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1.
Trials ; 22(1): 573, 2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1817236

ABSTRACT

BACKGROUND: SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes. METHODS AND DISCUSSION: CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831).


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renin-Angiotensin System , SARS-CoV-2
2.
Tuberk Toraks ; 70(1): 8-14, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1789611

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) and tuberculosis are serious and mortal diseases worldwide. There are few studies about the association between tuberculosis and COVID-19 pneumonia. We aimed to describe the characteristics of tuberculosis and COVID-19 co-infection cases in light of the literature. Materials and Methods: Tuberculosis patients who applied to the tuberculosis outpatient clinic between September 1-September 30, 2020, and patients hospitalized in the COVID-19 service between June 1- September 30, 2020, were retrospectively screened. Patients with tuberculosis and COVID-19 co-infection were recorded. Clinical, radiological, laboratory data, and treatments were recorded and analyzed. For the diagnosis of tuberculosis, sputum acid-resistant bacillus (ARB) smear or culture positivity or pathological diagnosis were used. For the diagnosis of COVID-19, positive real-time reverse transcription-polymerase chain reaction and/or typical radiological findings were sought. Result: Seven hundred and fifty-one patients' data at the tuberculosis outpatient clinic, 229 patients' data at the COVID-19 clinic were screened. Sixteen patients meet the criteria. COVID-19 infection rate in tuberculosis patients was 2.1%. Sixty-nine percent of the patients had received COVID-19 disease during diagnosis or initial tuberculosis treatment phase. There were no drugdrug interactions between anti-tuberculosis drugs and COVID-19 treatment. During the COVID-19 treatment, one patient (6%) died, 15 (94%) patients completed the treatment. Conclusions: : In our study, no effect of the coexistence of TB and COVID-19 on morbidity or mortality was observed. Although the number of patients is small, it can be said that patients with early TB disease and with widespread involvement may be riskier for COVID-19 infection. Frequent hospital visits by TB patients may be a risk for COVID-19. It may be beneficial to carry out the diagnosis and treatment of tuberculosis patients by tuberculosis dispensaries as in our country or authorized units to reduce the risk of hospital admissions and COVID-19 transmission.


Subject(s)
COVID-19 , Pneumonia , Tuberculosis, Pulmonary , Tuberculosis , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Humans , Retrospective Studies , Tuberculosis/complications , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis, Pulmonary/diagnosis , Turkey/epidemiology
3.
BMJ Open ; 12(4): e053961, 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1788959

ABSTRACT

OBJECTIVE: To describe the clinical outcomes of COVID-19 in a racially diverse sample from the US Southeast and examine the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with COVID-19 outcome. DESIGN, SETTING, PARTICIPANTS: This study is a retrospective cohort of 1024 patients with reverse-transcriptase PCR-confirmed COVID-19 infection, admitted to a 1242-bed teaching hospital in Alabama. Data on RAAS inhibitors use, demographics and comorbidities were extracted from hospital medical records. PRIMARY OUTCOMES: In-hospital mortality, a need of intensive care unit, respiratory failure, defined as invasive mechanical ventilation (iMV) and 90-day same-hospital readmissions. RESULTS: Among 1024 patients (mean (SD) age, 57 (18.8) years), 532 (52.0%) were African Americans, 514 (50.2%) male, 493 (48.1%) had hypertension, 365 (36%) were taking RAAS inhibitors. During index hospitalisation (median length of stay of 7 (IQR (4-15) days) 137 (13.4%) patients died; 170 (19.2%) of survivors were readmitted. RAAS inhibitor use was associated with lower in-hospital mortality (adjusted HR, 95% CI (0.56, (0.36 to 0.88), p=0.01) and no effect modification by race was observed (p for interaction=0.81). Among patients with hypertension, baseline RAAS use was associated with reduced risk of iMV, adjusted OR, 95% CI (aOR 0.58, 95% CI 0.36 to 0.95, p=0.03). Patients with heart failure were twice as likely to die from COVID-19, compared with patients without heart failure. CONCLUSIONS: In a retrospespective study of racially diverse patients, hospitalised with COVID-19, prehospitalisation use of RAAS inhibitors was associated with 40% reduction in mortality irrespective of race.


