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Bansal V, Jain NK, Lal A, Khedr A, Tekin A, Jama AB, Attallah N, Hassan E, Mushtaq HA, Robinson S, Kondori MJ, Koritala T, Armaignac DL, Christie AB, Raju U, Khanna A, Cartin-Ceba R, Sanghavi DK, La Nou A, Boman K, Kumar V, Walkey AJ, Domecq JP, Kashyap R, Khan SA, the Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group. The association between early corticosteroid use and the risk of secondary infections in hospitalized patients with COVID-19: a double-edged sword. Results from the international SCCM discovery viral infection and respiratory illness universal study (VIRUS) COVID-19 registry. Front Med (Lausanne) 2025; 12:1466346. [PMID: 40027890 PMCID: PMC11868930 DOI: 10.3389/fmed.2025.1466346] [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: 07/17/2024] [Accepted: 01/15/2025] [Indexed: 03/05/2025] Open
Abstract
Background Corticosteroids improve survival in hospitalized COVID-19 patients needing supplemental oxygen. However, concern exists about increased risk of secondary infections. This study investigated the impact of early corticosteroids use on these infections. Methods Data from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 registry were analyzed for adult patients, stratified by early corticosteroid use (within 48 h of admission). The primary outcome was documented secondary infections, including bacteremia, bacterial pneumonia, empyema, meningitis/encephalitis, septic shock, and ventilator-associated pneumonia. Univariate and multivariable logistic regression models were used to assess the association between early corticosteroids and these outcomes. Results Among 17,092 eligible patients, with 13.5% developed at least one secondary bacterial infection during hospitalization. Patients receiving early corticosteroids were older (median 63 years) compared to those who did not (median 60 years), with a similar gender distribution (42.5% vs. 44.2% female). Unadjusted analysis revealed a higher risk for any secondary infection (OR 1.93, 95% CI 1.76-2.12). This association persisted for specific infections including bacteremia (OR 2.0, 95% CI 1.58-2.54), bacterial pneumonia (OR 1.5, 95% CI 1.27-1.77), and septic shock (OR 1.67, 95% CI 1.44-1.93). However, the effect on meningitis/encephalitis (OR 0.62, 95% CI 0.24-1.57) and ventilator-associated pneumonia (VAP; OR 1.08, 95% CI 0.75-1.57) was non-significant. Adjusted analysis maintained significance for any secondary infection (OR 1.15, 95% CI 1.02-1.29), bacteremia (OR 1.43, 95% CI 1.09-1.88), and infections with unknown sources (OR 1.63, 95% CI 1.31-2.02). Notably, the association weakened and became non-significant for bacterial pneumonia (OR 0.98, 95% CI 0.81-1.20) and septic shock (OR 0.94, 95% CI 0.79-1.11), while it became significant for meningitis/encephalitis (OR 0.26, 95% CI 0.08-0.82). VAP remained non-significant (OR 0.87, 95% CI 0.56-1.34). Conclusion Early use of corticosteroids increased overall secondary infection risk in hospitalized COVID-19 patients, but the impact varied. Risk of bacteremia was notably increased, while the association with bacterial pneumonia and septic shock weakened after adjustment becoming non-significant and surprisingly reduced meningitis/encephalitis risk was noted suggesting the complexity of corticosteroid effects. Further research is needed to understand how corticosteroids influence specific secondary infections, and thereby optimize the treatment strategies.
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Affiliation(s)
- Vikas Bansal
- Division of Nephrology and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States
| | - Nitesh K. Jain
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
- Department of Critical Care Medicine, North East Georgia Health System, Gainesville, GA, United States
| | - Amos Lal
- Department of Critical Care Medicine, North East Georgia Health System, Gainesville, GA, United States
| | - Anwar Khedr
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Aysun Tekin
- Division of Nephrology and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States
| | - Abbas B. Jama
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Noura Attallah
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Esraa Hassan
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Hisham Ahmed Mushtaq
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Sara Robinson
- Department of Family Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Marjan Jahani Kondori
- Department of Family Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Thoyaja Koritala
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Donna Lee Armaignac
- Center for Advanced Analytics, Baptist Health South Florida, Miami, FL, United States
| | - Amy B. Christie
- Department of Trauma Critical Care, The Medical Center Navicent Health, Mercer University School of Medicine, Macon, GA, United States
| | | | - Ashish Khanna
- Section on Critical Care Medicine, Department of Anesthesiology, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, United States
| | - Rodrigo Cartin-Ceba
- Division of Critical Care Medicine, Department of Pulmonary Medicine, Mayo Clinic, Scottsdale, AZ, United States
| | - Devang K. Sanghavi
- Department of Critical Care Medicine, Mayo Clinic Florida, Jacksonville, FL, United States
| | - Abigail La Nou
- Department of Critical Care Medicine, Mayo Clinic Health System, Eau Claire, WI, United States
| | - Karen Boman
- Society of Critical Care Medicine, Mount Prospect, IL, United States
| | - Vishakha Kumar
- Society of Critical Care Medicine, Mount Prospect, IL, United States
| | - Allan J. Walkey
- Pulmonary Center, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States
| | - Juan Pablo Domecq
- Division of Nephrology and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
| | - Rahul Kashyap
- Division of Critical Care Medicine, Department of Anesthesiology and Perioperative Care, Mayo Clinic, Rochester, MN, United States
- Department of Medicine and Medical, Research, WellSpan Health, York, PA, United States
| | - Syed Anjum Khan
- Department of Critical Care Medicine, Mayo Clinic Health System, Mankato, MN, United States
