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1.
BMJ Open ; 11(12): e050051, 2021 12 31.
Article in English | MEDLINE | ID: covidwho-1599073

ABSTRACT

OBJECTIVES: SARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use. DESIGN: This is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality. SETTING: Medical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality. PARTICIPANTS: 9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed. OUTCOME MEASURE: Death from any cause within 60 days of COVID-19 diagnosis was examined. RESULTS: Discontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2-1.7). Initiating (OR: 0.3; 95% CI 0.2-0.5) or continuous (OR: 0.6; 95% CI 0.5-0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment. CONCLUSIONS: Recent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 Testing , Hospitals , Humans , SARS-CoV-2
2.
Drugs ; 82(1): 43-54, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1588657

ABSTRACT

OBJECTIVE: To determine the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) use and coronavirus disease 2019 (COVID-19) severity and outcomes in US veterans. PATIENTS AND METHODS: We retrospectively examined 27,556 adult US veterans who tested positive for COVID-19 between March to November 2020. Logistic regression and Cox proportional hazards models using propensity score (PS) for weight, adjustment, and matching were used to examine the odds of an event within 60 days following a COVID-19-positive case date and time to death, respectively, according to ACEI and/or ARB prescription within 6 months prior to the COVID-19-positive case date. RESULTS: The overlap PS weighted logistic regression model showed lower odds of an intensive care unit (ICU) admission (odds ratio [OR] 95% CI 0.77, 0.61-0.98) and death within 60 days (0.87, 0.79-0.97) with an ACEI or ARB prescription. Veterans with an ARB-only prescription also had lower odds of an ICU admission (0.64, 0.44-0.92). The overlap PS weighted model similarly showed a lower risk of time to all-cause mortality in veterans with an ACEI or ARB prescription (HR [95% CI]: 0.87, 0.79-0.97) and an ARB only prescription (0.78, 0.67-0.91). Veterans with an ACEI prescription had higher odds of experiencing a septic event within 60 days after the COVID-19-positive case date (1.22, 1.02-1.46). CONCLUSION: In this study of a national cohort of US veterans, we found that the use of an ACEI/ARB in patients with COVID-19 was not associated with increased mortality and other worse outcomes. Future studies should examine underlying pathways and further confirm the relationship of ACEI prescription with sepsis.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/epidemiology , Hypertension/drug therapy , Hypertension/epidemiology , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , COVID-19/mortality , Female , Humans , Intensive Care Units/statistics & numerical data , Logistic Models , Male , Middle Aged , Patient Acuity , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Sepsis/epidemiology , Veterans
3.
J Hum Hypertens ; 35(10): 828-836, 2021 10.
Article in English | MEDLINE | ID: covidwho-1575511

ABSTRACT

Concern has arisen about the role played in coronavirus disease 2019 (COVID-19) infection by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). This study was designed to assess the practice behaviors of physicians toward hypertension treatment with ACE-i or ARBs during the COVID-19 pandemic. A self-administered survey questionnaire consisting of 26 questions about current hypertension treatment with ACE-i/ ARBs was applied to cardiologists, internists, and family physicians in central and western Turkey, between 01 and 19 May 2020. A total of 460 physicians were approached, and 220 (47.8%) participated in the study. Of the total respondents, 78.7% reported that they had not changed their antihypertensive medication prescribing pattern, 8.6% of clinicians had changed ACE-i/ ARBs medicine of patients during the COVID-19 pandemic and 12.7% of them were undecided. The median (±interquartile range) score indicating general reliance level of physicians in ACE-i/ARBs therapy was 8 ± 4 (range, 1-10). In multiple comparison analyses, the general reliance level in ACE-i/ARBs, reliance level when starting a new ACEi/ARBs and changing behavior in heart failure patients were significantly different with regard to the specialties (p:0.02, p:0.009, p:0.005 respectively). Although most of the physicians found the publications about ACE-i/ ARBs during the COVID-19 pandemic untrustworthy, there were variable levels of knowledge and reliance among different physicians and specialty groups. In general, the ACE-i/ ARBs prescribing habits were not affected by safety concerns during the COVID-19 pandemic in Turkey.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Attitude , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Pandemics , Renin-Angiotensin System , SARS-CoV-2
4.
N Engl J Med ; 385(20): 1845-1855, 2021 11 11.
Article in English | MEDLINE | ID: covidwho-1510679

ABSTRACT

BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).


