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1
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Das S, Nath S, Shahjahan, Dey SK. Plausible mechanism of drug resistance and side-effects of COVID-19 therapeutics: a bottleneck for its eradication. Daru 2024; 32:801-823. [PMID: 39026019 PMCID: PMC11554973 DOI: 10.1007/s40199-024-00524-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 06/11/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few. OBJECTIVES Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children. METHODS We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports. RESULTS The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives. CONCLUSION COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.
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Affiliation(s)
- Swarnali Das
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, 208016, India
| | - Sreyashi Nath
- Imaging Cell Signaling and Therapeutics Lab, Advanced Centre for Training Research and Education in Cancer, Navi Mumbai, 410210, India
- Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India
| | - Shahjahan
- Laboratory for Structural Biology of Membrane Proteins, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India
| | - Sanjay Kumar Dey
- Laboratory for Structural Biology of Membrane Proteins, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India.
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2
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Jasiczek J, Doroszko A, Trocha T, Trocha M. Role of the RAAS in mediating the pathophysiology of COVID-19. Pharmacol Rep 2024; 76:475-486. [PMID: 38652364 PMCID: PMC11126499 DOI: 10.1007/s43440-024-00596-3] [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: 12/19/2023] [Revised: 04/04/2024] [Accepted: 04/05/2024] [Indexed: 04/25/2024]
Abstract
The renin-angiotensin-aldosterone system (RAAS) holds a position of paramount importance as enzymatic and endocrine homeostatic regulator concerning the water-electrolyte and acid-base balance. Nevertheless, its intricacy is influenced by the presence of various complementary angiotensins and their specific receptors, thereby modifying the primary RAAS actions. Angiotensin-converting enzyme 2 (ACE2) acts as a surface receptor for SARS-CoV-2, establishing an essential connection between RAAS and COVID-19 infection. Despite the recurring exploration of the RAAS impact on the trajectory of COVID-19 along with the successful resolution of many inquiries, its complete role in the genesis of delayed consequences encompassing long COVID and cardiovascular thrombotic outcomes during the post-COVID phase as well as post-vaccination, remains not fully comprehended. Particularly noteworthy is the involvement of the RAAS in the molecular mechanisms underpinning procoagulant processes throughout COVID-19. These processes significantly contribute to the pathogenesis of organ complications as well as determine clinical outcomes and are discussed in this manuscript.
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Affiliation(s)
- Jakub Jasiczek
- Department of Cardiology, Regional Specialist Hospital in Wrocław, Kamieńskiego 73a, Wrocław, 51-124, Poland
| | - Adrian Doroszko
- Department of Cardiology, 4th Military Hospital, Faculty of Medicine, Wroclaw University of Science and Technology, Weigla 5, Wrocław, 50-981, Poland
| | - Tymoteusz Trocha
- Faculty of Medicine, Wroclaw Medical University, Borowska 213, Wrocław, 50-556, Poland.
| | - Małgorzata Trocha
- Clinical Department of Diabetology and Internal Disease, Wroclaw Medical University, Borowska 213, Wrocław, 50-556, Poland
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3
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Baldelli A, Jerry Wong CY, Oguzlu H, Gholizadeh H, Guo Y, Ong HX, Singh A, Traini D, Pratap-Singh A. Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2. Int J Pharm 2024; 655:124009. [PMID: 38493838 DOI: 10.1016/j.ijpharm.2024.124009] [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: 01/26/2024] [Revised: 03/10/2024] [Accepted: 03/14/2024] [Indexed: 03/19/2024]
Abstract
Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.
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Affiliation(s)
- Alberto Baldelli
- Faculty of Land and Food Systems, The University of British Columbia, Canada; School of Agriculture and Food Sustainability, The University of Queensland, Australia.
| | - Chun Yuen Jerry Wong
- Respiratory Technology, Woolcock Institute of Medical Research, Sydney, Australia
| | - Hale Oguzlu
- Faculty of Dentistry, Department of Oral Biological and Medical Sciences, University of British Columbia, Canada
| | - Hanieh Gholizadeh
- Respiratory Technology, Woolcock Institute of Medical Research, Sydney, Australia
| | - Yigong Guo
- Faculty of Land and Food Systems, The University of British Columbia, Canada
| | - Hui Xin Ong
- Respiratory Technology, Woolcock Institute of Medical Research, Sydney, Australia; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University Australia Sydney, Australia
| | - Anika Singh
- Natural Health and Food Products Research Group, Centre for Applied Research, and Innovation (CARI), British Columbia Institute of Technology, Canada
| | - Daniela Traini
- Respiratory Technology, Woolcock Institute of Medical Research, Sydney, Australia; Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University Australia Sydney, Australia
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4
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Sarfraz A, Sarfraz Z, Bano S, Sarfraz M, Jaan A, Minhas A, Razzack AA, Patel G, Manish KC, Makkar SS, Garimella R, Pandav K, Almonte J, Paul T, Almonte T, Jimenez L, Pantoga JC, El Mazboudi N, Yatzkan G, Michel G, Michel J. Global Perspective on COVID-19 Therapies, Cardiovascular Outcomes, and Implications for Long COVID: A State-of-the-Art Review. J Community Hosp Intern Med Perspect 2024; 14:58-66. [PMID: 38966504 PMCID: PMC11221457 DOI: 10.55729/2000-9666.1308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 12/03/2023] [Accepted: 01/02/2024] [Indexed: 07/06/2024] Open
Abstract
The COVID-19 pandemic has resulted in many therapies, of which many are repurposed and used for other diseases in the last decade such in Influenza and Ebola. We intend to provide a robust foundation for cardiovascular outcomes of the therapies to better understand the rationale for the clinical trials that were conducted during the COVID-19 pandemic, and to gain more clarity on the steps moving forward should the repurposing provide clinical benefit in pandemic situations. With this state-of-the-art review, we aim to improve the understanding of the cardiovascular involvement of the therapies prior to, during, and after the COVID-19 pandemic to provide meaningful findings to the cardiovascular specialists and clinical trials for therapies, moving on from the period of pandemic urgency.
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Affiliation(s)
| | | | - Shehar Bano
- Fatima Jinnah Medical University, Lahore,
Pakistan
| | | | - Ali Jaan
- Rochester General Hospital, Rochester, NY,
USA
| | - Amna Minhas
- Fatima Jinnah Medical University, Lahore,
Pakistan
| | | | | | - KC Manish
- Larkin Health System, South Miami, Florida,
USA
| | | | | | | | | | - Trissa Paul
- Larkin Health System, South Miami, Florida,
USA
| | | | | | | | | | | | | | - Jack Michel
- Larkin Health System, South Miami, Florida,
USA
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5
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Srinivasa S, Kaur S, Dharani A, Choi E, Kalidas A, Slater R, Mifflin S. Clinical Outcomes of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in COVID-19 Patients With Pre-existing Cardiac Comorbidities: A Literature Review. Cureus 2023; 15:e51244. [PMID: 38283421 PMCID: PMC10821793 DOI: 10.7759/cureus.51244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/22/2023] [Indexed: 01/30/2024] Open
Abstract
The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of COVID-19 in patients with pre-existing cardiac comorbidities has become a large topic of discussion since the onset of the pandemic. Previous research primarily associates positive outcomes to the use of these drug classes due to their mechanism of action, which involves the downregulation of angiotensin I-converting enzyme 2 (ACE2) in the renin-angiotensin-aldosterone-system (RAAS) pathway, inflammatory mediators, and cytokines. Thus, these medications can convey preventative and protective effects in patients suffering from a SARS-CoV-2 infection. While we explored the studies that supported the positive outcomes of the use of these drugs in the first half of this review, we also expanded on the limitations of these studies in the latter portion. We also further explored the contradictory studies that indicated that using these antihypertensives can paradoxically increase the severity of COVID-19 infection as well. The studies in support of the use of these medications should consider epigenetic variations, ACE2 variants and acknowledge inherent genetic variations in certain ethnic groups as some have a predisposition for a severe COVID-19 infection. Additionally, mortality rates need to be taken into consideration in these studies as they naturally differ throughout the trajectory of the COVID-19 pandemic. While some studies are in support of the use of these antihypertensives despite other studies suggesting otherwise, further research is needed to explore the long-term effects of these antihypertensives and observe whether they are truly beneficial or not in reducing the severity of COVID-19 infections.
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Affiliation(s)
- Sandhya Srinivasa
- Medicine, University of the Incarnate Word School of Osteopathic Medicine, San Antonio, USA
| | - Simran Kaur
- Medicine, University of the Incarnate Word School of Osteopathic Medicine, San Antonio, USA
| | - Anam Dharani
- Medicine, University of the Incarnate Word School of Osteopathic Medicine, San Antonio, USA
| | - Ellen Choi
- Medicine, University of the Incarnate Word School of Osteopathic Medicine, San Antonio, USA
| | - Amar Kalidas
- Medicine, University of the Incarnate Word School of Osteopathic Medicine, San Antonio, USA
| | - Robert Slater
- Integrative Medicine, University of the Incarnate Word School of Osteopathic Medicine, San Antonio, USA
| | - Steven Mifflin
- Research and Development, University of the Incarnate Word School of Osteopathic Medicine, San Antonio, USA
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Caputo I, Bertoldi G, Driussi G, Cacciapuoti M, Calò LA. The RAAS Goodfellas in Cardiovascular System. J Clin Med 2023; 12:6873. [PMID: 37959338 PMCID: PMC10649249 DOI: 10.3390/jcm12216873] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 10/26/2023] [Accepted: 10/29/2023] [Indexed: 11/15/2023] Open
Abstract
In the last two decades, the study of the renin-angiotensin-aldosterone system (RAAS) has revealed a counterregulatory protective axis. This protective arm is characterized by ACE2/Ang 1-7/MasR and Ang 1-9 that largely counteracts the classic arm of the RAAS mediated by ACE/Ang II/AT1R/aldosterone and plays an important role in the prevention of inflammation, oxidative stress, hypertension, and cardiovascular remodeling. A growing body of evidence suggests that enhancement of this counterregulatory arm of RAAS represents an important therapeutic approach to facing cardiovascular comorbidities. In this review, we provide an overview of the beneficial effects of ACE2, Ang 1-7/MasR, and Ang 1-9 in the context of oxidative stress, vascular dysfunction, and organ damage.
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Affiliation(s)
| | | | | | | | - Lorenzo A. Calò
- Nephrology, Dialysis and Transplantation Unit, Department of Medicine—DIMED, University of Padua, Via Giustiniani, 2, 35128 Padova, Italy; (I.C.); (G.B.); (G.D.); (M.C.)
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7
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Seccia TM, Shagjaa T, Morpurgo M, Caroccia B, Sanga V, Faoro S, Venturini F, Iadicicco G, Lococo S, Mazzitelli M, Farnia F, Fioretto P, Kobayashi Y, Gregori D, Rossi GP. RAndomized Clinical Trial Of NAfamostat Mesylate, A Potent Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor, in Patients with COVID-19 Pneumonia. J Clin Med 2023; 12:6618. [PMID: 37892756 PMCID: PMC10607860 DOI: 10.3390/jcm12206618] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/02/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Even though SARS-CoV-2 was declared by WHO as constituting no longer a public health emergency, the development of effective treatments against SARS-CoV-2 infection remains a critical issue to prevent complications, particularly in fragile patients. The protease inhibitor nafamostat, currently used in Japan and Korea for pancreatitis, owing to its anticoagulant properties for disseminated intravascular coagulation (DIC), is appealing for the treatment of COVID-19 infection, because it potently inhibits the transmembrane protease serine 2 (TMPRSS2) that, after virus binding to ACE-2, allows virus entry into the cells and replication. Moreover, it could prevent the DIC and pulmonary embolism frequently associated with COVID-19 infection. The goal of the RAndomized Clinical Trial Of NAfamostat (RACONA) study, designed as a prospective randomized, double-blind placebo-controlled clinical trial, was to investigate the efficacy and safety of nafamostat mesylate (0.10 mg/kg/h iv for 7 days), on top of the optimal treatment, in COVID-19 hospitalized patients. We could screen 131 patients, but due to the predefined strict inclusion and exclusion criteria, only 15 could be randomized to group 1 (n = 7) or group 2 (n = 8). The results of an ad interim safety analysis showed similar overall trends for variables evaluating renal function, coagulation, and inflammation. No adverse events, including hyperkalemia, were found to be associated with nafamostat. Thus, the RACONA study showed a good safety profile of nafamostat, suggesting that it could be usefully used in COVID-19 hospitalized patients.
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Affiliation(s)
- Teresa Maria Seccia
- Internal Emergency Medicine Unit, Specialized Center for Blood Pressure Disorders-Regione Veneto, Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (T.M.S.); (T.S.); (V.S.)
| | - Tungalagtamir Shagjaa
- Internal Emergency Medicine Unit, Specialized Center for Blood Pressure Disorders-Regione Veneto, Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (T.M.S.); (T.S.); (V.S.)
| | - Margherita Morpurgo
- Department of Pharmaceutical & Pharmacological Sciences, University of Padua, 35131 Padua, Italy;
| | - Brasilina Caroccia
- Internal Emergency Medicine Unit, Specialized Center for Blood Pressure Disorders-Regione Veneto, Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (T.M.S.); (T.S.); (V.S.)
| | - Viola Sanga
- Internal Emergency Medicine Unit, Specialized Center for Blood Pressure Disorders-Regione Veneto, Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (T.M.S.); (T.S.); (V.S.)
| | - Sonia Faoro
- Pharmacy, University Hospital of Padua, 35126 Padua, Italy; (S.F.); (F.V.); (G.I.)
| | - Francesca Venturini
- Pharmacy, University Hospital of Padua, 35126 Padua, Italy; (S.F.); (F.V.); (G.I.)
| | - Girolama Iadicicco
- Pharmacy, University Hospital of Padua, 35126 Padua, Italy; (S.F.); (F.V.); (G.I.)
| | - Sara Lococo
- Pneumology, University Hospital of Padua, 35126 Padua, Italy;
| | - Maria Mazzitelli
- Infectious Diseases, University Hospital of Padua, 35126 Padua, Italy;
| | - Filippo Farnia
- Internal Medicine 3, University Hospital of Padua, 35128 Padua, Italy; (F.F.); (P.F.)
| | - Paola Fioretto
- Internal Medicine 3, University Hospital of Padua, 35128 Padua, Italy; (F.F.); (P.F.)
| | | | - Dario Gregori
- Biostatistics, Epidemiology and Public Health Unit, University of Padua, 35131 Padua, Italy;
| | - Gian Paolo Rossi
- Internal Emergency Medicine Unit, Specialized Center for Blood Pressure Disorders-Regione Veneto, Department of Medicine—DIMED, University of Padua, 35128 Padua, Italy; (T.M.S.); (T.S.); (V.S.)