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Khan MA, Mutahir S, Jabar G, Wenwei Z, Tariq MA, Almehizia AA, Mustafa M. DFT, Molecular Docking, ADME, and Cardiotoxicity Studies of Persuasive Thiazoles as Potential Inhibitors of the Main Protease of SARS-CoV-2. Chem Biodivers 2024; 21:e202401775. [PMID: 39161231 DOI: 10.1002/cbdv.202401775] [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: 07/22/2024] [Accepted: 08/19/2024] [Indexed: 08/21/2024]
Abstract
This study explores the capability of thiazoles as potent inhibitors of SARS-CoV-2 Mpro. Seventeen thiazoles (1-17) were screened for their linking affinity with the active site of SARS-CoV-2 Mpro and compared with the FDA-recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS-CoV-2 proteins, including spike receptor-linking zone, nucleocapsid protein N-terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA-approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6 M3 M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug-likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.
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Affiliation(s)
- Muhammad Asim Khan
- School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China
| | - Sadaf Mutahir
- School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China
| | - Gauhar Jabar
- Department of Chemistry, University of Sialkot, Sialkot, 51300, Pakistan
| | - Zhao Wenwei
- School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China
| | | | - Abdulrahman A Almehizia
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia
| | - Muhammad Mustafa
- Department of Chemistry, University of Sialkot, Sialkot, 51300, Pakistan
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Danaiyan S, Abbasi MM, Raeisi S, Argani H, Ghorbanihaghjo A, Shanehbandi D, Roshangar L, Poursistany H, Abedi S, Mohammadian J, Bahremani M, Rashtchizadeh N. The Effects of Remdesivir and Dexamethasone on Renal Sirtuin-1 Expression and Renal Function in Male Rats. Appl Biochem Biotechnol 2024; 196:632-642. [PMID: 37166648 PMCID: PMC10172727 DOI: 10.1007/s12010-023-04529-3] [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] [Accepted: 04/11/2023] [Indexed: 05/12/2023]
Abstract
Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5 mL/kg/day for 10 days); group B (REM) received REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days) and DEX (7 mg/kg/day, for 10 days); group D (DEX) received DEX (7 mg/kg/day for 10 days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0 mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation.
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Affiliation(s)
- Sepideh Danaiyan
- Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Biotechnology Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran
| | | | - Sina Raeisi
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Argani
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ghorbanihaghjo
- Biotechnology Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran
| | - Dariush Shanehbandi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Haniyeh Poursistany
- Department of Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Abedi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jamal Mohammadian
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mona Bahremani
- Biotechnology Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran
| | - Nadereh Rashtchizadeh
- Biotechnology Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran.
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Soheili M, Khateri S, Moradpour F, Mohammadzedeh P, Zareie M, Mortazavi SMM, Manifar S, Kohan HG, Moradi Y. The efficacy and effectiveness of COVID-19 vaccines around the world: a mini-review and meta-analysis. Ann Clin Microbiol Antimicrob 2023; 22:42. [PMID: 37208749 DOI: 10.1186/s12941-023-00594-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 05/10/2023] [Indexed: 05/21/2023] Open
Abstract
OBJECTIVES This meta-analysis evaluated the Efficacy and Effectiveness of several COVID-19 vaccines, including AstraZeneca, Pfizer, Moderna, Bharat, and Johnson & Johnson, to better estimate their immunogenicity, benefits, or side effects. METHODS Studies reporting the Efficacy and Effectiveness of COVID-19 vaccines from November 2020 to April 2022 were included. The pooled Effectiveness/Efficacy with a 95% confidence interval (95% CI) with Metaprop order was calculated. The results were presented in forest plots. Predefined subgroup analyses and sensitivity analyses were also performed. RESULTS A total of twenty articles were included in this meta-analysis. After the first dose of the vaccine, the total effectiveness of all COVID-19 vaccines in our study was 71% (95% CI 0.65, 0.78). The total effectiveness of vaccines after the second dose was 91% (95% CI 0.88, 0.94)). The total efficacy of vaccines after the first and second doses was 81% (95% CI 0.70, 0.91) and 71% (95% CI 0.62, 0.79), respectively. The effectiveness of the Moderna vaccine after the first and second dose was the highest among other studied vaccines ((74% (95% CI, 0.65, 0.83) and 93% (95% CI, 0.89, 0.97), respectively). The highest first dose overall effectiveness of the studied vaccines was against the Gamma variant (74% (95% CI, 0.73, 0.75)), and the highest effectiveness after the second dose was observed against the Beta variant (96% (95% CI, 0.96, 0.96)). The Efficacy for AstraZeneca and Pfizer vaccines after the first dose was 78% (95% CI, 0.62, 0.95) and 84% (95% CI, 0.77, 0.92), respectively. The second dose Efficacy for AstraZeneca, Pfizer, and Bharat was 67% (95% CI, 0.54, 0.80), 93% (95% CI, 0.85, 1.00), and 71% (95% CI, 0.61, 0.82), respectively. The overall efficacy of first and second dose vaccination against the Alfa variant was 84% (95% CI, 0.84, 0.84) and 77% (95% CI, 0.57, 0.97), respectively, the highest among other variants. CONCLUSION mRNA-based vaccines against COVID-19 showed the highest total efficacy and effectiveness than other vaccines. In general, administering the second dose produced a more reliable response and higher effectiveness than a single dose.
