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1.
Hypertension ; 79(11): 2601-2610, 2022 11.
Article in English | MEDLINE | ID: covidwho-2020594

ABSTRACT

BACKGROUND: Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19. METHODS: We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed. RESULTS: The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2-0.3]; P<0.001) compared to nontreated hypertensives (n=1305). CONCLUSIONS: Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure-lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic.


Subject(s)
COVID-19 , Cardiovascular Diseases , Hypertension , Humans , Male , Female , Middle Aged , Aged , Antihypertensive Agents/therapeutic use , COVID-19/complications , Pandemics , Hospital Mortality , Hypertension/complications , Hypertension/drug therapy , Hypertension/chemically induced , Calcium Channel Blockers/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Thiazides/therapeutic use , Cardiovascular Diseases/epidemiology , Hospitalization
2.
J Med Virol ; 94(10): 4727-4734, 2022 10.
Article in English | MEDLINE | ID: covidwho-1905892

ABSTRACT

Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)-19 infection. Patients with hypertension may receive both anti-COVID-19 and antihypertension therapies when infected with COVID-19. However, it is not clear how different classes of anti-hypertension drugs impact the outcome of COVID-19 treatment. Herein, we explore the association between the inpatient use of different classes of anti-hypertension drugs and mortality among patients with hypertension hospitalized with COVID-19. We totally collected data from 278 patients with hypertension diagnosed with COVID-19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single-cell RNA-sequencing (RNA-Seq) analysis of treatment-related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin-converting enzyme inhibitor/ß-block/diuretic drugs did not affect the mortality caused by COVID-19. Based on the analysis of four public data sets of single-cell RNA-Seq on COVID-19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID-19-related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID-19-related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID-19.


Subject(s)
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Calcium Channel Blockers/therapeutic use , Computational Biology , Humans , Hypertension/complications , Hypertension/drug therapy , Retrospective Studies , SARS-CoV-2
3.
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
5.
Br J Clin Pharmacol ; 88(6): 2830-2842, 2022 06.
Article in English | MEDLINE | ID: covidwho-1583679

ABSTRACT

AIMS: With growing evidence on the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19), we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. METHODS: We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank with data from the first 2 SARS-CoV-2 waves prior population-based vaccination. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. RESULTS: The use of either ß-blockers (BBs), calcium-channel blockers (CCBs) or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR (95%CI): 1.66 [1.43-1.93]) and ARB use (1.53 [1.30-1.81]). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (1.74 [1.30-2.33]) but not when compared to ARB users (1.26 [0.93-1.71]). The association between BB, CCB or diuretic use (compared to ACEI use) and 28-day mortality among hospitalized Covid-19 patients narrowly missed statistical significance (1.47 [0.99-2.18]) but it was statistically significant when the analysis was restricted to patients hospitalized during the second SARS-CoV-2 wave (1.80 [1.15-2.83]). CONCLUSION: Our results suggest protective effects of inhibition of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality, particularly with ACEI, among patients with pharmaceutically treated hypertension. If confirmed by randomized controlled trials, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.


Subject(s)
COVID-19 , Hypertension , Adrenergic beta-Antagonists/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Biological Specimen Banks , COVID-19/drug therapy , Calcium Channel Blockers/therapeutic use , Diuretics/therapeutic use , Hospitalization , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/epidemiology , Renin-Angiotensin System , Retrospective Studies , SARS-CoV-2 , United Kingdom/epidemiology
7.
BMJ ; 375: n2938, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1537932

Subject(s)
Adrenergic beta-Antagonists/adverse effects , Blood Pressure/drug effects , Diabetes Mellitus/prevention & control , Hypertension/drug therapy , Thiazides/adverse effects , Adrenergic beta-Antagonists/therapeutic use , Aminobutyrates/pharmacology , Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Biphenyl Compounds/pharmacology , Biphenyl Compounds/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , COVID-19/virology , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/therapeutic use , Cats , Diabetes Mellitus/etiology , Diabetes Mellitus, Type 2/drug therapy , Dogs , Drug Combinations , Gastric Inhibitory Polypeptide/adverse effects , Gastric Inhibitory Polypeptide/pharmacology , Gastric Inhibitory Polypeptide/therapeutic use , Heart Sounds/physiology , History, 20th Century , Humans , Hypertension/complications , Immunization, Passive/methods , Immunization, Passive/statistics & numerical data , Incretins/adverse effects , Incretins/pharmacology , Incretins/therapeutic use , Insulin Glargine/adverse effects , Insulin Glargine/history , Insulin Glargine/pharmacology , Insulin Glargine/therapeutic use , Meta-Analysis as Topic , Randomized Controlled Trials as Topic , SARS-CoV-2/genetics , Thiazides/therapeutic use , Valsartan/pharmacology , Valsartan/therapeutic use
8.
Hypertens Res ; 45(2): 360-363, 2022 02.
Article in English | MEDLINE | ID: covidwho-1510590