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8
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Umeh CA, Maoz H, Obi J, Dakoria R, Patel S, Maity G, Barve P. Remdesivir, dexamethasone and angiotensin-converting enzyme inhibitors use and mortality outcomes in COVID-19 patients with concomitant troponin elevation. World J Cardiol 2023; 15:427-438. [PMID: 37900264 PMCID: PMC10600781 DOI: 10.4330/wjc.v15.i9.427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 07/12/2023] [Accepted: 08/17/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND There are indications that viral myocarditis, demand ischemia, and renin-angiotensin-aldosterone system pathway activation play essential roles in troponin elevation in coronavirus disease 2019 (COVID-19) patients. Antiviral medications and steroids are used to treat viral myocarditis, but their effect in patients with elevated troponin, possibly from myocarditis, has not been studied. AIM To evaluate the effect of dexamethasone, remdesivir, and angiotensin-converting enzyme (ACE) inhibitors (ACEI) on mortality in COVID-19 patients with elevated troponin. METHODS Our retrospective observational study involved 1788 COVID-19 patients at seven hospitals in Southern California, United States. We did a backward selection Cox multivariate regression analysis to determine predictors of mortality in our study population. Additionally, we did a Kaplan Meier survival analysis in the subset of patients with elevated troponin, comparing survival in patients that received dexamethasone, remdesivir, and ACEI with those that did not. RESULTS The mean age was 66 years (range 20-110), troponin elevation was noted in 11.5% of the patients, and 29.9% expired. The patients' age [hazard ratio (HR) = 1.02, P < 0.001], intensive care unit admission (HR = 5.07, P < 0.001), and ventilator use (HR = 0.68, P = 0.02) were significantly associated with mortality. In the subset of patients with elevated troponin, there was no statistically significant difference in survival in those that received remdesivir (0.07), dexamethasone (P = 0.63), or ACEI (P = 0.8) and those that did not. CONCLUSION Although elevated troponin in COVID-19 patients has been associated with viral myocarditis and ACE II receptors, conventional viral myocarditis treatment, including antiviral and steroids, and ACEI did not show any effect on mortality in these patients.
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Affiliation(s)
- Chukwuemeka A Umeh
- Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
| | - Heather Maoz
- Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States.
| | - Jessica Obi
- Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
| | - Ruchi Dakoria
- Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
| | - Smit Patel
- Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
| | - Gargi Maity
- Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
| | - Pranav Barve
- Internal Medicine, Hemet Global Medical Center, Hemet, CA 92543, United States
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9
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Jonville-Bera AP, Gautier S, Micallef J, Massy N, Atzenhoffer M, Grandvuillemin A, Drici MD. Monitoring the safety of drugs and COVID-19 vaccines by the French Pharmacovigilance Centers during the pandemic: A win-win bet with Health Authorities! Therapie 2023; 78:467-475. [PMID: 37012154 PMCID: PMC9990876 DOI: 10.1016/j.therap.2023.03.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 02/28/2023] [Indexed: 03/09/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic virus was a "health crisis" and a significant burden also for the French pharmacovigilance system. It took its toll in 2 phases, the first being in early 2020 when very little was known, and during which the missions of the 31 Regional Pharmacovigilance Centers (RPVCs) from university hospitals were to detect adverse reactions of drugs used in the context of the disease. Whether as a possible aggravating role on COVID-19, or displaying a different safety profile during its course, or to assess safety of curative treatment, this phase preceded that of the arrival of dedicated vaccines. Then the RPVCs' missions were to detect, as early as possible, any new serious adverse effect leading to a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two distinct periods, signal detection remained the core business of the RPVCs. Each RPVC had to organize itself to handle an unprecedented surge of declarations and requests for advice, from health care professionals and patients alike. "Leading" RPVCs, who were in charge of monitoring vaccines, had to deal with an extraordinary workload (still going on to this date), to generate in real-time and on a weekly basis, a summary of all the adverse drug reaction (ADR) reports as well as an extended analysis of the different safety signals. The organization put in place at the beginning of the health crisis, adapted to the context of the vaccines, allowed to meet the challenge of real-time pharmacovigilance monitoring, and to identify many safety signals. Efficient "short-circuits exchanges" with the French Regional Pharmacovigilance Centers Network (RPVCN) were paramount to the National Agency for the Safety of Medicines and Health Products (ANSM) to develop an optimal collaborative partnership. The French RPVCN has shown at this occasion both agility and flexibility, swiftly adapting to vaccine- and media-related unrest, and demonstrated its effectiveness in the early detection of safety signals. This crisis also confirmed the superiority of manual/human signal detection over automated ones, as the most effective and powerful tool to date to rapidly detect and validate a new ADR and enable to elaborate rapid risk reduction measures. To maintain the performance of French RPVCN in signal detection and to monitor all drugs as they should, and as expected by our fellow citizens, a new funding model should be considered.
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Affiliation(s)
- Annie Pierre Jonville-Bera
- Service de pharmacosurveillance, centre régional de pharmacovigilance, centre Val de Loire, CHRU de Tours, 37000 Tours, France.
| | - Sophie Gautier
- Service de pharmacologie, centre régional de pharmacovigilance Nord Pas de Calais, CHRU de Lille, 59000 Lille, France
| | - Joëlle Micallef
- Service de pharmacologie, centre régional de pharmacovigilance, et université d'Aix Marseille, APHM, INSERM, Inst Neurosci Syst, UMR 1106, 13005 Marseille, France
| | - Nathalie Massy
- Service de pharmacologie médicale, centre régional de pharmacovigilance de Rouen, CHRU de Rouen, 76000 Rouen, France
| | - Marina Atzenhoffer
- Centre régional de pharmacovigilance, hospices civils de Lyon, 69000 Lyon, France
| | - Aurélie Grandvuillemin
- Service de pharmacologie, centre régional de pharmacovigilance de Nice, CHRU de Nice, 06000 Nice, France
| | - Milou-Daniel Drici
- Centre régional de pharmacovigilance de Bourgogne, CHRU de Dijon, 21000 Dijon, France
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10
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Jonville-Bera AP, Gautier S, Micallef J, Massy N, Atzenhoffer M, Drici MD, Grandvuillemin A. [Monitoring the safety of drugs and COVID-19 vaccines by the French Pharmacovigilance Centers during the pandemic: a win-win bet with Health Authorities!]. Therapie 2023; 78:477-488. [PMID: 36890032 PMCID: PMC9943552 DOI: 10.1016/j.therap.2023.02.009] [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: 01/16/2023] [Accepted: 02/21/2023] [Indexed: 02/23/2023]
Abstract
The pandemic subsequent to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus resulted, for the French institutional pharmacovigilance, in a "health crisis" in 2 phases: the coronavirus disease 2019 - "COVID-19" phase during which the missions of the Regional Pharmacovigilance Centres (RPVC) were to detect a possible impact of drugs on this disease, as whether existed a possible aggravating role of certain drugs, or the safety profile of drugs used for the management of COVID-19 could evolve. The second phase followed the availability of COVID-19 vaccines, during which the RPVCs' missions were to detect as early as possible any new serious adverse effect, source of a potential signal that would modify the benefit/risk ratio of a vaccine and require the implementation of health safety measures. During these two periods, signal detection remained the core business of the RPVCs. The RPVCs had to organize themselves to handle an historical surge of declarations and requests for advice, whereas the RPVCs in charge of monitoring vaccines had to deal with an extraordinary dense activity over a long period of time, in order to produce in real time and on a weekly basis, a summary of all the declarations and an analysis of safety signals. The national organization put in place made it possible to meet the challenge of real-time pharmacovigilance monitoring of 4 vaccines with conditional marketing authorizations. Short-circuit efficient exchanges with the French Regional Pharmacovigilance Centres Network was paramount for the French National Agency for medicines and health products (Agence nationale de sécurité du médicament et des produits de santé) to develop an optimal collaborative partnership. The RPVC network has shown agility and flexibility, has been able to adapt swiftly and demonstrated its effectiveness in the early detection of safety signals. This crisis confirmed the superiority of manual/human signal detection as the most effective and powerful tool to date, to rapidly detect a new adverse drug reaction and enable to elaborate rapid measures of risk reduction. In order to maintain the performance of French RPVCs in signal detection and to monitor all drugs as they should and as expected by our fellow citizens, a new funding model correcting the inadequacy of RPVCs' expertise resources in relation to the volume of reports should be considered.
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Affiliation(s)
- Annie Pierre Jonville-Bera
- Service de pharmacosurveillance, centre régional de pharmacovigilance Centre Val de Loire, CHRU de Tours, 37000 Tours, France.
| | - Sophie Gautier
- Service de pharmacologie, centre régional de pharmacovigilance Nord Pas de Calais, CHRU de Lille, 59000 Lille, France
| | - Joëlle Micallef
- Inserm, service de pharmacologie, université d'Aix-Marseille, UMR 1106, APHM, centre régional de pharmacovigilance, institut de neuroscience des systèmes, 13005 Marseille, France
| | - Nathalie Massy
- Service de pharmacologie médicale, centre régional de pharmacovigilance de Rouen, CHRU de Rouen, 76000 Rouen, France
| | - Marina Atzenhoffer
- Centre régional de pharmacovigilance, hospices civils de Lyon, 69000 Lyon, France
| | - Milou-Daniel Drici
- Service de pharmacologie, centre régional de pharmacovigilance de Nice, CHRU de Nice, 06000 Nice, France
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11
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Chang R, Yen-Ting Chen T, Wang SI, Hung YM, Chen HY, Wei CCJ. Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study. EClinicalMedicine 2023; 56:101783. [PMID: 36643619 PMCID: PMC9830133 DOI: 10.1016/j.eclinm.2022.101783] [Citation(s) in RCA: 167] [Impact Index Per Article: 83.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 11/14/2022] [Accepted: 11/28/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants. METHODS This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models. FINDINGS Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjögren's syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behçet's disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24). INTERPRETATION COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms. FUNDING Kaohsiung Veterans General Hospital (KSVGH111-113).
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Affiliation(s)
- Renin Chang
- Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Recreation and Sports Management, Tajen University, Pintung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Thomas Yen-Ting Chen
- Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Medical Research and Education, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Shiow-Ing Wang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yao-Min Hung
- Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital Taitung Branch, Taiwan
- College of Science and Engineering, National Taitung University, Taitung, Taiwan
- College of Health and Nursing, Meiho University, Pingtung, Taiwan
- Corresponding author. No. 1000, Gengsheng Rd., Taitung City, Taitung County, Taiwan.
| | - Hui-Yuan Chen
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Cheng-Chung James Wei
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
- Corresponding author. No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, Taiwan.
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12
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Gholami M, Zoughi M, Hasanzad M, Larijani B, Amoli MM. Haplotypic variants of COVID-19 related genes are associated with blood pressure and metabolites levels. J Med Virol 2023; 95:e28355. [PMID: 36443248 PMCID: PMC9877746 DOI: 10.1002/jmv.28355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 07/27/2022] [Accepted: 11/22/2022] [Indexed: 12/03/2022]
Abstract
The genetic association of coronavirus disease 2019 (COVID-19) with its complications has not been fully understood. This study aimed to identify variants and haplotypes of candidate genes implicated in COVID-19 related traits by combining the literature review and pathway analysis. To explore such genes, the protein-protein interactions and relevant pathways of COVID-19-associated genes were assessed. A number of variants on candidate genes were identified from Genome-wide association studies (GWASs) which were associated with COVID-19 related traits (p ˂ 10-6 ). Haplotypic blocks were assessed using haplotypic structures among the 1000 Genomes Project (r2 ≥ 0.8, D' ≥ 0.8). Further functional analyses were performed on the selected variants. The results demonstrated that a group of variants in ACE and AGT genes were significantly correlated with COVID-19 related traits. Three haplotypes were identified to be involved in the blood metabolites levels and the development of blood pressure. Functional analyses revealed that most GWAS index variants were expression quantitative trait loci and had transcription factor binding sites, exonic splicing enhancers or silencer activities. Furthermore, the proxy haplotype variants, rs4316, rs4353, rs4359, and three variants, namely rs2493133, rs2478543, and rs5051, were associated with blood metabolite and systolic blood pressure, respectively. These variants exerted more regulatory effects compared with other GWAS variants. The present study indicates that the genetic variants and candidate haplotypes of COVID-19 related genes are associated with blood pressure and blood metabolites. However, further observational studies are warranted to confirm these results.
