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Antecedentes y objetivos: El desarrollo de lesión renal aguda (FRA) durante la hospitalización por SARS-Cov2 se ha asociado a elevada morbi-mortalidad. El Registro FRA-COVID 19 SEN ha recogido datos de pacientes con este perfil durante los meses de la pandemia. El objetivo de este trabajo fue caracterizar la población española ingresada por COVID-19 que desarrolló FRA, con/ sin necesidades de tratamiento renal sustitutivo (TRS), modalidades terapéuticas utilizadas y resultados en términos de mortalidad Material y método: Estudio retrospectivo de datos procedentes de 30 hospitales españoles, recopilados en el Registro Español FRA COVID-19 desde mayo de 2020 hasta noviembre 2021. Se registraron variables clínicas y demográficas, datos relacionados con la gravedad de la COVID-19, con el FRA y de supervivencia. Mediante estudio de regresión multivariante se analizan los factores relacionados con la necesidad de TRS y con mortalidad. Resultados: Se registraron datos de 730 pacientes. El 71,9% eran hombres, con edad media 70 años (60-78). El 70,1% eran hipertensos, 32,9% diabéticos, 33,3% con enfermedad cardiovascular y 23,9% presentaban algún grado de enfermedad renal crónica. Desarrollaron neumonía el 94,6%, con necesidad de soporte ventilatorio en el 54,2% e ingreso en UCI en un 44,1% de los casos.La mediana de tiempo desde el inicio de síntomas COVID hasta la aparición de FRA fue de 6 días (4-10). En cuanto a la gravedad: 37,1% KDIGO I, 18,3% KDIGO II, 44,6% KDIGO III;requirieron TRS 235 pacientes (33,9%). Las técnicas continuas (TCRR) fueron las más empleadas (155 pac), seguidas de hemodiálisis (HD) intermitente (89 pac), HD diaria (36 pacientes), hemodiafiltración (HDF) 17 pac., y HD expandida (HDexp) en 24 casos. El hábito tabáquico (OR 3,41), la necesidad de soporte ventilatorio (OR 20,2), la cifra de creatinina máxima (OR 2,41) y el tiempo transcurrido desde el inicio de los síntomas hasta la aparición del FRA (OR 1,13) se identificaron como predictores de la necesidad de TRS en nuestra cohorte, mientras la edad se comporta como protector (OR: 0,95). El grupo que no requirió TRS se caracterizó por presentar mayor edad, menor gravedad de FRA y un tiempo de aparición y recuperación de la lesión renal más corto (p<0,05).El 38,6% de la cohorte falleció durante la hospitalización. La gravedad del FRA y la necesidad de TRS fue más frecuente en el grupo de fallecidos. En el análisis multivariante, edad (OR 1.03), enfermedad renal crónica previa (OR 2,21), desarrollo de neumonía (OR 2,89), soporte ventilatorio (OR 3,34) y TRS (OR: 2,28) se comportaron como factores predictores mientras que el tratamiento crónico con ARAII se comportó como factor protector (OR 0,55). Conclusiones: Del análisis del Registro FRA-COVID 19 SEN se deduce que los pacientes que presentaron FRA durante la hospitalización por COVID-19 tenían una edad media elevada, mayores comorbilidades y presentaron un cuadro de infección grave. Definimos dos patrones clínicos diferentes: un FRA de aparición precoz, en pacientes más ancianos que se resuelve en pocos días sin necesidad de TRS;y otro patrón más grave, con mayor requerimiento de TRS, y aparición tardía en el curso de la enfermedad, que se relacionó con mayor gravedad de la misma. La gravedad de la infección, la edad y la presencia de ERC previa al ingreso fueron factores determinantes en la mortalidad de estos pacientes, identificando el tratamiento crónico con ARA II como un factor protector de mortalidad.
