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Ishiga K, Wakui H, Azushima K, Kanaoka T, Kanai D, Kobayashi R, Kinguchi S, Okami N, Haze T, Iwano T, Sakai M, Ohki K, Oshikawa J, Kokuho T, Hanaoka M, Mitsuhashi H, Yamada Y, Yabana M, Toya Y, Tamura K. Clinical Course and Factors Correlated with Severe Morbidity and Mortality in Patients with Coronavirus Disease 2019 Undergoing Maintenance Dialysis in Kanagawa, Japan. Intern Med 2024; 63:3157-3163. [PMID: 39343571 DOI: 10.2169/internalmedicine.4199-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/01/2024] Open
Abstract
Objective Patients undergoing maintenance dialysis are at a higher risk of morbidity and mortality due to severe coronavirus disease 2019 (COVID-19) than the general population. However, longitudinal data regarding this subpopulation of patients are lacking. We therefore examined the prognosis of patients with COVID-19 undergoing maintenance dialysis between 2020 and 2023. In addition, we explored the factors correlated with COVID-19 severity, focusing on the transition thereof throughout the observational period. Methods The primary outcome was the progression to severe or fatal COVID-19. We evaluated the correlation between the primary outcome and baseline demographic and clinical characteristics of patients. Patients undergoing maintenance dialysis who were hospitalized for mild-to-moderate COVID-19 between February 2020 and April 2023 were enrolled at four institutions in Kanagawa, Japan. Results Of the 173 patients, 7 (4.0%) developed severe COVID-19, and 12 (6.9%) died. The severe/death cohort was significantly older, with a higher percentage of unvaccinated patients than the non-severe cohort (58.2% and 25.0%, respectively; p=0.016). Thymus and activation-regulated chemokine levels on admission were lower in the severe/death cohort than in the non-severe cohort, albeit not to a statistically significant degree (148±84 mg/dL and 342±657 pg/mL, respectively; p=0.082). A multivariate logistic regression analysis revealed that the odds ratio for severe morbidity or death was 0.23 (95% confidence interval: 0.07-0.75) for vaccinated patients. Conclusion In patients undergoing maintenance dialysis, the severity rate of COVID-19 is approximately 10%. Vaccination was correlated with a reduced risk of severe COVID-19.
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Affiliation(s)
- Kohei Ishiga
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Hiromichi Wakui
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Kengo Azushima
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Tomohiko Kanaoka
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Daisuke Kanai
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Ryu Kobayashi
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Sho Kinguchi
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Naohito Okami
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Tatsuya Haze
- YCU Center for Novel and Exploratory Clinical Trials (Y-NEXT), Yokohama City University Hospital, Japan
| | - Takehisa Iwano
- Department of Nephrology, Yokohama Minami Kyosai Hospital, Japan
| | - Masashi Sakai
- Department of Nephrology, Fujisawa City Hospital, Japan
| | | | - Jin Oshikawa
- Department of Nephrology, Yokohama Sakae Kyosai Hospital, Japan
| | | | - Masaaki Hanaoka
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
- Kohsaikai Kamioooka Jinsei Clinic, Japan
| | | | | | - Machiko Yabana
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
- Aiyukai Hana Clinic, Japan
| | - Yoshiyuki Toya
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Japan
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2
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Ibrahim R. The effect of pre-hospital use of RAS inhibitors on COVID-19 mortality. J Investig Med 2024; 72:863-875. [PMID: 39075674 DOI: 10.1177/10815589241270417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2024]
Abstract
The effect of pre-hospital use of renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)) on clinical outcomes of hypertensive patients with COVID-19 has been questioned due to conflicting reports on this issue. After applying exclusion criteria, 175 COVID-19 hospitalized patients admitted to the Tishreen Hospital from January 1 to July 31, 2021 were retrospectively enrolled in this study. Baseline characteristics and in-hospital mortality rate were assessed between hypertensive (N = 91, 52%) and non-hypertensive (N = 84, 48%) patients, as well as between patients taking ACEis/ARBs and non-ACEis/ARBs within the hypertensive group. A lower mortality rate (51.2 versus 31.9%, p = 0.009) was observed in the hypertensive group (mean age 64.6 years, 64.8% males) compared to the non-hypertensive (mean age 62.6 years, 66.7% males). Patients' mortality in the non-hypertensive group was associated with lower blood oxygen saturation (SPO2 = 75 versus 86%, p = 0.002), increased levels of inflammatory (CRP, white blood cell and neutrophils count), and tissue/renal injury markers (LDH, urea, and creatinine). In the hypertensive group, a lower mortality rate was noted in the ACEis/ARBs group compared to the non-ACEis/ARBs (24.1 versus 45.5%, p = 0.036), and this was associated with a decrease in D-DIMER levels, although not significant (1723 versus 2683 ng/mL, p > 0.05). Death in the non-ACEis/ARBs group was associated with decreased SPO2 and tissue/renal injury markers (LDH, CK, AST, urea, and creatinine). We concluded that hypertension is not a direct cause of poor prognosis in COVID-19 patients and that multi-organ damage is a significant indicator of death from COVID-19. RAS inhibitors could improve the survival of hypertensive COVID-19 patients.
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Affiliation(s)
- Rama Ibrahim
- Department of Biochemistry and Microbiology, Faculty of Pharmacy,Al-Sham Private University (ASPU), Lattakia, Syria
- Department of Biochemistry and Microbiology, Faculty of Pharmacy, Tishreen University, Lattakia, Syria
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Kai H. Shadow left by COVID-19 pandemic on the future. Hypertens Res 2024; 47:2917-2919. [PMID: 39090180 DOI: 10.1038/s41440-024-01789-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 06/07/2024] [Accepted: 06/08/2024] [Indexed: 08/04/2024]
Affiliation(s)
- Hisashi Kai
- Department of Cardiology, Kurume University Medical Center, Kurume, Japan.
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Natsume S, Satoh M, Murakami T, Sasaki M, Metoki H. The trends of antihypertensive drug prescription based on the Japanese national data throughout the COVID-19 pandemic period. Hypertens Res 2024; 47:2086-2090. [PMID: 38831090 PMCID: PMC11298402 DOI: 10.1038/s41440-024-01706-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 04/12/2024] [Accepted: 04/12/2024] [Indexed: 06/05/2024]
Abstract
In 2020, concerns arose about the potential adverse effects of angiotensin II type 1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on patients with the Coronavirus Disease 2019 (COVID-19). However, there is no national data on antihypertensive prescriptions during the COVID-19 pandemic in Japan. This study aimed to explore the trends in antihypertensive drug prescriptions in Japan throughout COVID-19 pandemic period. This study used data from the National Database (NDB) Open Data in Japan, an annual publication by the Ministry of Health, Labour and Welfare. To capture changes before and after social activity restrictions, the present study focused on extracting the number of prescribed oral medicine tablets for outpatients from the NDB Open Data from 2018 to 2021. The fiscal year 2020 exhibited the lowest for both outpatient claims and prescribed drugs. In contrast, all categories of antihypertensive drug prescription showed annual increases, and no specific changes in the prescription patterns of ARBs and ACEIs around fiscal year 2020 were observed. This study implies that antihypertensive drug prescriptions were adequately maintained throughout the COVID-19 pandemic in Japan.
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Affiliation(s)
- Shotaro Natsume
- Division of Public Health, Hygiene and Epidemiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan
- Division of Infection and Host Defense, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Japan
| | - Michihiro Satoh
- Division of Public Health, Hygiene and Epidemiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
- Department of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan.
- Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
| | - Takahisa Murakami
- Division of Public Health, Hygiene and Epidemiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan
- Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
| | - Masato Sasaki
- Division of Infection and Host Defense, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Japan
| | - Hirohito Metoki
- Division of Public Health, Hygiene and Epidemiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan
- Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
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Vinod P, Krishnappa V, Rathell W, Dogbey G, Patel H, Herzog W. Effect of Renin-Angiotensin-Aldosterone System Blockers on Adverse Outcomes in COVID-19 Patients. Cardiology 2024; 149:551-560. [PMID: 39038438 DOI: 10.1159/000540499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 07/18/2024] [Indexed: 07/24/2024]
Abstract
INTRODUCTION Angiotensin-converting enzyme 2 (ACE2) of the renin-angiotensin-aldosterone system (RAAS) serves as a functional receptor to gain entry into the cells for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and ACE2 is a potential virulent factor in infectivity. Our study aimed to ascertain the association of RAAS inhibitors with adverse cardiovascular and other outcomes in hospitalized COVID-19 patients. METHODS This is a retrospective study of medical records of ≥18-year-old patients hospitalized for COVID-19 from March 2020 to October 2020. Primary outcomes were acute cardiovascular events (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction type 1, acute congestive heart failure, acute stroke) and mortality. Secondary outcomes were respiratory failure, need for and duration of mechanical ventilation, acute deep vein thrombosis or pulmonary embolism (DVT/PE), and readmission rate. RESULTS Among 376 hospitalized COVID-19 patients, 149 were on RAAS inhibitors. No statistically significant differences were found between RAAS inhibitor and non-RAAS inhibitor groups with respect to acute cardiovascular events (6% vs. 6.2%, p = 0.94), acute DVT/PE (4.7% vs. 4.8%, p = 0.97), hypoxia (62.4% vs. 58.6%, p = 0.46), need for mechanical ventilation (18.1% vs. 16.7%, p = 0.72), mortality (19.5% vs. 22%, p = 0.56), and readmission rate (11.4% vs. 14.1%, p = 0.45). Some nuances discovered were a higher rate of hospitalizations among Native Americans receiving RAAS inhibitors (30.2% vs. 19.8%) and significantly lower levels of procalcitonin in patients on RAAS inhibitors. CONCLUSIONS Among hospitalized patients with COVID-19, those on RAAS inhibitors showed no significant differences in acute cardiovascular events, acute DVT/PE, hypoxia, need for mechanical ventilation, readmission, or mortality rate compared to those not on them. However, further large-scale studies are needed to validate these findings.
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Affiliation(s)
- Poornima Vinod
- Department of Internal Medicine, University of North Carolina Health Southeastern, Lumberton, North Carolina, USA
| | - Vinod Krishnappa
- Department of Internal Medicine, University of North Carolina Health Southeastern, Lumberton, North Carolina, USA
| | - William Rathell
- Department of Internal Medicine, University of North Carolina Health Southeastern, Lumberton, North Carolina, USA
| | - Godwin Dogbey
- Department of Research and Medical Education, Campbell University, Buies Creek, North Carolina, USA
| | - Hiten Patel
- Department of Cardiology, University of North Carolina Health Southeastern, Lumberton, North Carolina, USA
| | - William Herzog
- Department of Cardiology, University of North Carolina Health Southeastern, Lumberton, North Carolina, USA
- Department of Cardiology, Duke University, Durham, North Carolina, USA
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6
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Shukla AK, Awasthi K, Usman K, Banerjee M. Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus. World J Diabetes 2024; 15:606-622. [PMID: 38680697 PMCID: PMC11045416 DOI: 10.4239/wjd.v15.i4.606] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/22/2024] [Accepted: 02/27/2024] [Indexed: 04/11/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.
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Affiliation(s)
- Ashwin Kumar Shukla
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Komal Awasthi
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
| | - Kauser Usman
- Department of Medicine, King Georges’ Medical University, Lucknow 226003, Uttar Pradesh, India
| | - Monisha Banerjee
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, Uttar Pradesh, India
- Institute of Advanced Molecular Genetics, and Infectious Diseases (IAMGID), University of Lucknow, Lucknow 226007, Uttar Pradesh, India
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7
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Miura R, Okada K. Prescription of renin-angiotensin system inhibitors in Japan during the COVID-19 pandemic: interrupted time series study. Hypertens Res 2023; 46:2593-2602. [PMID: 37463982 DOI: 10.1038/s41440-023-01373-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 06/26/2023] [Accepted: 06/29/2023] [Indexed: 07/20/2023]
Abstract
We surveyed changes in angiotensin-converting enzyme inhibitor (ACEIs) and angiotensin II receptor blocker (ARBs) prescription trends during the coronavirus disease 2019 (COVID-19) pandemic in Japan. Data of 1,605,708 outpatients with hypertension were extracted from the Medical Data Vision database. Trends for prescription of ACEIs and ARBs were assessed by analyzing the proportion of these prescriptions in each month, between April 2018 and November 2020. The proportion of ARBs prescriptions changed significantly in trend between the peri-pandemic and pre-pandemic periods (-0.05%/month, P = 0.012). In contrast, the proportion of ACEIs prescriptions did not change significantly in trend in the peri-pandemic period (0.01%/month, P = 0.189). There was no suggestion that the prescribing of ACEIs and ARBs was affected by the COVID-19 pandemic.