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Affiliation(s)
- Morteza Gholami
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular‐Cellular Sciences InstituteTehran University of Medical SciencesTehranIran,Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Marziyeh Zoughi
- Metabolomics and genomics research center endocrinology and metabolism molecular‐cellular sciences instituteTehran University of medical sciencesTehranIran
| | - Mandana Hasanzad
- Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
| | - Mahsa M. Amoli
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular‐Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
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13
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Naseef H, AbuKhalil AD, Orabi T, Joza M, Mashaala C, Elsheik M, Dababat A, Qattosa M, Al-Shami N, Rabba AK. Correlation between Medications Used during COVID Infection and Post-conditions after the Acute Phase of Infection: A Cross-sectional Study. THE OPEN PUBLIC HEALTH JOURNAL 2022; 15. [DOI: 10.2174/18749445-v15-e221208-2022-100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 10/29/2022] [Accepted: 11/01/2022] [Indexed: 01/18/2023]
Abstract
Background:
During the COVID-19 pandemic, off-label medication prescribing and utilizing herbal products and multiple vitamins in the treatment, prevention, and symptom management of COVID-19 was an urgently needed practice to halt the SARS-CoV-2 infection crisis and progression.
Objectives:
This study aimed to determine the correlation between medications used during the pandemic and SARS-CoV-2 infection post-recovery symptoms.
Methods:
A cross-sectional questionnaire-based study was conducted on recovered COVID-19 patients. There were 20 multiple-choice questions, including patient demographics, treatment, and post-recovery symptoms. Chi-square and Fisher’s exact tests were used to investigate significant relationships. In addition, Binary logistic regression was performed to determine confounders. Data were analyzed using SPSS version 22.
Results:
Medications and supplements varied in their therapeutic effects on SARS-CoV-2 post-recovery symptoms. Patients who took vitamin D and calcium experienced increased symptom frequency, and patients taking ACE inhibitors experienced more headaches and coughs. Furthermore, patients receiving azithromycin were asymptomatic after recovery. Patients who took H2 antagonists reported persistent headaches and muscle pain.
Conclusion:
Patients infected with SARS-CoV-2 have responded differently to medications, multivitamins, and herbal supplements. Patients reported resolution of some symptoms and persistence of others post-recovery. Therefore, expert opinion should be considered in COVID-19 management until randomized controlled trials answer many questions and determine medications' safety and efficacy in prevention, treatment strategies, and symptoms of SARS-CoV-2 infection post-recovery.
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14
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Ramlal A, Nautiyal A, Baweja P, Kumar V, Mehta S, Mahto RK, Tripathi S, Shanmugam A, Pujari Mallikarjuna B, Raman P, Lal SK, Raju D, Rajendran A. Angiotensin-converting enzyme inhibitory peptides and isoflavonoids from soybean [ Glycine max (L.) Merr.]. Front Nutr 2022; 9:1068388. [PMID: 36505231 PMCID: PMC9730416 DOI: 10.3389/fnut.2022.1068388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/03/2022] [Indexed: 11/25/2022] Open
Abstract
Angiotensin-converting enzyme I (ACE I) is a zinc-containing metallopeptidase involved in the renin-angiotensin system (RAAS) that helps in the regulation of hypertension and maintains fluid balance otherwise, which results in cardiovascular diseases (CVDs). One of the leading reasons of global deaths is due to CVDs. RAAS also plays a central role in maintaining homeostasis of the CV system. The commercial drugs available to treat CVDs possess several fatal side effects. Hence, phytochemicals like peptides having plant-based origin should be explored and utilized as alternative therapies. Soybean is an important leguminous crop that simultaneously possesses medicinal properties. Soybean extracts are used in many drug formulations for treating diabetes and other disorders and ailments. Soy proteins and its edible products such as tofu have shown potential inhibitory activity against ACE. Thus, this review briefly describes various soy proteins and products that can be used to inhibit ACE thereby providing new scope for the identification of potential candidates that can help in the design of safer and natural treatments for CVDs.
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Affiliation(s)
- Ayyagari Ramlal
- Division of Genetics, Indian Council of Agricultural Research (ICAR)-Indian Agricultural Research Institute (IARI), New Delhi, India
| | - Aparna Nautiyal
- Department of Botany, Deshbandhu College, University of Delhi, New Delhi, India
| | - Pooja Baweja
- Department of Botany, Maitreyi College, University of Delhi, New Delhi, India
| | - Vikash Kumar
- Faculty of Agricultural Sciences, Institute of Applied Sciences and Humanities, GLA University, Mathura, Uttar Pradesh, India
| | - Sahil Mehta
- Department of Botany, Hansraj College, University of Delhi, New Delhi, India
| | - Rohit Kumar Mahto
- Division of Genetics, Indian Council of Agricultural Research (ICAR)-Indian Agricultural Research Institute (IARI), New Delhi, India
- School of Biotechnology, Institute of Science, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, India
| | - Shikha Tripathi
- Indian Council of Agricultural Research (ICAR)-National Institute for Plant Biotechnology (NIPB), New Delhi, India
- Department of Botany, Institute of Science, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, India
| | - Aravindam Shanmugam
- Centre for Plant Breeding and Genetics, Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu, India
| | - Bingi Pujari Mallikarjuna
- Division of Genetics, Indian Council of Agricultural Research (ICAR)-Indian Agricultural Research Institute (IARI), Regional Research Centre, Dharwad, Karnataka, India
| | - Pushpa Raman
- Department of Plant Breeding and Genetics, Tamil Nadu Rice Research Institute, Tamil Nadu Agricultural University, Aduthurai, Tamil Nadu, India
| | - S. K. Lal
- Division of Genetics, Indian Council of Agricultural Research (ICAR)-Indian Agricultural Research Institute (IARI), New Delhi, India
| | - Dhandapani Raju
- Division of Plant Physiology, Indian Council of Agricultural Research (ICAR)-Indian Agricultural Research Institute, New Delhi, India
| | - Ambika Rajendran
- Division of Genetics, Indian Council of Agricultural Research (ICAR)-Indian Agricultural Research Institute (IARI), New Delhi, India
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15
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Obeng EM, Fianu I, Danquah MK. Multivalent ACE2 engineering-A promising pathway for advanced coronavirus nanomedicine development. NANO TODAY 2022; 46:101580. [PMID: 35942040 PMCID: PMC9350675 DOI: 10.1016/j.nantod.2022.101580] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/26/2022] [Accepted: 07/30/2022] [Indexed: 05/06/2023]
Abstract
The spread of coronavirus diseases has resulted in a clarion call to develop potent drugs and vaccines even as different strains appear beyond human prediction. An initial step that is integral to the viral entry into host cells results from an active-targeted interaction of the viral spike (S) proteins and the cell surface receptor, called angiotensin-converting enzyme 2 (ACE2). Thus, engineered ACE2 has been an interesting decoy inhibitor against emerging coronavirus infestation. This article discusses promising innovative ACE2 engineering pathways for current and emerging coronavirus therapeutic development. First, we provide a brief discussion of some ACE2-associated human coronaviruses and their cell invasion mechanism. Then, we describe and contrast the individual spike proteins and ACE2 receptor interactions, highlighting crucial hotspots across the ACE2-associated coronaviruses. Lastly, we address the importance of multivalency in ACE2 nanomedicine engineering and discuss novel approaches to develop and achieve multivalent therapeutic outcomes. Beyond coronaviruses, these approaches will serve as a paradigm to develop new and improved treatment technologies against pathogens that use ACE2 receptor for invasion.
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Affiliation(s)
- Eugene M Obeng
- Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
| | - Isaac Fianu
- Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany
| | - Michael K Danquah
- Department of Chemical Engineering, University of Tennessee, 615 McCallie Ave, Chattanooga, TN 37403, United States
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16
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Gupta N, Settle L, Brown BR, Armaignac DL, Baram M, Perkins NE, Kaufman M, Melamed RR, Christie AB, Danesh VC, Denson JL, Cheruku SR, Boman K, Bansal V, Kumar VK, Walkey AJ, Domecq JP, Kashyap R, Aston CE. Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients With COVID-19. Crit Care Med 2022; 50:e744-e758. [PMID: 35894609 PMCID: PMC9469914 DOI: 10.1097/ccm.0000000000005627] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
OBJECTIVES To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN Retrospective observational study. SETTING Multicenter, international COVID-19 registry. SUBJECTS Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.
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Affiliation(s)
- Neha Gupta
- Department of Pediatrics, Division of Pediatric Critical Care, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Lisa Settle
- Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Brent R Brown
- Department of Medicine, Division of Pulmonary Critical Care, University of Oklahoma College of Medicine, Oklahoma City, OK
| | - Donna L Armaignac
- Center for Advanced Analytics, Baptist Health South Florida, Coral Gables, FL
| | - Michael Baram
- Department of Medicine, Thomas Jefferson University, Philadelphia, PA
| | - Nicholas E Perkins
- Department of Medicine, Division of Hospital Medicine, Prisma Health, Greenville, SC
| | - Margit Kaufman
- Departments of Anesthesiology and Critical Care Medicine, Englewood Health, Englewood, NJ
| | - Roman R Melamed
- Department of Critical Care, Abbott Northwestern Hospital, Allina Health, Minneapolis, MN
| | - Amy B Christie
- Department of Critical Care, Atrium Health Navicent, Macon, GA
| | - Valerie C Danesh
- Center for Applied Health Research, Baylor Scott & White Health, Dallas, TX
| | - Joshua L Denson
- Section of Pulmonary Diseases, Critical Care, and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA
| | - Sreekanth R Cheruku
- Department of Anesthesiology and Pain Management, UT Southwestern Medical Center, Dallas, TX
| | - Karen Boman
- Society of Critical Care Medicine, Mount Prospect, IL
| | - Vikas Bansal
- Department of Anesthesia and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | | | - Allan J Walkey
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, and Evans Center of Implementation and Improvement Sciences, Department of Medicine, Boston University School of Medicine, Boston, MA
| | - Juan P Domecq
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Rahul Kashyap
- Department of Anesthesia and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Christopher E Aston
- Biomedical and Behavioral Methodology Core, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK
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17
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Li YX, Wang HB, Li J, Jin JB, Hu JB, Yang CL. Targeting pulmonary vascular endothelial cells for the treatment of respiratory diseases. Front Pharmacol 2022; 13:983816. [PMID: 36110525 PMCID: PMC9468609 DOI: 10.3389/fphar.2022.983816] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/08/2022] [Indexed: 11/24/2022] Open
Abstract
Pulmonary vascular endothelial cells (VECs) are the main damaged cells in the pathogenesis of various respiratory diseases and they mediate the development and regulation of the diseases. Effective intervention targeting pulmonary VECs is of great significance for the treatment of respiratory diseases. A variety of cell markers are expressed on the surface of VECs, some of which can be specifically combined with the drugs or carriers modified by corresponding ligands such as ICAM-1, PECAM-1, and P-selectin, to achieve effective delivery of drugs in lung tissues. In addition, the great endothelial surface area of the pulmonary vessels, the “first pass effect” of venous blood in lung tissues, and the high volume and relatively slow blood perfusion rate of pulmonary capillaries further promote the drug distribution in lung tissues. This review summarizes the representative markers at the onset of respiratory diseases, drug delivery systems designed to target these markers and their therapeutic effects.
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Affiliation(s)
- Yi-Xuan Li
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, China
| | - Hong-Bo Wang
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
| | - Jing Li
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
| | - Jian-Bo Jin
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
| | - Jing-Bo Hu
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, China
- *Correspondence: Jing-Bo Hu, ; Chun-Lin Yang,
| | - Chun-Lin Yang
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
- *Correspondence: Jing-Bo Hu, ; Chun-Lin Yang,
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18
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Ning L, Liu M, Gou Y, Yang Y, He B, Huang J. Development and application of ribonucleic acid therapy strategies against COVID-19. Int J Biol Sci 2022; 18:5070-5085. [PMID: 35982905 PMCID: PMC9379410 DOI: 10.7150/ijbs.72706] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 07/16/2022] [Indexed: 11/17/2022] Open
Abstract
The Coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), remaining a global health crisis since its outbreak until now. Advanced biotechnology and research findings have revealed many suitable viral and host targets for a wide range of therapeutic strategies. The emerging ribonucleic acid therapy can modulate gene expression by post-transcriptional gene silencing (PTGS) based on Watson-Crick base pairing. RNA therapies, including antisense oligonucleotides (ASO), ribozymes, RNA interference (RNAi), aptamers, etc., were used to treat SARS-CoV whose genome is similar to SARV-CoV-2, and the past experience also applies for the treatment of COVID-19. Several studies against SARS-CoV-2 based on RNA therapeutic strategy have been reported, and a dozen of relevant preclinical or clinical trials are in process globally. RNA therapy has been a very active and important part of COVID-19 treatment. In this review, we focus on the progress of ribonucleic acid therapeutic strategies development and application, discuss corresponding problems and challenges, and suggest new strategies and solutions.