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Background: Angiotensin-converting enzyme 2(ACE2), the receptor for SARSCoV-2, is highly expressed in the kidneys. ACE2 also possess a unique function to facilitate amino acid absorption. A persistent elevation in plasma ACE2 during COVID-19 is related to increased mortality. The present study sought to explore the relationship between urine ACE2(uACE2) and renal outcomes in COVID-19 patients. Method(s): In 104 COVID-19 patients without acute kidney injury(AKI), 43 patients with COVID-19-mediated AKI, and 36 non-COVID-19 controls, uACE2, urine tumor necrosis factor receptors I and II(uTNF-RI and uTNF-RII), neutrophil gelatinaseassociated lipocalin(uNGAL), and urine albumin-creatinine ratio were measured. We also assessed ACE2 staining in autopsy kidney samples and generated a propensityscore matched subgroup to perform a targeted urine metabolomic study to describe the characteristic urine signature of COVID-19. Result(s): uACE2 was increased in patients with COVID-19, and further increased in those that developed AKI(Figure 1). After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with over 3-fold higher risk(OR 3.05,95%CI:1.23-7.58, p=0.017) of developing AKI. Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII, suggesting that ADAM17 could be responsible for ACE2 shedding. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in COVID-19 patients, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2(Figure 1). Conclusion(s): Elevated uACE2 is related to AKI in patients with COVID-19. The loss of tubular ACE2 during SARS-CoV-2 infection demonstrates a potential link between aminoaciduria and proximal tubular injury.
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Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease-19 (COVID-19). The present study aims to evaluate the impact of a booster vaccine dose and breakthrough SARS-CoV-2 infections on humoral immunity three months after the booster dose. Method(s): This is a multicentric and prospective study assessing anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6-and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Result(s): 711 patients (67% male, 67 [20-89] years) were included. Of them, 545 (77%) patients had received an early booster and 166 (23%) a late booster. At 6 months, 64 (9%) patients had negative humoral response (3% of early booster and 29% of late booster participants, p=0.001) and 58 (91%) of them had seroconverted at 9 months, when, 5/545 (0.9%) patients in the early booster cohort and 1/166 (0.6%) in the late booster cohort remained antibody negative (p=NS). During follow-up, 35 patients (5%) developed COVID-19. Antibody titers at 9 months were independently associated to lower time from booster (B -0.12, p=0.043), COVID-19 (B 2.29, p<0.001) and mRNA-1273 booster (B 1.17, p=0.001). Conclusion(s): In hemodialysis patients, higher rates of anti-Spike antibody development were associated to mRNA-1273 booster, lower time from booster and breakthrough SARS-CoV-2 infection.
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Background: Information about humoral and cellular responses to SARS-CoV-2 vaccination in patients with Multiple Sclerosis (PwMS) and other autoimmune diseases (AID) is scarce. Objective: To determine humoral and cellular responses after SARS-CoV-2 vaccination in PwMS and anti-CD20-treated patients with other AID. Methods: Ongoing prospective study performed in two Catalan MS centres from February 2021. Unvaccinated adult pwMS and other anti-CD20-treated AID were recruited. Demographic, clinical and laboratory data were obtained. Whole blood samples were obtained before and 30-90 days after vaccination. The humoral response to SARS-CoV-2 was qualitatively and quantitatively measured before and after vaccination with commercial chemiluminescence immunoassays targeting SARS-CoV-2 antibodies against spike (TrimericS, IgG anti-S) and nucleocasid proteins (Elecsys, Ig anti-N). In 150 selected patients according to diseasemodifying therapy (DMT), the SARS-CoV-2 specific T-cell response was assessed after vaccination by a whole blood Interferon-Gamma Release immuno Assay (IGRA) that uses two Qiagen proprietary mixes of SARS-CoV-2 S protein (Ag.1 and Ag.2) selected to activate both CD4 and CD8 T cells. Results: 457 patients have been enrolled in the study (anti-CD20 therapy n=164, S1P DMTs n=37, natalizumab n=32, cladribine n=29, alemtuzumab n=31, other DMTs n=129, no DMT n=35). Participants characteristics are: mean age 48.1 years (SD 12.0), 69% female, 422 pwMS (29.4% progressive forms) and 35 with other AID, disease duration 13.9 years (IQR 14.1), median EDSS 3.0 (IQR 3.0). 450 have been fully vaccinated (94.2% mRNA vaccine). Pre-vaccination samples were collected 0.33 days (SD 0.5) before the first vaccine dose of which 12 (3.35%) had positive anti S/N immunoglobulin (Ig). As of June 30th, 42 post-vaccination samples have been obtained (1.3 months [SD 0.42] after the 2nd vaccination dose). Positive IgG rates were 44.8% (n=13/29) for CD20s, 100% (8/8) for other DMTs and 100% (4/4) for no DMT. No anti-N Ig were detected. Media titres of anti-S IgG were lower in anti-CD20-treated patients (7.8 [IQR 50.1]) compared to untreated patients (800 [0], p<0.01) or other DMTs (755 [228], p<0.01). Conclusions: Initial results of the study suggest blunted anti-S/N Ig response under anti-CD20 therapy. Knowledge of the cellular response in these patients will be crucial. Data from the cellular study and the completed humoral study will be presented at the meeting.
