Angiotensin-converting enzyme 2 (ACE2) in COVID-19 and other diseases.

The coronavirus SARS-CoV-2 was detected in isolates of pneumonia patients in January 2020. The virus cannot multiply extracellularly but requires access to the cells of a host organism. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor, to which it docks with its spikes. ACE2 belongs to the renin angiotensin system (RAS), whose inhibitors have been used for years against high blood pressure. Renin is an endopeptidase that is predominantly formed in the juxtaglomerular apparatus of the kidney and cleaves the decapeptide angiotensin I (Ang I) from angiotensinogen. Through the angiotensin-converting enzyme (ACE), another 2 C-terminal amino acids are removed from Ang I, so that finally the active octapeptide angiotensin II (Ang II) is formed. The biological effect of Ang II via the angiotensin II receptor subtype 1 (AT1-R) consists of vasoconstriction, fibrosis, proliferation, inflammation, and thrombosis formation. ACE2 is a peptidase that is a homolog of ACE. ACE2 is predominantly expressed by pulmonary alveolar epithelial cells in humans and has been detected in arterial and venous endothelial cells. In contrast to the dicarboxy-peptidase ACE, ACE2 is a monocarboxypeptidase that cleaves only one amino acid from the C-terminal end of the peptides. ACE2 can hydrolyze the nonapeptide Ang-(1-9) from the decapeptide Ang I and the heptapeptide Ang-(1-7) from the octapeptide Ang II. Ang-(1-7) acts predominantly antagonistically (vasodilatory, anti-fibrotic, anti-proliferative, anti-inflammatory, anti-thrombogenetically) via the G protein-coupled Mas receptor to the AT1-R-mediated effects of Ang II. In the pathogenesis of COVID-19 infection, it is therefore assumed that there is an imbalance due to overstimulation of the AT1 receptor in conjunction with a weakening of the biological effects of the Mas receptor.Copyright © 2022 Dustri-Verlag Dr. K. Feistle.

The effect of ACE inhibitors and ARBs on outcomes in hospitalized patients with COVID-19.

BACKGROUND: Contradictory opinions exist regarding the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with hypertension, which is the most common comorbidity associated with COVID-19. Herein, the effects of ACEIs and ARBs on outcomes of COVID-19 patients were evaluated. METHODS: In this cross-sectional study, the outcomes of COVID-19 patients were compared between patients who received pretreatment ACEIs or ARBs and those who did not. RESULTS: The incidence of moderate and severe forms of COVID-19 was significantly higher in patients taking ACEI/ARB drugs (P-value = 0.012). Also, patients taking ACEI/ARB drugs (P-value = 0.034), patients with hypertension (P-value = 0.011), and patients with dyslipidemia (P-value = 0.011) experienced more severe forms of COVID-19. There was an association between increased length of hospital stay and dyslipidemia (P-value = 0.033) and the use of ACEI/ARB drugs (P-value = 0.041), while no correlation was found between other parameters in univariate linear regression analysis as well as multivariate linear regression. There was an association between increased mortality of patients with increasing age (P-value < 0.001), BMI greater than 30 kg/m2 (P-value = 0.02), asthma (P-value = 0.003), and dyslipidemia (P-value = 0.045). CONCLUSIONS: ACEI/ARB drugs put COVID-19 patients at high risk for moderate to severe forms of COVID-19 and higher length of hospital stay. Although, it is notable that these drugs did not significantly affect specific adverse outcomes of COVID-19, such as the need for admission to the intensive care unit (ICU), length of ICU stay, ventilation, and mortality.