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Affiliation(s)
- Lin Ning
- School of Healthcare Technology, Chengdu Neusoft University, Sichuan, China.,School of Life Science and Technology, University of Electronic Science and Technology of China, Sichuan, China
| | - Mujiexin Liu
- Ineye Hospital of Chengdu University of TCM, Sichuan, China
| | - Yushu Gou
- School of Life Science and Technology, University of Electronic Science and Technology of China, Sichuan, China
| | - Yue Yang
- School of Life Science and Technology, University of Electronic Science and Technology of China, Sichuan, China
| | - Bifang He
- Medical College, Guizhou University, Guizhou, China
| | - Jian Huang
- School of Life Science and Technology, University of Electronic Science and Technology of China, Sichuan, China
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19
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Arefin S, Hernandez L, Ward LJ, Schwarz A, Barany P, Stenvinkel P, Kublickiene K. Angiotensin-converting enzyme 2 and transmembrane protease serine 2 in female and male patients with end-stage kidney disease. Eur J Clin Invest 2022; 52:e13786. [PMID: 35366343 PMCID: PMC9541326 DOI: 10.1111/eci.13786] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/24/2022] [Accepted: 03/31/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Individuals with chronic kidney disease are affected by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to multiple comorbidities and altered immune system. The first step of the infection process is the binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2) receptor, followed by its priming by transmembrane protease serine 2 (TMPRSS2). We hypothesized that circulating soluble ACE2 levels, as well as the expressions of ACE2 and TMPRSS2 in the microvasculature, are increased in patients with end-stage kidney disease (ESKD). METHODS A total of 210 participants were enrolled, representing 80 ESKD patients and 73 non-CKD controls for soluble ACE2, and 31 ESKD and 26 non-CKD controls for vasculature and fat tissue bioassays. We have assessed ACE2 expression in blood using ELISA and in tissue using immunofluorescence. RESULTS Soluble ACE2 levels were higher in ESKD patients compared to controls; however, there is no sex difference observed. In ESKD and controls, soluble ACE2 positively correlated with Interleukin 6 (IL-6) and C-reactive protein (CRP), respectively. Similarly, ACE2 tissue expression in the vasculature was higher in ESKD patients; moreover, this higher ACE2 expression was observed only in male ESKD patients. In addition, TMPRSS2 expression was observed in vessels from males and females but showed no sex difference. The expression of ACE2 receptor was higher in ESKD patients on ACE-inhibitor/angiotensin blocker treatment. CONCLUSION ESKD is associated with increased ACE2 levels in the circulation and pronounced in male vasculature; however, further studies are warranted to assess possible sex differences on specific treatment regime(s) for different comorbidities present in ESKD.
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Affiliation(s)
- Samsul Arefin
- Division of Renal Medicine, Department of Clinical Science, Intervention & Technology, Karolinska Institutet, Stockholm, Sweden
| | - Leah Hernandez
- Division of Renal Medicine, Department of Clinical Science, Intervention & Technology, Karolinska Institutet, Stockholm, Sweden
| | - Liam J Ward
- Division of Renal Medicine, Department of Clinical Science, Intervention & Technology, Karolinska Institutet, Stockholm, Sweden.,Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden
| | - Angelina Schwarz
- Division of Renal Medicine, Department of Clinical Science, Intervention & Technology, Karolinska Institutet, Stockholm, Sweden
| | | | - Peter Barany
- Division of Renal Medicine, Department of Clinical Science, Intervention & Technology, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine, Department of Clinical Science, Intervention & Technology, Karolinska Institutet, Stockholm, Sweden
| | - Karolina Kublickiene
- Division of Renal Medicine, Department of Clinical Science, Intervention & Technology, Karolinska Institutet, Stockholm, Sweden
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20
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Daoui O, Elkhattabi S, Chtita S. Rational identification of small molecules derived from 9,10-dihydrophenanthrene as potential inhibitors of 3CL pro enzyme for COVID-19 therapy: a computer-aided drug design approach. Struct Chem 2022; 33:1667-1690. [PMID: 35818588 PMCID: PMC9261181 DOI: 10.1007/s11224-022-02004-z] [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: 05/08/2022] [Accepted: 06/23/2022] [Indexed: 01/11/2023]
Abstract
Small molecules such as 9,10-dihydrophenanthrene derivatives have remarkable activity toward inhibition of SARS-CoV-2 3CLpro and COVID-19 proliferation, which show a strong correlation between their structures and bioactivity. Therefore, these small compounds could be suitable for clinical pharmaceutical use against COVID-19. The objective of this study was to remodel the structures of 9,10-dihydrophenanthrene derivatives to achieve a powerful biological activity against 3CLpro and favorable pharmacokinetic properties for drug design and discovery. Therefore, by the use of bioinformatics techniques, we developed robust 3D-QSAR models that are capable of describing the structure-activity relationship for 46 molecules based on 9,10-dihydrophenanthrene derivatives using CoMFA/SE (R 2 = 0.97, Q 2 = 0.81, R 2 pred = 0.95, c R 2 p = 0.71) and CoMSIA/SEHDA (R 2 = 0.94, Q 2 = 0.76, R 2 pred = 0.91, c R 2 p = 0.65) techniques. Accordingly, 96 lead compounds were generated based on a template molecule that showed the highest observed activity in vitro (T40, pIC50 = 5.81) and predicted their activities and bioavailability in silico. The rational screening outputs of 3D-QSAR, Molecular docking, ADMET, and MM-GBSA led to the identification of 9 novel modeled molecules as potent noncovalent drugs against SARS-CoV-2-3CLpro. Finally, by molecular dynamics simulations, the stability and structural dynamics of 3CLpro free and complex (PDB code: 6LU7) were discussed in the presence of samples of 9,10-dihydrophenanthrene derivative in an aqueous environment. Overall, the retrosynthesis of the proposed drug compounds in this study and the evaluation of their bioactivity in vitro and in vivo may be interesting for designing and discovering a new drug effective against COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-02004-z.
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Affiliation(s)
- Ossama Daoui
- Laboratory of Engineering, Systems and Applications, National School of Applied Sciences, Sidi Mohamed Ben Abdellah-Fez University, BP Box 72, Fez, Morocco
| | - Souad Elkhattabi
- Laboratory of Engineering, Systems and Applications, National School of Applied Sciences, Sidi Mohamed Ben Abdellah-Fez University, BP Box 72, Fez, Morocco
| | - Samir Chtita
- Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, B.P 7955 Casablanca, Morocco
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21
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Macedo AVS, de Barros E Silva PGM, de Paula TC, Moll-Bernardes RJ, Mendonça Dos Santos T, Mazza L, Feldman A, Arruda GDAS, de Albuquerque DC, de Sousa AS, de Souza OF, Gibson CM, Granger CB, Alexander JH, Lopes RD. Discontinuing vs continuing ACEIs and ARBs in hospitalized patients with COVID-19 according to disease severity: Insights from the BRACE CORONA trial. Am Heart J 2022; 249:86-97. [PMID: 35405099 PMCID: PMC8993458 DOI: 10.1016/j.ahj.2022.04.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 04/05/2022] [Indexed: 05/07/2023]
Abstract
BACKGROUND We explored the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with COVID-19 according to baseline disease severity. METHODS We randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity. RESULTS At presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 [SD 6.3] days) and continuation (mean 23.8 [SD 6.5] days), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 [SD 9.5] days) than continuation (mean 21.6 [SD 7.6] days), with a mean ratio of 0.90 (95% CI 0.81-1.00; P-interaction = .01). The impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity. CONCLUSIONS Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NCT04364893).
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Affiliation(s)
- Ariane Vieira Scarlatelli Macedo
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Hospital São Luiz Jabaquara, São Paulo, Brazil; Programa de Pós-Graduação em Medicina Translacional, Universidade Federal de São Paulo, São Paulo, Brazil; Brazilian Clinical Research Institute, São Paulo, Brazil
| | | | - Thiago Ceccatto de Paula
- Hospital São Luiz Jabaquara, São Paulo, Brazil; Brazilian Clinical Research Institute, São Paulo, Brazil
| | | | - Tiago Mendonça Dos Santos
- Brazilian Clinical Research Institute, São Paulo, Brazil; Insper Institute of Education and Research, São Paulo, Brazil
| | - Lilian Mazza
- Brazilian Clinical Research Institute, São Paulo, Brazil
| | - Andre Feldman
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Hospital São Luiz Anália Franco, São Paulo, Brazil
| | - Guilherme D Andréa Saba Arruda
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Hospital São Luiz São Caetano, São Caetano do Sul, Brazil
| | - Denílson Campos de Albuquerque
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | - Andrea Silvestre de Sousa
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Olga Ferreira de Souza
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Rede D'Or São Luiz (RDSL), São Paulo, Brazil; Hospital Copa D'Or, Rio de Janeiro, Brazil
| | | | | | - John H Alexander
- Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
| | - Renato D Lopes
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Programa de Pós-Graduação em Medicina Translacional, Universidade Federal de São Paulo, São Paulo, Brazil; Brazilian Clinical Research Institute, São Paulo, Brazil; Rede D'Or São Luiz (RDSL), São Paulo, Brazil; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
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22
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ÜNAL ÇETİN E, BEYAZIT Y, BEYAZIT F, TANOĞLU A, HAZNEDAROĞLU İC. The pathobiological harmony between the local pulmonary/ bone marrow RAS and its management via tissue-RAS modulating agents in COVID-19. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1090521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to public health and healthcare systems. It presents unusual pathophysiological effects mainly characterized by immune-inflammatory response and prothrombotic state causing acute respiratory distress syndrome and multiple organ failure. SARS-CoV-2 enters target cells after binding to the angiotensin-converting enzyme 2 (ACE2) receptor and therefore has a direct effect on the renin-angiotensin system (RAS). Apart from affecting numerous organs including lungs, heart, gastrointestinal system, spleen, brain and kidneys, the spike protein of SARS-CoV-2 could attack hematopoietic stem cells and hematopoietic progenitor cells in bone marrow (BM) microenvironment together with the precursor and mature blood cells. Within this hematopoietic viral spread context, it is crucial to search the clinicopathological correlations of COVID-19 in order to develop specific potential therapeutics against pleiotropic SARS-CoV-2 actions. Therefore, pharmacological disruption of the pathological cross-talk of local BM RAS and pulmonary RAS via administration of the tissue-RAS modulating agents such as soluble ACE2, angiotensin (1-7), TXA127 and MAS receptor agonists may prevent the clinical progression of the COVID-19 syndrome via reducing the hematopoietic virus propagation and systemic multi-organ spread.
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Affiliation(s)
| | | | | | - Alpaslan TANOĞLU
- SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL SULTAN ABDÜLHAMİD HAN SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ
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23
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Choi H, Lee JH, Park HK, Lee E, Kim MS, Kim HJ, Park BE, Kim HN, Kim N, Jang SY, Bae MH, Yang DH, Park HS, Cho Y. Impact of the COVID-19 Pandemic on Patient Delay and Clinical Outcomes for Patients With Acute Myocardial Infarction. J Korean Med Sci 2022; 37:e167. [PMID: 35638194 PMCID: PMC9151994 DOI: 10.3346/jkms.2022.37.e167] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 04/12/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND It has been known that the fear of contagion during the coronavirus disease 2019 (COVID-19) creates time delays with subsequent impact on mortality in patients with acute myocardial infarction (AMI). However, difference of time delay and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI between the COVID-19 pandemic and pre-pandemic era has not been fully investigated yet in Korea. The aim of this study was to investigate the impact of COVID-19 pandemic on time delays and clinical outcome in patients with STEMI or non-STEMI compared to the same period years prior. METHODS A total of 598 patients with STEMI (n = 195) or non-STEMI (n = 403) who underwent coronary angiography during the COVID-19 pandemic (February 1 to April 30, 2020) and pre-pandemic era (February 1 to April 30, 2017, 2018, and 2019) were analyzed in this study. Main outcomes were the incidence of time delay, cardiac arrest, and in-hospital death. RESULTS There was 13.5% reduction in the number of patients hospitalized with AMI during the pandemic compared to pre-pandemic era. In patients with STEMI, door to balloon time tended to be longer during the pandemic compared to pre-pandemic era (55.7 ± 12.6 minutes vs. 60.8 ± 13.0 minutes, P = 0.08). There were no significant differences in cardiac arrest (15.6% vs. 10.4%, P = 0.397) and in-hospital mortality (15.6% vs. 10.4%, P = 0.397) between pre-pandemic and the pandemic era. In patients with non-STEMI, symptom to door time was significantly longer (310.0 ± 346.2 minutes vs. 511.5 ± 635.7 minutes, P = 0.038) and the incidence of cardiac arrest (0.9% vs. 3.5%, P = 0.017) and in-hospital mortality (0.3% vs. 2.3%, P = 0.045) was significantly greater during the pandemic compared to pre-pandemic era. Among medications, angiotensin converting enzyme inhibitors/angiotensin type 2 receptor blockers (ACE-I/ARBs) were underused in STEMI (64.6% vs. 45.8%, P = 0.021) and non-STEMI (67.8% vs. 57.0%, P = 0.061) during the pandemic. CONCLUSION During the COVID-19 pandemic, there has been a considerable reduction in hospital admissions for AMI, time delay, and underuse of ACE-I/ARBs for the management of AMI, and this might be closely associated with the excess death in Korea.
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Affiliation(s)
- Hyohun Choi
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Jang Hoon Lee
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea.
| | - Hyuk Kyoon Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Eunkyu Lee
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Myeong Seop Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Hyeon Jeong Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Bo Eun Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Hong Nyun Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea
| | - Namkyun Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea
| | - Se Yong Jang
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea
| | - Myung Hwan Bae
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea
| | - Dong Heon Yang
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hun Sik Park
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yongkeun Cho
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- School of Medicine, Kyungpook National University, Daegu, Korea
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24
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Caputo I, Caroccia B, Frasson I, Poggio E, Zamberlan S, Morpurgo M, Seccia TM, Calì T, Brini M, Richter SN, Rossi GP. Angiotensin II Promotes SARS-CoV-2 Infection via Upregulation of ACE2 in Human Bronchial Cells. Int J Mol Sci 2022; 23:ijms23095125. [PMID: 35563515 PMCID: PMC9102833 DOI: 10.3390/ijms23095125] [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: 03/28/2022] [Revised: 05/01/2022] [Accepted: 05/02/2022] [Indexed: 12/15/2022] Open
Abstract
Blockers of the renin-angiotensin system (RAS) have been reported to increase the angiotensin converting enzyme (ACE)2, the cellular receptor of SARS-CoV-2, and thus the risk and course of COVID-19. Therefore, we investigated if angiotensin (Ang) II and RAS blockers affected ACE2 expression and SARS-CoV-2 infectivity in human epithelial bronchial Calu-3 cells. By infectivity and spike-mediated cell–cell fusion assays, we showed that Ang II acting on the angiotensin type 1 receptor markedly increased ACE2 at mRNA and protein levels, resulting in enhanced SARS-CoV-2 cell entry. These effects were abolished by irbesartan and not affected by the blockade of ACE-1-mediated Ang II formation with ramipril, and of ACE2- mediated Ang II conversion into Ang 1-7 with MLN-4760. Thus, enhanced Ang II production in patients with an activated RAS might expose to a greater spread of COVID-19 infection in lung cells. The protective action of Angiotensin type 1 receptor antagonists (ARBs) documented in these studies provides a mechanistic explanation for the lack of worse outcomes in high-risk COVID-19 patients on RAS blockers.