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BACKGROUND AND AIMS: Age and chronic kidney disease have been described as mortality risk factors for coronavirus disease 2019 (COVID-19). Currently, an important percentage of patients in hemodialysis are elderly. This study aimed to investigate the impact of COVID-19 in this population and to determine risk factors associated with mortality. METHOD: Data was obtained from the Spanish COVID-19 CKD Working Group Registry, that included patients in renal replacement therapy (dialysis and kidney transplantation) infected by COVID-19. From March 18, 2020, to August 27, 2020, 1165 patients on hemodialysis affected by COVID-19 were included in the Registry. A total of 328 patients were under 65 years-old and 837 were 65 years old or older (elderly group). RESULTS: Mortality was 18.6% higher (95% confidence interval (CI): 13.8%-23.4%) in the elderly hemodialysis patients compared to the non-elderly group (see figure). Death from COVID-19 infection was increased 5.5-fold in hemodialysis patients compared to mortality in the general population for a similar period, and there was an age-associated mortality increase in both populations (see figure 1). In multivariate Cox regression analysis, age (hazard ratio (HR) 1.58, 95% CI: 1.31-1.92), dyspnea at presentation (HR 1.61, 95% CI: 1.20-2.16), pneumonia (HR 1.76, 95% CI: 1.12-2.75) and admission to hospital (HR 4.13, 95% CI: 1.92-8.88) were identified as independent mortality risk factors in the elderly hemodialysis population. Treatment with glucocorticoids reduced the risk of death (HR 0.71, 95% CI: 0.51-0.98) in aged patients on hemodialysis. CONCLUSION: Mortality is dramatically increased in elderly hemodialysis patients affected by COVID-19. Age, dyspnea at presentation, pneumonia or hospitalization are factors associated with a worse prognosis, after adjusting dialysis population to other confounding factors. Treatment with glucocorticoids could be a therapeutic option for this specific population. (Table Presented).