ABSTRACT

We aimed to perform a systematic review and meta-analysis to determine the overall effect of the preadmission/prediagnosis use of calcium channel blockers (CCBs) on the clinical outcomes in hypertensive patients with COVID-19. A systematic literature search with no language restriction was conducted in electronic databases in July 2021 to identify eligible studies. A random-effects model was used to estimate the pooled summary measure for outcomes of interest with the preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs at 95% confidence intervals (CIs). The meta-analysis revealed a significant reduction in the odds of all-cause mortality with the preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs (pooled OR = 0.65; 95% CI 0.49-0.86) and a significant reduction in the odds of severe illness with preadmission/prediagnosis use of CCBs relative to the nonuse of CCBs (pooled OR = 0.61; 95% CI 0.44-0.84), and is associated with adequate evidence to reject the model hypothesis of 'no significant difference' at the current sample size. The potential protective effects offered by CCBs in hypertensive patients with COVID-19 merit large-scale prospective investigations.


Subject(s)
COVID-19 , Hypertension , Calcium Channel Blockers/therapeutic use , Humans , Hypertension/drug therapy , Prospective Studies , SARS-CoV-2
9.
Free Radic Biol Med ; 177: 189-200, 2021 12.
Article in English | MEDLINE | ID: covidwho-1466351

ABSTRACT

As hypoxia is a major driver for the pathophysiology of COVID-19, it is crucial to characterize the hypoxic response at the cellular and molecular levels. In order to augment drug repurposing with the identification of appropriate molecular targets, investigations on therapeutics preventing hypoxic cell damage is required. In this work, we propose a hypoxia model based on alveolar lung epithelial cells line using chemical inducer, CoCl2 that can be used for testing calcium channel blockers (CCBs). Since recent studies suggested that CCBs may reduce the infectivity of SARS-Cov-2, we specifically select FDA approved calcium channel blocker, nifedipine for the study. First, we examined hypoxia-induced cell morphology and found a significant increase in cytosolic calcium levels, mitochondrial calcium overload as well as ROS production in hypoxic A549 cells. Secondly, we demonstrate the protective behaviour of nifedipine for cells that are already subjected to hypoxia through measurement of cell viability as well as 4D imaging of cellular morphology and nuclear condensation. Thirdly, we show that the protective effect of nifedipine is achieved through the reduction of cytosolic calcium, mitochondrial calcium, and ROS generation. Overall, we outline a framework for quantitative analysis of mitochondrial calcium and ROS using 3D imaging in laser scanning confocal microscopy and the open-source image analysis platform ImageJ. The proposed pipeline was used to visualize mitochondrial calcium and ROS level in individual cells that provide an understanding of molecular targets. Our findings suggest that the therapeutic value of nifedipine may potentially be evaluated in the context of COVID-19 therapeutic trials.


Subject(s)
COVID-19 , Nifedipine , A549 Cells , Calcium , Calcium Channel Blockers/pharmacology , Calcium Channel Blockers/therapeutic use , Cell Death , Humans , Hypoxia/drug therapy , Nifedipine/pharmacology , SARS-CoV-2 , Superoxides
10.
Curr Neurovasc Res ; 18(1): 162-168, 2021.
Article in English | MEDLINE | ID: covidwho-1374189

ABSTRACT

BACKGROUND: Robust evidence has described that Parkinson´s disease (PD) is associated with an increased risk for developing epileptic seizures. In fact, an interplay between PD and epilepsy has been of interest for many years. An emerging hypothesis is that inflammation could link both diseases. OBJECTIVE: Bearing in mind the experience of our group in the field of Ca2+/cAMP signalling pathways, this article discussed, beyond inflammation, the role of these signalling pathways in this link between PD and epilepsy. METHODS: Publications involving Ca2+/cAMP signalling pathways, PD, and epilepsy (alone or combined) were collected by searching PubMed and EMBASE. RESULTS: The comprehension of the interplay between PD and epilepsy could improve the drug therapy. In addition, a Ca2+ signalling dyshomeostasis due to Coronavirus disease 2019 (COVID-19), an emerging and rapidly evolving situation, has been reported. CONCLUSION: Thus, this article also debated recent findings about therapeutics involving Ca2+ channel blockers for preventing Ca2+ signalling dyshomeostasis due to COVID-19, including the correlation among COVID-19, epilepsy, and PD.


