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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Chin Med J (Engl) ; 134(13): 1602-1609, 2021 Jun 16.
Article in English | MEDLINE | ID: covidwho-1270760

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
8.
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
9.
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
10.
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
11.
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
12.
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
13.
BMC Infect Dis ; 21(1): 262, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1136209

ABSTRACT

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/complications , Calcium Channel Blockers/therapeutic use , Hypertension/complications , Hypertension/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/mortality , Calcium Channel Blockers/adverse effects , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Mortality , Propensity Score , Proportional Hazards Models , Renin-Angiotensin System , United Kingdom , Young Adult
15.
Drug Saf ; 43(12): 1297-1308, 2020 12.
Article in English | MEDLINE | ID: covidwho-1092868

ABSTRACT

INTRODUCTION: The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. OBJECTIVE: The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. METHODS: This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. RESULTS: Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89-1.06) or ARB (HR 0.98, 95% CI 0.89-1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. CONCLUSIONS: ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/mortality , Hospitalization , Renin-Angiotensin System , Adolescent , Adult , Aged , Aged, 80 and over , Calcium Channel Blockers/therapeutic use , Case-Control Studies , Cohort Studies , Female , Humans , Intensive Care Units , Italy , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Young Adult
16.
Trials ; 22(1): 60, 2021 Jan 18.
Article in English | MEDLINE | ID: covidwho-1067261

ABSTRACT

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/drug therapy , Calcium Channel Blockers/therapeutic use , Magnesium Sulfate/therapeutic use , Administration, Inhalation , Blood Gas Analysis , Bronchodilator Agents , COVID-19/physiopathology , Cough/physiopathology , Dyspnea/physiopathology , Humans , Hypoxia/physiopathology , Iran , Nebulizers and Vaporizers , Randomized Controlled Trials as Topic , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome , Vasodilator Agents , Ventilation-Perfusion Ratio
17.
J Am Heart Assoc ; 10(3): e019669, 2021 02 02.
Article in English | MEDLINE | ID: covidwho-1066983

ABSTRACT

Background Previous reports suggest that the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may upregulate angiotensin-converting enzyme 2 receptors and increase severe acute respiratory syndrome coronavirus 2 infectivity. We evaluated the association between ACEI or ARB use and coronavirus disease 2019 (COVID-19) infection among patients with hypertension. Methods and Results We identified patients with hypertension as of March 1, 2020 (index date) from Kaiser Permanente Southern California. Patients who received ACEIs, ARBs, calcium channel blockers, beta blockers, thiazide diuretics (TD), or no therapy were identified using outpatient pharmacy data covering the index date. Outcome of interest was a positive reverse transcription polymerase chain reaction test for COVID-19 between March 1 and May 6, 2020. Patient sociodemographic and clinical characteristics were identified within 1 year preindex date. Among 824 650 patients with hypertension, 16 898 (2.0%) were tested for COVID-19. Of those tested, 1794 (10.6%) had a positive result. Overall, exposure to ACEIs or ARBs was not statistically significantly associated with COVID-19 infection after propensity score adjustment (odds ratio [OR], 1.06; 95% CI, 0.90-1.25) for ACEIs versus calcium channel blockers/beta blockers/TD; OR, 1.10; 95% CI, 0.91-1.31 for ARBs versus calcium channel blockers/beta blockers/TD). The associations between ACEI use and COVID-19 infection varied in different age groups (P-interaction=0.03). ACEI use was associated with lower odds of COVID-19 among those aged ≥85 years (OR, 0.30; 95% CI, 0.12-0.77). Use of no antihypertensive medication was significantly associated with increased odds of COVID-19 infection compared with calcium channel blockers/beta blockers/TD (OR, 1.32; 95% CI, 1.11-1.56). Conclusions Neither ACEI nor ARB use was associated with increased likelihood of COVID-19 infection. Decreased odds of COVID-19 infection among adults ≥85 years using ACEIs warrants further investigation.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/epidemiology , Calcium Channel Blockers/therapeutic use , Delivery of Health Care, Integrated/methods , Hypertension/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , United States/epidemiology , Young Adult
18.
Hypertension ; 77(3): 833-842, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-1021180