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BACKGROUND: COVID-19 infection manifests as pneumonia associated with multiple organ failure, and death. Acute kidney injury is a risk factor for mortality. There is limited scientific literature on COVID-19 infection and allergic tubulointerstitial nephritis, its clinical course and short- and long-term prognosis. METHOD: We performed a retrospective study where medical records of 60 patients with histological diagnosis of allergic tubulointerstitial nephritis from January 2009 to November 2020. In these patients, we studied the incidence of COVID-19 infection, clinical characteristics and prognosis from March to the actual date. RESULTS: Of 60 patients with allergic tubulointerstitial nephritis, 6 (10%) patients were diagnosed with COVID-19. The first case, an 85-year-old woman with a history of metastatic melanoma treated with nivolumab and allergic tubulointerstitial nephritis by immunobiological agents in 2018, diagnosed with mild COVID-19 infection in April 2020 without deterioration of renal function in controls at 3 and 6 months of follow-up. The second case, a 51-year-old woman with a history of large B-cell lymphoma with plasmacytic differentiation and progression to multiple myeloma of lambda light chains and allergic tubulointerstitial nephritis due to chemotherapy since 2019, admitted for acute pyelonephritis and PRES syndrome secondary to first dose of bortezomib complicated with COVID-19 nosocomial pneumonia and acute pancreatitis treated with corticosteroids and broad spectrum antibiotic therapy;she died of abdominal refractory septic shock. The third patient, a 64-year-old man without prior renal impairment, was admitted for severe COVID-19 pneumonia and acute kidney injury secondary to acute tubulointerstitial nephritis of uncertain etiology that required orotracheal intubation and continuous veno-venous hemodiafiltration for a week who received methylprednisolone in bolus for 3 days and continued treatment with corticosteroid therapy with complete recovery of renal function and improvement in proteinuria at 3 months of follow-up. The fourth patient, an 82-yearold woman with acute kidney injury AKIN 3 secondary to acute allergic tubulointerstitial nephritis related to ciprofloxacin complicated with severe COVID-19 nosocomial pneumonia, who died despite ventilatory support and high-dose steroids therapy and tocilizumab. The fifth patient, a 75-year-old with a history of metastatic lung adenocarcinoma treated with immunobiological agents and allergic tubulointerstitial nephritis in 2018, admitted in march 2020 for mild COVID-19 pneumonia treated with steroids and hydroxychloroquine without deterioration of respiratory and kidney function. The sixth patient, an 86-years-old man with acute kidney injury AKIN 3 due to acute allergic tubulointerstitial nephritis secondary to proton-binding inhibitors and nosocomial COVID-19 infección with improvement of kidney function with steroids therapy only. CONCLUSION: Our 6 patients with allergic tubulointerstitial nephritis and COVID-19 infection presented different spectrum of the disease. It seems that nosocomial COVID-19 infection in patients admitted with recent diagnosis of acute allergic tubulointerstitial nephritis presented a worse clinical prognosis compared with long-term diagnosed acute tubulointerstitial nephritis. Further studies with a larger sample size are needed.
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BACKGROUND AND AIMS: COVID-19 infection is responsible for respiratory infection with variable clinical expression from its asymptomatic form to severe pneumonia associated with acute respiratory distress syndrome and death. Risk factors related to higher mortality are age over 65 years, cardiovascular, pulmonary and kidney disease, hypertension, and diabetes. There is limited scientific literature on COVID-19 infection and previous kidney disease, specifically in patients with glomerular and tubular kidney disease. The aim of this study was to determine general characteristics, analytical parameters and clinical evolution of patients with kidney disease who have undergone kidney biopsy and who presented infection or high suspicion of infection by COVID-19. Identify mortality and associated risk factors. METHOD: we studied patients with high clinical suspicion of infection or confirmed infection by COVID-19 from March 2020 to May 15, 2020 of all patients who underwent percutaneous renal biopsy at the Vall d'Hebron Hospital between January 2013 and December 2019. RESULTS: 39 of the 553 patients have been diagnosed with COVID-19 infection since March 2020. The average age was 63615 years and 48.7% were male. Hypertension was present in 79.5% of patients, chronic kidney disease without renal replacement therapy in 76.9%, and cardiovascular disease in 64.1%. Nasopharyngeal swab was performed in 26 patients;older patients (p=0.01), patients with hypertension (p=0.005), immunosuppression (p=0.01), use of RAS-blocking drugs (p=0.04) and gastrointestinal symptoms (p=0.02) were more likely to be tested for COVID-19. 22 patients required hospitalization and 15.4% died. In the bivariate analysis, mortality was associated with older age (p=0.03), cardiovascular disease (p=0.05), chronic obstructive pulmonary disease (COPD) (p=0.05) and low hemoglobin levels (p=0.006). Adjusted Cox regression showed that low hemoglobin levels (10.12±1.89g/dL) at admission had 1.81 greater risk of mortality [1.04-3.13;p=0.04]. CONCLUSION: Patients with COVID-19 infection and kidney disease confirmed by kidney biopsy presented mortality of 15.4%. Swab test for COVID-19 was more likely to be performed in older, hypertensive, use of RAS-blocking drugs, immunosuppressed patients and those with gastrointestinal symptoms. Low hemoglobin is a risk factor for mortality.