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Affiliation(s)
- Ryosuke Miura
- Department of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, 1-12-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8512, Japan.
| | - Kouji Okada
- Department of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, 1-12-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8512, Japan
- Division of Clinical Pharmaceutics and Pharmacy Practice, Tohoku Medical and Pharmaceutical University, 1-12-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8512, Japan
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8
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Abha Mishra KM, Podili R, Pathlavath TS, Sethi KK. A critical review on brain and heart axis response in COVID-19 patients: Molecular mechanisms, mediators, biomarkers, and therapeutics. J Biochem Mol Toxicol 2023; 37:e23409. [PMID: 37341157 DOI: 10.1002/jbt.23409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 06/01/2023] [Accepted: 06/08/2023] [Indexed: 06/22/2023]
Abstract
Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.
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Affiliation(s)
- K M Abha Mishra
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
| | - Runesh Podili
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
| | - Teja S Pathlavath
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
| | - Kalyan K Sethi
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
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9
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Muchaili L, Mweene BC, Masenga SK. Renin-Angiotensin System Inhibitors and the COVID-19 Pandemic. Am J Hypertens 2023; 36:360-362. [PMID: 37010128 PMCID: PMC10267615 DOI: 10.1093/ajh/hpad031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 03/30/2023] [Indexed: 04/04/2023] Open
Affiliation(s)
- Lweendo Muchaili
- HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
| | - Bislom C Mweene
- HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
| | - Sepiso K Masenga
- HAND Research Group, School of Medicine and Health Sciences, Mulungushi University, Livingstone, Zambia
- School of Public Health, University of Zambia, Lusaka, Zambia
- Vanderbilt Institute for Global Health, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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10
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Chambergo-Michilot D, Runzer-Colmenares FM, Segura-Saldaña PA. Discontinuation of Antihypertensive Drug Use Compared to Continuation in COVID-19 Patients: A Systematic Review with Meta-analysis and Trial Sequential Analysis. High Blood Press Cardiovasc Prev 2023; 30:265-279. [PMID: 37171528 PMCID: PMC10177739 DOI: 10.1007/s40292-023-00579-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 05/04/2023] [Indexed: 05/13/2023] Open
Abstract
INTRODUCTION COVID-19 related mortality is about 2%, and it increases with comorbidities, like hypertension. Regarding management, there is debatable evidence about the benefits of continuation vs. discontinuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB). AIM We performed a systematic review to assess the effects and safety of in-hospital discontinuation compared to continuation of ACEI/ARB in COVID-19 patients. METHODS We systematically searched on PubMed, Scopus, and EMBASE from inception to June 19, 2021. We included observational studies and trials that compared the effects and safety of continuing ACEI/ARB compared to discontinuing it in COVID-19 patients. Effects sizes for dichotomous variables were expressed as risk ratios (RR) and 95% confidence intervals. For continuous variables, effects were expressed as mean difference (MD). We used random effect models with the inverse variance method. We assessed certainty of evidence using the GRADE approach. RESULTS We included three open-label randomized controlled trials and five cohort studies. We found that the continuation group had lower risk of death compared with the discontinuation group only in the cohort group (RR: 0.46, 95% CI: 0.24-0.90), but not in the RCT group (RR: 1.22, 95% CI: 0.75-2.00). The ICU admission rate was significantly lower in the continuation group (RR: 0.46, 95% CI: 0.31-0.68) in the cohort group, but not in RCT group (RR: 1.03, 95% CI: 0.67-1.59). We did not find significant differences between groups regarding hospitalization length, hypotension, AKI needing renal replacement therapy, mechanical ventilation, new or worsening heart failure, myocarditis, renal replacement therapy, arrhythmias, thromboembolic events and SOFA AUC. The GRADE approach revealed that the certainty ranged from moderate to high level. CONCLUSIONS There is no significant difference in mortality and other outcomes between continuation and discontinuation groups.
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Affiliation(s)
- Diego Chambergo-Michilot
- Universidad Científica del Sur, Lima, Peru.
- CHANGE Research Working Group, Carrera de Medicina Humana, Universidad Científica del Sur, Lima, Peru.
| | | | - Pedro A Segura-Saldaña
- Department of Cardiology Research, Torres de Salud National Research Center, Lima, Peru
- Ingeniería Biomédica, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
- Departamento de Cardiología, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru
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11
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Nozato Y, Yamamoto K, Rakugi H. Hypertension management before and under the COVID-19 pandemic: lessons and future directions. Hypertens Res 2023:10.1038/s41440-023-01253-7. [PMID: 36997633 PMCID: PMC10060937 DOI: 10.1038/s41440-023-01253-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/11/2023] [Accepted: 02/17/2023] [Indexed: 03/31/2023]
Abstract
Hypertension is a significant risk factor for cardiovascular diseases. The prevalence of hypertension and its complications is increasing yearly, yet it remains inadequately controlled worldwide. It has already been recognized that self-management, including self-measured blood pressure monitoring at home, is more important than office blood pressure monitoring. The practical application of telemedicine using digital technology was already underway. COVID-19 has promoted the popularization of these management systems in primary care, although the COVID-19 pandemic disrupted lifestyle and healthcare access. At the beginning of the pandemic, we were at the mercy of information on whether certain antihypertensive drugs, for example, might pose a risk of infection in the face of unknown infectious diseases. Over the past three years, however, much knowledge has been accumulated. It has been scientifically proven that there is no serious problem in managing hypertension in the same way as before the pandemic. That is to control blood pressure mainly through home blood pressure monitoring and continuing conventional drug therapy while modifying lifestyle. On the other hand, in the New Normal era, it is necessary to accelerate digital hypertension management and the establishment of new social networks and medical systems to prepare for the re-emergence of future pandemics while continuing to protect against infection. This review will summarize the lessons and future directions we learned from the impact of the COVID-19 pandemic on hypertension management. The COVID-19 pandemic has disrupted our daily life, restricted access to healthcare, and altered some of the conventional management of hypertension.
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12
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Fedorchenko Y, Zimba O. Comorbidities in the COVID-19 Pandemic: Scopus-Based Bibliometric Analysis. J Korean Med Sci 2023; 38:e93. [PMID: 36942396 PMCID: PMC10027540 DOI: 10.3346/jkms.2023.38.e93] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 02/16/2023] [Indexed: 03/12/2023] Open
Abstract
BACKGROUND Comorbidities attract enormous attention amid the coronavirus disease 2019 (COVID-19) pandemic. Mapping knowledge based on these clinical conditions is increasingly important since the pandemic is still raging and primarily affecting subjects with chronic diseases and comorbidities. Clinical presentation and complications of COVID-19 are still hot topics which are explored in numerous evidence-based publications. The aim of this study was to analyze Scopus-indexed COVID-19 papers covering comorbidities. METHODS Searches through the Scopus database were performed on September 19, 2022 using the following keywords: "Diabetes mellitus" OR "Cardiovascular Diseases" OR "Rheumatic Diseases" OR "Obesity" OR "Malignancies" AND "COVID-19." All retrieved articles were analyzed using the following categories: document type, authorship, keywords, journal, citation score, country of origin, and language. Using the software tool VOSviewer version 1.6.18, we visualized the network of authors and keywords co-occurrence of the most prevalent comorbidities reported in connection with COVID-19. RESULTS Reports on COVID-19 and diabetes mellitus (DM) were most frequently published (n = 12,282). The US was the most productive country (n = 3,005) in the field of COVID-19 and comorbidities. There were 1,314 documents on COVID-19 and rheumatic diseases which is the least number in comparison with other comorbidities (COVID-19 and DM: 12,282, COVID-19 and cardiovascular disease: 9,911, COVID-19 and obesity: 7,070, and COVID-19 and malignancies: 1,758). CONCLUSION This mapping of COVID-19-related documents in connection with comorbidities may prioritize future research directions.
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Affiliation(s)
- Yuliya Fedorchenko
- Department of Pathophysiology, Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine.
| | - Olena Zimba
- Department of Clinical Rheumatology and Immunology, University Hospital in Krakow, Krakow, Poland
- National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
- Department of Internal Medicine N2, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
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Angeli F, Zappa M, Reboldi G, Gentile G, Trapasso M, Spanevello A, Verdecchia P. The spike effect of acute respiratory syndrome coronavirus 2 and coronavirus disease 2019 vaccines on blood pressure. Eur J Intern Med 2023; 109:12-21. [PMID: 36528504 PMCID: PMC9744686 DOI: 10.1016/j.ejim.2022.12.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/07/2022] [Accepted: 12/12/2022] [Indexed: 12/14/2022]
Abstract
Among the various comorbidities potentially worsening the clinical outcome in patients hospitalized for the acute respiratory syndrome coronavirus-2 (SARS-CoV-2), hypertension is one of the most prevalent. However, the basic mechanisms underlying the development of severe forms of coronavirus disease 2019 (COVID-19) among hypertensive patients remain undefined and the direct association of hypertension with outcome in COVID-19 is still a field of debate. Experimental and clinical data suggest that SARS-CoV-2 infection promotes a rise in blood pressure (BP) during the acute phase of infection. Acute increase in BP and high in-hospital BP variability may be tied with acute organ damage and a worse outcome in patients hospitalized for COVID-19. In this context, the failure of the counter-regulatory renin-angiotensin-system (RAS) axis is a potentially relevant mechanism involved in the raise in BP. It is well recognized that the efficient binding of the Spike (S) protein to angiotensin converting enzyme 2 (ACE2) receptors mediates the virus entry into cells. Internalization of ACE2, downregulation and malfunction predominantly due to viral occupation, dysregulates the protective RAS axis with increased generation and activity of angiotensin (Ang) II and reduced formation of Ang1,7. Thus, the imbalance between Ang II and Ang1-7 can directly contribute to excessively rise BP in the acute phase of SARS-CoV-2 infection. A similar mechanism has been postulated to explain the raise in BP following COVID-19 vaccination ("Spike Effect" similar to that observed during the infection of SARS-CoV-2). S proteins produced upon vaccination have the native-like mimicry of SARS-CoV-2 S protein's receptor binding functionality and prefusion structure and free-floating S proteins released by the destroyed cells previously targeted by vaccines may interact with ACE2 of other cells, thereby promoting ACE2 internalization and degradation, and loss of ACE2 activities.
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Affiliation(s)
- Fabio Angeli
- Department of Medicine and Surgery, University of Insubria, Varese, 21100, Italy; Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, 21049, Italy.
| | - Martina Zappa
- Department of Medicine and Surgery, University of Insubria, Varese, 21100, Italy
| | - Gianpaolo Reboldi
- Department of Medicine, and Centro di Ricerca Clinica e Traslazionale (CERICLET), University of Perugia, Perugia, 06100, Italy
| | - Giorgio Gentile
- College of Medicine and Health. University of Exeter, Exeter, United Kingdom and Department of Nephrology, Royal Cornwall Hospitals NHS Trust, Truro, United Kingdom
| | - Monica Trapasso
- Dipartimento di Igiene e Prevenzione Sanitaria, PSAL, Sede Territoriale di Varese, ATS Insubria, Varese, 21100, Italy
| | - Antonio Spanevello
- Department of Medicine and Surgery, University of Insubria, Varese, 21100, Italy; Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, 21049, Italy
| | - Paolo Verdecchia
- Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, and Fondazione Umbra Cuore e Ipertensione-ONLUS, Perugia, 06100, Italy
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14
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Kurdi A, Mueller T, Weir N. An umbrella review and meta-analysis of renin-angiotensin system drugs use and COVID-19 outcomes. Eur J Clin Invest 2023; 53:e13888. [PMID: 36205627 PMCID: PMC9874890 DOI: 10.1111/eci.13888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND Despite the availability of extensive literature on the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) on COVID-19 outcomes, the evidence is still controversial. We aimed to provide a comprehensive assessment of the effect of ACEIs/ARBs on COVID-19-related outcomes by summarising the currently available evidence. METHODS An umbrella review was conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 February 2021. Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19-related clinical outcomes were eligible. Studies' quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random-effects modelling including several subgroup analyses. Heterogenicity was assessed using I2 statistic. The study protocol was registered in PROSPERO (CRD42021233398) and reported using PRISMA guidelines. RESULTS Overall, 47 reviews were eligible for inclusion. Out of the nine COVID-19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR = 0.80, 95%CI = 0.75-0.86; I2 = 51.9%), death/ICU admission as composite outcome (OR = 0.86, 95%CI = 0.80-0.92; I2 = 43.9%), severe COVID-19 (OR = 0.86, 95%CI = 0.78-0.95; I2 = 68%) and hospitalisation (OR = 1.23, 95%CI = 1.04-1.46; I2 = 76.4%). The significant reduction in death/ICU admission, however, was higher among studies which presented adjusted measure of effects (OR = 0.63, 95%CI = 0.47-0.84) and were of moderate quality (OR = 0.74, 95%CI = 0.63-0.85). CONCLUSIONS Collective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on both reducing severe COVID-19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID-19.