Ras and Sars-Cov-2 Interaction: Short Review of the Latest Evidence

Coronavirus SARS-CoV-2 is responsible for the coronavirus disease (COVID-19) cause of the recent global pandemic, which is causing thousands of deaths worldwide and represents a health challenge with few precedents in human history. The angiotensin 2 conversion enzyme (ACE-2) has been identified as the receptor that facilitates access to SARSCoV-2 in cells;evidence shows that its concentration varies during the various stages of viral infection. Therapeutic agents modifying the renin-angiotensin system (RAS) may be able to modulate the concentration of ACE-2 and the various components of the system. In this article we examine the latest evidence on the association between the use of RAS modifying agents and coronavirus 2019 (COVID-19) disease caused by SARS-CoV-2. Our investigation and critical literature research does not suggest discontinuation of ACEIs/ARBs treatment in clinical practice as there is a lack of robust evidence. However, we recommend further well-structured epidemiological studies investigating this sensitive issue that may provide important new suggestions for implementing guidelines.Copyright © Vitiello A., Ferrara F., 2023.

Angioedema induced by angiotensin-converting enzyme inhibitors: An analysis of hospitalizations during the covid-19 pandemic.

BACKGROUND: The pathogenesis of angioedema induced by angiotensin-converting enzyme inhibitors is based on the accumulation of bradykinin as a result of angiotensin-converting enzyme blockade. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 receptor, which may inhibit its production and thereby lead to an increase in bradykinin levels. Thus, SARS-CoV-2 infection may be a likely trigger for the development of angioedema. AIMS: This study aimed to analyze cases of hospitalizations of patients with angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers during the coronavirus disease 2019 (COVID-19) pandemic. MATERIALS AND METHODS: This study retrospectively analyzed medical records of patients admitted to the Vitebsk Regional Clinical Hospital between May 2020 and December 2020 with isolated (without urticaria) angioedema while receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In all patients, smears from the naso and oropharynx for COVID-19 were analyzed by polymerase chain reaction. RESULT(S): Fifteen inpatients (9 men and 6 women) aged 44-72 years were admitted because of emergent events, of which 53.6% had isolated angioedema. In two cases, a concomitant diagnosis of mild COVID-19 infection was established with predominant symptoms of angioedema, including edema localized in the face, tongue, sublingual area, and soft palate. All patients had favorable disease outcomes. CONCLUSION(S): Patients with angiotensin-converting enzyme inhibitor-induced angioedema may require hospitalization to monitor upper respiratory tract patency. There were cases of a combination of angiotensin-converting enzyme inhibitor-induced angioedema and mild COVID-19. Issues requiring additional research include the effect of SARS- CoV-2 infection on the levels of bradykinin and its metabolites, the triggering role of COVID-19 in the development of angioedema in patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, recommendations for the management of patients with angiotensin-converting enzyme inhibitor-induced angioedema, and a positive result for COVID-19.Copyright © 2020 Pharmarus Print Media All rights reserved.

Pain in Covid-19 and Features of Pathogenetic Molecular Mechanisms

Although it has been almost three years since the World Health Organization (WHO) declared a pandemic, COVID-19 is still an unsolved problem, thereby attracting great scientific interest. The disease has a heterogeneous clinical picture with multiple manifestations from different organs and systems. Currently, COVID-19 is perceived as a polysyndromic inflammatory disease involving not only the respiratory system, but also the musculoskeletal system, the cardiovascular system, the skin, the excretory and the nervous system, and is accompanied by a number of hematological, gastrohepatoenterological and endocrine disorders. Various pain phenomena also appear in the clinical presentation of the disease, often as a single manifestation or in combination with symptoms from different organs and systems. The pathogenesis of pain is complex and there is still no consensus on the exact driving mechanisms. Several different signaling pathways play an important role in the generation of pain impulses and perception. They are different for different types of pain. At this stage, the role of angiotensin-converting enzyme 2 (ACE), the renin-angiotensin system (RAC), angiotensin 2 receptors (AT2R), direct neuronal invasion of the virus, the involvement of pro-inflammatory cytokines, hypoxia, the involvement of macrophages, is discussed. as well as the role of overactivity of the immune system, causing the so-called "cytokine storm". Pain is the result of complex biochemical processes influenced to varying degrees by biological, physiological and social factors. Our knowledge at this stage remains scarce and is the subject of many studies on the key pathogenic mechanisms. Therefore, the purpose of this review is to describe the known mechanisms for the occurrence and persistence of pain in patients with COVID-19, as well as to classify the pain phenomena and present its most common localizations. The diagnosis and treatment of COVID-19 and associated pain should be carried out by a multidisciplinary team of specialists, given the heterogeneous clinical presentation of the disease.Copyright © 2023 Medical Information Center. All rights reserved.