Subject(s)
Anesthesiology/organization & administration , COVID-19/epidemiology , Health Care Surveys/statistics & numerical data , Pandemics , SARS-CoV-2 , Anesthesiologists/organization & administration , Anesthesiology/statistics & numerical data , Bed Conversion/statistics & numerical data , COVID-19/therapy , Cost-Benefit Analysis , Critical Care/statistics & numerical data , Hospital Bed Capacity/statistics & numerical data , Humans , Intensive Care Units , Personnel Staffing and Scheduling , Spain/epidemiologyABSTRACT
Background: ACE2 is a component of the renin-angiotensin system(RAS) that mainly degrades angiotensin II to angiotensin(1-7). It is expressed in renal tubular cells. Lung type 2 alveolar cells also express ACE2 where it acts as a receptor for SARS-CoV-2, which is responsible for the current coronavirus disease 2019(COVID-19) pandemic. A controversy raised regarding the use of RAS blockers in COVID-19 patients despite its demonstrated efficacy in cardiovascular disease. We studied the effect of ramipril on ACE2 expression in experimental diabetes. Methods: 12 weeks old diabetic db/db mice were given ramipril(8 mg/Kg/day) or vehicle during 8 weeks. db/m mice were used as controls. ACE2 expression and enzymatic activity were studied in kidney, heart and lung. Results: In non-treated db/db, ACE2 mRNA expression was increased in kidney(p<0.0001) and ramipril treatment reversed this effect. In heart, ACE2 expression decreased in db/db when compared to db/m(p=0.028) and ramipril had no effect. We found no differences in lung. ACE2 enzymatic activity was increased 23% in kidney and 22% in lung of db/db mice when compared to db/m. Ramipril treatment decreased ACE2 activity 25% in the lung and 13% in the kidney when compared to untreated db/db. In the heart, ACE2 activity tended to decrease in db/db mice when compared to db/m, and increased with ramipril, but did not exceed the cardiac ACE2 activity of the db/m. Conclusions: ACE2 is increased in the kidney and in the lung, and decreased in the heart of diabetic mice. Ramipril treatment restores ACE2. Our results suggest that diabetes and hypertension may per se be risk factors for COVID-19 and not the treatment with ACE inhibitors, which may exert a protective effect on COVID-19 infection.
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Background: SARS-CoV-2 coronavirus pandemic has significant impact on the general population, and chronic hemodialysis patients presented a poor prognosis with a mortality rate around 25%. Data from severe acute kidney injury(AKI) and acute renal replacement therapy(RRT) is scarce. We present the preliminary results of AKI COVID-19 Registry of the Spanish Society of Nephrology. Methods: The online Registry began operating on May 21th. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. Patients were diagnosed with SARS-Cov-2 infection based on PCR of the virus. Results: One week after the AKI COVID registry started, 54 patients with AKI with RRT and COVID-19 from 11 Hospitals. Age was 64+9years and 55% men. 65% hypertension, 31% diabetes mellitus, 14% cardiovascular disease, 26% chronic kidney disease, 6% neoplasm, 29% obesity, 8% chronic obstructive pulmonary disease, and6% smokers. Previous treatment: 10% immunosuppressive, 20% ACEi, 25% ARBs, 14% antiplatelets, and 10% anticoagulants. Clinical characteristics: 92% common respiratory symptoms, 96% pneumonia, 90% required intensive care unit(ICU) and 87% mechanic ventilation. 32% albuminuria, 18% hematuria, and 50% AKI with preserved urine output. Time from COVID-19 symptoms start to AKI 12.3+8days, time ICU 19.8+5days. APACHE at UCI admission 15+7. 81% lymphopenia. RRT was needed in 91% 13.4+12days: 55% received continuous RRT, and 72% anticoagulation. Kidney biopsy was not performed. Mortality 46.3% (60% males), and 4% remained under RRT. Time from AKI to renal function recovery 25+14 days. 65.2% death patients had hypertension. No differences were observed in comorbidities, chronic treatments, renal clinical characteristics, dialysis modality and mortality. Decreased lymphocyte count was associated with worse patient prognosis (dead 495±260 vs. survivors 789±460,p=0.023). Conclusions: The mortality in AKI with RRT and COVID-19 is alarming high. Severe AKI associated with COVID-19 disease is more frequent in males. Interestingly, half of the patients preserved urine output. Severe lymphopenia was associated with mortality. More data from the AKI COVID-19 registry will help us to enlighten the prognosis and risk factors associated to mortality.