Subject(s)
COVID-19 , Heart Failure , Hypertension , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , Heart Failure/complications , Heart Failure/drug therapy , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/epidemiology , Male , Middle Aged , Renin-Angiotensin System , Retrospective Studies
4.
BMJ Open ; 12(4): e055464, 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1784817

ABSTRACT

OBJECTIVES: To describe public attitudes and knowledge around antibiotic activity, resistance and use. DESIGN: Face-to-face household 18 question survey using computer-assisted data collection undertaken by Ipsos Market and Opinion Research International. SETTING: Randomly selected households across England, January-February 2020. PARTICIPANTS: 2022 adults (aged 15+,) including 521 black, Asian and minority ethnic (BAME) participants, and 406 aged 15-25 years olds. MAIN OUTCOME MEASURES: Responses to questions about antibiotic activity, resistance and expectations for antibiotics and trust in healthcare professionals. Analyses were weighted to obtain estimates representative of the population with multivariable analysis undertaken for questions with five or more significant univariate variables. RESULTS: 84% stated they would be pleased if their general practitioner (GP) said they did not need antibiotics. Trust in GPs to make antibiotic decisions remains high (89%) and has increased for nurses (76%) and pharmacists (71%). Only 21% would challenge an antibiotic decision; this was significantly greater in BAME participants (OR 2.5; 95% CI 1.89 to 3.35). 70% reported receiving advice when prescribed antibiotics. Belief in benefits of antibiotics for ear infections was very high (68%). Similar to 2017, 81% agreed that antibiotics work for bacterial, 28% cold and influenza viruses. 84% agreed antibiotic resistant bacteria (ARB) are increasing, only 50% agreed healthy people can carry ARB and 39% agreed there was nothing they personally could do about ARB. Social grade DE and BAME participants, and those with less education had significantly less understanding about antibiotics and resistance. CONCLUSIONS: As trust in healthcare practitioners is high, we need to continue antibiotic education and other interventions at GP surgeries and community pharmacies but highlight that most ear infections are not benefitted by antibiotics. Targeted interventions are needed for socioeconomic DE, BAME groups and previous antibiotic users. We need to explore if increasing perceived personal responsibility for preventing ARB reduces antibiotic use.


Subject(s)
Angiotensin Receptor Antagonists , Anti-Bacterial Agents , Adolescent , Adult , Angiotensin-Converting Enzyme Inhibitors , Anti-Bacterial Agents/therapeutic use , Health Knowledge, Attitudes, Practice , Humans , Surveys and Questionnaires , Young Adult
5.
Am J Ther ; 29(1): e74-e84, 2020 Dec 28.
Article in English | MEDLINE | ID: covidwho-1778978

ABSTRACT

BACKGROUND: SARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold. AREAS OF UNCERTAINTY: These findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease. DATA SOURCES: We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020. THERAPEUTIC ADVANCES: Ten studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91-1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98-1.10), I2 = 0%. CONCLUSION: Cumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Hospitalization , Humans , SARS-CoV-2
6.
Front Biosci (Landmark Ed) ; 27(2): 48, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1772157