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Affiliation(s)
- Ilaria Caputo
- Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy; (I.C.); (B.C.); (S.Z.); (T.M.S.)
| | - Brasilina Caroccia
- Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy; (I.C.); (B.C.); (S.Z.); (T.M.S.)
| | - Ilaria Frasson
- Department of Molecular Medicine-DMM, University of Padua, 35121 Padua, Italy; (I.F.); (S.N.R.)
| | - Elena Poggio
- Department of Biology, University of Padua, 35131 Padua, Italy; (E.P.); (M.B.)
| | - Stefania Zamberlan
- Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy; (I.C.); (B.C.); (S.Z.); (T.M.S.)
| | - Margherita Morpurgo
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy;
| | - Teresa M. Seccia
- Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy; (I.C.); (B.C.); (S.Z.); (T.M.S.)
| | - Tito Calì
- Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy;
| | - Marisa Brini
- Department of Biology, University of Padua, 35131 Padua, Italy; (E.P.); (M.B.)
| | - Sara N. Richter
- Department of Molecular Medicine-DMM, University of Padua, 35121 Padua, Italy; (I.F.); (S.N.R.)
| | - Gian Paolo Rossi
- Specialized Center for Blood Pressure Disorders-Regione Veneto and Internal Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy; (I.C.); (B.C.); (S.Z.); (T.M.S.)
- Correspondence:
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25
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Liu A, Raja xavier J, Singh Y, Brucker SY, Salker MS. Molecular and Physiological Aspects of SARS-CoV-2 Infection in Women and Pregnancy. Front Glob Womens Health 2022; 3:756362. [PMID: 35284910 PMCID: PMC8908006 DOI: 10.3389/fgwh.2022.756362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 02/01/2022] [Indexed: 01/08/2023] Open
Abstract
Whilst scientific knowledge about SARS-CoV-2 and COVID-19 is rapidly increasing, much of the effects on pregnant women is still unknown. To accommodate pregnancy, the human endometrium must undergo a physiological transformation called decidualization. These changes encompass the remodeling of endometrial immune cells leading to immunotolerance of the semi-allogenic conceptus as well as defense against pathogens. The angiotensin converting enzyme 2 (ACE2) plays an important regulatory role in the renin-angiotensin-system (RAS) and has been shown to be protective against comorbidities known to worsen COVID-19 outcomes. Furthermore, ACE2 is also crucial for decidualization and thus for early gestation. An astounding gender difference has been found in COVID-19 with male patients presenting with more severe cases and higher mortality rates. This could be attributed to differences in sex chromosomes, hormone levels and behavior patterns. Despite profound changes in the female body during pregnancy, expectant mothers do not face worse outcomes compared with non-pregnant women. Whereas mother-to-child transmission through respiratory droplets during labor or in the postnatal period is known, another question of in utero transmission remains unanswered. Evidence of placental SARS-CoV-2 infection and expression of viral entry receptors at the maternal-fetal interface suggests the possibility of in utero transmission. SARS-CoV-2 can cause further harm through placental damage, maternal systemic inflammation, and hindered access to health care during the pandemic. More research on the effects of COVID-19 during early pregnancy as well as vaccination and treatment options for gravid patients is urgently needed.
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Affiliation(s)
- Anna Liu
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
| | - Janet Raja xavier
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
| | - Yogesh Singh
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
- Institute of Medical Genetics and Applied Genomics, Eberhard Karls University, Tübingen, Germany
| | - Sara Y. Brucker
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
| | - Madhuri S. Salker
- Research Institute of Women's Health, Eberhard Karls University, Tübingen, Germany
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26
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Nozari F, Hamidizadeh N. The Effects of Different Classes of Antihypertensive Drugs on Patients with COVID-19 and Hypertension: A Mini-Review. Int J Hypertens 2022; 2022:5937802. [PMID: 35075396 PMCID: PMC8783136 DOI: 10.1155/2022/5937802] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/04/2021] [Accepted: 01/06/2022] [Indexed: 12/22/2022] Open
Abstract
Hypertension is a major risk factor for cardiovascular disease. Previous studies showed that patients with hypertension are at an increased risk of developing severe COVID-19 infection. Therefore, proper blood pressure control in hypertensive patients with COVID-19 is of great importance. In this review, we discussed the effects of different classes of antihypertensive drugs on patients with hypertension and COVID-19.
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Affiliation(s)
- Farnoosh Nozari
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasrin Hamidizadeh
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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27
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Quan Y, Li L, Yin Z, Chen S, Yi J, Lang J, Zhang L, Yue Q, Zhao J. Bulbus Fritillariae Cirrhosae as a Respiratory Medicine: Is There a Potential Drug in the Treatment of COVID-19? Front Pharmacol 2022; 12:784335. [PMID: 35126123 PMCID: PMC8811224 DOI: 10.3389/fphar.2021.784335] [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: 09/27/2021] [Accepted: 12/03/2021] [Indexed: 01/08/2023] Open
Abstract
Bulbus fritillariae cirrhosae (BFC) is one of the most used Chinese medicines for lung disease, and exerts antitussive, expectorant, anti-inflammatory, anti-asthmatic, and antioxidant effects, which is an ideal therapeutic drug for respiratory diseases such as ARDS, COPD, asthma, lung cancer, and pulmonary tuberculosis. Through this review, it is found that the therapeutic mechanism of BFC on respiratory diseases exhibits the characteristics of multi-components, multi-targets, and multi-signaling pathways. In particular, the therapeutic potential of BFC in terms of intervention of “cytokine storm”, STAT, NF-κB, and MAPK signaling pathways, as well as the renin-angiotensin system (RAS) that ACE is involved in. In the “cytokine storm” of SARS-CoV-2 infection there is an intense inflammatory response. ACE2 regulates the RAS by degradation of Ang II produced by ACE, which is associated with SARS-CoV-2. For COVID-19, may it be a potential drug? This review summarized the research progress of BFC in the respiratory diseases, discussed the development potentiality of BFC for the treatment of COVID-19, explained the chemical diversity and biological significance of the alkaloids in BFC, and clarified the material basis, molecular targets, and signaling pathways of BFC for the respiratory diseases. We hope this review can provide insights on the drug discovery of anti-COVID-19.
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Affiliation(s)
- Yunyun Quan
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
- Department of Pharmacognosy, West China School of Pharmacy Sichuan University, Chengdu, China
| | - Li Li
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
| | - Zhujun Yin
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
| | - Shilong Chen
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
| | - Jing Yi
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
| | - Jirui Lang
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
| | - Lu Zhang
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
| | - Qianhua Yue
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
| | - Junning Zhao
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, China
- Department of Pharmacognosy, West China School of Pharmacy Sichuan University, Chengdu, China
- *Correspondence: Junning Zhao,
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28
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Copur S, Kanbay A, Kanbay M. Should we continue to use renin-angiotensin-aldosterone system blockers in patients with COVID-19? Clin Kidney J 2022; 15:852-854. [PMID: 35498886 PMCID: PMC8755383 DOI: 10.1093/ckj/sfac001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Indexed: 11/17/2022] Open
Abstract
Patients with chronic kidney disease, chronic heart failure and hypertension have an increased risk of coronavirus disease 2019 (COVID-19)-related death. Renin–angiotensin–aldosterone system (RAS) blockers are commonly prescribed to decrease morbidity and mortality in these conditions. Following the pre-clinical demonstration of COVID-19 viral entry into cells via angiotensin-converting enzyme-2, the use of RAS blockers was questioned in infected individuals. Theodorakopoulou et al. extensively review the pathophysiology behind that hypothesis and observational or clinical trials on RAS blockers and COVID-19. Despite being a scientific hot spot of an ongoing debate, discontinuation of RAS blockers is not associated with improved clinical outcomes in COVID-19 and may have potential harmful effects, including exacerbation of the underlying disease.
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Affiliation(s)
- Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Asiye Kanbay
- Department of Pulmonary Medicine, Istanbul Medicana Atasehir Hospital, Istanbul, Turkey
| | - Mehmet Kanbay
- Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey
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29
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Amin M, Chondra U, Mostafa E, Alam M. Green seaweed Ulva lactuca, a potential source of bioactive peptides revealed by in silico analysis. INFORMATICS IN MEDICINE UNLOCKED 2022. [DOI: 10.1016/j.imu.2022.101099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
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30
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Laloglu E, Alay H. Endocan as a potential marker in diagnosis and predicting disease severity in COVID-19 patients: a promising biomarker for patients with false-negative RT-PCR. Ups J Med Sci 2022; 12:8211. [PMID: 35140869 PMCID: PMC8788653 DOI: 10.48101/ujms.v127.8211] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 11/15/2021] [Accepted: 12/15/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Endothelial-specific molecule 1 (endocan) has emerged as an inflammatory biomarker in recent years. The purpose of this study was to investigate the diagnostic value of serum endocan levels in the prediction of COVID-19 disease among patients with a false-negative reverse transcription polymerase change reaction (RT-PCR) test, and also to determine its correlation with the clinical severity of the disease. METHODS Thirty patients with positive RT-PCR results and 30 with false-negative RT-PCR results, both with suspected COVID-19 in terms of clinical, radiological, and laboratory findings, were included in the study. Thirty healthy controls were also enrolled. RESULTS Serum endocan levels were estimated to be 821.8 ± 99.3 pg/mL in COVID-19 RT-PCR (+) patients, 803.9 ± 97.0 pg/mL in RT-PCR false (-) patients with suspected COVID-19, and 382.9 ± 37.5 pg/mL in the control group. No significant difference was observed between RT-PCR (+) and RT-PCR false (-) patients (P = 0.68). However, serum endocan levels differed significantly between patient groups and control group (P < 0.05). With a cut-off value of 444.2 pg/mL serum endocan levels differentiated COVID-19 cases from healthy individuals with 92% sensitivity and 80% specificity. Moreover, a significant positive correlation was observed between serum endocan levels and clinical severity (P < 0.01, r = 0.94). CONCLUSIONS There is a need for different laboratory markers capable of assisting diagnosis and showing COVID-19 infection in suspected COVID-19 RT-PCR false-negative patients. Endocan levels can be used as an assistant blood test for identifying COVID-19 patients with false-negative RT-PCR tests and in determining the clinical severity of the disease.
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Affiliation(s)
- Esra Laloglu
- Department of Medical Biochemistry, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Handan Alay
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
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Talebi-Taher M, Najafi MH, Behzad S. COVID-19 and RAAS inhibitors: is there a final conclusion? IRANIAN JOURNAL OF MICROBIOLOGY 2021; 13:728-736. [PMID: 35222849 PMCID: PMC8816704 DOI: 10.18502/ijm.v13i6.8071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19), the first pandemic caused by a human infecting coronavirus, has drawn global attention from the first time it appeared in Wuhan city of China in late December 2019. Detection of the responsible viral pathogen, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by WHO, and its possible pathogenesis lead to the forming of many hypotheses about the factors that may affect the patients' outcome. One of the SARS-CoV-2 infection concerns was the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in COVID-19 patients' morbidity and mortality. Studies demonstrated that because SARS-CoV-2 uses human ACE2 cell receptors as an entry receptor to invade the cells, there might be an association between antihypertensive drugs such as RAAS inhibitors (specifically ACEIs and ARBs) and the COVID-19 disease. Data are scarce and conflicting regarding ACEI or ARB consumption and how it influences disease outcomes, and a single conclusion has not been reached yet. According to the literature review in our article, the most evidentially supported theory about the use of RAAS inhibitors in COVID-19 is that these medications, including ACEI/ARB, are not associated with the increased risk of infection, disease severity, and patient prognosis. However, further studies are needed to support the hypothesis.
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Affiliation(s)
- Mahshid Talebi-Taher
- Department of Infectious Diseases and Tropical Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Corresponding author: Mahshid Talebi-Taher, MD, Department of Infectious Diseases and Tropical Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Tel: +98-9123835372 Fax: +98-2166507056 ;
| | | | - Shima Behzad
- Department of Cardiology, School of Medicine, Azad University, Tehran, Iran
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Larsen NW, Stiles LE, Miglis MG. Preparing for the long-haul: Autonomic complications of COVID-19. Auton Neurosci 2021; 235:102841. [PMID: 34265539 PMCID: PMC8254396 DOI: 10.1016/j.autneu.2021.102841] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 06/13/2021] [Accepted: 06/28/2021] [Indexed: 12/25/2022]
Abstract
As global numbers of COVID-19 grow, chronic neurological symptoms, including those of autonomic dysfunction, are being reported with increasing frequency. Mounting evidence suggests that many patients experience chronic and sometimes debilitating symptoms long after their acute infectious period, leading to the new diagnostic category of post-acute COVID syndrome. Many symptoms of post-acute COVID syndrome appear autonomic in nature, suggesting that autonomic impairment may play a central role in the underlying pathophysiology. In this review, we discuss the autonomic symptoms and manifestations of post-acute COVID syndrome, potential mechanisms involved, and future directions for a better understanding of this novel condition.
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Affiliation(s)
- Nicholas W Larsen
- Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, USA
| | - Lauren E Stiles
- Department of Neurology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA
| | - Mitchell G Miglis
- Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, USA.