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Affiliation(s)
- Amanj Kurdi
- Strathclyde Institute of Pharmacy and Biomedical Science, University of StrathclydeGlasgowScotlandUK
- Department of Pharmacology and ToxicologyCollege of Pharmacy, Kurdistan Region Government, Hawler Medical UniversityErbilIraq
- Division of Public Health Pharmacy and ManagementSchool of Pharmacy, Sefako Makgatho Health Sciences UniversityPretoriaSouth Africa
| | - Tanja Mueller
- Strathclyde Institute of Pharmacy and Biomedical Science, University of StrathclydeGlasgowScotlandUK
| | - Natalie Weir
- Strathclyde Institute of Pharmacy and Biomedical Science, University of StrathclydeGlasgowScotlandUK
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Abstract
The pandemic of COVID-19 in worldwide causes recent millions of morbidity and mortality in all countries and is the most important challenge in the world in recent years. Coronavirus is a single-stranded RNA virus and infection with COVID-19 leads to acute respiratory distress syndrome, lung inflammation, cytokine storm, and death. The other complications include endothelial dysfunction, activation of coagulation, thromboembolic events, and vascular disease. Cardiovascular complications such as myocardial and stroke ischemia, pulmonary thromboembolism, systemic arterial, and deep vein thrombosis were reported. In this review, we presented immuno-pathological mechanisms and the effects of COVID-19 on the cardiovascular system, heart, vessels, coagulation system, and molecular glance of immuno-inflammation to the COVID-19's pathology on the cardiovascular system.
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Affiliation(s)
- Entezar Mehrabi Nasab
- Department of Cardiology, School of Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Cardiology, School of Medicine, Valiasr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hassan Aghajani
- Department of Cardiology, School of Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Hassanzadeh Makoei
- Department of Cardiology, School of Medicine, Ayatollah Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Seyyed Shamsadin Athari
- Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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16
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Batty JA, Hall M. Trends in ACEi and ARB expenditure: Compelling case for competition in generic drug markets. Int J Cardiol 2023; 370:419-420. [PMID: 36414045 DOI: 10.1016/j.ijcard.2022.11.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 11/16/2022] [Indexed: 11/21/2022]
Affiliation(s)
- Jonathan A Batty
- Clinical and Population Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Worsley Building, Clarendon Way, University of Leeds, LS2 9NL, UK; Leeds Institute for Data Analytics, Worsley Building, Clarendon Way, University of Leeds, LS2 9NL, UK.
| | - Marlous Hall
- Clinical and Population Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, Worsley Building, Clarendon Way, University of Leeds, LS2 9NL, UK; Leeds Institute for Data Analytics, Worsley Building, Clarendon Way, University of Leeds, LS2 9NL, UK
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17
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Sun H, Du Y, Kumar R, Buchkovich N, He P. Increased circulating microparticles contribute to severe infection and adverse outcomes of COVID-19 in patients with diabetes. Am J Physiol Heart Circ Physiol 2022; 323:H1176-H1193. [PMID: 36269646 PMCID: PMC9678425 DOI: 10.1152/ajpheart.00409.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Patients with diabetes infected with COVID-19 have greater mortality than those without comorbidities, but the underlying mechanisms remain unknown. This study aims to identify the mechanistic interactions between diabetes and severe COVID-19. Microparticles (MPs), the cell membrane-derived vesicles released on cell activation, are largely increased in patients with diabetes. To date, many mechanisms have been postulated for increased severity of COVID-19 in patients with underlying conditions, but the contributions of excessive MPs in patients with diabetes have been overlooked. This study characterizes plasma MPs from normal human subjects and patients with type 2 diabetes in terms of amount, cell origins, surface adhesive properties, ACE2 expression, spike protein binding capacity, and their roles in SARS-CoV-2 infection. Results showed that over 90% of plasma MPs express ACE2 that binds the spike protein of SARS-CoV-2. MPs in patients with diabetes increase 13-fold in quantity and 11-fold in adhesiveness when compared with normal subjects. Perfusion of human plasma with pseudo-typed SARS-CoV-2 virus or spike protein-bound MPs into human endothelial cell-formed microvessels-on-a chip demonstrated that MPs from patients with diabetes, not normal subjects, interact with endothelium and carry SARS-CoV-2 into cells through endocytosis, providing additional virus entry pathways and enhanced infection. Results also showed a large percentage of platelet-derived tissue factor-bearing MPs in diabetic plasma, which could contribute to thrombotic complications with SARS-CoV-2 infection. This study reveals a dual role of diabetic MPs in promoting SARS-CoV-2 entry and propagating vascular inflammation. These findings provide novel mechanistic insight into the high prevalence of COVID-19 in patients with diabetes and their propensity to develop severe vascular complications.NEW & NOTEWORTHY This study provides the first evidence that over 90% of human plasma microparticles express ACE2 that binds SARS-CoV-2 S protein with high affinity. Thus, the highly elevated adhesive circulating microparticles identified in patients with diabetes not only have greater SARS-CoV-2 binding capacity but also enable additional viral entry through virus-bound microparticle-endothelium interactions and enhanced infection. These findings reveal a novel mechanistic insight into the adverse outcomes of COVID-19 in patients with diabetes.
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Affiliation(s)
- Haoyu Sun
- 1Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania
| | - Yong Du
- 1Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania
| | - Rinki Kumar
- 2Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania
| | - Nicholas Buchkovich
- 2Department of Microbiology and Immunology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania
| | - Pingnian He
- 1Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania
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18
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Choudhary R, Pervez A, Kumar B, Singh Patel US, Verma VK, Ojha S. Assessment of Kidney Involvement in COVID-19 Patient. Cureus 2022; 14:e28964. [PMID: 36237801 PMCID: PMC9548075 DOI: 10.7759/cureus.28964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 09/06/2022] [Indexed: 01/08/2023] Open
Abstract
Background and aim: Physicians need to be aware of the difficulties that SARS-CoV-2 infection brings to other regions of the body, such as the kidneys, even though the key emphasis is on pulmonary characteristics. The most frequent kidney complication among COVID-19 hospitalized patients is considered acute kidney injury (AKI). This study aimed to describe overall different aspects of acute kidney injury (AKI) in COVID-19 patients admitted to JLNMCH during the COVID-19 pandemic and to determine the prevalence of AKI among COVID-19 hospitalized patients. Methods and materials: All adult patients (over the age of 18 years) who screened positive for COVID-19 in a swab specimen from areas of nasopharyngeal by reverse transcriptase polymerase chain reaction and then hospitalized were included in the study. Information was gathered on the patient's demographics, general medical history, and drugs prescribed. From past medical information, associated comorbidities and home pharmaceuticals were identified. We gathered hospitalization information, such as duration of stay in ICU, details about the application of mechanical ventilation, information regarding extracorporeal membrane aeration, details of the use of vasopressor administration, and baseline results of laboratory test along with baseline clinical information during 48 hours of hospitalization. Results: The percentage of patients with no history of AKI requiring traumatic mechanical ventilation was 79.4%, while the percentage of patients with no history of AKI not requiring traumatic mechanical ventilation was 11.5%. The difference was relevant statistically (p<0.001). The percentage of patients with AKI of any stage requiring traumatic mechanical ventilation was 22.8%, while the percentage of patients with no history of AKI not requiring traumatic mechanical ventilation was 76.8%. The difference was relevant statistically (p<0.022). Conclusion: We discovered that AKI was a rather typical finding among hospitalized COVID-19 patients. Patients hospitalized for COVID-19 had a poor prognosis if they developed AKI.
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19
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Greco M, Angelotti G, Caruso PF, Zanella A, Stomeo N, Costantini E, Protti A, Pesenti A, Grasselli G, Cecconi M. Outcome prediction during an ICU surge using a purely data-driven approach: A supervised machine learning case-study in critically ill patients from COVID-19 Lombardy outbreak. Int J Med Inform 2022; 164:104807. [PMID: 35671585 PMCID: PMC9161686 DOI: 10.1016/j.ijmedinf.2022.104807] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 05/02/2022] [Accepted: 05/30/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE COVID-19 disease frequently affects the lungs leading to bilateral viral pneumonia, progressing in some cases to severe respiratory failure requiring ICU admission and mechanical ventilation. Risk stratification at ICU admission is fundamental for resource allocation and decision making. We assessed performances of three machine learning approaches to predict mortality in COVID-19 patients admitted to ICU using early operative data from the Lombardy ICU Network. METHODS This is a secondary analysis of prospectively collected data from Lombardy ICU network. A logistic regression, balanced logistic regression and random forest were built to predict survival on two datasets: dataset A included patient demographics, medications before admission and comorbidities, and dataset B included respiratory data the first day in ICU. RESULTS Models were trained on 1484 patients on four outcomes (7/14/21/28 days) and reached the greatest predictive performance at 28 days (F1-score: 0.75 and AUC: 0.80). Age, number of comorbidities and male gender were strongly associated with mortality. On dataset B, mode of ventilatory assistance at ICU admission and fraction of inspired oxygen were associated with an increase in prediction performances. CONCLUSIONS Machine learning techniques might be useful in emergency phases to reach good predictive performances maintaining interpretability to gain knowledge on complex situations and enhance patient management and resources.
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Affiliation(s)
- Massimiliano Greco
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Giovanni Angelotti
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Pier Francesco Caruso
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy.
| | - Alberto Zanella
- Dipartimento di Anestesia, Rianimazione ed Emergenza-Urgenza, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Niccolò Stomeo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Elena Costantini
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Alessandro Protti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Antonio Pesenti
- Dipartimento di Anestesia, Rianimazione ed Emergenza-Urgenza, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Giacomo Grasselli
- Dipartimento di Anestesia, Rianimazione ed Emergenza-Urgenza, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Maurizio Cecconi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
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20
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Sanyal D, Banerjee S, Bej A, Chowdhury VR, Uversky VN, Chowdhury S, Chattopadhyay K. An integrated understanding of the evolutionary and structural features of the SARS-CoV-2 spike receptor binding domain (RBD). Int J Biol Macromol 2022; 217:492-505. [PMID: 35841961 PMCID: PMC9278002 DOI: 10.1016/j.ijbiomac.2022.07.022] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/29/2022] [Accepted: 07/04/2022] [Indexed: 12/23/2022]
Abstract
Conventional drug development strategies typically use pocket in protein structures as drug-target sites. They overlook the plausible effects of protein evolvability and resistant mutations on protein structure which in turn may impair protein-drug interaction. In this study, we used an integrated evolution and structure guided strategy to develop potential evolutionary-escape resistant therapeutics using receptor binding domain (RBD) of SARS-CoV-2 spike-protein/S-protein as a model. Deploying an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence-space. Guided by molecular simulation and structure network analysis we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility. Using fuzzy C-means clustering we combined evolutionary and structural features of RBD and identified a critical region. Subsequently, we used computational drug screening using a library of 1615 small molecules and identified one lead molecule, which is expected to target the identified region, critical for evolvability and structural stability of RBD. This integrated evolution-structure guided strategy to develop evolutionary-escape resistant lead molecules have potential general applications beyond SARS-CoV-2.
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Affiliation(s)
- Dwipanjan Sanyal
- Protein Folding and Dynamics Group, Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India
| | - Suharto Banerjee
- Protein Folding and Dynamics Group, Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India
| | - Aritra Bej
- Protein Folding and Dynamics Group, Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India
| | - Vaidehi Roy Chowdhury
- Protein Folding and Dynamics Group, Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India
| | - Vladimir N Uversky
- Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Laboratory of New Methods in Biology, Institute for Biological Instrumentation of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Pushchino, Moscow region 142290, Russia
| | - Sourav Chowdhury
- Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
| | - Krishnananda Chattopadhyay
- Protein Folding and Dynamics Group, Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.