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Background: COVID-19 is a novel coronavirus currently at the centre of a global pandemic, and patients with cardiovascular risk factors such as hypertension and diabetes are at risk of a serious complication such as hospitalization and death. Chronic kidney disease (CKD) increased cardiovascular risk and >90% of CKD patients presented hypertension. The prognosis and lethality of COVID-19 in patients with biopsy-proven kidney disease has not been previously studied. Methods: Data included patients who underwent a kidney biopsy at the Vall d'Hebron Hospital between January 2013 and February 2020 with diagnostic confirmation and those with high clinical suspicion of SARS-CoV-2 infection during the period from March to May 2020. Results: Of 553 patients, 39(7%) were diagnosed with SARS-CoV2 infection. The mean age was 63.4±15 years. 48.7% were male, 31 hypertension, 19 diabetic, 12 obese and 18 patients had lung disease. The renal histological diagnosis of glomerulonephritis with extracapillary proliferation in 10.3%, allergic interstitial nephritis in 10.3 %, secondary GSFS in 8.5% and diabetic nephropathy in 10.3%. 4 patients were on hemodialysis and 6 had a kidney transplant. Creatinine before infection was 1.52mg/ dL±0,66. 17 patients were under immunosuppressive treatment (14 with prednisone, 8 mycophenolate, 6 tacrolimus, 1 rituximab). 26 patients had confirmation of SARS-CoV2 infection with RT PCR obtained from nasopharyngeal swab. 22 patients required hospital admission [average hospital stay was 16 days±11], of which 4 in the ICU and 6 (15%) died. 15 patients received lopinavir/ritornavir;23 patients, azithromycin;20 patients, hydroxychloroquine;6 patients, tocilizumab;9 patients, intravenous corticosteroids. 11 patients presented impaired renal function, of which 3 were transplanted and 8 with CKD. CKD patients under RAS blockade had less mortality than patients without RAS blockade treatment (29% vs 0%, p=0.014). Conclusions: COVID-19 was diagnosed in 7% of our CKD patients with kidney biopsy. The mortality was 15%, lower than the reported in hemodialysis patients. RAS blockade is not exerting a deleterious effect in our CKD patients with COVID-19 infection, suggesting that they should not be withdrawn.
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Background: There have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in full length (FL) membrane bound ACE2, the main receptor for SARs-CoV-2, that could enhance the risk and worsen the clinical course of COVID -19. Information on the impact of ACE deficiency and AT1 blockade on ACE2 expression at target sites is required to understand this issue. Methods: Kidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes. Results: In global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0.05. In ACE 8/8 mice that over-express cardiac ACE protein but has no kidney ACE expression, ACE2 protein in kidney membranes wasalso decreased (38 % of the WT, p<0.01). In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein to the level of 37%, p<0.01 and 76%, p <0.05 of that of vehicle control mice, respectively. In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control) or telmisartan (93% of control). Conclusions: Genetic kidney ACE deficiency, suppressed ACE enzyme activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 expression in kidney membranes. These findings altogether suggest that ACE2 protein abundance at two potential target sites for SARS-CoV-2 infection is decreased or unaffected by RAS blockers. Since these medications do not increase ACE2 expression in lung or kidney epithelia, we conclude that they likely would not pose a risk for increased susceptibility to COVID -19.