ABSTRACT

BACKGROUND: Thymosin-α1 has been implicated into the treatment of novel respiratory virus Coronavirus Disease 2019 (COVID-19), but the underlying mechanisms are still disputable. AIM: Herein we aimed to reveal a previously unrecognized mechanism that thymosin-α1 prevents COVID-19 by binding with angiotensin-converting enzyme (ACE), which was inspired from the tool of network pharmacology. METHODS: KEGG pathway enrichment of thymosin-α1 treating COVID-19 was analyzed by Database of Functional Annotation Bioinformatics Microarray Analysis, then core targets were validated by ligand binding kinetics assay and fluorometric detection of ACE and ACE2 enzymatic activity. The production of angiotensin I, angiotensin II, angiotensin (1-7) and angiotensin (1-9) were detected by enzyme linked immunosorbent assay. RESULTS: We found that thymosin-α1 impaired the expressions of angiotensin-converting enzyme 2 and angiotensin (1-7) of human lung epithelial cells in a dose-dependent way (p < 0.001). In contrast, thymosin-α1 had no impact on their ACE and angiotensin (1-9) expressions but significantly inhibited the enzymatic activity of ACE (p > 0.05). CONCLUSION: The bioinformatic findings of network pharmacology and the corresponding pharmacological validations have revealed that thymosin-α1 treatment could decrease ACE2 expression in human lung epithelial cells, which strengthens the potential clinical applications of thymosin-α1 to prevent severe acute respiratory syndrome coronavirus 2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , Humans , SARS-CoV-2 , Thymalfasin/pharmacology
7.
BMC Nephrol ; 23(1): 117, 2022 03 24.
Article in English | MEDLINE | ID: covidwho-1770497

ABSTRACT

BACKGROUND: Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. METHODS: We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. RESULTS: In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. CONCLUSIONS: Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.


Subject(s)
COVID-19 , Dipeptidyl-Peptidase IV Inhibitors , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Animals , COVID-19/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Kidney/metabolism , Nephrectomy , Rats , SARS-CoV-2 , Sodium-Glucose Transporter 2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
8.
Chin Med J (Engl) ; 134(13): 1602-1609, 2021 Jun 16.
Article in English | MEDLINE | ID: covidwho-1769421

ABSTRACT

BACKGROUND: Hypertension is considered an important risk factor for the coronavirus disease 2019 (COVID-19). The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system (RAAS) inhibitors, calcium channel blockers (CCBs), and beta-blockers. The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied. METHODS: We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. Clinical and laboratory characteristics were extracted from electronic medical records. Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records. The primary clinical endpoint was all-cause mortality. Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration. Logistic regression was used to explore the risk factors associated with mortality and prognosis. Propensity score matching was used to balance the confounders between different anti-hypertensive treatments. Kaplan-Meier curves were used to compare the cumulative recovery rate. Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups. RESULTS: Among 4569 hospitalized patients with COVID-19, 31.7% (1449/4569) had a history of hypertension. There were significant differences in mortality rates between hypertensive patients with CCBs (7/359) and those without (21/359) (1.95% vs. 5.85%, risk ratio [RR]: 0.32, 95% confidence interval [CI]: 0.13-0.76, χ2 = 7.61, P = 0.0058). After matching for confounders, the mortality rates were similar between the RAAS inhibitor (4/236) and non-RAAS inhibitor (9/236) cohorts (1.69% vs. 3.81%, RR: 0.43, 95% CI: 0.13-1.43, χ2 = 1.98, P = 0.1596). Hypertensive patients with beta-blockers (13/340) showed no statistical difference in mortality compared with those without (11/340) (3.82% vs. 3.24%, RR: 1.19, 95% CI: 0.53-2.69, χ2 = 0.17, P = 0.6777). CONCLUSIONS: In our study, we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension, while CCBs could improve prognosis.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Child , China , Humans , Hypertension/drug therapy , Prognosis , Retrospective Studies , SARS-CoV-2
9.
BMC Cardiovasc Disord ; 22(1): 123, 2022 03 23.
Article in English | MEDLINE | ID: covidwho-1759693

ABSTRACT

BACKGROUND: The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients. METHODS: Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission. RESULTS: A total of 737 patients were included-538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58-0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7-22.8 days) in ICU and 6.7 days (5.9-7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1-18.6 days) and 6.4 days (5.1-7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge. CONCLUSIONS: In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay. Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Cohort Studies , Critical Illness , Hospital Mortality , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Prospective Studies , Renin-Angiotensin System , Retrospective Studies
11.
Int J Mol Sci ; 23(3)2022 Feb 04.
Article in English | MEDLINE | ID: covidwho-1745038

ABSTRACT

This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders.


Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Immunomodulation/drug effects , Animals , Antihypertensive Agents/pharmacology , COVID-19 , Humans
12.
J Cardiovasc Pharmacol ; 79(3): 311-314, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1730738

ABSTRACT

ABSTRACT: Early during the Coronavirus disease 2019 (Covid-19) pandemic, concerns were raised regarding potential adverse outcomes in patients taking angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). These concerns were based on animal studies showing increased ACE-2 expression in mice treated with ACEI/ARB. This is a single-center, retrospective, cohort study of 289 patients diagnosed with 2019 Novel Coronavirus (SARS-CoV-2) hospitalized between March of 2020 and June of 2020. The study was intended to investigate the impact of ACEIs and/or ARBs on in-hospital mortality, intensive care unit (ICU) admission, postadmission hemodialysis requirement, and the need for mechanical ventilation in patients with COVID-19. This cohort of 289 patients included 139 of 289 women (48%) with a mean age of 61 ± 19 years. Patients using ACEIs/ARBs were older (69.68 vs. 57.9 years; P < 0.0001), more likely to have a history of hypertension (97% vs. 36%; P < 0.0001), diabetes mellitus (48% vs. 20.9%; P < 0.0001), chronic heart failure (11.39% vs. 4.29%; P < 0.0512), coronary artery disease (20.25% vs. 7.14%; P < 0.0025), stroke/Transient Ischemic Attack (7.59% vs. 2.38%; P < 0.0761), chronic kidney disease (11.39% vs. 3.33%; P < 0.0167), atrial fibrillation/flutter (18.99% vs. 7.14%; P < 0.0080), and dementia (22.7% vs. 11.4%; P < 0.0233) compared with the nonuser group. There was significantly higher in-hospital mortality in patients using ACEIs/ARBs than nonusers, respectively (32.9% vs. 15.2%; P < 0.0015). However, a multivariate logistics regression analysis performed to adjust for common confounders demonstrated no significant difference in all-cause in-patient mortality (P 0.7141). Admission to ICU, postadmission hemodialysis requirement, and mechanical ventilation showed no significant differences between the 2 groups (P = NS). This study suggests that the use of ACEIs and ARBs in patients with COVID-19 was not found to significantly increase all-cause in-hospital mortality, ICU admissions, and hemodialysis and mechanical ventilation requirements.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Animals , COVID-19/drug therapy , Cohort Studies , Female , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Mice , Renin-Angiotensin System , Retrospective Studies , SARS-CoV-2
13.
Int J Oncol ; 60(4)2022 04.
Article in English | MEDLINE | ID: covidwho-1726131

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is highly infectious and pathogenic. Among patients with severe SARS­CoV­2­caused by corona virus disease 2019 (COVID­19), those complicated with malignant tumor are vulnerable to COVID­19 due to compromised immune function caused by tumor depletion, malnutrition and anti­tumor treatment. Cancer is closely related to the risk of severe illness and mortality in patients with COVID­19. SARS­CoV­2 could promote tumor progression and stimulate metabolism switching in tumor cells to initiate tumor metabolic modes with higher productivity efficiency, such as glycolysis, for facilitating the massive replication of SARS­CoV­2. However, it has been shown that infection with SARS­CoV­2 leads to a delay in tumor progression of patients with natural killer cell (NK cell) lymphoma and Hodgkin's lymphoma, while SARS­CoV­2 elicited anti­tumor immune response may exert a potential oncolytic role in lymphoma patients. The present review briefly summarized potential carcinogenicity and oncolytic characteristics of SARS­CoV­2 as well as strategies to protect patients with cancer during the COVID­19 pandemic.