Subject(s)
Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Biphenyl Compounds/therapeutic use , Heart Failure/prevention & control , Myocardial Infarction/drug therapy , Ramipril/therapeutic use , Valsartan/therapeutic use , Aged , Aminobutyrates/adverse effects , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Biphenyl Compounds/adverse effects , Cardiovascular Diseases/mortality , Double-Blind Method , Drug Combinations , Female , Hospitalization/statistics & numerical data , Humans , Hypotension/chemically induced , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/mortality , Proportional Hazards Models , Ramipril/adverse effects , Stroke Volume , Valsartan/adverse effects , Ventricular Dysfunction, Left/etiology
6.
Am J Emerg Med ; 38(7): 1488-1493, 2020 07.
Article in English | MEDLINE | ID: covidwho-1450042

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords "COVID 19," "SARS-CoV-2," and "treatment." All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Drug Therapy, Combination , Emergency Service, Hospital , Humans , Hydroxychloroquine/therapeutic use , Interleukin-6/antagonists & inhibitors , Pandemics , Pyrazines/therapeutic use , Randomized Controlled Trials as Topic , SARS-CoV-2
7.
Ann Med ; 53(1): 1673-1675, 2021 12.
Article in English | MEDLINE | ID: covidwho-1437738

ABSTRACT

In the setting of the raging COVID-19 pandemic, the search for innovative therapeutics is desperately sought after. As we learn more about the characteristics and metabolic health of patients and as our understanding of COVID-19 pathophysiology and treatment progresses, so is our understanding of medication effects that might increase disease severity. As of late, ACE inhibitors have been under investigation for a potential increase in illness severity due to ACE2 upregulation. Given our knowledge of other nutrient-pharmaceutical interactions, could the ACE inhibitor impact on COVID be due to something else? In this paper, we discuss the possibility that ACE inhibitors might be affecting COVID-19 patients by causing zinc insufficiency.KEY MESSAGESZinc deficiency caused by chronic ACE inhibitor usage may exacerbate the pathogenicity of COVID-19 in susceptible patients.A multi-center study is needed to assess the zinc levels of patients with COVID-19 who are taking ACE inhibitors and other medications that may result in low zinc levels.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/drug therapy , Zinc/deficiency , Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Drug Interactions , Female , Humans , Male , Nutritional Status/drug effects , Pharmaceutical Preparations , Risk Factors , SARS-CoV-2/genetics , Severity of Illness Index , Zinc/blood
8.
Cardiovasc Hematol Disord Drug Targets ; 20(3): 181-184, 2020.
Article in English | MEDLINE | ID: covidwho-1435708

ABSTRACT

Nowadays Coronavirus Disease 2019 (Covid-19) is increasing mortality all over the world mercilessly. We are learning almost every day about its new symptoms and that it mutates quickly. This disease has tied us up and made us desperate. The death rate from this disease has increased in patients who had pre-existing medical conditions, especially cardiovascular ones, by eliminating the angiotensin-converting enzyme (ACE)-2 receptor in the lungs. Also, ACE1 and angiotensin receptor blockers (ARB) may stimulate ACE2 expression and worse the prognosis. Intravenous infusions of ACEIs and ARBs in experimental animals increase the number of ACE2 receptors. Therefore, it may be one of the reasons that COVID-19 infects the cells of patients treating hypertension. However, most of the congress of cardiology do not recommend to discontinue these anti-hypertensive drugs. Therefore, this brief report evaluates Covid-19 in the view of cardiovascular diseases taking into account current reports and suggests some possible solutions to keep the virus under control.


Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Age Factors , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antihypertensive Agents/therapeutic use , COVID-19/complications , COVID-19/mortality , Cardiovascular Diseases/metabolism , Humans , Hypertension/drug therapy , Pandemics , SARS-CoV-2 , Severity of Illness Index , Thromboembolism/etiology , Thromboembolism/physiopathology
9.
BMJ Open ; 11(9): e053393, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1416682

ABSTRACT

OBJECTIVES: The widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) by patients with chronic conditions raised early concerns on the potential exacerbation of COVID-19 severity and fatality. Previous studies addressing this question have used standard methods that may lead to biased estimates when analysing hospital data because of the presence of competing events and event-related dependency. We investigated the association of ACEIs/ARBs' use with COVID-19 disease outcomes using time-to-event data in a multistate setting to account for competing events and minimise bias. SETTING: Nationwide surveillance data from 119 Belgian hospitals. PARTICIPANTS: Medical records of 10 866 patients hospitalised from 14 March 2020to 14 June 2020 with a confirmed SARS-CoV-19 infection and information about ACEIs/ARBs' use. PRIMARY OUTCOME MEASURE: Multistate, multivariate Cox-Markov models were used to estimate the hazards of patients transitioning through health states from admission to discharge or death, along with transition probabilities calculated by combining the baseline cumulative hazard and regression coefficients. RESULTS: After accounting for potential confounders, there was no discernable association between ACEIs/ARBs' use and transfer to intensive care unit (ICU). Contrastingly, for patients without ICU transfer, ACEIs/ARBs' use was associated with a modest increase in recovery (HR 1.07, 95% CI 1.01 to 1.13, p=0.027) and reduction in fatality (HR 0.83, 95% CI 0.75 to 0.93, p=0.001) transitions. For patients transferred to ICU admission, no evidence of an association between ACEIs/ARBs' use and recovery (HR 1.16, 95% CI 0.97 to 1.38, p=0.098) or in-hospital death (HR 0.91, 95% CI 0.73 to 1.12, p=0.381) was observed. Male gender and older age were significantly associated with higher risk of ICU admission or death. Chronic cardiometabolic comorbidities were also associated with less recovery. CONCLUSIONS: For the first time, a multistate model was used to address magnitude and direction of the association of ACEIs/ARBs' use on COVID-19 progression. By minimising bias, this study provided a robust indication of a protective, although modest, association with recovery and survival.


Subject(s)
COVID-19 , Hypertension , Aged , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Belgium/epidemiology , Hospital Mortality , Hospitals , Humans , Male , SARS-CoV-2
11.
BMJ Open Diabetes Res Care ; 9(1)2021 09.
Article in English | MEDLINE | ID: covidwho-1398617