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21
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Franczyk B, Rysz J, Miłoński J, Konecki T, Rysz-Górzyńska M, Gluba-Brzózka A. Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19? Pharmaceuticals (Basel) 2022; 15:739. [PMID: 35745658 PMCID: PMC9230944 DOI: 10.3390/ph15060739] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/31/2022] [Accepted: 05/31/2022] [Indexed: 12/13/2022] Open
Abstract
The COVID-19 pandemic is associated with a global health crisis and the greatest challenge for scientists and doctors. The virus causes severe acute respiratory syndrome with an outcome that is fatal in more vulnerable populations. Due to the need to find an efficient treatment in a short time, there were several drugs that were repurposed or repositioned for COVID-19. There are many types of available COVID-19 therapies, including antiviral agents (remdesivir, lopinavir/ritonavir, oseltamivir), antibiotics (azithromycin), antiparasitics (chloroquine, hydroxychloroquine, ivermectin), and corticosteroids (dexamethasone). A combination of antivirals with various mechanisms of action may be more efficient. However, the use of some of these medicines can be related to the occurrence of adverse effects. Some promising drug candidates have been found to be ineffective in clinical trials. The knowledge of pharmacogenetic issues, which translate into variability in drug conversion from prodrug into drug, metabolism as well as transport, could help to predict treatment efficiency and the occurrence of adverse effects in patients. However, many drugs used for the treatment of COVID-19 have not undergone pharmacogenetic studies, perhaps as a result of the lack of time.
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Affiliation(s)
- Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (B.F.); (J.R.)
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (B.F.); (J.R.)
| | - Jarosław Miłoński
- Department of Otolaryngology, Laryngological Oncology, Audiology and Phoniatrics, Medical University of Lodz, 90-549 Lodz, Poland;
| | - Tomasz Konecki
- Department of Urology, Medical University of Lodz, 90-549 Lodz, Poland;
| | - Magdalena Rysz-Górzyńska
- Department of Ophthalmology and Visual Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland;
| | - Anna Gluba-Brzózka
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland; (B.F.); (J.R.)
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22
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Increased Risk of COVID-19 in Patients with Diabetes Mellitus-Current Challenges in Pathophysiology, Treatment and Prevention. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19116555. [PMID: 35682137 PMCID: PMC9180541 DOI: 10.3390/ijerph19116555] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 05/10/2022] [Accepted: 05/25/2022] [Indexed: 01/08/2023]
Abstract
Coronavirus disease-COVID-19 (coronavirus disease 2019) has become the cause of the global pandemic in the last three years. Its etiological factor is SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus type 2). Patients with diabetes (DM-diabetes mellitus), in contrast to healthy people not suffering from chronic diseases, are characterised by higher morbidity and mortality due to COVID-19. Patients who test positive for SARCoV-2 are at higher risk of developing hyperglycaemia. In this paper, we present, analyse and summarize the data on possible mechanisms underlying the increased susceptibility and mortality of patients with diabetes mellitus in the case of SARS-CoV-2 infection. However, further research is required to determine the optimal therapeutic management of patients with diabetes and COVID-19.
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23
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Wu VC, Lin YF, Teng NC, Yang SY, Chou NK, Tsao CH, Chen YM, Chueh JS, Chen L. Angiotensin II Receptor Blocker Associated With Less Outcome Risk in Patients With Acute Kidney Disease. Front Pharmacol 2022; 13:714658. [PMID: 35517809 PMCID: PMC9065477 DOI: 10.3389/fphar.2022.714658] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 03/02/2022] [Indexed: 01/22/2023] Open
Abstract
Objective: The aim of this study was to explore the respective use of angiotensin-converting-enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) on the outcomes of patients who could be weaned from dialysis-requiring acute kidney injury (AKI-D). Methods: This case-control study enrolled 41,731 patients who were weaned from AKI-D for at least 7 days from Taiwan's National Health Insurance Administration. We further grouped AKI-D patients according to ACEi and ARB use to evaluate subsequent risks of all-cause mortality and re-dialysis. The outcomes included the all-cause mortality and new-onset of end-stage kidney disease (ESKD; re-dialysis) following withdraw from AKI-D. Results: A total of 17,141 (41.1%) patients surviving AKI-D could be weaned from dialysis for at least 7 days. The overall events of mortality were 366 (48.9%) in ACEi users, 659 (52.1%) in ARB users, and 6,261 (41.3%) in ACEi/ARB nonusers, during a mean follow-up period of 1.01 years after weaning from AKI-D. In regard to all-cause of mortality, pre-dialysis ARB users had lower incidence than ACEi users [hazard ratio (HR 0.82), p = 0.017]. Compared with ACEi/ARB nonusers, continuing ARB users had a significantly low risk of long-term all-cause mortality (adjusted hazard ratio 0.51, p = 0.013) after propensity score matching. However, new users of ACEi at the acute kidney disease (AKD) period had a higher risk of re-dialysis after weaning than ACEi/ARB nonusers (aHR 1.82, p < 0.001), whereas neither ACEi nor ARB users confronted significantly increased risks of hyperkalemia after weaning. Conclusions: Compared with patients without ACEi/ARB, those continuing to use ARB before the event and after weaning had low all-cause mortality, while new users of ACEi at AKD had increased risk of re-dialysis. AKI-D patients continuing to use ACEi or ARB did not have higher risk of hyperkalemia. Future prospective randomized trials are expected to confirm these findings.
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Affiliation(s)
- Vin-Cent Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Feng Lin
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Nai-Chi Teng
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
| | - Shao-Yu Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Nai-Kuan Chou
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Hao Tsao
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Yung-Ming Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jeff S Chueh
- Glickman Urological and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, United States.,Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
| | - Likwang Chen
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
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Shah NP, Clare RM, Chiswell K, Navar AM, Shah BR, Peterson ED. Trends of blood pressure control in the U.S. during the COVID-19 pandemic. Am Heart J 2022; 247:15-23. [PMID: 34902314 PMCID: PMC8662834 DOI: 10.1016/j.ahj.2021.11.017] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 11/16/2021] [Indexed: 02/06/2023]
Abstract
Importance COVID-19 altered lifestyles and disrupted routine health care. Whether blood pressure (BP) control worsened during COVID-19 is unknown. Objective To understand whether home BP control worsened during COVID-19 across the United States (US) . Design, Setting, and Participants A population-based analysis of home BP data from 72,706 participants enrolled in a digital health hypertension control program. Data was compared before (January 2019 to March 2020) and during (April 2020 to August 2020) COVID-19. Main Outcomes and Measures Monthly mean home BP readings, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were quantified before and during the pandemic. Multivariable adjustments were made for age, sex, race, region, and months enrolled. Home BP readings were also classified based on monthly averages and highest home BP readings into risk groups: Stage 2 HTN: BP> = 135 or DBP> = 85; Uncontrolled HTN: SBP> = 145 or DBP> = 95; or Severely uncontrolled HTN: SBP> = 160 or DBP> = 100). Results Overall, 72,706 participants were enrolled in a digital health hypertension program between 1/1/2019 and 8/31/2020. Compared with participants pre-COVID-19 (n = 33,440), those during COVID-19 (n = 39,266) were of similar age (mean 53.0 ± 10.7 years vs 53.3 ± 10.8 years); sex (46% vs 50.6% female) and race (29.1% vs 34.2% non-white). Relative to pre-Covid (Apr-Aug 2019) the mean monthly number of home BP readings rose during COVID-19 (Apr-Aug, 2020), from 7.3 to 9.3 per month (P < .001). During COVID-19, participants had higher monthly adjusted mean SBP (131.6 mmHg vs. 127.5 mmHg, P < .001); DBP (80.2 mmHg vs. 79.2 mmHg, P < .001); and MAP (97.4 mmHg vs. 95.3 mmHg; P < .001). Relative to the pre-pandemic period, during COVID-19 the proportion of participants with a mean monthly BP classified as uncontrolled or severely uncontrolled hypertension also rose, 15% vs 19% and 4% vs 5%, respectively Conclusions and Relevance Based on home BP readings, mean monthly BP rose modestly after COVID-19, despite increased utilization of home monitoring. Further studies are needed to examine the longitudinal effects of the pandemic on cardiovascular disease risk factors, the impact of these on long-term population health.
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Aparisi Á, Catalá P, Amat-Santos IJ, Marcos-Mangas M, López-Otero D, Veras C, López-Pais J, Cabezón-Villalba G, Cacho Antonio CE, Candela J, Antúnez-Muiños P, Gil JF, González Ferrero T, Rojas G, Pérez-Poza M, Uribarri A, Otero-García O, García-Granja PE, Jiménez Ramos V, Revilla A, Dueñas C, Gómez I, González-Juanatey JR, San Román JA. Chronic use of renin–angiotensin–aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis. MEDICINA CLÍNICA (ENGLISH EDITION) 2022; 158:315-323. [PMID: 35531305 PMCID: PMC9063316 DOI: 10.1016/j.medcle.2021.04.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 04/13/2021] [Indexed: 11/08/2022]
Abstract
Background Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin–angiotensin–aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. Methods We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. Results Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (−0.151 [95% CI −0.218, −0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (−0.167 [95% CI −0.220, −0.114]) and during hospitalization (0.090 [−0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224–0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42–0.8]) among hypertensive COVID-19. Conclusion Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.
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Sato K, White N, Fanning JP, Obonyo N, Yamashita MH, Appadurai V, Ciullo A, May M, Worku ET, Helms L, Ohshimo S, Juzar DA, Suen JY, Bassi GL, Fraser JF, Arora RC. Impact of renin-angiotensin-aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study. BMC Cardiovasc Disord 2022; 22:123. [PMID: 35321649 PMCID: PMC8942148 DOI: 10.1186/s12872-022-02565-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 03/16/2022] [Indexed: 01/08/2023] Open
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 .
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Affiliation(s)
- Kei Sato
- Critical Care Research Group, The Prince Charles Hospital, Level 3, Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
| | - Nicole White
- Australian Centre for Health Services Innovation (AusHSI) and Centre for Healthcare Transformation, Queensland University of Technology (QUT), Brisbane, QLD, Australia
| | - Jonathon P Fanning
- Critical Care Research Group, The Prince Charles Hospital, Level 3, Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Nchafatso Obonyo
- Critical Care Research Group, The Prince Charles Hospital, Level 3, Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Wellcome Trust Centre for Global Health Research, Imperial College London, London, UK
- Initiative to Develop African Research Leaders/KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
| | - Michael H Yamashita
- Section of Cardiac Surgery, Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Vinesh Appadurai
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Department of Cardiology, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Anna Ciullo
- Division of Emergency Medicine, Department of Surgery, University of Utah Health, Salt Lake City, UT, 84132, USA
| | - Meryta May
- Department of Microbiology, Sullivan Nicolaides Pathology, Brisbane, QLD, Australia
| | - Elliott T Worku
- Adult Intensive Care Services, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Leticia Helms
- Critical Care Research Group, The Prince Charles Hospital, Level 3, Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia
| | - Shinichiro Ohshimo
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Dafsah A Juzar
- Intensive Cardiovascular Care Unit, National Cardiovascular Center Harapan Kita, Jakarta, Indonesia
- Division Intensive & Emergency Cardiovascular Care, Department Cardiology and Vascular Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Jacky Y Suen
- Critical Care Research Group, The Prince Charles Hospital, Level 3, Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Gianluigi Li Bassi
- Critical Care Research Group, The Prince Charles Hospital, Level 3, Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
| | - John F Fraser
- Critical Care Research Group, The Prince Charles Hospital, Level 3, Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Adult Intensive Care Services, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Rakesh C Arora
- Section of Cardiac Surgery, Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
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Aghamirza Moghim Aliabadi H, Eivazzadeh‐Keihan R, Beig Parikhani A, Fattahi Mehraban S, Maleki A, Fereshteh S, Bazaz M, Zolriasatein A, Bozorgnia B, Rahmati S, Saberi F, Yousefi Najafabadi Z, Damough S, Mohseni S, Salehzadeh H, Khakyzadeh V, Madanchi H, Kardar GA, Zarrintaj P, Saeb MR, Mozafari M. COVID-19: A systematic review and update on prevention, diagnosis, and treatment. MedComm (Beijing) 2022; 3:e115. [PMID: 35281790 PMCID: PMC8906461 DOI: 10.1002/mco2.115] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 12/18/2021] [Accepted: 12/19/2021] [Indexed: 01/09/2023] Open
Abstract
Since the rapid onset of the COVID-19 or SARS-CoV-2 pandemic in the world in 2019, extensive studies have been conducted to unveil the behavior and emission pattern of the virus in order to determine the best ways to diagnosis of virus and thereof formulate effective drugs or vaccines to combat the disease. The emergence of novel diagnostic and therapeutic techniques considering the multiplicity of reports from one side and contradictions in assessments from the other side necessitates instantaneous updates on the progress of clinical investigations. There is also growing public anxiety from time to time mutation of COVID-19, as reflected in considerable mortality and transmission, respectively, from delta and Omicron variants. We comprehensively review and summarize different aspects of prevention, diagnosis, and treatment of COVID-19. First, biological characteristics of COVID-19 were explained from diagnosis standpoint. Thereafter, the preclinical animal models of COVID-19 were discussed to frame the symptoms and clinical effects of COVID-19 from patient to patient with treatment strategies and in-silico/computational biology. Finally, the opportunities and challenges of nanoscience/nanotechnology in identification, diagnosis, and treatment of COVID-19 were discussed. This review covers almost all SARS-CoV-2-related topics extensively to deepen the understanding of the latest achievements (last updated on January 11, 2022).