Subject(s)
COVID-19/complications , Neoplasms/etiology , SARS-CoV-2 , Androgen Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 Vaccines/immunology , Humans , Neoplasms/prevention & control , Neoplasms/therapy , Probiotics/administration & dosage , Tumor Virus Infections/complications
15.
Dtsch Med Wochenschr ; 145(10): 682-686, 2020 05.
Article in German | MEDLINE | ID: covidwho-1721664

ABSTRACT

Twenty years ago, an enzyme homologous to the previously known angiotensin-converting enzyme (ACE) was identified, and subsequently named ACE2. In the renin-angiotensin system (RAS), ACE2 has counter-regulatory functions against the classical effector peptide angiotensin II, for example in blood pressure regulation and cardiovascular remodeling. However, ACE2 provides an initially unexpected interesting link between virology and cardiovascular medicine. That is, ACE2 represents the binding receptor for the cellular uptake of SARS-CoV and SARS-CoV-2 viruses. Thus, ACE2 is relevant for COVID-19. In this context, it was suspected that therapy with RAS blockers might promote transmission and complications of COVID-19 by upregulation of ACE2 expression. The aim of this short review is, to describe the link between the RAS, particularly ACE2, and COVID-19. Based on our analysis and evaluation of the available findings, we justify our conclusion: important drugs such as ACE inhibitors and angiotensin receptor blockers should continue to be prescribed according to guidelines to stable patients in the context of the COVID-19 pandemic.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Coronavirus Infections/drug therapy , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/drug therapy , Renin-Angiotensin System/physiology , Angiotensin-Converting Enzyme 2 , Betacoronavirus , COVID-19 , Coronavirus Infections/physiopathology , Humans , Pandemics , Pneumonia, Viral/physiopathology , Receptors, Virus/antagonists & inhibitors , Receptors, Virus/physiology , SARS-CoV-2
16.
Clin Infect Dis ; 72(6): 1105-1107, 2021 03 15.
Article in English | MEDLINE | ID: covidwho-1722226
17.
Eur J Clin Microbiol Infect Dis ; 39(6): 1021-1026, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1718753

ABSTRACT

Since December 2019, the infection of the new coronavirus (COVID-19) caused an outbreak of new coronavirus pneumonia in Wuhan, China, and caused great public concern. Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. In addition, ACE2 is a potential therapeutic target. This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Betacoronavirus/metabolism , Coronavirus Infections , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral , Pneumonia , SARS Virus/metabolism , Severe Acute Respiratory Syndrome , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Humans , Pneumonia/etiology , Pneumonia/therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/drug therapy
18.
Adv Exp Med Biol ; 1327: 205-214, 2021.
Article in English | MEDLINE | ID: covidwho-1718516

ABSTRACT

The exaggerated host response to Sars-CoV-2 plays an important role in COVID-19 pathology but provides a therapeutic opportunity until definitive virus targeted therapies and vaccines become available. Given a central role of endothelial dysfunction and systemic inflammation, repurposing ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, and aspirin has been of interest. In this retrospective, single-center study, we evaluated the primary outcomes of mortality and ICU admission in 587 hospitalized patients with documented COVID-19 with or without ACEIs, ARBs, statins, and aspirin. Atorvastatin was associated with reduced mortality, which persisted after adjusting for age, lockdown status, and other medications (OR: 0.18. 95% CI: 0.06-0.49, P = 0.001). ACEIs were also associated with reduced mortality in the crude model (OR: 0.20, CI: 0.06-0.66, P = 0.008), as ACEIs and ARBs were combined as a single group (OR: 0.35, CI: 0.16-0.75, P = 0.007), although ARBs alone did not reach statistical significance. There was no association between any medications and risk of ICU admission. Aspirin only achieved a significant association of reduced mortality in a subgroup of patients with diabetes in the crude model (OR: 0.17, CI: 0.04-0.80, P = 0.02). The reduced mortality observed with atorvastatin is consistent with other literature, and consideration should be given to atorvastatin as a COVID-19 treatment. While there was suggested benefit of ACEIs and ARBs in the present study, other studies are varied and further studies are warranted to recommend employing these medications as a treatment strategy. Nevertheless, this study combined with others continues to give credibility that ACEIs and ARBs are safe to continue in the setting of COVID-19.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypertension , Aldosterone , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensins , Aspirin/therapeutic use , COVID-19/drug therapy , Communicable Disease Control , Hospitals , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intensive Care Units , Renin , Retrospective Studies , SARS-CoV-2
19.
High Blood Press Cardiovasc Prev ; 29(2): 115-123, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1706541

