects. This is the first study to detect SARS-CoV-2 S1 antigen using an LFIA with matched pair consisting of ACE2 and antibody. Our findings will be helpful to detect the S1 antigen of SARS-CoV-2 from COVID-19 patients.

COVID-19 and the kidney.

COVID-19 is primarily considered a respiratory illness, but the kidney may be one of the targets of SARS-CoV-2 infection, since the virus enters cells through the angiotensin-converting enzyme 2 receptor, which is found in abundance in the kidney. Information on kidney involvement in COVID-19 is limited but is evolving rapidly. This article discusses the pathogenesis of acute kidney injury (AKI) in COVID-19, its optimal management, and the impact of COVID-19 on patients with chronic kidney disease, patients with end-stage kidney disease on dialysis, and kidney transplant recipients.

SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle.

OBJECTIVE: To determine the susceptibility of the endometrium to infection by-and thereby potential damage from-SARS-CoV-2. DESIGN: Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets. SETTING: Infertility research department affiliated with a public hospital. PATIENT(S): Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. RESULT(S): Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. ACE2, TMPRSS4, CTSB, CTSL, and MX1 expression increased toward the window of implantation. TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not statistically significantly altered across the cycle. ACE2, TMPRSS4, CTSB, CTSL, BSG, and MX1 expression increased with age, especially in early phases of the cycle. CONCLUSION(S): Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age. Further, TMPRSS4, along with BSG-mediated viral entry into cells, could imply a susceptible environment for SARS-CoV-2 entry via different mechanisms. Additional studies are warranted to determine the true risk of endometrial infection by SARS-CoV-2 and implications for fertility treatments.

Molecular mechanisms and epidemiology of COVID-19 from an allergist's perspective.

The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the host angiotensin-converting enzyme 2 receptor in lung and airway cells. Binding requires the help of another host protein, transmembrane protease serine S1 member 2. Several factors likely contribute to the efficient transmission of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a 10- to 20-fold higher receptor-binding capacity compared with previous pandemic coronaviruses. In addition, because asymptomatic persons infected with SARS-CoV-2 have high viral loads in their nasal secretions, they can silently and efficiently spread the disease. PCR-based tests have emerged as the criterion standard for the diagnosis of infection. Caution must be exercised in interpreting antibody-based tests because they have not yet been validated, and may give a false sense of security of being "immune" to SARS-CoV-2. We discuss how the development of some symptoms in allergic rhinitis can serve as clues for new-onset COVID-19. There are mixed reports that asthma is a risk factor for severe COVID-19, possibly due to differences in asthma endotypes. The rapid spread of COVID-19 has focused the efforts of scientists on repurposing existing Food and Drug Administration-approved drugs that inhibit viral entry, endocytosis, genome assembly, translation, and replication. Numerous clinical trials have been launched to identify effective treatments for COVID-19. Initial data from a placebo-controlled study suggest faster time to recovery in patients on remdesivir; it is now being evaluated in additional controlled studies. As discussed in this review, till effective vaccines and treatments emerge, it is important to understand the scientific rationale of pandemic-mitigation strategies such as wearing facemasks and social distancing, and implement them.

Informe diário de evidências COVID-19: busca realizada em 20 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 20, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos.

Informe diário de evidências COVID-19: busca realizada em 15 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 15, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 6 protocolos.

Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease 2019 in Wenzhou, China.

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.

Urological implications of SARS CoV-19.

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19), pandemic has afflicted > 3.3 million people around the world since December 2019. Though, more than 1000 publications have appeared in scientific journals addressing a plethora of questions, there is a considerable hiatus in understanding of the behavior and natural history of the virus and its impact on urology. Also, a modified approach is the need of hour in taking care of patients as urologists should safeguard their teams, families, and patients. MATERIAL AND METHODS: The authors have used guidelines from USA, Canada, UK, Europe and India for making recommendations to help urologist define their own policies that may have to be fine-tuned on the basis of continued and evolving challenges they would encounter and the local resources at their disposal. RESULTS: COVID-19 do effect genitourinary system from kidney to testis. The authors provide scientific basis to urologists to help identify patients by remote consultation who are likely to be harmed by coming to the hospital, and not to miss those who need hospitalization for diagnostic or therapeutic interventions. There is uncompromised need of specific precautions during surgery to safe guard the surgeon and his team along with the patient. CONCLUSIONS: Urological operations during COVID-19 pandemic should be limited to emergency cases during the acute phase with an exit strategy planned in a staggered manner, based on the scientific risk stratification. Telemedicine (e-clinics or virtual clinics) would help achieve the goal of risk stratification.