Subject(s)
Calcium Signaling , Cyclic AMP , Epilepsy/complications , Inflammation/complications , Parkinson Disease/complications , Signal Transduction , COVID-19/complications , Calcium Channel Blockers/therapeutic use , Epilepsy/physiopathology , Humans , Inflammation/physiopathology , Parkinson Disease/physiopathology
11.
J Am Heart Assoc ; 10(15): e021154, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1331849

ABSTRACT

Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin-angiotensin aldosterone system (RAAS) inhibitor use and COVID-19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID-19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine-learning-derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID-19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74-1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID-19 (HR, 0.92; 95% CI, 0.70-1.22), and 64 died with COVID-19 (HR, 1.22; 95% CI, 0.68-2.19). The severity of COVID-19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89-1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID-19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID-19 pandemic.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Hypertension/drug therapy , Risk Assessment , Aged , Antihypertensive Agents/classification , Antihypertensive Agents/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Calcium Channel Blockers/therapeutic use , Female , Humans , Hypertension/epidemiology , Hypertension/prevention & control , Male , Middle Aged , Outcome Assessment, Health Care , Renin-Angiotensin System/drug effects , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sodium Chloride Symporter Inhibitors/therapeutic use , Sweden/epidemiology
12.
Am Heart J ; 240: 46-57, 2021 10.
Article in English | MEDLINE | ID: covidwho-1316364

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are known to impact the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The association between chronic therapy with these medications and infection risk remains unclear. OBJECTIVES: The objective was to determine the association between prior ACEI or ARB therapy and SARS-CoV-2 infection among patients with hypertension in the U.S. Veteran's Affairs health system. METHODS: We compared the odds of SARS-CoV-2 infection among three groups: patients treated with ACEI, treated with ARB, or treated with alternate first-line anti-hypertensives without ACEI/ARB. We excluded patients with alternate indications for ACEI or ARB therapy. We performed an augmented inverse propensity weighted analysis with adjustment for demographics, region, comorbidities, vitals, and laboratory values. RESULTS: Among 1,724,723 patients with treated hypertension, 659,180 were treated with ACEI, 310,651 with ARB, and 754,892 with neither. Before weighting, patients treated with ACEI or ARB were more likely to be diabetic and use more anti-hypertensives. There were 13,278 SARS-CoV-2 infections (0.8%) between February 12, 2020 and August 19, 2020. Patients treated with ACEI had lower odds of SARS-CoV-2 infection (odds ratio [OR] 0.93; 95% CI: 0.89-0.97) while those treated with ARB had similar odds (OR 1.02; 95% CI: 0.96-1.07) compared with patients treated with alternate first-line anti-hypertensives without ACEI/ARB. In falsification analyses, patients on ACEI did not have a difference in their odds of unrelated outcomes. CONCLUSIONS: Our results suggest the safety of continuing ACEI and ARB therapy. The association between ACEI therapy and lower odds of SARS-CoV-2 infection requires further investigation.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/epidemiology , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Adrenergic beta-Antagonists/therapeutic use , Aged , Angiotensin II Type 2 Receptor Blockers , Calcium Channel Blockers/therapeutic use , Case-Control Studies , Comorbidity , Confidence Intervals , Diabetes Mellitus/epidemiology , Female , Humans , Male , Middle Aged , Odds Ratio , Propensity Score , Receptors, Virus , SARS-CoV-2 , Sodium Chloride Symporter Inhibitors/therapeutic use , United States/epidemiology , United States Department of Veterans Affairs , Veterans/statistics & numerical data
13.
Diabetes Metab Syndr ; 15(5): 102210, 2021.
Article in English | MEDLINE | ID: covidwho-1313054