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Moftakhar L, Piraee E, Mohammadi Abnavi M, Moftakhar P, Azarbakhsh H, Valipour A. Epidemiological Features and Predictors of Mortality in Patients with COVID-19 with and without Underlying Hypertension. Int J Hypertens 2021; 2021:7427500. [PMID: 34676114 PMCID: PMC8526257 DOI: 10.1155/2021/7427500] [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: 04/23/2021] [Revised: 09/03/2021] [Accepted: 09/12/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUNDS Individuals with hypertension are at higher risk of COVID-19 infection and related mortality. This study was carried out to assess the epidemiological features and predictors of mortality in patients with COVID-19 with hypertension. METHODS In this retrospective study, the epidemiological characteristics of two groups of patients with COVID-19 with hypertension (1927) and without hypertension (39030) were compared. Chi-square test was applied to evaluate the differences between qualitative variables in two study groups. Logistic regression was also used to determine predictors of mortality in patients with COVID-19 and in patients with COVID-19 with hypertension. RESULTS The prevalence of hypertension in patients with COVID-19 was 4.7%, and 24.37% of COVID-19 related deaths occurred in these individuals. The average age of hypertension and nonhypertension patients was 61 and 37 years, respectively. Fever, cough, headache, anorexia, fatigue, and comorbid diseases, such as cardiovascular disease, chronic lung and kidney disease, diabetes, immunodeficiency disease, and thyroid disease, were significantly more frequent in people with hypertension than those without hypertension. The chances of mortality in patient with COVID-19 were 1.8 times higher in individuals with dyspnea, 1.25 in individuals with fever, 1.33 in individuals with cough, 3.6 in patients with hypertension, 2.21 in diabetics, and 2.2 in individuals with cardiovascular disease. Also, individuals with COVID-19 with hypertension that had dyspnea, immunodeficiency, and cardiovascular disease were at higher risk of mortality. CONCLUSION Hypertension is a serious threat to patients with COVID-19. Therefore, in order to control these patients more precisely and reduce mortality in them, it is extremely important to develop prevention and treatment strategies.
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Affiliation(s)
- Leila Moftakhar
- Abadan University of Medical Sciences, Abadan, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Elahe Piraee
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Parisa Moftakhar
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | | | - Aliasghar Valipour
- Department of Public Health, Abadan Faculty of Medical Sciences, Abadan, Iran
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Human Cell Receptors and Downstream Cascades: A Review of Molecular Aspects and Potential Therapeutic Targets in COVID-19. ARCHIVES OF PEDIATRIC INFECTIOUS DISEASES 2021. [DOI: 10.5812/pedinfect.113298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Context: There have been two coronavirus-related pandemics during the past 18 years, including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV in 2002 and 2012, respectively. In 2019, Seven years after the emergence of MERS, a new coronavirus (i.e., SARS-CoV-2) was detected in several patients. SARS-CoV-2 spread widely, and its high prevalence enabled the virus to start a new pandemic in 2020. It is believed that the higher infectivity of the virus in comparison to that of SARS-CoV is related to its molecular interaction affinity of transmembrane spike glycoprotein and human angiotensin-converting enzyme 2 (ACE-2) cell receptors. Moreover, the primary reason for the high case fatality rate (CFR) is the cytokine storm and acute respiratory distress syndrome (ARDS) because of the immune system response to the invaders. Hence, a solid understanding of the components involved in the mechanism of viral entry and immune system response is crucial for finding approaches to disrupt the virus-cell interplay and neutralizing its impacts on the host immune system. In this review, we investigated the molecular aspect and potential therapeutic targets associated with cell receptors and downstream signaling cascades. Evidence Acquisition: A systematic search was implemented on several online databases, including Google Scholar, PubMed, and Scopus during 2019-2021 using the following keywords: "SARS-CoV-2", "COVID-19", "ACE-2", "Therapeutic Targets", "Acute Respiratory Distress Syndrome", and "Cytokine Storm". Results: Various internal or external agents are responsible for the virus infectivity and stimulating acute immune system response. Since currently there is no cure for the treatment of COVID-19, several repurposed drugs can be employed to disrupt the process of viral entry and mitigate the symptoms raised by the cytokine storm. Inhibition of several agents, including signal transduction mediators and TMPRSS2 may be momentous. Conclusions: Despite the increase in the CFR, no drugs were developed with significant efficacy. Understanding the virus entry mechanism and the immune system’s role could help us surmount the problems in developing a promising drug or employing the repurposed ones.
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Peñalvo JL, Genbrugge E, Mertens E, Sagastume D, van der Sande MAB, Widdowson MA, Van Beckhoven D. Insights into the association of ACEIs/ARBs use and COVID-19 prognosis: a multistate modelling study of nationwide hospital surveillance data from Belgium. BMJ Open 2021; 11:e053393. [PMID: 34531225 PMCID: PMC8449849 DOI: 10.1136/bmjopen-2021-053393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES The widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) by patients with chronic conditions raised early concerns on the potential exacerbation of COVID-19 severity and fatality. Previous studies addressing this question have used standard methods that may lead to biased estimates when analysing hospital data because of the presence of competing events and event-related dependency. We investigated the association of ACEIs/ARBs' use with COVID-19 disease outcomes using time-to-event data in a multistate setting to account for competing events and minimise bias. SETTING Nationwide surveillance data from 119 Belgian hospitals. PARTICIPANTS Medical records of 10 866 patients hospitalised from 14 March 2020to 14 June 2020 with a confirmed SARS-CoV-19 infection and information about ACEIs/ARBs' use. PRIMARY OUTCOME MEASURE Multistate, multivariate Cox-Markov models were used to estimate the hazards of patients transitioning through health states from admission to discharge or death, along with transition probabilities calculated by combining the baseline cumulative hazard and regression coefficients. RESULTS After accounting for potential confounders, there was no discernable association between ACEIs/ARBs' use and transfer to intensive care unit (ICU). Contrastingly, for patients without ICU transfer, ACEIs/ARBs' use was associated with a modest increase in recovery (HR 1.07, 95% CI 1.01 to 1.13, p=0.027) and reduction in fatality (HR 0.83, 95% CI 0.75 to 0.93, p=0.001) transitions. For patients transferred to ICU admission, no evidence of an association between ACEIs/ARBs' use and recovery (HR 1.16, 95% CI 0.97 to 1.38, p=0.098) or in-hospital death (HR 0.91, 95% CI 0.73 to 1.12, p=0.381) was observed. Male gender and older age were significantly associated with higher risk of ICU admission or death. Chronic cardiometabolic comorbidities were also associated with less recovery. CONCLUSIONS For the first time, a multistate model was used to address magnitude and direction of the association of ACEIs/ARBs' use on COVID-19 progression. By minimising bias, this study provided a robust indication of a protective, although modest, association with recovery and survival.
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Affiliation(s)
- José L Peñalvo
- Unit of Non-Communicable Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerpen, Belgium
| | - Els Genbrugge
- Unit of Non-Communicable Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerpen, Belgium
| | - Elly Mertens
- Unit of Non-Communicable Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerpen, Belgium
| | - Diana Sagastume
- Unit of Non-Communicable Diseases, Department of Public Health, Institute of Tropical Medicine, Antwerpen, Belgium
| | - Marianne A B van der Sande
- Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium
- Global Health Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands
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Rinoldi C, Zargarian SS, Nakielski P, Li X, Liguori A, Petronella F, Presutti D, Wang Q, Costantini M, De Sio L, Gualandi C, Ding B, Pierini F. Nanotechnology-Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID-19 Vaccines. SMALL METHODS 2021; 5:e2100402. [PMID: 34514087 PMCID: PMC8420172 DOI: 10.1002/smtd.202100402] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 07/04/2021] [Indexed: 05/07/2023]
Abstract
In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA-based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists' enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology-assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in-depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology-mediated RNA therapies are discussed.
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Affiliation(s)
- Chiara Rinoldi
- Department of Biosystems and Soft MatterInstitute of Fundamental Technological ResearchPolish Academy of Sciencesul. Pawińskiego 5BWarsaw02‐106Poland
| | - Seyed Shahrooz Zargarian
- Department of Biosystems and Soft MatterInstitute of Fundamental Technological ResearchPolish Academy of Sciencesul. Pawińskiego 5BWarsaw02‐106Poland
| | - Pawel Nakielski
- Department of Biosystems and Soft MatterInstitute of Fundamental Technological ResearchPolish Academy of Sciencesul. Pawińskiego 5BWarsaw02‐106Poland
| | - Xiaoran Li
- Innovation Center for Textile Science and TechnologyDonghua UniversityWest Yan'an Road 1882Shanghai200051China
| | - Anna Liguori
- Department of Chemistry “Giacomo Ciamician” and INSTM UdR of BolognaUniversity of BolognaVia Selmi 2Bologna40126Italy
| | - Francesca Petronella
- Institute of Crystallography CNR‐ICNational Research Council of ItalyVia Salaria Km 29.300Monterotondo – Rome00015Italy
| | - Dario Presutti
- Institute of Physical ChemistryPolish Academy of Sciencesul. M. Kasprzaka 44/52Warsaw01‐224Poland
| | - Qiusheng Wang
- Innovation Center for Textile Science and TechnologyDonghua UniversityWest Yan'an Road 1882Shanghai200051China
| | - Marco Costantini
- Institute of Physical ChemistryPolish Academy of Sciencesul. M. Kasprzaka 44/52Warsaw01‐224Poland
| | - Luciano De Sio
- Department of Medico‐Surgical Sciences and BiotechnologiesResearch Center for BiophotonicsSapienza University of RomeCorso della Repubblica 79Latina04100Italy
- CNR‐Lab. LicrylInstitute NANOTECArcavacata di Rende87036Italy
| | - Chiara Gualandi
- Department of Chemistry “Giacomo Ciamician” and INSTM UdR of BolognaUniversity of BolognaVia Selmi 2Bologna40126Italy
- Interdepartmental Center for Industrial Research on Advanced Applications in Mechanical Engineering and Materials TechnologyCIRI‐MAMUniversity of BolognaViale Risorgimento 2Bologna40136Italy
| | - Bin Ding
- Innovation Center for Textile Science and TechnologyDonghua UniversityWest Yan'an Road 1882Shanghai200051China
| | - Filippo Pierini
- Department of Biosystems and Soft MatterInstitute of Fundamental Technological ResearchPolish Academy of Sciencesul. Pawińskiego 5BWarsaw02‐106Poland
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Khalili A, Karim H, Bayat G. Theoretical Assessment of Therapeutic Effects of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors on COVID-19. IRANIAN JOURNAL OF MEDICAL SCIENCES 2021; 46:312-316. [PMID: 34305244 PMCID: PMC8288492 DOI: 10.30476/ijms.2021.88753.1949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 02/09/2021] [Accepted: 02/27/2021] [Indexed: 11/19/2022]
Affiliation(s)
- Azadeh Khalili
- Department of Physiology-Pharmacology-Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.,Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Hosein Karim
- Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Gholamreza Bayat
- Department of Physiology-Pharmacology-Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.,Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
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Baslilar S, Saylan B. Patients with hypertension hospitalized with COVID-19 pneumonia using angiotensinconverting enzyme inhibitors and angiotensin II receptor blockers or other antihypertensives: retrospective analysis of 435 patients. Ann Saudi Med 2021; 41:268-273. [PMID: 34618609 PMCID: PMC8497007 DOI: 10.5144/0256-4947.2021.268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension (HT). Whether the use of these drugs increases the infectivity of novel coronavirus and results in an additional risk for morbidity and mortality of COVID-19 is a matter of interest. OBJECTIVES Assess the effect of ACEI/ARBs compared with other hypertensives on the clinical course and outcome in COVID-19 pneumonia. DESIGN Retrospective. SETTINGS Tertiary care hospital. PATIENTS AND METHODS We collected data on adult inpatients with COVID-19 pneumonia using ACEI/ARBs versus other antihypertensives between 15 March 2020, and 15 February 2021. MAIN OUTCOME MEASURES Severity, clinical course, mortality, and time to PCR negativity between patients using ACEI/ARBs and other antihypertensives. SAMPLE SIZE 435 RESULTS: ACEI/ARBs were used by 203 patients (46.6%) (median age: 71 [41-94] years), while 232 patients (53.4%) were using other antihypertensives (median age: 69 [22-93] years, P=.645 vs age of ACEI/ARB users). There were no statistically significant differences between the ACEI/ARBs users and non-users in the number of patients admitted to intensive care (65 cases [32%] vs. 74 cases [31.9%], P=.978), the median duration of stay in hospital (8 [1-54] days vs.7 [1-55] days, P=.806) the median duration of ICU stay (8 [1-40] days vs. 6 [1-25] days), and the mortality rate (48 cases [23.6%] vs. 61 [26.3%], P=.525). While the median days before transfer to the ICU was shorter in ACE/ARBI non-users (2 [1-15] days vs. 3 [1-21] days, P=.02), the difference was not important clinically. The median time to PCR negativity was similar in ACEI/ARBs users and non-users (13 [7-34] days for users and 13 [5-45] days for non-users), (P=.083). CONCLUSIONS ACEI/ARB use is probably unrelated to poor prognosis in COVID-19 pneumonia inpatients. ACEI/ARBs did not prolong the time to PCR negativity. We conclude that using ACEI/ARBs probably does not increase the infectivity of SARS-CoV-2. LIMITATIONS Pharmacological therapies were not discussed in detail. The use of corticosteroids may affect the time to PCR negativity. We could not analyze the effect of obesity because of a lack of data. CONFLICT OF INTEREST None.