ABSTRACT

INTRODUCTION: People with type 2 diabetes (T2D) have an increased rate of hospitalization and mortality related to COVID-19. To identify ahead of time those who are at risk of developing severe diseases and potentially in need of intensive care, we investigated the independent associations between longitudinal glycated hemoglobin (HbA1c), the impact of common medications (metformin, insulin, ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and corticosteroids) and COVID-19 severity in people with T2D. RESEARCH DESIGN AND METHODS: Retrospective cohort study was conducted using deidentified claims and electronic health record data from the OptumLabs Data Warehouse across the USA between January 2017 and November 2020, including 16 504 individuals with T2D and COVID-19. A univariate model and a multivariate model were applied to evaluate the association between 2 and 3-year HbA1c average, medication use between COVID-19 diagnosis and intensive care unit admission (if applicable), and risk of intensive care related to COVID-19. RESULTS: With covariates adjusted, the HR of longitudinal HbA1c for risk of intensive care was 1.12 (per 1% increase, p<0.001) and 1.48 (comparing group with poor (HbA1c ≥9%) and adequate glycemic control (HbA1c 6%-9%), p<0.001). The use of corticosteroids and the combined use of insulin and metformin were associated with significant reduction of intensive care risk, while ACEIs and ARBs were not associated with reduced risk of intensive care. CONCLUSIONS: Two to three-year longitudinal glycemic level is independently associated with COVID-19-related severity in people with T2D. Here, we present a potential method to use HbA1c history, which presented a stronger association with COVID-19 severity than single-point HbA1c, to identify in advance those more at risk of intensive care due to COVID-19 in the T2D population. The combined use of metformin and insulin and the use of corticosteroids might be significant to prevent patients with T2D from becoming critically ill from COVID-19.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 Testing , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Humans , Retrospective Studies , SARS-CoV-2
12.
PLoS One ; 16(3): e0248498, 2021.
Article in English | MEDLINE | ID: covidwho-1388907

ABSTRACT

We report onset, course, correlations with comorbidities, and diagnostic accuracy of nasopharyngeal swab in 539 individuals suspected to carry SARS-COV-2 admitted to the hospital of Crema, Italy. All individuals underwent clinical and laboratory exams, SARS-COV-2 reverse transcriptase-polymerase chain reaction on nasopharyngeal swab, and chest X-ray and/or computed tomography (CT). Data on onset, course, comorbidities, number of drugs including angiotensin converting enzyme (ACE) inhibitors and angiotensin-II-receptor antagonists (sartans), follow-up swab, pharmacological treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Among 411 SARS-COV-2 patients (67.7% males) median age was 70.8 years (range 5-99). Chest CT was performed in 317 (77.2%) and showed interstitial pneumonia in 304 (96%). Fatality rate was 17.5% (74% males), with 6.6% in 60-69 years old, 21.1% in 70-79 years old, 38.8% in 80-89 years old, and 83.3% above 90 years. No death occurred below 60 years. Non-invasive respiratory support rate was 27.2% and ICU admission 6.8%. Charlson comorbidity index and high C-reactive protein at admission were significantly associated with death. Use of ACE inhibitors or sartans was not associated with outcomes. Among 128 swab negative patients at admission (63.3% males) median age was 67.7 years (range 1-98). Chest CT was performed in 87 (68%) and showed interstitial pneumonia in 76 (87.3%). Follow-up swab turned positive in 13 of 32 patients. Using chest CT at admission as gold standard on the entire study population of 539 patients, nasopharyngeal swab had 80% accuracy. Comorbidity network analysis revealed a more homogenous distribution 60-40 aged SARS-COV-2 patients across diseases and a crucial different interplay of diseases in the networks of deceased and survived patients. SARS-CoV-2 caused high mortality among patients older than 60 years and correlated with pre-existing multiorgan impairment.


Subject(s)
COVID-19/pathology , Comorbidity , Adolescent , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , C-Reactive Protein/analysis , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Child , Child, Preschool , Female , Hospitalization/statistics & numerical data , Humans , Italy , Male , Middle Aged , Risk Factors , SARS-CoV-2/isolation & purification , Treatment Outcome , Young Adult
17.
Pharmacol Res ; 173: 105848, 2021 11.
Article in English | MEDLINE | ID: covidwho-1373221

ABSTRACT

Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomized clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Health Equity/trends , Pharmacology, Clinical/trends , Randomized Controlled Trials as Topic/methods , Sex Characteristics , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/blood , COVID-19/drug therapy , COVID-19/immunology , Gonadal Steroid Hormones/antagonists & inhibitors , Gonadal Steroid Hormones/blood , Humans , Pharmacology, Clinical/methods , Precision Medicine/methods , Precision Medicine/trends
18.
Zool Res ; 42(5): 633-636, 2021 Sep 18.
Article in English | MEDLINE | ID: covidwho-1369995