Discontinuation of Antihypertensive Drug Use Compared to Continuation in COVID-19 Patients: A Systematic Review with Meta-analysis and Trial Sequential Analysis.

INTRODUCTION: COVID-19 related mortality is about 2%, and it increases with comorbidities, like hypertension. Regarding management, there is debatable evidence about the benefits of continuation vs. discontinuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB). AIM: We performed a systematic review to assess the effects and safety of in-hospital discontinuation compared to continuation of ACEI/ARB in COVID-19 patients. METHODS: We systematically searched on PubMed, Scopus, and EMBASE from inception to June 19, 2021. We included observational studies and trials that compared the effects and safety of continuing ACEI/ARB compared to discontinuing it in COVID-19 patients. Effects sizes for dichotomous variables were expressed as risk ratios (RR) and 95% confidence intervals. For continuous variables, effects were expressed as mean difference (MD). We used random effect models with the inverse variance method. We assessed certainty of evidence using the GRADE approach. RESULTS: We included three open-label randomized controlled trials and five cohort studies. We found that the continuation group had lower risk of death compared with the discontinuation group only in the cohort group (RR: 0.46, 95% CI: 0.24-0.90), but not in the RCT group (RR: 1.22, 95% CI: 0.75-2.00). The ICU admission rate was significantly lower in the continuation group (RR: 0.46, 95% CI: 0.31-0.68) in the cohort group, but not in RCT group (RR: 1.03, 95% CI: 0.67-1.59). We did not find significant differences between groups regarding hospitalization length, hypotension, AKI needing renal replacement therapy, mechanical ventilation, new or worsening heart failure, myocarditis, renal replacement therapy, arrhythmias, thromboembolic events and SOFA AUC. The GRADE approach revealed that the certainty ranged from moderate to high level. CONCLUSIONS: There is no significant difference in mortality and other outcomes between continuation and discontinuation groups.

Screening of Cardiovascular Disease's Risk Factors Among Community Pharmacies in Rural India

Introduction: The main prevention of cardiovascular disease (CVD) and healthcare cost reduction depend on the early identification and treatment of cardiovascular disease (CVD) risk factors through screening. Hypertension, obesity, a large waist circumference, smoking, poor diets, physical inactivity, and excessive alcohol consumption are well-known and potentially treatable risk factors for cardiovascular disease. This allows for early detection of instances, informs the start of CVD prevention medication, and is also very cost-effective. Method(s): At rural India, between March and August 2021, a cross-sectional survey was conducted in community pharmacies. One thousand two hundred healthy individuals were screened for signs of obesity, high blood pressure, waist circumference, and history of smoking and alcohol intake. A structured questionnaire was used to get participants' physical activity and diet. Result(s): The gender split of the 1200 participants who were screened was 67.8% male and 32.3% female. Participants' ages ranged from 18 to 60 years old in 43.3% of cases, 41 to 60 years old in 26.3%, and over 60 in 30.4% of cases. There were 43.7% of drinkers and 47.3% of smokers, respectively. A BMI of 25 kg/m2 or more indicates being overweight, whereas a BMI of 30 kg/m2 indicates being obese. Using a diagnostic cutoff of >140/90mmHg prevalence of hypertension was 44.3%, and 14.9% out of these were previously hypertensive. 31.5% had high waist circumference, 13.9% had insufficient physical activity, and 34.9% had insufficient intake of fruits and vegetables. Conclusion(s): The majority felt that screening for CVD risk factors was helpful, and more than one-fourth of the study participants had two or more CVD risk factors combined. A cost-effective strategy for the primary prevention of CVD that can have a positive influence on the healthcare delivery system is the capacity to further discover previously undetected risk factors.Copyright © 2023, Global Research Online. All rights reserved.