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Affiliation(s)
- Hooman Aghamirza Moghim Aliabadi
- Protein Chemistry LaboratoryDepartment of Medical BiotechnologyBiotechnology Research CenterPasteur Institute of IranTehranIran
- Advance Chemical Studies LaboratoryFaculty of ChemistryK. N. Toosi UniversityTehranIran
| | | | - Arezoo Beig Parikhani
- Department of Medical BiotechnologyBiotechnology Research CenterPasteur InstituteTehranIran
| | | | - Ali Maleki
- Department of ChemistryIran University of Science and TechnologyTehranIran
| | | | - Masoume Bazaz
- Department of Medical BiotechnologyBiotechnology Research CenterPasteur InstituteTehranIran
| | | | | | - Saman Rahmati
- Department of Medical BiotechnologyBiotechnology Research CenterPasteur InstituteTehranIran
| | - Fatemeh Saberi
- Department of Medical BiotechnologySchool of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran
| | - Zeinab Yousefi Najafabadi
- Department of Medical BiotechnologySchool of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
- ImmunologyAsthma & Allergy Research InstituteTehran University of Medical SciencesTehranIran
| | - Shadi Damough
- Department of Medical BiotechnologyBiotechnology Research CenterPasteur InstituteTehranIran
| | - Sara Mohseni
- Non‐metallic Materials Research GroupNiroo Research InstituteTehranIran
| | | | - Vahid Khakyzadeh
- Department of ChemistryK. N. Toosi University of TechnologyTehranIran
| | - Hamid Madanchi
- School of MedicineSemnan University of Medical SciencesSemnanIran
- Drug Design and Bioinformatics UnitDepartment of Medical BiotechnologyBiotechnology Research CenterPasteur Institute of IranTehranIran
| | - Gholam Ali Kardar
- Department of Medical BiotechnologySchool of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
- ImmunologyAsthma & Allergy Research InstituteTehran University of Medical SciencesTehranIran
| | - Payam Zarrintaj
- School of Chemical EngineeringOklahoma State UniversityStillwaterOklahomaUSA
| | - Mohammad Reza Saeb
- Department of Polymer TechnologyFaculty of ChemistryGdańsk University of TechnologyGdańskPoland
| | - Masoud Mozafari
- Department of Tissue Engineering & Regenerative MedicineIran University of Medical SciencesTehranIran
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Labandeira-Garcia JL, Labandeira CM, Valenzuela R, Pedrosa MA, Quijano A, Rodriguez-Perez AI. Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment. Biomedicines 2022; 10:502. [PMID: 35203711 PMCID: PMC8962306 DOI: 10.3390/biomedicines10020502] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 02/07/2023] Open
Abstract
A massive worldwide vaccination campaign constitutes the main tool against the COVID-19 pandemic. However, drug treatments are also necessary. Antivirals are the most frequently considered treatments. However, strategies targeting mechanisms involved in disease aggravation may also be effective. A major role of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 has been suggested. The main link between RAS and COVID-19 is angiotensin-converting enzyme 2 (ACE2), a central RAS component and the primary binding site for SARS-CoV-2 that facilitates the virus entry into host cells. An initial suggestion that the susceptibility to infection and disease severity may be enhanced by angiotensin type-1 receptor blockers (ARBs) and ACE inhibitors (ACEIs) because they increase ACE2 levels, led to the consideration of discontinuing treatments in thousands of patients. More recent experimental and clinical data indicate that ACEIs and, particularly, ARBs can be beneficial for COVID-19 outcome, both by reducing inflammatory responses and by triggering mechanisms (such as ADAM17 inhibition) counteracting viral entry. Strategies directly activating RAS anti-inflammatory components such as soluble ACE2, Angiotensin 1-7 analogues, and Mas or AT2 receptor agonists may also be beneficial. However, while ACEIs and ARBs are cheap and widely used, the second type of strategies are currently under study.
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Affiliation(s)
- Jose L. Labandeira-Garcia
- Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (C.M.L.); (R.V.); (M.A.P.); (A.Q.)
- Networking Research Center on Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain
| | - Carmen M. Labandeira
- Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (C.M.L.); (R.V.); (M.A.P.); (A.Q.)
- Neurology Service, Hospital Alvaro Cunqueiro, University Hospital Complex, 36213 Vigo, Spain
| | - Rita Valenzuela
- Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (C.M.L.); (R.V.); (M.A.P.); (A.Q.)
- Networking Research Center on Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain
| | - Maria A. Pedrosa
- Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (C.M.L.); (R.V.); (M.A.P.); (A.Q.)
- Networking Research Center on Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain
| | - Aloia Quijano
- Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (C.M.L.); (R.V.); (M.A.P.); (A.Q.)
| | - Ana I. Rodriguez-Perez
- Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; (C.M.L.); (R.V.); (M.A.P.); (A.Q.)
- Networking Research Center on Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain
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Castagna F, Xue X, Saeed O, Kataria R, Puius YA, Patel SR, Garcia MJ, Racine AD, Sims DB, Jorde UP. Hospital bed occupancy rate is an independent risk factor for COVID-19 inpatient mortality: a pandemic epicentre cohort study. BMJ Open 2022; 12:e058171. [PMID: 35168984 PMCID: PMC8852235 DOI: 10.1136/bmjopen-2021-058171] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 01/26/2022] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION COVID-19 first struck New York City in the spring of 2020, resulting in an unprecedented strain on our healthcare system and triggering multiple changes in public health policy governing hospital operations as well as therapeutic approaches to COVID-19. We examined inpatient mortality at our centre throughout the course of the pandemic. METHODS This is a retrospective chart review of clinical characteristics, treatments and outcome data of all patients admitted with COVID-19 from 1 March 2020 to 28 February 2021. Patients were grouped into 3-month quartiles. Hospital strain was assessed as per cent of occupied beds based on a normal bed capacity of 1491. RESULTS Inpatient mortality decreased from 25.0% in spring to 10.8% over the course of the year. During this time, use of remdesivir, steroids and anticoagulants increased; use of hydroxychloroquine and other antibiotics decreased. Daily bed occupancy ranged from 62% to 118%. In a multivariate model with all year's data controlling for demographics, comorbidities and acuity of illness, percentage of bed occupancy was associated with increased 30-day in-hospital mortality of patients with COVID-19 (0.7% mortality increase for each 1% increase in bed occupancy; HR 1.007, CI 1.001 to 1.013, p=0.004) CONCLUSION: Inpatient mortality from COVID-19 was associated with bed occupancy. Early reduction in epicentre hospital bed occupancy to accommodate acutely ill and resource-intensive patients should be a critical component in the strategic planning for future pandemics.
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Affiliation(s)
- Francesco Castagna
- Albert Einstein College of Medicine, Bronx, New York, USA
- Division of Cardiology, Montefiore Medical Center, Bronx, New York, USA
| | - Xiaonan Xue
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Omar Saeed
- Albert Einstein College of Medicine, Bronx, New York, USA
- Division of Cardiology, Montefiore Medical Center, Bronx, New York, USA
| | - Rachna Kataria
- Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Yoram A Puius
- Albert Einstein College of Medicine, Bronx, New York, USA
- Division of Infectious Diseases, Montefiore Medical Center, Bronx, New York, USA
| | - Snehal R Patel
- Albert Einstein College of Medicine, Bronx, New York, USA
- Division of Cardiology, Montefiore Medical Center, Bronx, New York, USA
| | - Mario J Garcia
- Albert Einstein College of Medicine, Bronx, New York, USA
- Division of Cardiology, Montefiore Medical Center, Bronx, New York, USA
| | - Andrew D Racine
- Albert Einstein College of Medicine, Bronx, New York, USA
- Department of Pediatrics, Montefiore Medical Center, Bronx, New York, USA
| | - Daniel B Sims
- Albert Einstein College of Medicine, Bronx, New York, USA
- Division of Cardiology, Montefiore Medical Center, Bronx, New York, USA
| | - Ulrich P Jorde
- Albert Einstein College of Medicine, Bronx, New York, USA
- Division of Cardiology, Montefiore Medical Center, Bronx, New York, USA
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Águila Gordo D, Martínez del Rio J, Piqueras Flores J. Changes in antihypertensive treatment in surviving patients SARS-CoV-2 respiratory infection and its cardiovascular impact after one year of follow-up. MEDICINA CLÍNICA (ENGLISH EDITION) 2022; 158:196-197. [PMID: 35128062 PMCID: PMC8801868 DOI: 10.1016/j.medcle.2021.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
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Klhůfek J. The role of angiotensin-converting enzyme 2 in the pathogenesis of COVID-19: the villain or the hero? Acta Clin Belg 2022; 77:211-218. [PMID: 32597377 DOI: 10.1080/17843286.2020.1786324] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Angiotensin-converting enzyme 2 (ACE 2) is the entry receptor for the novel coronavirus SARS-CoV-2, the aetiological agent of COVID-19. At the same time, ACE 2 expression decreases during COVID-19. Two seemingly contradictory relationships between the expression of ACE 2 and COVID-19 have been reported. Increased level of expression of ACE 2 may be a risk factor for the development of COVID-19 infection, while reduced ACE 2 expression during COVID-19 leads to acute respiratory distress syndrome. This article provides a comprehensive overview of available scientific knowledge about the role of ACE 2 in the pathogenesis of COVID-19, which is available up to current day. Also, it discusses unknown factors that we will have to reveal in order to understand the whole role of ACE 2 in the pathogenesis of COVID-19.
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Affiliation(s)
- Josef Klhůfek
- Department of Pharmacy, T. Bata Regional Hospital, Zlín, Czech Republic
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32
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P N, R. N, B. V, S. R, A. S. COVID-19: Invasion, pathogenesis and possible cure - A review. J Virol Methods 2022; 300:114434. [PMID: 34919978 PMCID: PMC8669942 DOI: 10.1016/j.jviromet.2021.114434] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 12/08/2021] [Accepted: 12/13/2021] [Indexed: 12/24/2022]
Abstract
Today, Coronavirus disease (COVID-19) which is believed to be transmitted from bats to humans where the people of Wuhan city, China exposed to the wet animal market is an important international public health anxiety (Xiong et al., 2020). Although, several measures were undertaken to treat the diseases by various medical advancements and by a variety of treatment procedures, still the mortality is higher. Hence, social distancing has been implemented to control the current outburst of this pandemic which spreads through human to human transmission. As a consequence, there is a need to completely understand the route of invasions of the virus into the humans and the target receptors besides the other factors leading to the disease. Several vaccines and drugs have been developed with its own pros and cons. Many are still under the various phase of R&D and clinical trials. Here we highlight the possible entry molecules, pathogenesis, symptomatology, probable cure and the recently developed vaccines for the existing pandemic due to the COVID-19.
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Affiliation(s)
- Nitin P
- Research and Development Section, Verena Haptic & VR Systems, Bhuvaneswari Nagar, Velachery, Chennai, 600042, Tamil Nadu, India
| | - Nandhakumar R.
- Department of Applied Chemistry, Karunya Institute of Technology and Sciences (Deemed to be University), Coimbatore, 641114, Tamil Nadu, India,Corresponding author at: Professor, Department of Applied Chemistry, Karunya Institute of Technology and Sciences(deemed to be University), Coimbatore - 641114, Tamil Nadu, India
| | - Vidhya B.
- Centre for Nanoscience and Genomics, Karunya Institute of Technology and Sciences (Deemed to be University), Coimbatore, 641114, Tamil Nadu, India,Corresponding author
| | - Rajesh S.