ABSTRACT

Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a real challenge for health-care systems worldwide. Male sex, older age and the coexistence of chronic comorbidities have been described as the most relevant conditions associated with a worse prognosis. Early reports suggested that hypertension might represent a risk factor for susceptibility to SARS-CoV-2 infection, a more severe course of COVID-19 and increased COVID-19-related deaths. Nevertheless, the independent role of hypertension remains under debate, since hypertension is often associated with the older age and other cardiovascular (CV) risk factors in the general population, which may also contribute to the SARS-Cov-2 infection and COVID-19. Moreover, the role of antihypertensive drugs, primarily angiotensin-converting inhibitors (ACEIs) and ARBs (angiotensin receptor blockers) in COVID-19 development and outcome appears controversial. Indeed, preclinical studies using these classes of drugs have suggested a potential upregulation of angiotensin-converting-enzyme 2 (ACE2) which is the key binding receptor promoting cell entry of SARS-CoV-2 in the organism. Renin-angiotensin system (RAS) blockers may potentially upregulate ACE2, hence, it has been initially hypothesized that these agents might contribute to a higher risk of SARS-CoV-2 infection and progressive course of COVID-19. However, several clinical reports do not support a detrimental role of RAS blockers in COVID-19, and an intense debate about the withdrawal or maintenance of chronic therapy with ACEi/ARB has been developed. In this review we will discuss the available evidence on the role of hypertension and antihypertensive drugs on SARS-CoV-2 infection and COVID-19 development.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Male , Renin-Angiotensin System , SARS-CoV-2
20.
Am J Cardiol ; 167: 133-138, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1702670

ABSTRACT

Antecedent use of renin-angiotensin system inhibitors (RASi) prevents clinical deterioration and protects against cardiovascular/thrombotic complications of COVID-19, for indicated patients. Uncertainty exists regarding treatment continuation throughout infection and doing so with concomitant medications. Hence, the purpose of this study is to evaluate the differential effect of RASi continuation in patients hospitalized with COVID-19 according to diuretic use. We used the Coracle registry, which contains data of hospitalized patients with COVID-19 from 4 regions of Italy. We used Firth logistic regression for adult (>50 years) cases with admission on/after February 22, 2020, with a known discharge status as of April 1, 2020. There were 286 patients in this analysis; 100 patients (35.0%) continued RASi and 186 (65%) discontinued. There were 98 patients treated with a diuretic; 51 (52%) of those continued RASi. The in-hospital mortality rates in patients treated with a diuretic and continued versus discontinued RASi were 8% versus 26% (p = 0.0179). There were 188 patients not treated with a diuretic; 49 (26%) of those continued RASi. The in-hospital mortality rates in patients not treated with a diuretic and continued versus discontinued RASi were 16% versus 9% (p = 0.1827). After accounting for age, cardiovascular disease, and laboratory values, continuing RASi decreased the risk of mortality by approximately 77% (odds ratio 0.23, 95% confidence interval 0.06 to 0.95, p = 0.0419) for patients treated with diuretics, but did not alter the risk in patients treated with RASi alone. Continuing RASi in patients concomitantly treated with diuretics was associated with reduced in-hospital mortality.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/therapy , Cardiovascular Diseases/drug therapy , Deprescriptions , Hospital Mortality , Sodium Chloride Symporter Inhibitors/therapeutic use , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Aged , Aged, 80 and over , COVID-19/mortality , Drug Therapy, Combination , Female , Hospitalization , Humans , Italy , Logistic Models , Male , Middle Aged , Registries , Renin-Angiotensin System , SARS-CoV-2
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