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Affiliation(s)
- Seyma Baslilar
- From the Department of Pulmonology, Umraniye Training and Research Hospital, Istanbul, Turkey
| | - Bengu Saylan
- From the Department of Pulmonology, Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey
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Rajput A, Thakur A, Rastogi A, Choudhury S, Kumar M. Computational identification of repurposed drugs against viruses causing epidemics and pandemics via drug-target network analysis. Comput Biol Med 2021; 136:104677. [PMID: 34332351 PMCID: PMC8299294 DOI: 10.1016/j.compbiomed.2021.104677] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 07/20/2021] [Indexed: 12/20/2022]
Abstract
Viral epidemics and pandemics are considered public health emergencies. However, traditional and novel antiviral discovery approaches are unable to mitigate them in a timely manner. Notably, drug repurposing emerged as an alternative strategy to provide antiviral solutions in a timely and cost-effective manner. In the literature, many FDA-approved drugs have been repurposed to inhibit viruses, while a few among them have also entered clinical trials. Using experimental data, we identified repurposed drugs against 14 viruses responsible for causing epidemics and pandemics such as SARS-CoV-2, SARS, Middle East respiratory syndrome, influenza H1N1, Ebola, Zika, Nipah, chikungunya, and others. We developed a novel computational "drug-target-drug" approach that uses the drug-targets extracted for specific drugs, which are experimentally validated in vitro or in vivo for antiviral activity. Furthermore, these extracted drug-targets were used to fetch the novel FDA-approved drugs for each virus and prioritize them by calculating their confidence scores. Pathway analysis showed that the majority of the extracted targets are involved in cancer and signaling pathways. For SARS-CoV-2, our method identified 21 potential repurposed drugs, of which 7 (e.g., baricitinib, ramipril, chlorpromazine, enalaprilat, etc.) have already entered clinical trials. The prioritized drug candidates were further validated using a molecular docking approach. Therefore, we anticipate success during the experimental validation of our predicted FDA-approved repurposed drugs against 14 viruses. This study will assist the scientific community in hastening research aimed at the development of antiviral therapeutics.
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Affiliation(s)
- Akanksha Rajput
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39-A, Chandigarh, 160036, India
| | - Anamika Thakur
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39-A, Chandigarh, 160036, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Amber Rastogi
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39-A, Chandigarh, 160036, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Shubham Choudhury
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39-A, Chandigarh, 160036, India
| | - Manoj Kumar
- Virology Unit and Bioinformatics Centre, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Sector 39-A, Chandigarh, 160036, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
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Sharma P, Reddy PK, Kumar B. Trace Element Zinc, a Nature's Gift to Fight Unprecedented Global Pandemic COVID-19. Biol Trace Elem Res 2021; 199:3213-3221. [PMID: 33170448 PMCID: PMC7654355 DOI: 10.1007/s12011-020-02462-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 10/28/2020] [Indexed: 12/11/2022]
Abstract
With the advent of twenty-first century, we are in cruel grip of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the associated illness being called as COVID-19. Since its outbreak in December 2019 in Wuhan, China, there are no medicines to cure the disease till date. Based on their experience, scientists say that developing a coronavirus vaccine could take at least a year. There are many steps in place before the vaccine comes for the distribution like its safety and cost-effectiveness, especially for the developing countries. In this scenario, the only way to prevent the disease is by following certain safety guidelines and to boost up the body's immune system. Zinc, a crucial trace element involved in several biological and metabolic processes, has been found to play a pivotal role in promoting and appropriately regulating the host defense mechanisms against viral infections. Zinc is naturally present in some foods, fortified in others and also available as dietary supplement. The current RDA (Recommended Daily Allowance) of zinc is 12 and 10 mg for males and females respectively. Zinc is the second most common trace mineral after iron in the cell. It is present in all organs and tissues in the body as it forms catalytic component of all 6 classes of enzymes encompassing almost 2000 enzymes in the body. Zinc is biologically essential for cellular processes, including growth and development, as well as DNA synthesis and RNA transcription. Zinc deficiency results in a number of metabolic changes besides a compromised immune system. In this review, the role of zinc in regulating the host defense and viral replication is being discussed with the main focus on COVID-19.
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Affiliation(s)
- Priyanka Sharma
- Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India.
| | - Prasanna Kumar Reddy
- Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India
| | - Bhuvnesh Kumar
- Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India
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Almutlaq M, Alamro AA, Alroqi F, Barhoumi T. Classical and Counter-Regulatory Renin-Angiotensin System: Potential Key Roles in COVID-19 Pathophysiology. CJC Open 2021; 3:1060-1074. [PMID: 33875979 PMCID: PMC8046706 DOI: 10.1016/j.cjco.2021.04.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 04/08/2021] [Indexed: 02/08/2023] Open
Abstract
In the current COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 uses angiotensin-converting enzyme-2 (ACE-2) receptors for cell entry, leading to ACE-2 dysfunction and downregulation, which disturb the balance between the classical and counter-regulatory renin-angiotensin system (RAS) in favor of the classical RAS. RAS dysregulation is one of the major characteristics of several cardiovascular diseases; thus, adjustment of this system is the main therapeutic target. RAS inhibitors-particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs)-are commonly used for treatment of hypertension and cardiovascular disease. Patients with cardiovascular diseases are the group most commonly seen among those with COVID-19 comorbidity. At the beginning of this pandemic, a dilemma occurred regarding the use of ACEIs and ARBs, potentially aggravating cardiovascular and pulmonary dysfunction in COVID-19 patients. Urgent clinical trials from different countries and hospitals reported that there is no association between RAS inhibitor treatment and COVID-19 infection or comorbidity complication. Nevertheless, the disturbance of the RAS that is associated with COVID-19 infection and the potential treatment targeting this area have yet to be resolved. In this review, the link between the dysregulation of classical RAS and counter-regulatory RAS activities in COVID-19 patients with cardiovascular metabolic diseases is investigated. In addition, the latest findings based on ACEI and ARB administration and ACE-2 availability in relation to COVID-19, which may provide a better understanding of the RAS contribution to COVID-19 pathology, are discussed, as they are of the utmost importance amid the current pandemic.
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Affiliation(s)
- Moudhi Almutlaq
- King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
- Moudhi Almutlaq, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh 11461, Saudi Arabia. Tel.: +1-966-543-159145.
| | - Abir Abdullah Alamro
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Fayhan Alroqi
- King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
- Department of Pediatrics, King Abdulaziz Medical City, King Abdullah Specialized Children's Hospital, Riyadh, Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Tlili Barhoumi
- King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Corresponding authors: Dr Tlili Barhoumi, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Riyadh 11461, Saudi Arabia. Tel.: +1-966-543-159145.
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Núñez-Gil IJ, Olier I, Feltes G, Viana-Llamas MC, Maroun-Eid C, Romero R, Fernández-Rozas I, Uribarri A, Becerra-Muñoz VM, Alfonso-Rodriguez E, García-Aguado M, Elola J, Castro-Mejía A, Pepe M, Garcia-Prieto JF, Gonzalez A, Ugo F, Cerrato E, Bondia E, Raposeiras-Roubin S, Mendez JLJ, Espejo C, López-Masjuan Á, Marin F, López-Pais J, Abumayyaleh M, Corbi-Pascual M, Liebetrau C, Ramakrishna H, Estrada V, Macaya C, Fernandez-Ortiz A. Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry. Am Heart J 2021; 237:104-115. [PMID: 33845032 PMCID: PMC8047303 DOI: 10.1016/j.ahj.2021.04.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 04/03/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site. METHODS HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications. RESULTS We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure. CONCLUSION RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications.
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Affiliation(s)
- Iván J Núñez-Gil
- Hospital Clínico San Carlos, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
| | - Iván Olier
- Liverpool Centre for Cardiovascular Science, Liverpool John Moores University, Liverpool, United Kingdom
| | | | | | - Charbel Maroun-Eid
- Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain
| | - Rodolfo Romero
- Hospital Universitario Getafe, Universidad Europea de Madrid, Madrid, Spain
| | | | - Aitor Uribarri
- Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Victor M Becerra-Muñoz
- Unidad de Gestión Clínica Área del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Málaga, Spain
| | | | | | - Javier Elola
- Instituto para la Mejora de la Asistencia Sanitaria, IMAS, Madrid, Spain
| | - Alex Castro-Mejía
- Hospital General del norte de Guayaquil IESS Los Ceibos, Guayaquil, Ecuador
| | - Martino Pepe
- Azienda ospedaliero-universitaria consorziale policlinico di Bari, Bari, Italy
| | | | - Adelina Gonzalez
- Hospital Universitario Infanta Sofia, San Sebastian de los Reyes, Madrid, Spain
| | | | - Enrico Cerrato
- San Luigi Gonzaga University Hospital, Orbassano and Rivoli Infermi Hospital, Rivoli (Turin), Italy
| | - Elvira Bondia
- Hospital Clínico Universitario, Incliva, Universidad de Valencia, Valencia, Spain
| | - Sergio Raposeiras-Roubin
- Hospital Universitario Álvaro Cunqueiro, Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain
| | | | - Carolina Espejo
- Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain
| | | | - Francisco Marin
- Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, CIBERCV, Murcia, Spain
| | - Javier López-Pais
- Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain
| | - Mohammad Abumayyaleh
- University Medical Center Mannheim (UMM), University of Heidelberg, Mannheim, Germany
| | | | | | | | - Vicente Estrada
- Hospital Clínico San Carlos, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Carlos Macaya
- Hospital Clínico San Carlos, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Antonio Fernandez-Ortiz
- Hospital Clínico San Carlos, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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Lukito AA, Widysanto A, Lemuel TAY, Prasetya IB, Massie B, Yuniarti M, Lumbuun N, Pranata R, Meidy C, Wahjoepramono EJ, Yusuf I. Candesartan as a tentative treatment for COVID-19: A prospective non-randomized open-label study. Int J Infect Dis 2021; 108:159-166. [PMID: 34038766 PMCID: PMC8142270 DOI: 10.1016/j.ijid.2021.05.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/05/2021] [Accepted: 05/11/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND This study aimed to investigate whether the addition of candesartan to the standard care regimen improved the outcome in patients with coronavirus 2019 (COVID-19). METHODS A prospective non-randomized open-label study was undertaken from May to August 2020 on 75 subjects (aged 18-70 years) hospitalized in Siloam Kelapa Dua Hospital. Uni- and multi-variable Cox regression analyses were performed to obtain hazard ratios (HRs). The primary outcomes were: (1) length of hospital stay; (2) time to negative swab; and (3) radiological outcome (time to improvement on chest X ray). RESULTS None of the 75 patients with COVID-19 required intensive care. All patients were angiotensin-receptor-blocker naïve. In comparison with the control group, the candesartan group had a significantly shorter hospital stay [adjusted HR 2.47, 95% confidence interval (CI) 1.16-5.29] after adjusting for a wide range of confounders, and no increased risk of intensive care. In the non-obese subgroup, the candesartan group had a shorter time to negative swab (unadjusted HR 2.11, 95% CI 1.02-4.36; adjusted HR 2.40, 95% CI 1.08-5.09) and shorter time to improvement in chest x ray (adjusted HR 2.82, 95% CI 1.13-7.03) compared with the control group. CONCLUSION Candesartan significantly reduces the length of hospital stay after adjustment for covariates. All primary outcomes improved significantly in the non-obese subgroup receiving candesartan.
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Affiliation(s)
- Antonia Anna Lukito
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia; Mochtar Riady Institute of Nanotechnology, Tangerang, Indonesia.
| | - Allen Widysanto
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia
| | - Theo Audi Yanto Lemuel
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia
| | - Ignatius Bima Prasetya
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia
| | - Billy Massie
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia
| | - Mira Yuniarti
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia
| | | | - Raymond Pranata
- Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia
| | - Cindy Meidy
- Pelita Harapan University, Tangerang, Indonesia
| | - Eka Julianta Wahjoepramono
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Siloam Hospitals, Tangerang, Indonesia
| | - Irawan Yusuf
- Medical Science Group Team, Tangerang, Indonesia; Pelita Harapan University, Tangerang, Indonesia; Mochtar Riady Institute of Nanotechnology, Tangerang, Indonesia
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Xu F, Wen Y, Hu X, Wang T, Chen G. The Potential Use of Vitamin C to Prevent Kidney Injury in Patients with COVID-19. Diseases 2021; 9:46. [PMID: 34203409 PMCID: PMC8293113 DOI: 10.3390/diseases9030046] [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: 05/24/2021] [Revised: 06/17/2021] [Accepted: 06/24/2021] [Indexed: 02/07/2023] Open
Abstract
The newly found SARS-CoV-2 has led to the pandemic of COVID-19, which has caused respiratory distress syndrome and even death worldwide. This has become a global public health crisis. Unfortunately, elders and subjects with comorbidities have high mortality rates. One main feature of COVID-19 is the cytokine storm, which can cause damage in cells and tissues including the kidneys. Here, we reviewed the current literature on renal impairments in patients with COVID-19 and analyzed the possible etiology and mechanisms. In addition, we investigated the potential use of vitamin C for the prevention of renal injury in those patients. It appears that vitamin C could be helpful to improve the outcomes of patients with COVID-19. Lastly, we discussed the possible protective effects of vitamin C on renal functions in COVID-19 patients with existing kidney conditions.
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Affiliation(s)
- Feng Xu
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; (F.X.); (Y.W.)
| | - Yawei Wen
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; (F.X.); (Y.W.)
| | - Xinge Hu
- Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, USA; (X.H.); (T.W.)
| | - Tiannan Wang
- Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, USA; (X.H.); (T.W.)
| | - Guoxun Chen
- Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN 37996, USA; (X.H.); (T.W.)