USE OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEIs) AND ANGIOTENSIN-RECEPTOR BLOCKERS (ARBs) AND INCIDENCE OF PNEUMONIA OR INFLUENZA OR COVID-19: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: The respiratory tract infections (RTIs), including pneumonia, influenza and Coronavirus Disease 2019 (COVID-19), are the leading cause of hospitalization and mortality worldwide, contributing to elevated healthcare and societal costs. There is conflicting evidences about the effects of angiotensin converting enzyme inhibitor (ACEIs) or angiotensin II receptor blockers (ARBs) on the susceptibility of RTIs. Method(s): Systematic review of interventional and observational studies that reported use of ACEI or/and ARB on incidence of pneumonia or influenza or COVID-19. Searching was conducted in the databases of PubMed, Excerpta Medica Database (Embase), Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), including the Cochrane Library until April 2022, and references of retrieved relevant articles. We assessed the quality of included studies by using Cochrane Collaboration Risk of Bias tool for Randomized Controlled Trials and Newcastle-Ottawa Scale for observational studies. DerSimonian Laird random-effects meta-analysis was conducted to pool effects for the incidence of pneumonia, influenza and COVID-19. Subgroup analyses were carried according to baseline morbidities (hypertension or cardiovascular diseases, cerebrovascular diseases, chronic kidney disease (CKD) and other non-communicable diseases). Pooled estimates of odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were computed, and heterogeneity among studies was assessed using Cochran's Q test and the I2 metrics, with two tailed P values. Result(s): 73 studies met the inclusion criteria, of which 38 studies assessed the odds of pneumonia, 32 studies assessed Covid-19 and 3 studies assessed influenza. The quality of included studies was moderate. Use of ACEIs was associated with a significantly reduced odds of pneumonia (23 studies: OR 0.74, 95% CI 0.64 to 0.85;I2=76.8%), of COVID-19 (24 studies: OR 0.87, 95% CI 0.82 to 0.92;I2=81.9%) and influenza (3 studies: OR 0.75, 95% CI 0.57 to 0.98, I2=97.7%), compared with control treatment. Use of ARBs was also associated with reduced odds of COVID-19 (25 studies: OR 0.90, 95% CI 0.83 to 0.97;I2=91.9%), but not with odds of pneumonia or influenza. These findings remain consistent in the community population, patients with history of cerebrovascular diseases or cardiovascular diseases, but not in those with CKD, diabetes and chronic obstructive pulmonary diseases. Conclusion(s): The current evidence favours a putative protective role of ACEIs, not ARB in odds of pneumonia, COVID-19 and influenza. Patient populations that may benefit most are those within the community, history of cerebrovascular diseases and cardiovascular diseases. No conflict of interestCopyright © 2023

Evaluation of the Effect of Underlying Diseases on Mortality of COVID-19 Patients: A Study of 19,985 Cases

Background: The outbreak of a new coronavirus in China in 2019 (COVID-19) caused a global health crisis. Objective(s): This study was performed to investigate the effect of different underlying diseases on mortality in patients with COVID-19. Method(s): This retrospective cohort study was performed on COVID-19 patients admitted to the Shahid Rahimi and Sohada-ye Ashayer teaching hospitals in Khorramabad, Iran, from 2019 to 2021. Data on disease severity, clinical manifestations, mortality, and underlying disorders were collected and analyzed using the SPSS software version 22 at a 95% confidence interval and 0.05 sig-nificance level. Result(s): The study included 9653 men (48%) and 10332 women (52%). Patients with chronic kidney diseases, cancer, chronic obstruc-tive pulmonary disease, hypertension, cardiovascular disease, and diabetes were at higher mortality risk than those without these underlying diseases, respectively. However, there was no significant relationship between asthma and mortality. Also, age > 50 years, male gender, oxygen saturation < 93 on admission, and symptoms lasting <= 5 days were associated with increased mortality. Conclusion(s): Since patients with underlying diseases are at higher mortality risk, they should precisely follow the advice provided by health authorities and receive a complete COVID-19 vaccination series.Copyright © 2022, Author(s).