- Department of Applied Physics, Karunya Institute of Technology and Sciences (Deemed to be University), Coimbatore, 641114, Tamil Nadu, India
| | - Sakunthala A.
- Department of Applied Physics, Karunya Institute of Technology and Sciences (Deemed to be University), Coimbatore, 641114, Tamil Nadu, India
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33
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Batta Y, King C, Johnson J, Haddad N, Boueri M, Haddad G. Sequelae and Comorbidities of COVID-19 Manifestations on the Cardiac and the Vascular Systems. Front Physiol 2022; 12:748972. [PMID: 35095546 PMCID: PMC8795698 DOI: 10.3389/fphys.2021.748972] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 10/28/2021] [Indexed: 01/08/2023] Open
Abstract
COVID-19 patients with pre-existing cardiovascular conditions are at greater risk of severe illness due to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. This review evaluates the highest risk factors for these patients, not limited to pre-existing hypertension, cardiac arrhythmias, hypercoagulation, ischemic heart disease, and a history of underlying heart conditions. SARS-CoV-2 may also precipitate de novo cardiac complications. The interplay between existing cardiac conditions and de novo cardiac complications is the focus of this review. In particular, SARS-CoV-2 patients present with hypercoagulation conditions, cardiac arrhythmias, as significant complications. Also, cardiac arrhythmias are another well-known cardiovascular-related complication seen in COVID-19 infections and merit discussion in this review. Amid the pandemic, myocardial infarction (MI) has been reported to a high degree in SARS-CoV-2 patients. Currently, the specific causative mechanism of the increased incidence of MI is unclear. However, studies suggest several links to high angiotensin-converting enzyme 2 (ACE2) expression in myocardial and endothelial cells, systemic hyper-inflammation, an imbalance between myocardial oxygen supply and demand, and loss of ACE2-mediated cardio-protection. Furthermore, hypertension and SARS-CoV-2 infection patients' prognosis has shown mixed results across current studies. For this reason, an in-depth analysis of the interactions between SARS-CoV2 and the ACE2 cardio-protective mechanism is warranted. Similarly, ACE2 receptors are also expressed in the cerebral cortex tissue, both in neurons and glia. Therefore, it seems very possible for both cardiovascular and cerebrovascular systems to be damaged leading to further dysregulation and increased risk of mortality risk. This review aims to discuss the current literature related to potential complications of COVID-19 infection with hypertension and the vasculature, including the cervical one. Finally, age is a significant prognostic indicator among COVID-19 patients. For a mean age group of 70 years, the main presenting symptoms include fever, shortness of breath, and a persistent cough. Elderly patients with cardiovascular comorbidities, particularly hypertension and diabetes, represent a significant group of critical cases with increased case fatality rates. With the current understanding of COVID-19, it is essential to explore the mechanisms by which SARS-CoV-2 operates to improve clinical outcomes for patients suffering from underlying cardiovascular diseases and reduce the risk of such conditions de novo.
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Affiliation(s)
- Yashvardhan Batta
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - Cody King
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - John Johnson
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | - Natasha Haddad
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
| | | | - Georges Haddad
- Department Physiology and Biophysics, College of Medicine, Howard University, Washington, DC, United States
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Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry. J Cardiovasc Dev Dis 2022; 9:jcdd9010015. [PMID: 35050225 PMCID: PMC8781822 DOI: 10.3390/jcdd9010015] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 01/02/2022] [Accepted: 01/05/2022] [Indexed: 02/07/2023] Open
Abstract
Background: It is uncertain whether exposure to renin–angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. Methods: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. Results: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). Conclusions: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.
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Oto OA, Kardeş S, Guller N, Safak S, Dirim AB, Başhan Y, Demir E, Artan AS, Yazıcı H, Turkmen A. Impact of the COVID-19 pandemic on interest in renal diseases. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:711-718. [PMID: 34341920 PMCID: PMC8328136 DOI: 10.1007/s11356-021-15675-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/23/2021] [Indexed: 06/13/2023]
Abstract
There is an information gap about the public's interest in nephrological diseases in the COVID-19 era. The objective was to identify public interest in kidney diseases during the pandemic. In this infodemiology study, Google Trends was queried for a total of 50 search queries corresponding to a broad spectrum of nephrological diseases and the term "nephrologist." Two time intervals of 2020 (March 15-July 4 and July 5-October 31) were compared to similar time intervals of 2016-2019 for providing information on interest in different phases of the pandemic. Compared to the prior 4 years, analyses showed significant decreases in relative search volume (RSV) in the majority (76%) of search queries on March 15-July 4, 2020 period. However, RSV of the majority of search queries (≈70%) on July 5-October 31, 2020 period was not significantly different from similar periods of the previous 4 years, with an increase in search terms of amyloidosis, kidney biopsy, hematuria, chronic kidney disease, hypertension, nephrolithiasis, acute kidney injury, and Fabry disease. During the early pandemic, there have been significant decreases in search volumes for many nephrological diseases. However, this trend reversed in the period from July 5 to October 31, 2020, implying the increased need for information on kidney diseases. The results of this study enable us to understand how COVID-19 impacted the interest in kidney diseases and demands/needs for kidney diseases by the general public during the pandemic.
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Affiliation(s)
- Ozgur Akin Oto
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
| | - Sinan Kardeş
- Department of Medical Ecology and Hydroclimatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Nurane Guller
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Seda Safak
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ahmet Burak Dirim
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Yağmur Başhan
- Department of Nephrology, Haseki Education Research Hospital, Istanbul, Turkey
| | - Erol Demir
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ayse Serra Artan
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Halil Yazıcı
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Aydın Turkmen
- Department of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Singh B, Singh D, Verma V, Yadav R, Kumar R. Angiotensin-converting enzyme 2 as a potential therapeutic target for COVID-19: A review. J Pharm Anal 2021; 12:215-220. [PMID: 34934510 PMCID: PMC8677424 DOI: 10.1016/j.jpha.2021.12.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 12/04/2021] [Accepted: 12/14/2021] [Indexed: 02/06/2023] Open
Abstract
As of August 16, 2021, there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease (COVID-19), and the pandemic remains a global challenge. To date, no effective and approved drugs are available for the treatment of COVID-19. Angiotensin-converting enzyme 2 (ACE2) plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Notably, ACE2 density is influenced by medical conditions, such as hypertension, or by drugs, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which can change the fate of SARS-CoV-2 infectivity. ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells. Different strategies aimed at blocking ACE2 with small molecules, peptides, and antibodies, or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2 (hrsACE2) are currently under investigation. In this article, we review the current state of knowledge that emphasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target. The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease. It has not yet been established whether hypertension and other comorbidities, independent of age, have a direct role in COVID-19. Therefore, the use of renin-angiotensin system inhibitors, ACEIs and ARBs, should not be discontinued during COVID-19 treatment.
Blockage of the interaction between the SARS-CoV-2 S protein and ACE2 as a strategy to treat COVID-19 is underway. ACE2 upregulation leads to the increased release of soluble ACE2. Increasing the levels of soluble ACE2 and hrsACE2 has the potential to prevent SARS-CoV-2 infection and reverse lung injury.
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Affiliation(s)
- Bhagat Singh
- Department of Medical Laboratory Technology, Faculty of Paramedical Sciences, Uttar Pradesh University of Medical Sciences, Etawah, 206130, India
| | - Dheer Singh
- Department of Anaesthesiology and Critical Care, Uttar Pradesh University of Medical Sciences, Etawah, 206130, India
| | - Vinod Verma
- Stem Cell Research Centre, Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Ramakant Yadav
- Department of Neurology, Uttar Pradesh University of Medical Sciences, Etawah, 206130, India
| | - Raj Kumar
- Department of Neurosurgery, Uttar Pradesh University of Medical Sciences, Etawah, 206130, India
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Renin-angiotensin System Blocker in COVID-19. A Single Center Study. J Cardiovasc Pharmacol 2021; 79:311-314. [PMID: 34861663 DOI: 10.1097/fjc.0000000000001189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 11/08/2021] [Indexed: 11/26/2022]
Abstract
Early during the Covid-19 pandemic, concerns were raised regarding potential adverse outcomes in patients taking ACEIs/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, post-admission hemodialysis requirement and the need for mechanical ventilation in patients with COVID-19. This cohort of 289 patients included 139/289 (48%) women 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/TIA 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 to the non-user group. There was significantly higher in-hospital mortality in patients using ACEIs/ARBs than non-users 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, post-admission hemodialysis requirement, and mechanical ventilation showed no significant differences between the two 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.
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Sharifi Y, Payab M, Mohammadi-Vajari E, Aghili SMM, Sharifi F, Mehrdad N, Kashani E, Shadman Z, Larijani B, Ebrahimpur M. Association between cardiometabolic risk factors and COVID-19 susceptibility, severity and mortality: a review. J Diabetes Metab Disord 2021; 20:1743-1765. [PMID: 34222055 PMCID: PMC8233632 DOI: 10.1007/s40200-021-00822-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 05/23/2021] [Indexed: 02/08/2023]
Abstract
The novel coronavirus, which began spreading from China Wuhan and gradually spreaded to most countries, led to the announcement by the World Health Organization on March 11, 2020, as a new pandemic. The most important point presented by the World Health Organization about this disease is to better understand the risk factors that exacerbate the course of the disease and worsen its prognosis. Due to the high majority of cardio metabolic risk factors like obesity, hypertension, diabetes, and dyslipidemia among the population over 60 years old and higher, these cardio metabolic risk factors along with the age of these people could worsen the prognosis of the coronavirus disease of 2019 (COVID-19) and its mortality. In this study, we aimed to review the articles from the beginning of the pandemic on the impression of cardio metabolic risk factors on COVID-19 and the effectiveness of COVID-19 on how to manage these diseases. All the factors studied in this article, including hypertension, diabetes mellitus, dyslipidemia, and obesity exacerbate the course of Covid-19 disease by different mechanisms, and the inflammatory process caused by coronavirus can also create a vicious cycle in controlling these diseases for patients.
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Affiliation(s)
- Yasaman Sharifi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Yaas Diabetes and Metabolic Diseases Research Center, Indiana University School of Medicine, Indianapolis, IN 46202 US
| | - Moloud Payab
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Erfan Mohammadi-Vajari
- Student of Medicine, School of Medicine, Gilan University of Medical Sciences, Rasht, Iran
| | - Seyed Morsal Mosallami Aghili
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farshad Sharifi
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Neda Mehrdad
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Nursing Care Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Elham Kashani
- Department of Obstetrics and Gynecology, Golestan University of Medical Sciences, Golestan, Iran
| | - Zhaleh Shadman
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahbube Ebrahimpur
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Ferreira JP, Girerd N, Rocca HPBL, Pellicori P, Cleland JG, Rossignol P, Zannad F. No influence of spironolactone on plasma concentrations of angiotensin-converting enzyme 2: Findings from the HOMAGE randomized trial. Arch Cardiovasc Dis 2021; 114:814-817. [PMID: 34772647 PMCID: PMC8576594 DOI: 10.1016/j.acvd.2021.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 10/12/2021] [Accepted: 10/21/2021] [Indexed: 12/12/2022]
Affiliation(s)
- João Pedro Ferreira
- Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), centre d'investigations cliniques-plurithématique 1433, Nancy, France; Unidade de Investigaçao Cardiovascular-UnIC, Faculdade de Medicina Universidade do Porto, Porto, Portugal.
| | - Nicolas Girerd
- Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), centre d'investigations cliniques-plurithématique 1433, Nancy, France
| | | | - Pierpaolo Pellicori
- Clinical Trials Unit, Robertson Institute of Biostatistics, University of Glasgow, University Avenue, Glasgow, UK
| | - John G Cleland
- Clinical Trials Unit, Robertson Institute of Biostatistics, University of Glasgow, University Avenue, Glasgow, UK
| | - Patrick Rossignol
- Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), centre d'investigations cliniques-plurithématique 1433, Nancy, France
| | - Faiez Zannad
- Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), centre d'investigations cliniques-plurithématique 1433, Nancy, France
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Yadullahi Mir WA, Siddiqui AH, Valecha G, Patel S, Ayub F, Upadhyay R, Alhajri SA, Gaire S, Shrestha DB. A Narrative Review of Existing Options for COVID-19-Specific Treatments. Adv Virol 2021; 2021:8554192. [PMID: 34804163 PMCID: PMC8604608 DOI: 10.1155/2021/8554192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 10/16/2021] [Indexed: 12/15/2022] Open
Abstract
The new coronavirus disease 2019 (COVID-19) was declared a global pandemic in early 2020. The ongoing COVID-19 pandemic has affected morbidity and mortality tremendously. Even though multiple drugs are being used throughout the world since the advent of COVID-19, only limited treatment options are available for COVID-19. Therefore, drugs targeting various pathologic aspects of the disease are being explored. Multiple studies have been published to demonstrate their clinical efficacy until now. Based on the current evidence to date, we summarized the mechanism, roles, and side effects of all existing treatment options to target this potentially fatal virus.