ABSTRACT

AIMS: This meta-analysis aims to analyze the association of calcium channel blocker (CCB) use with COVID-19 clinical outcomes. METHODS: PubMed, ProQuest, Science Direct, Scopus, and medRxiv databases were searched systematically in a limited period. The primary outcome was mortality. RESULTS: A total of 119,298 patients from 31 eligible studies were included. Pooled analysis of the random-effect model revealed CCB was not associated with reduced mortality (OR = 1.21 [95%CI: 0.98-1.49], p = 0.08). Interestingly, subgroup analysis in hypertensive patients revealed significantly reduced mortality (OR = 0.69 [95%CI: 0.52-0.91], p = 0.009). CONCLUSION: CCB usage was not associated with the outcome of COVID-19. However, CCB was associated with a decreased mortality rate in hypertensive COVID-19 patients.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Calcium Channel Blockers/therapeutic use , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , Female , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/mortality , Male , Middle Aged , Mortality , Prognosis , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Severity of Illness Index , Treatment Outcome , Virus Internalization/drug effects
14.
Front Immunol ; 12: 686699, 2021.
Article in English | MEDLINE | ID: covidwho-1311375

ABSTRACT

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. The acute phase of the infection may in certain individuals be followed by another longer phase of disease (long COVID) of unknown etiology probably associated in certain cases with autoimmune activation. It has been shown that COVID-19 can trigger autoantibody production and in genetically predisposed patients may cause the onset or exacerbation of autoimmune diseases. We are reporting a case of mild COVID-19 infection complicated by autoantibody production and cutaneous and gastrointestinal symptoms and subsequently diagnosed with systemic sclerosis (SSc). A 47-year-old man with no history of any autoimmune diseases and in good health became sick together with his family on the 12th of November with mild symptoms: tiredness, fever, cough, and sore throat. Oropharyngeal swab for SARS-CoV-2 tested positive. He was isolated at home and did not require hospitalization. Three weeks later he presented with clinical manifestation compatible with suspicion of SSc. He briefly presented with skin rush, periorbital edema and conjunctivitis, vomiting, dysphagia, burning sensation in the skin, above all in the fingertips and around the mouth, puffy fingers, Raynaud's phenomenon, pain at the fingertip of the middle finger where a depressed area was noticed without a clear ulceration. ANA showed a strongly positive nucleolar pattern. Anti-PM/Scl 75 and PM/Scl 100 resulted positive. High-resolution computed tomography (HCRT) showed early stage of interstitial lung disease (ILD). The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical and radiological pictures according to the ACR/EULAR classification (scores: puffy finger, 2; ILD, 2; Raynaud's phenomenon, 3; SSc related antibodies, 3; total 10). There are several cases described in the medical literature of possible new onset of SLE after COVID-19 infection. This is the first case that describes a possible new onset of SSc. Conclusion: SARS-CoV-2 may trigger systemic sclerosis.


Subject(s)
Autoimmune Diseases/etiology , Autoimmunity , COVID-19/complications , SARS-CoV-2/genetics , Scleroderma, Systemic/etiology , Autoantibodies/immunology , COVID-19/immunology , COVID-19/virology , Calcium Channel Blockers/therapeutic use , Follow-Up Studies , Humans , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/etiology , Male , Middle Aged , Proton Pump Inhibitors/therapeutic use , Raynaud Disease/diagnosis , Raynaud Disease/etiology , Scleroderma, Systemic/drug therapy , Tomography, X-Ray Computed , Treatment Outcome
15.
Yonsei Med J ; 62(7): 577-583, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1285267

ABSTRACT

PURPOSE: We aimed to investigate whether the use of cardiovascular drugs in coronavirus disease 2019 (COVID-19) patients with hypertension as a comorbidity has a significant effect on the incidence and associated mortality rate of COVID-19. MATERIALS AND METHODS: Data covering the period between January 1, 2020 and June 4, 2020 were extracted from The National Health Insurance Service-COVID-19 (NHIS-COVID-19) database in South Korea and analyzed as a population-based cohort study. RESULTS: A total of 101657 hypertensive adults aged 20 years or older were included for final analysis. Among them, 1889 patients (1.9%) were diagnosed with COVID-19 between January 1, 2020 and June 4, 2020, and hospital mortality occurred in 193 patients (10.2%). In a multivariable model, the use of beta-blockers was associated with an 18% lower incidence of COVID-19 [odds ratio (OR): 0.82, 95% confidence interval (CI): 0.69-0.98; p=0.029]. Among 1889 hypertensive patients diagnosed with COVID-19, the use of a calcium channel blocker (CCB) was associated with a 42% lower hospital mortality rate (OR: 0.58, 95% CI: 0.38-0.89; p=0.012). The use of other cardiovascular drugs was not associated with the incidence of COVID-19 or hospital mortality rate among COVID-19 patients. Similar results were observed in all 328374 adults in the NHIS-COVID-19 database, irrespective of the presence of hypertension. CONCLUSION: In South Korea, beta-blockers exhibited potential benefits in lowering the incidence of COVID-19 among hypertensive patients. Furthermore, CCBs may lower the hospital mortality rate among hypertensive COVID-19 patients. These findings were also applied to the general adult population, regardless of hypertension.