An updated meta-analysis: The effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the mortality of hypertensive patients with confirmed COVID-19 infection

Background: One of the most common co-morbidities identified among COVID-19 patients was hypertension. Debates on use of Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin-Receptor blockers (ARB) emerged due to an interaction of the said drugs with Angiotensin-converting enzyme 2 (ACE2), an enzyme which is a point of entry of coronavirus. This study aims to give an update on the work of Zhang et al13 in exploring the association of ACEI/ARB use on mortality and disease severity. Method(s): This meta-analysis involves review of observational studies among hypertensive COVID-19 patients with composite data on ACEI and ARB use. The literature search included studies published from December 2019 until June 30, 2020. Analyses were performed determining the odds ratio of each event using the raw data obtained from each study. Random effects model and Cochran-Mantel-Haenszel Method were utilized at 95% confidence interval. To check for heterogeneity, X2 test and I2 statistic were calculated. Subgroup analyses on ACEI users and ARB users were also done. Cochrane Review Manager (REVMAN 5.3) was used and Forest plots were generated. In this update, the total population of patients with confirmed COVID-19 infection was more than 50,000 with hypertensive patients comprising more than half of the sample population. The analyses done manifested decreased frequency of both outcomes with ACEI/ARB use. Result(s): The calculated odds ratio for mortality and disease severity were 0.63 and 0.56, respectively. However, a statistically significant heterogeneity existed for both outcomes. Subgroup analyses among ACEI users versus ACEI/ARB non-users (odds ratio for mortality = 0.95, I2 = 0%;and odds ratio for disease severity = 0.30, I2 = 0%), and ARB users versus ACEI/ARB non-users (odds ratio for mortality = 0.70, I2 =f 68%;and odds ratio for disease severity = 0.48, I2 = 77%) also manifested decreased frequency of both outcomes. However, significant heterogeneity exists among the ARB users, which is in contrary among the ACEI users. Conclusion(s): The use of ACEI contributes to a statistically significant reduction of mortality and disease severity among hypertensive patients with confirmed COVID-19 infection. We recommend continuing analysis of association of ACEI and ARB use and clinical outcomes since recent analysis suggests a beneficial effect especially in the ACEI group. At present, our findings are still in line with the current recommendation to not discontinue the use of ACEI and ARB among our hypertensive patients.

Cardiovascular System and COVID-19

Objective Different hypotheses suggest a contradictory association of statins, angiotensin receptor blockers(ARBs) or angiotensin-converting enzyme(ACE) inhibitors with potential adverse or favorable effects in patients with Coronavirus disease 2019(COVID-19). This study aimed to compare the association of statins, ARB, and ACE inhibitors in COVID-19 and in pneumonia. Design and Method All patients with laboratory-confirmed COVID-19 through April 16, 2020, in Korea were retrieved. We evaluated the association of statins, ARBs, and ACE inhibitors on COVID-19-related mortality within 60 days. Furthermore, a comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. Lastly, meta-analysis was performed to compare the results of this study and other reports. Results The median age of the 10,448 COVID-19 patients was 45 years, and statins, ARBs and ACE inhibitors were prescribed in 533 (5.1%), 1,231(11.8%) and 47(0.4%) patients, respectively. As of April 24, 228 patients (2.2%) succumbed to death. After adjusting age, sex, residential area, the history of comorbidities, Cox regression showed significant decrease in HR by 36% associated with statin use (HR 0.635, 95% CI 0.424 - 0.951, p = 0.0274). However, ARBs group showed neutral association (HR 1.034, 95% CI 0.765 - 1.399, p = 0.8270) and ACE inhibitor groups showed insignificant results mainly due to small sample size (HR 0.736, 95% CI 0.314 - 1.726, p = 0.4810). When comparing the HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019, the trend of statins and ACE inhibitors showed similar benefit, whereas the protective effect of ARBs observed in the retrospective cohort was lost in the COVID-19 patients. Meta-analysis including the results of this study showed significant benefit of statins and ACE inhibitors, whereas neutral association with ARBs and the mortality. Conclusions Statins were associated with significantly lower mortality of COVID-19, consistent with usual pneumonia patients. While ARBs or ACE inhibitors were not associated with fatal outcome, the possible beneficial effect of ARBs observed in usual pneumonia was attenuated in COVID-19.