ABSTRACT

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/epidemiology , Hypertension/drug therapy , Pandemics , Receptors, Virus/drug effects , SARS-CoV-2/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/etiology , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/therapeutic use , Comorbidity , Disease Susceptibility , Drug Utilization , Female , Follow-Up Studies , France/epidemiology , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hypertension/epidemiology , Intubation, Intratracheal/statistics & numerical data , Male , Middle Aged , Retrospective Studies , Young Adult
19.
J Cardiol ; 77(5): 482-491, 2021 05.
Article in English | MEDLINE | ID: covidwho-899185

ABSTRACT

BACKGROUND: The association of antihypertensive drugs with the risk and severity of COVID-19 remains unknown. METHODS AND RESULTS: We systematically searched PubMed, MEDLINE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and medRxiv for publications before July 13, 2020. Cohort studies and case-control studies that contain information on the association of antihypertensive agents including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCBs), ß-blockers, and diuretics with the risk and severity of COVID-19 were selected. The random or fixed-effects models were used to pool the odds ratio (OR) with 95% confidence interval (CI) for the outcomes. The literature search yielded 53 studies that satisfied our inclusion criteria, which comprised 39 cohort studies and 14 case-control studies. These studies included a total of 2,100,587 participants. We observed no association between prior usage of antihypertensive medications including ACEIs/ARBs, CCBs, ß-blockers, or diuretics and the risk and severity of COVID-19. Additionally, when only hypertensive patients were included, the severity and mortality were lower with prior usage of ACEIs/ARBs (overall OR of 0.81, 95% CI 0.66-0.99, p < 0.05 and overall OR of 0.77, 95% CI 0.66-0.91, p < 0.01). CONCLUSIONS: Taken together, usage of antihypertensive drugs is not associated with the risk and severity of COVID-19. Based on the current available literature, it is not recommended to abstain from the usage of these drugs in COVID-19 patients. REGISTRATION: The meta-analysis was registered on OSF (https://osf.io/ynd5g).


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Adrenergic beta-Antagonists/therapeutic use , COVID-19/prevention & control , Calcium Channel Blockers/therapeutic use , Case-Control Studies , Diuretics/therapeutic use , Humans , Hypertension/complications , SARS-CoV-2
20.
ACS Chem Neurosci ; 11(15): 2145-2148, 2020 08 05.
Article in English | MEDLINE | ID: covidwho-646274

ABSTRACT

Studies have shown that the calcium ion (Ca2+) plays important roles both in Alzheimer's dementia and SARS-CoV S-mediated fusion to host cell entry. An elevated level of intracellular calcium causes neuronal dysfunction, cell death, and apoptosis. Dysregulation of calcium has also been shown to increase the production of amyloid beta (Aß) protein, the hallmark of Alzheimer's dementia. Reversely, deposition of Aß is also responsible for calcium dysregulation. On the other hand, it has been well investigated that viruses can disturb host cell Ca2+ homeostasis as well as modulate signal transduction mechanisms. Viruses can also hijack the host cell calcium channels and pumps to release more intracellular Ca2+ to utilize for their life cycle. Even though evidence has not been reported on SARS-CoV-2 concerning Ca2+ regulation, however, it has been well established that Ca2+ is essential for viral entry, viral gene replication, and virion maturation and release. Recent reports suggest that SARS-CoV needs two Ca2+ ions to fuse with the host cell at the entry step. Furthermore, some calcium channel blockers (CCBs), such as nimodipine, memantine, etc., have been reported to be effective in the treatment of dementia in Alzheimer's disease (AD) as well as have shown inhibition in various virus infections.


Subject(s)
Alzheimer Disease/drug therapy , Betacoronavirus , Calcium Channel Blockers/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/psychology , COVID-19 , Calcium/metabolism , Calcium Channel Blockers/chemistry , Calcium Channel Blockers/pharmacology , Calcium Channels/metabolism , Coronavirus Infections/metabolism , Coronavirus Infections/psychology , Humans , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/psychology , SARS-CoV-2 , Treatment Outcome
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