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Affiliation(s)
| | | | - Gautam Valecha
- Department of Oncology, Presbyterian Healthcare Services, Albuquerque, NM, USA
| | - Shawn Patel
- Department of Internal Medicine, The Carle Illinois College of Medicine, Champaign, IL, USA
| | - Fatima Ayub
- Department of Internal Medicine, The Carle Illinois College of Medicine, Champaign, IL, USA
| | - Riddhi Upadhyay
- Department of Internal Medicine, The Carle Illinois College of Medicine, Champaign, IL, USA
| | - Sana Ahmed Alhajri
- Department of Pediatrics, University of Illinois Chicago, Chicago, IL, USA
| | - Suman Gaire
- Department of Emergency Medicine, Palpa Hospital, Palpa, Nepal
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Wu C, Qu G, Wang L, Cao S, Xia D, Wang B, Fan X, Wang C. Clinical Characteristics and Inflammatory Immune Responses in COVID-19 Patients With Hypertension: A Retrospective Study. Front Pharmacol 2021; 12:721769. [PMID: 34759820 PMCID: PMC8573086 DOI: 10.3389/fphar.2021.721769] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/18/2021] [Indexed: 11/21/2022] Open
Abstract
Coronavirus disease (COVID-19) patients with cardiovascular and metabolic disorders have been found to have a high risk of developing severe conditions with high mortality, further affecting the prognosis of COVID-19. However, the effect of hypertension and angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) agents on the clinical characteristics and inflammatory immune responses in COVID-19 patients is still undefined. In this study, 90 COVID-19 patients were divided into hypertension and nonhypertension groups. The hypertension group was divided into well-controlled and poorly controlled subgroups based on blood pressure levels; moreover, hypertensive patients were also divided into ACEI/ARB and non-ACEI/ARB subgroups according to the administration of ACEI/ARB antihypertensive agents. The clinical characteristics of and inflammatory immune biomarker levels in the different groups of COVID-19 patients were compared, and the association between the combined effect of hypertension with ACEI/ARB antihypertensive agents and the severity of COVID-19 was examined. The results showed that the levels of aminotransferase (AST) and hs-cTnI were higher in the hypertension group compared with the nonhypertension group. The long-term use of ACEI/ARB agents in patients had statistically significantly lower AST, low-density lipoprotein cholesterol (LDL-C), and oxygen uptake and lower white cell count, neutrophil count, and levels of CD4, CD8, CRP, and PCT but without statistical significance. In addition, compared with COVID-19 patients without hypertension, hypertensive patients without the use of ACEI/ARB had a higher risk of developing severity of COVID-19 (for poorly controlled patients: OR = 3.97, 95% CI = 1.03–15.30; for well-controlled patients: OR = 6.48, 95% CI = 1.77–23.81). Hypertension could cause organ damage in COVID-19 patients, but the long-term use of ACEI/ARB agents may be beneficial to alleviate this injury.
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Affiliation(s)
- Chaoran Wu
- Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guangbo Qu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Lei Wang
- Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Shiyu Cao
- Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Dandan Xia
- Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Baolong Wang
- Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Xiaoyun Fan
- Department of Geriatric Respiratory and Critical Care, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Changhui Wang
- Department of Cardiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Ionescu M, Stoian AP, Rizzo M, Serban D, Nuzzo D, Mazilu L, Suceveanu AI, Dascalu AM, Parepa IR. The Role of Endothelium in COVID-19. Int J Mol Sci 2021; 22:11920. [PMID: 34769350 PMCID: PMC8584762 DOI: 10.3390/ijms222111920] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 10/27/2021] [Accepted: 10/31/2021] [Indexed: 01/08/2023] Open
Abstract
The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin-angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.
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Affiliation(s)
- Mihaela Ionescu
- Cardiology Department, Faculty of Medicine, Ovidius University of Constanţa, 900527 Constanţa, Romania; (M.I.); (I.R.P.)
| | - Anca Pantea Stoian
- Diabetes, Nutrition, and Metabolic Diseases Department, Faculty of Medicine, Carol Davila University, 050474 Bucharest, Romania; (A.P.S.); (M.R.)
| | - Manfredi Rizzo
- Diabetes, Nutrition, and Metabolic Diseases Department, Faculty of Medicine, Carol Davila University, 050474 Bucharest, Romania; (A.P.S.); (M.R.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90100 Palermo, Italy
| | - Dragos Serban
- Forth Surgery Department, Emergency University Hospital Bucharest and Faculty of Medicine, Carol Davila University, 050474 Bucharest, Romania;
| | - Domenico Nuzzo
- Italian National Research Council, Institute for Research and Biomedical Innovation (CNR-IRIB), 90100 Palermo, Italy
| | - Laura Mazilu
- Oncology Department, Faculty of Medicine, Ovidius University of Constanţa, 900527 Constanţa, Romania;
| | - Andra Iulia Suceveanu
- Internal Medicine Department, Faculty of Medicine, Ovidius University of Constanţa, 900527 Constanţa, Romania;
| | - Ana Maria Dascalu
- Department of Ophthalmology, Emergency University Hospital Bucharest and Faculty of Medicine, Carol Davila University, 050474 Bucharest, Romania;
| | - Irinel Raluca Parepa
- Cardiology Department, Faculty of Medicine, Ovidius University of Constanţa, 900527 Constanţa, Romania; (M.I.); (I.R.P.)
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Gameiro J, Fonseca JA, Oliveira J, Marques F, Bernardo J, Costa C, Carreiro C, Braz S, Lopes JA. Acute kidney injury in hospitalized patients with COVID-19: A Portuguese cohort. Nefrologia 2021; 41:689-698. [PMID: 36165158 PMCID: PMC8800378 DOI: 10.1016/j.nefroe.2022.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 04/18/2021] [Indexed: 06/16/2023] Open
Abstract
INTRODUCTION The incidence of acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients ranges from 0.5% to 35% and has been associated with worse prognosis. The purpose of this study was to evaluate the incidence, severity, duration, risk factors and prognosis of AKI in hospitalized patients with COVID-19. METHODS We conducted a retrospective single-center analysis of 192 hospitalized COVID-19 patients from March to May of 2020. AKI was diagnosed using the Kidney Disease Improving Global Outcome (KDIGO) classification based on serum creatinine (SCr) criteria. Persistent and transient AKI were defined according to the Acute Disease Quality Initiative (ADQI) workgroup definitions. RESULTS In this cohort of COVID-19 patients, 55.2% developed AKI (n=106). The majority of AKI patients had persistent AKI (n=64, 60.4%). Overall, in-hospital mortality was 18.2% (n=35) and was higher in AKI patients (28.3% vs. 5.9%, p<0.001, unadjusted OR 6.03 (2.22-16.37), p<0.001). In this multivariate analysis, older age (adjusted OR 1.07 (95% CI 1.02-1.11), p=0.004), lower Hb level (adjusted OR 0.78 (95% CI 0.60-0.98), p=0.035), duration of AKI (adjusted OR 7.34 for persistent AKI (95% CI 2.37-22.72), p=0.001) and severity of AKI (adjusted OR 2.65 per increase in KDIGO stage (95% CI 1.32-5.33), p=0.006) were independent predictors of mortality. CONCLUSION AKI was frequent in hospitalized patients with COVID-19. Persistent AKI and higher severity of AKI were independent predictors of in-hospital mortality.
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Affiliation(s)
- Joana Gameiro
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal.
| | - José Agapito Fonseca
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
| | - João Oliveira
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
| | - Filipe Marques
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
| | - João Bernardo
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
| | - Claudia Costa
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
| | - Carolina Carreiro
- Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
| | - Sandra Braz
- Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
| | - José António Lopes
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Lisboa Norte, EPE, Av. Prof. Egas Moniz, 1649-035 Lisboa, Portugal
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Siller A, Wachter GA, Neururer S, Pfeifer B, Astl M, Borena W, Kimpel J, Elmer S, Spöck F, Vales A, Mühlbacher A, Gaber M, Willeit P, Schennach H. Prevalence of SARS-CoV-2 antibodies in healthy blood donors from the state of Tyrol, Austria, in summer 2020. Wien Klin Wochenschr 2021; 133:1272-1280. [PMID: 34698961 PMCID: PMC8546400 DOI: 10.1007/s00508-021-01963-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/28/2021] [Indexed: 01/08/2023]
Abstract
Background Seroepidemiological studies provide important insight into the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) in our society. We aimed to determine seropositivity of SARS-CoV‑2 antibodies and its cross-sectional correlates in a large cohort of blood donors. Methods In this observational cohort study, we tested healthy blood donors residing in Tyrol, Austria, for SARS-CoV‑2 antibodies using the Abbott SARS-CoV‑2 IgG chemiluminescent microparticle immunoassay. We estimated 95% confidence intervals (95% CI) of seroprevalences using bootstrapping and tested for differences by participant characteristics using logistic regression. Findings Between 8 June and 4 September 2020, we screened 5345 healthy individuals at local blood donor sessions (mean age 42.7 years, SD 13.5 years, 46.7% female). Overall seroprevalence was 3.1% (95% CI 2.7–3.6%, 165 cases), which is 5.1-fold higher (95% CI 4.5–6.0%) than the case number identified by the health authorities in the state-wide testing program (0.6%; 4536 out of 757,634). Seroprevalence was higher in the district Landeck (16.6%, P < 0.001) and in individuals aged < 25 years (4.7%, P = 0.043), but did not differ by gender, blood types, or medication intake. The odds ratio for seropositivity was 2.51 for participants who had travelled to Ischgl (1.49–4.21, P = 0.001), 1.39 who had travelled to other federal states (1.00–1.93, P = 0.052), and 2.41 who had travelled abroad (1.61–3.63, P < 0.001). Compared to participants who had a suspected/confirmed SARS-CoV‑2 infection but were seronegative, seropositive participants more frequently reported loss of smell (odds ratio = 2.49, 1.32–4.68, P = 0.005) and taste (odds ratio = 2.76, 1.54–4.92, P = 0.001). Conclusion In summer 2020, SARS-CoV‑2 seroprevalence in Tyrolean blood donors was 3.1%. Our study revealed regional variation and associations with young age, travel history and specific symptoms.
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Affiliation(s)
- Anita Siller
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria
| | - Gregor A Wachter
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria
| | - Sabrina Neururer
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Bernhard Pfeifer
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria.,Division for healthcare network and telehealth, UMIT-Private University for Health Sciences, Medical Informatics and Technology GmbH, Hall, Austria
| | - Manfred Astl
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria
| | - Wegene Borena
- Institute for Virology, Department for Hygiene, Microbiology and Public Health, Medical University of Innsbruck, Innsbruck, Austria
| | - Janine Kimpel
- Institute for Virology, Department for Hygiene, Microbiology and Public Health, Medical University of Innsbruck, Innsbruck, Austria
| | - Sebastian Elmer
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria
| | - Franziska Spöck
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria
| | - Anja Vales
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria
| | - Annelies Mühlbacher
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria
| | - Manfred Gaber
- Blood donor service Tyrol of the Austrian Red Cross, Rum, Austria
| | - Peter Willeit
- Clinical Epidemiology Team, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. .,Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
| | - Harald Schennach
- Central Institute for Blood Transfusion and Immunology, Tirol Kliniken GmbH, Anichstraße 35, 6020, Innsbruck, Austria.
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Angeli F, Verdecchia P, Reboldi G. Pharmacotherapy for hypertensive urgency and emergency in COVID-19 patients. Expert Opin Pharmacother 2021; 23:235-242. [PMID: 34634987 PMCID: PMC8544668 DOI: 10.1080/14656566.2021.1990264] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction Hypertension is a common chronic disorder in patients hospitalized for coronavirus disease 2019 (COVID-19). Furthermore, an exaggerated cardiovascular response with persistently raised blood pressure during hospitalization seems independently associated with in-hospital all-cause mortality, intensive care unit admission and heart failure. However, the real burden of elevated blood pressure during the acute phase of COVID-19 remains undefined. Areas covered The authors review the available evidence on the pharmacotherapy for the treatment of acute elevations in blood pressure (including hypertensive urgency and emergency) in COVID-19 patients. Expert opinion Acute elevations in blood pressure and unstable in-hospital blood pressure may be associated with organ damage and worse outcome in patients with COVID-19. In this setting, hypertensive emergencies require immediate reduction in blood pressure through intravenous treatment according to specific features and goals. Conversely, hypertensive urgencies usually require solely oral treatment. Diuretics, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and calcium channel blockers may be of benefit in treating COVID-19 patients with elevated blood pressure values.