The evaluation of Serum angiotensin-converting enzyme 2 (ACE2)levels and its relationship with clinical outcome in patients with Coronavirus disease 2019 (COVID-19)

Background: Coronavirus disease 2019 (COVID-19) caused a major pandemic around world. Considering conflicting information on effect of Angiotensin-converting enzyme 2 (ACE2) and inhibitors of this enzyme on COVID19, we aimed to measure levels of ACE2 in COVID-19 patients and investigate determining factors for their outcome. Method(s): This cross-sectional study was performed on 78 COVID-19 patients that referred to Afzalipour tertiary teaching hospital. Patients enrolled into study after confirmation of the diagnosis of COVID-19 by polymerase chain reaction test. We assess plasma ACE2 levels with an Enzyme-linked immunosorbent assay. The patients followed for if they discharged or deceased. Result(s): 58 out of 78 studied patients discharged (74.4%) and 20 ones (25.6%) deceased. The median length of stay in deceased group was 17.5 days and in discharged ones was 10.0 days (P=0.003). The median levels of ACE2 in discharged and deceased patients was (0.6 ng/mL) and (0.5 ng/mL), respectively which showed no significant difference(P<0.116). The median serum ACE2 levels in 19 patients who received Angiotensin-converting enzyme inhibitors or Angiotensin II receptor blockers were significantly different from those who did not (59 patients) (0.53 ng/mL vs 0.59 ng/mL, respectively) (P=0.041). Conclusion(s): The ACE2 serum level was not related to length of stay and nor to the outcome of COVID-19 patients;however, it was lower in patients received ACE inhibitors or ARBs, which may come with this suggestion that further studies might show the ACE inhibitors or ARBs affection on disease severity or patient's outcome.

The effect of ACE inhibitors on inflammation and clinical end-points in COVID-19 patients Relationship of ACE inhibitors to COVID-19 patients

Aim: COVID-19 infection has affected the whole world. It has been speculated that the virus might hold on to angiotensin-converting enzyme 2 (ACE 2) surfaces of type 2 alveolar cells. ACE inhibitors and angiotensin receptor antagonists (ARBs) are essential antihypertensive and cardiac failure drugs in the guidelines. In this study, we aimed to find the effect of these drugs on clinical, laboratory courses, and outcomes of COVID-19 patients. Material(s) and Method(s): We included 109 patients in this study. There were 43 patients in the ACE/ARB group and 66 patients in the non-ACE/ARB group. The mean age was 60 years in the ACE/ARB group and 52 years old in the non-ACE/ARB group. Basal symptoms, hemogram, CRP, D-dimer, LDH, Ferritin, AST, duration of hospitalization, percentage of intensive care unit (ICU) need, length of stay in ICU were compared between the groups. Result(s): The mean age in the ACE/ARB group was higher than in the other group and was statistically significant (p=.027). The initial symptoms were not different. There were no differences between the laboratory results of the groups. The ICU need was higher in the patients who do not use the drug than in the users (p<.020). Discussion(s): ACE/ARB usage in COVID-19 patients did not worsen the course of the disease. However, ACE/ARB users before COVID-19 pandemic were taken to ICU at a low rate.Copyright © 2022, Derman Medical Publishing. All rights reserved.