Subject(s)
COVID-19 , Hypertension , Adult , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Cohort Studies , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/epidemiology , Incidence , Republic of Korea/epidemiology , SARS-CoV-2
16.
BMC Infect Dis ; 21(1): 527, 2021 Jun 05.
Article in English | MEDLINE | ID: covidwho-1251747

ABSTRACT

BACKGROUND: Reports on the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. METHODS: We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). RESULTS: A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. CONCLUSIONS: RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Hypertension/drug therapy , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/therapeutic use , Comorbidity , Humans , Hypertension/complications , Odds Ratio , Renin-Angiotensin System/drug effects , Risk Factors , Severity of Illness Index , Treatment Outcome
17.
Cells ; 10(5)2021 05 07.
Article in English | MEDLINE | ID: covidwho-1223961

ABSTRACT

The flavonoid naringenin (Nar), present in citrus fruits and tomatoes, has been identified as a blocker of an emerging class of human intracellular channels, namely the two-pore channel (TPC) family, whose role has been established in several diseases. Indeed, Nar was shown to be effective against neoangiogenesis, a process essential for solid tumor progression, by specifically impairing TPC activity. The goal of the present review is to illustrate the rationale that links TPC channels to the mechanism of coronavirus infection, and how their inhibition by Nar could be an efficient pharmacological strategy to fight the current pandemic plague COVID-19.


Subject(s)
COVID-19/drug therapy , Calcium Channel Blockers/pharmacology , Calcium Channels/metabolism , Flavanones/pharmacology , Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Arabidopsis/metabolism , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Calcium Channel Blockers/therapeutic use , Drug Evaluation, Preclinical , Endosomes/drug effects , Endosomes/metabolism , Endosomes/virology , Flavanones/therapeutic use , Humans , Lysosomes/drug effects , Lysosomes/metabolism , Lysosomes/virology , Neoplasms/blood supply , Neoplasms/pathology , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Pandemics/prevention & control , SARS-CoV-2/pathogenicity , Vacuoles/metabolism , Virus Internalization/drug effects
18.
J Med Virol ; 93(2): 854-862, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196405

ABSTRACT

To evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) vs calcium channel blockers (CCBs) on the progression of Corona Virus Disease 2019 (COVID-19) patients with hypertension in Wuhan. This retrospective single-center case series analyzed COVID-19 patients with hypertension, treated with ACEIs/ARBs or CCBs at the Tongji Hospital of Wuhan City, China from 25th January to 15th March 2020. After propensity score matching analysis, 76 patients were selected into two groups. Univariate and multivariable analyses were conducted to determine factors related to improvement measures and outcome measures by Cox proportional hazard regression models. Among 157 patients with confirmed COVID-19 combined hypertension, including 73 males and 84 females, a median age of 67.28 ± 9.11 vs 65.39 ± 10.85 years. A univariable analysis indicated that clinical classification, lymphocyte count, and interleukin-2 receptor were associated with a lengthened negative time of nucleic acid, with a significant difference between two groups (P = .036). Furthermore, we found no obvious difference in nucleic acid conversion time between ACEIs/ARBs and CCBs groups (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: [0.97, 3.38]; P = .18) in the multivariable analysis as well as chest computed tomography improved time (HR: 0.73; 95% CI [0.45, 1.2]; P = .87), and hospitalization time between ACEIs/ARBs and CCBs groups (HR: 1.06; 95% CI [0.44, 1.1]; P = .83). Our study provided additional evidence of no obvious difference in progress and prognosis between ACEIs/ACEIs and CCBs group, which may suggest ACEIs/ARBs may have scarcely influence on increasing the clinical severe situations of COVID-19 patients with hypertension.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , Calcium Channel Blockers/therapeutic use , Hypertension/epidemiology , Aged , COVID-19/epidemiology , China , Disease Progression , Female , Hospitalization/statistics & numerical data , Humans , Hypertension/virology , Male , Middle Aged , Propensity Score , Proportional Hazards Models , Retrospective Studies
19.
Eur Rev Med Pharmacol Sci ; 25(7): 3136-3144, 2021 04.
Article in English | MEDLINE | ID: covidwho-1194855