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Affiliation(s)
- Fabio Angeli
- Department of Medicine and Surgery, University of Insubria - Varese and Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS, Tradat, Italy
| | - Paolo Verdecchia
- Fondazione Umbra Cuore E Ipertensione-ONLUS and Division of Cardiology, Hospital S. Maria Della Misericordia, Perugia, Italy
| | - Gianpaolo Reboldi
- Department of Medicine, and Centro Di Ricerca Clinica E Traslazionale (CERICLET), University of Perugia, Perugia, Italy
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Sandhu AT, Kohsaka S, Lin S, Woo CY, Goldstein MK, Heidenreich PA. Renin-angiotensin-aldosterone system inhibitors and SARS-CoV-2 infection: an analysis from the veteran's affairs healthcare system. Am Heart J 2021; 240:46-57. [PMID: 34126079 PMCID: PMC8196226 DOI: 10.1016/j.ahj.2021.06.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 06/07/2021] [Indexed: 12/15/2022]
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.
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Affiliation(s)
- Alexander T Sandhu
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA.
| | - Shun Kohsaka
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
| | - Shoutzu Lin
- Medical Service, VA Palo Alto Health Care System, Palo Alto, CA
| | | | - Mary K Goldstein
- Medical Service, VA Palo Alto Health Care System, Palo Alto, CA; Center for Health Policy and Primary Care and Outcomes Research, Department of Medicine, Stanford, CA
| | - Paul A Heidenreich
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA; Medical Service, VA Palo Alto Health Care System, Palo Alto, CA
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Touyz RM, Boyd MO, Guzik T, Padmanabhan S, McCallum L, Delles C, Mark PB, Petrie JR, Rios F, Montezano AC, Sykes R, Berry C. Cardiovascular and Renal Risk Factors and Complications Associated With COVID-19. CJC Open 2021; 3:1257-1272. [PMID: 34151246 PMCID: PMC8205551 DOI: 10.1016/j.cjco.2021.05.020] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 05/28/2021] [Indexed: 01/08/2023] Open
Abstract
The current COVID-19 pandemic, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus, represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase, and subsequent chronic phase). The major cardiometabolic drivers identified as having epidemiologic and mechanistic associations with COVID-19 are abnormal adiposity, dysglycemia, dyslipidemia, and hypertension. Hypertension is of particular interest, because components of the renin-angiotensin system (RAS), which are critically involved in the pathophysiology of hypertension, are also implicated in COVID-19. Specifically, angiotensin-converting enzyme-2 (ACE2), a multifunctional protein of the RAS, which is part of the protective axis of the RAS, is also the receptor through which SARS-CoV-2 enters host cells, causing viral infection. Cardiovascular and cardiometabolic comorbidities not only predispose people to COVID-19, but also are complications of SARS-CoV-2 infection. In addition, increasing evidence indicates that acute kidney injury is common in COVID-19, occurs early and in temporal association with respiratory failure, and is associated with poor prognosis, especially in the presence of cardiovascular risk factors. Here, we discuss cardiovascular and kidney disease in the context of COVID-19 and provide recent advances on putative pathophysiological mechanisms linking cardiovascular disease and COVID-19, focusing on the RAS and ACE2, as well as the immune system and inflammation. We provide up-to-date information on the relationships among hypertension, diabetes, and COVID-19 and emphasize the major cardiovascular diseases associated with COVID-19. We also briefly discuss emerging cardiovascular complications associated with long COVID-19, notably postural tachycardia syndrome (POTS).
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Affiliation(s)
- Rhian M. Touyz
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Marcus O.E. Boyd
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Tomasz Guzik
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Sandosh Padmanabhan
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Linsay McCallum
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Christian Delles
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Patrick B. Mark
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - John R. Petrie
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Francisco Rios
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Augusto C. Montezano
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Robert Sykes
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
| | - Colin Berry
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation, Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
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Fagyas M, Bánhegyi V, Úri K, Enyedi A, Lizanecz E, Mányiné IS, Mártha L, Fülöp GÁ, Radovits T, Pólos M, Merkely B, Kovács Á, Szilvássy Z, Ungvári Z, Édes I, Csanádi Z, Boczán J, Takács I, Szabó G, Balla J, Balla G, Seferovic P, Papp Z, Tóth A. Changes in the SARS-CoV-2 cellular receptor ACE2 levels in cardiovascular patients: a potential biomarker for the stratification of COVID-19 patients. GeroScience 2021; 43:2289-2304. [PMID: 34674152 PMCID: PMC8529378 DOI: 10.1007/s11357-021-00467-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 09/22/2021] [Indexed: 01/25/2023] Open
Abstract
Angiotensin-converting enzyme 2 (ACE2) is essential for SARS-CoV-2 cellular entry. Here we studied the effects of common comorbidities in severe COVID-19 on ACE2 expression. ACE2 levels (by enzyme activity and ELISA measurements) were determined in human serum, heart and lung samples from patients with hypertension (n = 540), heart transplantation (289) and thoracic surgery (n = 49). Healthy individuals (n = 46) represented the controls. Serum ACE2 activity was increased in hypertensive subjects (132%) and substantially elevated in end-stage heart failure patients (689%) and showed a strong negative correlation with the left ventricular ejection fraction. Serum ACE2 activity was higher in male (147%), overweight (122%), obese (126%) and elderly (115%) hypertensive patients. Primary lung cancer resulted in higher circulating ACE2 activity, without affecting ACE2 levels in the surrounding lung tissue. Male sex resulted in elevated serum ACE2 activities in patients with heart transplantation or thoracic surgery (146% and 150%, respectively). Left ventricular (tissular) ACE2 activity was unaffected by sex and was lower in overweight (67%), obese (62%) and older (73%) patients with end-stage heart failure. There was no correlation between serum and tissular (left ventricular or lung) ACE2 activities. Neither serum nor tissue (left ventricle or lung) ACE2 levels were affected by RAS inhibitory medications. Abandoning of ACEi treatment (non-compliance) resulted in elevated blood pressure without effects on circulating ACE2 activities. ACE2 levels associate with the severity of cardiovascular diseases, suggestive for a role of ACE2 in the pathomechanisms of cardiovascular diseases and providing a potential explanation for the higher mortality of COVID-19 among cardiovascular patients. Abandoning RAS inhibitory medication worsens the cardiovascular status without affecting circulating or tissue ACE2 levels.
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Affiliation(s)
- Miklós Fagyas
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
- Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Viktor Bánhegyi
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
- Doctoral School of Kálmán Laki, University of Debrecen, Debrecen, Hungary
- Department of Cardiac Surgery, University of Halle, Halle (Saale), Germany
| | - Katalin Úri
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
| | - Attila Enyedi
- Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Erzsébet Lizanecz
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
- Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Ivetta Siket Mányiné
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
| | - Lilla Mártha
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
| | - Gábor Áron Fülöp
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
- Doctoral School of Kálmán Laki, University of Debrecen, Debrecen, Hungary
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Tamás Radovits
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Miklós Pólos
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Béla Merkely
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Árpád Kovács
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
- Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zoltán Szilvássy
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zoltán Ungvári
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - István Édes
- Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zoltán Csanádi
- Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Judit Boczán
- Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - István Takács
- Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Gábor Szabó
- Department of Cardiac Surgery, University of Halle, Halle (Saale), Germany
| | - József Balla
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, Budapest, Hungary
| | - György Balla
- HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, Budapest, Hungary
- Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Petar Seferovic
- Heart Failure Center, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Zoltán Papp
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary
- HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, Budapest, Hungary
| | - Attila Tóth
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond street, Debrecen, 4032, Hungary.
- HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
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Formanowicz D, Gutowska K, Szawulak B, Formanowicz P. The Crosstalk between SARS-CoV-2 Infection and the RAA System in Essential Hypertension-Analyses Using Systems Approach. Int J Mol Sci 2021; 22:ijms221910518. [PMID: 34638859 PMCID: PMC8508810 DOI: 10.3390/ijms221910518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 09/19/2021] [Accepted: 09/22/2021] [Indexed: 11/16/2022] Open
Abstract
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the coronavirus disease of 2019 (COVID-19) pandemic, has affected and continues to affect millions of people across the world. Patients with essential arterial hypertension and renal complications are at particular risk of the fatal course of this infection. In our study, we have modeled the selected processes in a patient with essential hypertension and chronic kidney disease (CKD) suffering from COVID-19, emphasizing the function of the renin-angiotensin-aldosterone (RAA) system. The model has been built in the language of Petri nets theory. Using the systems approach, we have analyzed how COVID-19 may affect the studied organism, and we have checked whether the administration of selected anti-hypertensive drugs (angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs)) may impact the severity of the infection. Besides, we have assessed whether these drugs effectively lower blood pressure in the case of SARS-CoV-2 infection affecting essential hypertensive patients. Our research has shown that neither the ACEIs nor the ARBs worsens the course infection. However, when assessing the treatment of hypertension in the active SARS-CoV-2 infection, we have observed that ARBs might not effectively reduce blood pressure; they may even have the slightly opposite effect. On the other hand, we have confirmed the effectiveness of arterial hypertension treatment in patients receiving ACEIs. Moreover, we have found that the simultaneous use of ARBs and ACEIs averages the effects of taking both drugs, thus leading to only a slight decrease in blood pressure. We are a way from suggesting that ARBs in all hypertensive patients with COVID-19 are ineffective, but we have shown that research in this area should still be continued.
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Affiliation(s)
- Dorota Formanowicz
- Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland;
| | - Kaja Gutowska
- Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland; (K.G.); (B.S.)
| | - Bartłomiej Szawulak
- Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland; (K.G.); (B.S.)
| | - Piotr Formanowicz
- Institute of Computing Science, Poznan University of Technology, 60-965 Poznan, Poland; (K.G.); (B.S.)
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland
- Correspondence:
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Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells. Redox Biol 2021; 46:102099. [PMID: 34509916 PMCID: PMC8372492 DOI: 10.1016/j.redox.2021.102099] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 08/10/2021] [Accepted: 08/11/2021] [Indexed: 01/08/2023] Open
Abstract
The outbreak of COVID-19 has remained uncontained with urgent need for robust therapeutics. We have previously reported sex difference of COVID-19 for the first time indicating male predisposition. Males are more susceptible than females, and more often to develop into severe cases with higher mortality. This predisposition is potentially linked to higher prevalence of cigarette smoking. Nonetheless, we found for the first time that cigarette smoking extract (CSE) had no effect on angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) expression in endothelial cells. The otherwise observed worse outcomes in smokers is likely linked to baseline respiratory diseases associated with chronic smoking. Instead, we hypothesized that estrogen mediated protection might underlie lower morbidity, severity and mortality of COVID-19 in females. Of note, endothelial inflammation and barrier dysfunction are major mediators of disease progression, and development of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. Therefore, we investigated potential protective effects of estrogen on endothelial cells against oxidative stress induced by interleukin-6 (IL-6) and SARS-CoV-2 spike protein (S protein). Indeed, 17β-estradiol completely reversed S protein-induced selective activation of NADPH oxidase isoform 2 (NOX2) and reactive oxygen species (ROS) production that are ACE2-dependent, as well as ACE2 upregulation and induction of pro-inflammatory gene monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to effectively attenuate endothelial dysfunction. Effects of IL-6 on activating NOX2-dependent ROS production and upregulation of MCP-1 were also completely attenuated by 17β-estradiol. Of note, co-treatment with CSE had no additional effects on S protein stimulated endothelial oxidative stress, confirming that current smoking status is likely unrelated to more severe disease in chronic smokers. These data indicate that estrogen can serve as a novel therapy for patients with COVID-19 via inhibition of initial viral responses and attenuation of cytokine storm induced endothelial dysfunction, to substantially alleviate morbidity, severity and mortality of the disease, especially in men and post-menopause women. Short-term administration of estrogen can therefore be readily applied to the clinical management of COVID-19 as a robust therapeutic option.
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