A CASE REPORT OF 'RETROPERITONEAL FIBROSIS CAUSING RENOVASCULAR HYPERTENSION' ASSOCIATED WITH SARS-CoV2

Introduction: Retroperitoneal fibrosis (RPF) is a rare disease which can be primary (idiopathic) or secondary to drugs, tumors or infections. We are reporting the first case of RPF causing renal atrophy, renal artery stenosis and renovascular hypertension associated with SARS-CoV2. Method(s): A 37-year-old female nurse presented to her PCP with a new-onset of hypertension. She had recovered from severe SARS-CoV2 infection merely two months ago. Physical examination was remarkable for BP 170/110 mmHg, HR 88 beats/min, BMI of 31 alongside trace pitting edema. Initial lab data showed her creatinine to be 1.1mg/dl and ultrasound of her kidneys showed an atrophied right kidney with a size of 7.8 cm while the left kidney was 11.6 cm. An ultrasound KUB of that same time showed that the size of the right kidney was 10.4 cm and left 11.5 with normal renal parenchyma. She was started on amlodipine 10 mg and valsartan 160 mg per day. Two weeks later she was referred to a nephrologist when her creatinine was increased to 3.1 mg/dl. Renovascular hypertension secondary to right renal artery stenosis or thrombus was suspected. Autoimmune & hypercoagulable work up was negative. CT angiogram showed an ill-defined, poorly enhancing retroperitoneal soft tissue thickening draping the mid abdominal aorta, the origin of SMA, and bilateral renal arteries which terminated above the aortoiliac bifurcation. This, RPF, involved segment of 8.6 cm of the mid and lower abdominal aorta, causing moderate narrowing of proximal SMA, short segment narrowing of proximal left main and accessory renal artery, and diffuse long segmental narrowing of the right main renal artery. RPF encasement of right renal artery lead to poor right renal nephrogram and atrophic kidney. (Figure no A: Abdominal contrast-enhanced computed tomographic (CT) scan showing the encasement of the both renal arteries by the retroperitoneal fibrosis (RPF).Figure no B : Renal angiogram showing the renal artery stenosis on right side) Acute kidney injury (AKI) was initially thought to be due to angiotensin receptor blockade in the setting of bilateral renal artery stenosis. Valsartan was swapped for metoprolol and the serum creatinine levels decreased to 1.5 mg/dl in two weeks. Prednisone was started for RPF at a dose of 60 mg per day with a slow taper over 4 months. Over the next 8 weeks, creatinine became normal and blood pressure was controlled with amlodipine 2.5 mg/day. Subsequently at 4 months her creatinine was 1.0 mg/dl and she was off all anti-hypertensive drugs. A repeat CTA after 6 months showed that there was significant reduction in RPF. Atrophic right kidney was noted without any significant interval change. RPF, renal artery stenosis, renovascular hypertension and right renal atrophy was strongly suspected to be associated with SARS-Cov2 since none of these were identified prior to her suffering from SARS-CoV2. Result(s): [Formula presented] [Formula presented] Conclusion(s): To our knowledge, this is the first case of RPF associated with SARS-CoV-2 causing renovascular hypertension and renal atrophy. Local and systemic production of IL-6, TGF- beta and Th2 cytokines has been demonstrated in idiopathic RPF and pulmonary fibrosis due to SARS-CoV2. The presumptive pathogenesis could involve SARS-Cov2 induced release of IL-6 and other cytokines which can activate B cells and fibroblasts. No conflict of interestCopyright © 2023

Family History of Alport Syndrome with Spectrum of Chronic Kidney Disease, Dialysis and Transplantation