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression. In the present study, we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-CoV-2. Results revealed that SARS-CoV-2 replication was delayed in hypertensive mouse lungs. In contrast, SARS-CoV-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-CoV-2-infected normotensive mice. Furthermore, antihypertensive treatment alleviated lung inflammation induced by SARS-CoV-2 replication (interleukin (IL)-1ß up-regulation and increased immune cell infiltration). No differences in lung inflammation were observed between the SARS-CoV-2-infected normotensive mice and hypertensive mice. Our findings suggest that captopril treatment may alleviate COVID-19 progression but not affect viral replication.


Subject(s)
Antihypertensive Agents/therapeutic use , COVID-19/complications , Captopril/therapeutic use , Hypertension/complications , Lung Diseases/drug therapy , SARS-CoV-2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antihypertensive Agents/pharmacology , Captopril/pharmacology , Gene Expression Regulation/drug effects , Inflammation/complications , Inflammation/drug therapy , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Lung Diseases/etiology , Lung Diseases/virology , Mice , Virus Replication/drug effects
19.
Korean J Intern Med ; 36(Suppl 1): S123-S131, 2021 03.
Article in English | MEDLINE | ID: covidwho-1369806

ABSTRACT

BACKGROUND/AIMS: There are concerns that the use of renin-angiotensin system (RAS) blockers may increase the risk of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or progressing to a severe clinical course after infection. This this study aimed to investigate the influence of RAS blockers on the risk and severity of SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study analyzing nationwide claims data of 215,184 adults who underwent SARS-CoV-2 tests in South Korea. The SARS-CoV-2 positive rates and clinical outcomes were evaluated according to the use of RAS blockers in patients with hypertension (n = 64,243). RESULTS: In total, 38,919 patients with hypertension were on RAS blockers. The SARS-CoV-2 positive rates were significantly higher in the RAS blocker group than in the control group after adjustments (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 1.10 to 1.36; p < 0.001), and matching by propensity score (adjusted OR, 1.16; 95% CI, 1.03 to 1.32; p = 0.017). Among the 1,609 SARS-CoV-2-positive patients with hypertension, the use of RAS blockers was not associated with poor outcomes, such as mortality (adjusted OR, 0.81; 95% CI, 0.56 to 1.17; p = 0.265), and a composite of admission to the intensive care unit and mortality (adjusted OR, 0.95; 95% CI, 0.73 to 1.22; p = 0.669). Analysis in the propensity scorematched population showed consistent results. CONCLUSION: In this Korean nationwide claims dataset, the use of RAS blockers was associated with a higher risk to SARS-CoV-2 infection but not with higher mortality or other severe clinical courses.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/therapy , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Administrative Claims, Healthcare , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Databases, Factual , Female , Humans , Hypertension/diagnosis , Hypertension/mortality , Hypertension/physiopathology , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Treatment Outcome
20.
Eur J Clin Invest ; 51(11): e13582, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1365071

ABSTRACT

BACKGROUND: A systematic analysis of concomitant arterial hypertension in COVID-19 patients and the impact of angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID-19 in presence and absence of arterial hypertension. MATERIALS AND METHODS: Out of 5837 COVID-19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all-cause mortality over 40 days of follow-up. RESULTS: Patients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non-invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it. In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality. CONCLUSIONS: The mortality rate and in-hospital complications might be increased in COVID-19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/epidemiology , Heart Failure/epidemiology , Hypertension/epidemiology , Pneumonia/epidemiology , Respiratory Insufficiency/epidemiology , Sepsis/epidemiology , Age Factors , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/metabolism , COVID-19/therapy , Creatinine/metabolism , Female , Germany/epidemiology , Hospital Mortality , Humans , Hypertension/drug therapy , Italy/epidemiology , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Multivariate Analysis , Noninvasive Ventilation , Proportional Hazards Models , Registries , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiology
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