ABSTRACT

OBJECTIVE: Disruption of intracellular Ca2+ homeostasis via excessive and pathological Ca2+ release from the endoplasmic reticulum (ER) and/or sarcoplasmic reticulum (SR) through ryanodine receptor (RyRs) Ca2+ channels play a critical role in the pathology of systemic inflammatory response syndrome (SIRS) and associated multiple organ dysfunction syndrome (MODS) in sepsis or septic shock. Dantrolene, a potent inhibitor of RyRs, is expected to ameliorate SIRS and MODS and decrease mortality in sepsis or septic shock patients. This review summarized the potential mechanisms of therapeutic effects of dantrolene in sepsis or septic shock at molecular, cell, and organ levels and provided suggestions and strategies for future clinical studies.


Subject(s)
COVID-19/drug therapy , Calcium Channel Blockers/therapeutic use , Dantrolene/therapeutic use , Sepsis/drug therapy , COVID-19/metabolism , Calcium/metabolism , Drug Repositioning , Endoplasmic Reticulum/metabolism , Humans , Mortality , Multiple Organ Failure , Ryanodine Receptor Calcium Release Channel/metabolism , SARS-CoV-2 , Sarcoplasmic Reticulum/metabolism , Sepsis/metabolism , Shock, Septic/drug therapy , Shock, Septic/metabolism
20.
Am J Nephrol ; 52(3): 250-260, 2021.
Article in English | MEDLINE | ID: covidwho-1171574

ABSTRACT

INTRODUCTION: Use of certain antihypertensive medications has been an area of interest during the COVID-19 pandemic, and several hypotheses have been developed regarding the effects of renin-angiotensin system blockers as well as calcium channel blockers in those infected with COVID-19. We seek to determine the association between exposure to ACEI, ARB, and CCB and outcomes in those admitted to the hospital with COVID-19 infection. METHODS: This retrospective cohort study included 841 adult patients hospitalized with COVID-19 infection at the University of Chicago Medical Center between March 25 and June 22, 2020. Out of these 841, 453 patients had a personal history of hypertension. For the first part, we evaluated primary outcomes of in-hospital mortality and ICU admission in hospitalized COVID-19 patients based on their exposure to particular medications regardless of a personal history of hypertension and compared them with those who were not on these medications. For the second part, we evaluated the aforementioned outcomes in 453 patients with a personal history of hypertension based on their medication exposure. Secondary outcomes of length of stay, readmission rate, and new-onset dialysis requirement were also compared across the study groups. RESULTS: Out of 841 patients, 111 (13.19%) were on ACEI/ARB (median age: 66.1, SD 15.4; 52.25% females) and 730 (86.80%) were not on them (median age: 56.6, SD 20.3; 50.14% females), while 277 (32.93%) used CCB (median age: 64.6, SD 15.2; 57.04% females) and 564 (67.06%) did not use CCB (median age: 54.6, SD 21.2; 47.16% females). After adjusting for demographics and covariates, neither ACEI/ARB nor CCB exposure was associated with any effect on mortality, but ACEI/ARB exposure was associated with 42% reduction in risk of ICU admissions (OR 0.58, 95% CI [0.35, 0.95], p value 0.03). In addition, combined use of ACEI/ARB and CCB was associated with statistically significant (45%) reduction in ICU admission (OR 0.55, 95% CI [0.32, 0.94], p value 0.029). Out of 453 patients with a personal history of hypertension, 85 (18.76%) were taking ACEI/ARB (median age 65, SD 15.6; 56.47% females) and 368 (81.24%) were not on ACEI/ARB (median age 62.8, SD 16.4; 54.89% females), while 208 (45.92%) out of 453 were on CCB (median age 65; SD 14.8; 60.1% females) and 245 (54.08%) were not on CCB (median age 61.7, SD 17.3; 51.02% females). In the fully adjusted model in this group, ACEI use was associated with 71% reduction in in-house mortality (OR 0.29, 95% CI [0.09, 0.93], p value 0.03). DISCUSSION/CONCLUSION: Among all hospitalized patients with COVID-19 infection, exposure to ACEI/ARB, as well as combined exposure to ACEI/ARB and CCB, were associated with reduced incidence of ICU admissions. In those admitted patients who had a personal history of hypertension, there was a trend towards reduced in-hospital mortality in those exposed to ACEI.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/mortality , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Aged , COVID-19/complications , COVID-19/drug therapy , COVID-19/ethnology , Chicago/epidemiology , Female , Humans , Hypertension/complications , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Retrospective Studies
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