Introduction: Alport syndrome should be considered in the differential diagnosis of patients with persistent microhematuria. Electron microscopic examination of renal tissue remains the most widely available and applied means for diagnosing AS. The presence of diffuse thickening and multilamellation of the GBM predicts a progressive nephropathy, regardless of family history. Unfortunately, ultrastructural information alone does not establish the mode of transmission in a particular family. Method(s): 18 years-old male patient was followed in the clinic due to persistent microscopic haematuria and proteinuria. Family history is significant for one brother in his early 20s, who started to have the presentation early in life and his initial biopsy showed thin basement membrane disease. The brother subsequently progressed to renal failure and a repeat biopsy confirmed the presence of Alport syndrome. Another brother had end-stage renal disease and underwent renal transplantation. The patient status was revised, and genetic studies confirmed the presence of an autosomal recessive type of Alport syndrome involving collagen for A3 chain COL4A3. His kidney function remained stable initially with an estimated GFR of approximately 90 mL/min/1.73 m2. The most recent eGFR is around 70 ml/min/1.73 m2. His proteinuria disappeared once Losartan 25 mg was added to Ramipril 5 mg. His blood pressure has been on target. Creatinine increased to 147 micromol/L and he was diagnosed as having acute kidney injury on chronic renal disease which was obvious post covid infection, then back to baseline. Current proteinuria 3 g/g Cr on Angiotensin receptor blockers. BP 110/70, all other systemic examination is unremarkable. No hearing or visual abnormalities. Result(s): The initial renal manifestations in early childhood include asymptomatic-persistent microscopic hematuria and rarely gross hematuria. At the onset, the serum creatinine and blood pressure are normal. Over time, proteinuria, hypertension, and progressive renal insufficiency develop. ESRD usually occurs between the ages of 16 and 35 years and rarely can occur between 45 and 60 years. Renal biopsy findings of thinning and multilaminar splitting of the glomerular capillary basement membrane seen on electron microscopic examination are pathognomonic. In 2013, an expert panel issued guidelines recommending genetic testing as the gold standard for the diagnosis of Alport syndrome. Currently, a skin biopsy using commercially available monoclonal antibody against the type IV collagen alpha-5 chain (COL4A5). If the protein is clearly absent in a suspected male, a diagnosis of Alport syndrome can be made without further testing. Conclusion(s): Males with X-linked AS due to a deletion mutation of the alpha 5 chain of type IV collagen usually progress to ESRD by the second or third decade of life. Likewise, patients with autosomal recessive AS due to mutations affecting alpha 3 or 4 chains of type IV collagen tend to progress to ESRD by age 30. Autosomal-dominant AS with heterozygous mutations of COL4A3 or COL4A4 usually has a slower progression of CKD. Treatment is blood pressure control with RAAS inhibitors where clinically appropriate. Cyclosporine may be helpful in some patients with stage I and II CKD with significant proteinuria. Caution using calcineurin inhibitors is indicated in all patients with more advanced CKD stages due to potential nephrotoxicity. No conflict of interestCopyright © 2023

SARS-CoV-2 infection and smoking: What is the association? A brief review.

Susceptibility to severe illness from COVID-19 is anticipated to be associated with cigarette smoking as it aggravates the risk of cardiovascular and respiratory illness, including infections. This is particularly important with the advent of a new strain of coronaviruses, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) that has led to the present pandemic, coronavirus disease 2019 (COVID-19). Although, the effects of smoking on COVID-19 are less described and controversial, we presume a link between smoking and COVID-19. Smoking has been shown to enhance the expression of the angiotensin-converting enzyme-2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) key entry genes utilized by SARS-CoV-2 to infect cells and induce a 'cytokine storm', which further increases the severity of COVID-19 clinical course. Nevertheless, the impact of smoking on ACE-2 and TMPRSS2 receptors expression remains paradoxical. Thus, further research is necessary to unravel the association between smoking and COVID-19 and to pursue the development of potential novel therapies that are able to constrain the morbidity and mortality provoked by this infectious disease. Herein we present a brief overview of the current knowledge on the correlation between smoking and the expression of SARS-CoV-2 key entry genes, clinical manifestations, and disease progression.

Biomarkers of COVID-19 and technologies to combat SARS-CoV-2.

Due to the unprecedented public health crisis caused by COVID-19, our first contribution to the newly launching journal, Advances in Biomarker Sciences and Technology, has abruptly diverted to focus on the current pandemic. As the number of new COVID-19 cases and deaths continue to rise steadily around the world, the common goal of healthcare providers, scientists, and government officials worldwide has been to identify the best way to detect the novel coronavirus, named SARS-CoV-2, and to treat the viral infection - COVID-19. Accurate detection, timely diagnosis, effective treatment, and future prevention are the vital keys to management of COVID-19, and can help curb the viral spread. Traditionally, biomarkers play a pivotal role in the early detection of disease etiology, diagnosis, treatment and prognosis. To assist myriad ongoing investigations and innovations, we developed this current article to overview known and emerging biomarkers for SARS-CoV-2 detection, COVID-19 diagnostics, treatment and prognosis, and ongoing work to identify and develop more biomarkers for new drugs and vaccines. Moreover, biomarkers of socio-psychological stress, the high-technology quest for new virtual drug screening, and digital applications are described.