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Suravajhala R, Parashar A, Choudhir G, Kumar A, Malik B, Nagaraj VA, Padmanaban G, Polavarapu R, Suravajhala P, Kishor PBK. Molecular docking and dynamics studies of curcumin with COVID-19 proteins. ACTA ACUST UNITED AC 2021; 10:44. [PMID: 34131556 PMCID: PMC8192041 DOI: 10.1007/s13721-021-00312-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/28/2021] [Accepted: 05/05/2021] [Indexed: 02/07/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is caused by a Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), which is a positive-strand RNA virus. The SARS-CoV-2 genome and its association to SAR-CoV-1 vary from ca. 66 to 96% depending on the type of betacoronavirideae family members. With several drugs, viz. chloroquine, hydroxychloroquine, ivermectin, artemisinin, remdesivir, azithromycin considered for clinical trials, there has been an inherent need to find distinctive antiviral mechanisms of these drugs. Curcumin, a natural bioactive molecule has been shown to have therapeutic potential for various diseases, and its effect on COVID-19 is also currently being explored. In this study, we show the binding potential of curcumin targeted to a variety of SARS-CoV-2 proteins, viz. spike glycoproteins (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), spike protein-ACE2 (PDB ID: 6M17) along with nsp10 (PDB ID: 6W4H) and RNA dependent RNA polymerase (PDB ID: 6M71) structures. Furthermore, representative docking complexes were validated using molecular dynamics simulations and mechanistic studies at 100 ns was carried on nucleocapsid and nsp10 proteins with curcumin complexes which resulted in stable and efficient binding energies and correlated with that of docked binding energies of the complexes. Both the docking and simulation studies indicate that curcumin has the potential as an antiviral against COVID-19.
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Affiliation(s)
- Renuka Suravajhala
- Department of Chemistry, Manipal University Jaipur, Jaipur, 303 007 Rajasthan India
- Bioclues.org, Hyderabad, India
| | - Abhinav Parashar
- Department of Biotechnology, Vignan’s Foundation for Science, Technology and Research (Deemed To Be University), Vadlamudi, Guntur, 522 213 Andhra Pradesh India
| | - Gourav Choudhir
- Centre for Rural Development and Technology, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi, 110 016 India
| | - Anuj Kumar
- Bioinformatics Laboratory, Uttarakhand Council for Biotechnology (UCB), Biotech Bhawan, Haldi, U.S. Nagar, Pantnagar, 263 145 Uttarakhand India
| | - Babita Malik
- Department of Chemistry, Manipal University Jaipur, Jaipur, 303 007 Rajasthan India
| | | | | | | | - Prashanth Suravajhala
- Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Jaipur, 320 001 Rajasthan India
- Bioclues.org, Hyderabad, India
| | - P. B. Kavi Kishor
- Department of Biotechnology, Vignan’s Foundation for Science, Technology and Research (Deemed To Be University), Vadlamudi, Guntur, 522 213 Andhra Pradesh India
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Rubin SJS, Falkson SR, Degner NR, Blish CA. Safety of ACE-I and ARB medications in COVID-19: A retrospective cohort study of inpatients and outpatients in California. J Clin Transl Sci 2021; 5:e8. [PMID: 34611496 PMCID: PMC7605244 DOI: 10.1017/cts.2020.489] [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: 05/08/2020] [Revised: 05/26/2020] [Accepted: 05/27/2020] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION There is significant interest in the use of angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) in coronavirus disease 2019 (COVID-19) and concern over potential adverse effects since these medications upregulate the severe acute respiratory syndrome coronavirus 2 host cell entry receptor ACE2. Recent studies on ACE-I and ARB in COVID-19 were limited by excluding outpatients, excluding patients by age, analyzing ACE-I and ARB together, imputing missing data, and/or diagnosing COVID-19 by chest computed tomography without definitive reverse transcription polymerase chain reaction (RT-PCR), all of which are addressed here. METHODS We performed a retrospective cohort study of 1023 COVID-19 patients diagnosed by RT-PCR at Stanford Hospital through April 8, 2020 with a minimum follow-up time of 14 days to investigate the association between ACE-I or ARB use with outcomes. RESULTS Use of ACE-I or ARB medications was not associated with increased risk of hospitalization, intensive care unit admission, or death. Compared to patients with charted past medical history, there was a lower risk of hospitalization for patients on ACE-I (odds ratio (OR) 0.43; 95% confidence interval (CI) 0.19-0.97; P = 0.0426) and ARB (OR 0.39; 95% CI 0.17-0.90; P = 0.0270). Compared to patients with hypertension not on ACE-I or ARB, patients on ARB medications had a lower risk of hospitalization (OR 0.09; 95% CI 0.01-0.88; P = 0.0381). CONCLUSIONS These findings suggest that the use of ACE-I and ARB is not associated with adverse outcomes and may be associated with improved outcomes in COVID-19, which is immediately relevant to care of the many patients on these medications.
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Affiliation(s)
- Samuel J. S. Rubin
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Samuel R. Falkson
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Nicholas R. Degner
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Catherine A. Blish
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- Chan-Zuckerberg Biohub, San Francisco, CA, USA
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Borchers C, Thyagarajan A, Rapp CM, Travers JB, Sahu RP. Evaluation of SARS-CoV-2 Spike S1 Protein Response on PI3K-Mediated IL-8 Release. Med Sci (Basel) 2021; 9:30. [PMID: 34069835 PMCID: PMC8162560 DOI: 10.3390/medsci9020030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/05/2021] [Accepted: 05/08/2021] [Indexed: 01/19/2023] Open
Abstract
A novel coronavirus related to a condition known as a severe acute respiratory syndrome (SARS) was termed as SARS Coronavirus-19 (SARS-CoV-2 or COVID-19), which has caused an unprecedented global pandemic. Extensive efforts have been dedicated worldwide towards determining the mechanisms of COVID-19 associated pathogenesis with the goals of devising potential therapeutic approaches to mitigate or overcome comorbidities and mortalities. While the mode of SARS-CoV-2 infection, its structural configuration, and mechanisms of action, including the critical roles of the Spike protein have been substantially explored, elucidation of signaling pathways regulating its cellular responses is yet to be fully determined. Notably, phosphoinositide 3-kinases (PI3K) and its downstream pathway have been exploited among potential therapeutic targets for SARS-CoV-2, and its activation modulates the release of cytokines such as IL-8. To that end, the current studies were sought to determine the response of the SARS-CoV-2 Spike S1 protein on PI3K-mediated IL-8 release using relevant and widely used cellular models. Overall, these studies indicate that PI3K signaling does not directly mediate Spike S1 protein-induced IL-8 release in these cellular models.
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Affiliation(s)
- Christina Borchers
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45345, USA; (C.B.); (A.T.); (C.M.R.); (J.B.T.)
| | - Anita Thyagarajan
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45345, USA; (C.B.); (A.T.); (C.M.R.); (J.B.T.)
| | - Christine M. Rapp
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45345, USA; (C.B.); (A.T.); (C.M.R.); (J.B.T.)
| | - Jeffrey B. Travers
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45345, USA; (C.B.); (A.T.); (C.M.R.); (J.B.T.)
- Department of Dermatology, Wright State Physicians, Wright State University, Dayton, OH 45345, USA
| | - Ravi P. Sahu
- Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45345, USA; (C.B.); (A.T.); (C.M.R.); (J.B.T.)
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Mehrabadi ME, Hemmati R, Tashakor A, Homaei A, Yousefzadeh M, Hemati K, Hosseinkhani S. Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity. Biomed Pharmacother 2021; 137:111363. [PMID: 33582450 PMCID: PMC7862910 DOI: 10.1016/j.biopha.2021.111363] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 01/29/2021] [Accepted: 02/02/2021] [Indexed: 12/24/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of COVID-19, is reported to increase the rate of mortality worldwide. COVID-19 is associated with acute respiratory symptoms as well as blood coagulation in the vessels (thrombosis), heart attack and stroke. Given the requirement of angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 entry into host cells, here we discuss how the downregulation of ACE2 in the COVID-19 patients and virus-induced shift in ACE2 catalytic equilibrium, change the concentrations of substrates such as angiotensin II, apelin-13, dynorphin-13, and products such as angiotensin (1-7), angiotensin (1-9), apelin-12, dynorphin-12 in the human body. Substrates accumulation ultimately induces inflammation, angiogenesis, thrombosis, neuronal and tissue damage while diminished products lead to the loss of the anti-inflammatory, anti-thrombotic and anti-angiogenic responses. In this review, we focus on the viral-induced imbalance between ACE2 substrates and products which exacerbates the severity of COVID-19. Considering the roadmap, we propose multiple therapeutic strategies aiming to rebalance the products of ACE2 and to ameliorate the symptoms of the disease.
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Affiliation(s)
| | - Roohullah Hemmati
- Department of Biology, Faculty of Basic Sciences, Shahrekord University, Sharekord, Iran; Biotechnology Research Institute, Shahrekord University, Shahrekord, Iran; COVID-19 research group, Faculty of Basic Sciences, Shahrekord Univesity, Shahrekord, Iran.
| | - Amin Tashakor
- Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin, Ireland; School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ahmad Homaei
- Department of Marine Biology, Faculty of Marine Science and Technology, University of Hormozgan, Bandar Abbas, Iran
| | | | - Karim Hemati
- Department of Anesthesiology and Pain, Iran University of Medical Sciences, Tehran, Iran
| | - Saman Hosseinkhani
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
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Liu J, Virani SS, Alam M, Denktas AE, Hamzeh I, Khalid U. Coronavirus disease-19 and cardiovascular disease: A risk factor or a risk marker? Rev Med Virol 2021; 31:e2172. [PMID: 32959951 PMCID: PMC7536956 DOI: 10.1002/rmv.2172] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 08/29/2020] [Accepted: 08/31/2020] [Indexed: 12/19/2022]
Abstract
Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to provide a succinct review about the pathophysiology and cardiac manifestations of COVID-19, as well as treatment considerations and the various adaptations made to the current healthcare structure as a result of the pandemic.
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Affiliation(s)
- Jing Liu
- Department of MedicineSection of CardiologyBaylor College of MedicineHoustonTexasUSA
| | - Salim S. Virani
- Department of MedicineSection of CardiologyBaylor College of MedicineHoustonTexasUSA
- Department of MedicineMichael E. DeBakey VA Medical CenterSection of CardiologyHoustonTexasUSA
| | - Mahboob Alam
- Department of MedicineSection of CardiologyBaylor College of MedicineHoustonTexasUSA
| | - Ali E. Denktas
- Department of MedicineSection of CardiologyBaylor College of MedicineHoustonTexasUSA
| | - Ihab Hamzeh
- Department of MedicineSection of CardiologyBaylor College of MedicineHoustonTexasUSA
| | - Umair Khalid
- Department of MedicineSection of CardiologyBaylor College of MedicineHoustonTexasUSA
- Department of MedicineMichael E. DeBakey VA Medical CenterSection of CardiologyHoustonTexasUSA
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Orlando V, Coscioni E, Guarino I, Mucherino S, Perrella A, Trama U, Limongelli G, Menditto E. Drug-utilisation profiles and COVID-19. Sci Rep 2021; 11:8913. [PMID: 33903671 PMCID: PMC8076316 DOI: 10.1038/s41598-021-88398-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 03/24/2021] [Indexed: 02/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has substantially challenged healthcare systems worldwide. By investigating population characteristics and prescribing profiles, it is possible to generate hypotheses about the associations between specific drug-utilisation profiles and susceptibility to COVID-19 infection. A retrospective drug-utilisation study was carried out using routinely collected information from a healthcare database in Campania (Southern Italy). We aimed to discover the prevalence of drug utilisation (monotherapy and polytherapy) in COVID-19 versus non-COVID-19 patients in Campania (~ 6 million inhabitants). The study cohort comprised 1532 individuals who tested positive for COVID-19. Drugs were grouped according to the Anatomical Therapeutic Chemical (ATC) classification system. We noted higher prevalence rates of the use of drugs in the ATC categories C01, B01 and M04, which was probably linked to related comorbidities (i.e., cardiovascular and metabolic). Nevertheless, the prevalence of the use of drugs acting on the renin-angiotensin system, such as antihypertensive drugs, was not higher in COVID-19 patients than in non-COVID-19 patients after adjustments for age and sex. These results highlight the need for further case-control studies to define the effects of medications and comorbidities on susceptibility to and associated mortality from COVID-19.
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Affiliation(s)
- Valentina Orlando
- CIRFF, Center of Drug Utilisation and Pharmacoeconomics, University of Naples Federico II, 80131, Naples, Italy.
- Department of Pharmacy, Center of Drug Utilisation and Pharmacoeconomics, University of Naples Federico II, 80131, Naples, Italy.
| | - Enrico Coscioni
- Division of Cardiac Surgery, AOU San Giovanni di Dio E Ruggi d'Aragona, 84131, Salerno, Italy
| | - Ilaria Guarino
- CIRFF, Center of Drug Utilisation and Pharmacoeconomics, University of Naples Federico II, 80131, Naples, Italy
| | - Sara Mucherino
- CIRFF, Center of Drug Utilisation and Pharmacoeconomics, University of Naples Federico II, 80131, Naples, Italy
- Department of Pharmacy, Center of Drug Utilisation and Pharmacoeconomics, University of Naples Federico II, 80131, Naples, Italy
| | - Alessandro Perrella
- Infectious Disease of Healthcare Direction, AORN Antonio Cardarelli, 80131, Naples, Italy
| | - Ugo Trama
- Regional Pharmaceutical Unit, Campania Region, 80143, Naples, Italy
| | - Giuseppe Limongelli
- Department of Translational Medical Science, University of Campania Luigi Vanvitelli, Monaldi Hospital, 80131, Naples, Italy
| | - Enrica Menditto
- CIRFF, Center of Drug Utilisation and Pharmacoeconomics, University of Naples Federico II, 80131, Naples, Italy.
- Department of Pharmacy, Center of Drug Utilisation and Pharmacoeconomics, University of Naples Federico II, 80131, Naples, Italy.
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