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Affiliation(s)
- Marzieh Soheili
- Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, 1215 Wilbraham Road, Springfield, MA, 01119, USA
| | - Sorour Khateri
- Department of Physical Medicine and Rehabilitation, School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Farhad Moradpour
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Pardis Mohammadzedeh
- Department of Epidemiology and Biostatistics, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mostafa Zareie
- Department of Epidemiology and Biostatistics, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Seyede Maryam Mahdavi Mortazavi
- Pediatric Gastroenterology Fellowship, Department of Pediatrics, School of Medicine, Namazi teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sima Manifar
- Massachusetts College of Pharmacy and Health Sciences (MCPHS), 179 Longwood Avenue, Boston, MA, 02115, USA
| | - Hamed Gilzad Kohan
- Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, 1215 Wilbraham Road, Springfield, MA, 01119, USA.
| | - Yousef Moradi
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
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Abdallah YEH, Chahal S, Jamali F, Mahmoud SH. Drug-disease interaction: Clinical consequences of inflammation on drugs action and disposition. JOURNAL OF PHARMACY & PHARMACEUTICAL SCIENCES : A PUBLICATION OF THE CANADIAN SOCIETY FOR PHARMACEUTICAL SCIENCES, SOCIETE CANADIENNE DES SCIENCES PHARMACEUTIQUES 2023; 26:11137. [PMID: 36942294 PMCID: PMC9990632 DOI: 10.3389/jpps.2023.11137] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 01/23/2023] [Indexed: 02/07/2023]
Abstract
Inflammation is a culprit in many conditions affecting millions of people worldwide. A plethora of studies has revealed that inflammation and inflammatory mediators such as cytokines and chemokines are associated with altered expression and activity of various proteins such as those involved in drug metabolism, specifically cytochrome P450 enzymes (CYPs). Emphasis of most available reports is on the inflammation-induced downregulation of CYPs, subsequently an increase in their substrate concentrations, and the link between the condition and the inflammatory mediators such as interleukin-6 and tumor necrosis factor alpha. However, reports also suggest that inflammation influences expression and/or activity of other proteins such as those involved in the drug-receptor interaction. These multifaced involvements render the clinical consequence of the inflammation unexpected. Such changes are shown in many inflammatory conditions including rheumatoid arthritis, Crohn's disease, acute respiratory illnesses as well as natural processes such as aging, among others. For example, some commonly used cardiovascular drugs lose their efficacy when patients get afflicted with inflammatory conditions such as rheumatoid arthritis and Crohn's disease. Interestingly, this is despite increased concentration subsequent to reduced clearance. The observation is attributed to a simultaneous reduction in the expression of target receptor proteins such as the calcium and potassium channel and β-adrenergic receptor as well as the metabolic enzymes. This narrative review summarizes the current understanding and clinical implications of the inflammatory effects on both CYPs and drug-receptor target proteins.
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Dhanavade MJ, Sonawane KD. Role of Nutrition in COVID-19: Present Knowledge and Future Guidelines. CURRENT NUTRITION & FOOD SCIENCE 2022. [DOI: 10.2174/1573401318666220324115443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Maruti J. Dhanavade
- Department of Microbiology, Bharati Vidyapeeth\'s Dr. Patangrao Kadam Mahavidyalaya, Sangli, Maharashtra, India
| | - Kails D. Sonawane
- Department of Biochemistry, Shivaji University, Kolhapur, Maharashtra, India
- Department of Microbiology, Shivaji University, Kolhapur, Maharashtra, India
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Jin ZM, Shi JC, Zheng M, Chen QL, Zhou YY, Cheng F, Cai J, Jiang XG. Increased levels of lactate dehydrogenase and hypertension are associated with severe illness of COVID-19. World J Clin Cases 2022; 10:128-135. [PMID: 35071512 PMCID: PMC8727272 DOI: 10.12998/wjcc.v10.i1.128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/26/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is amid an ongoing pandemic. It has been shown that patients with cardiovascular comorbidities are at higher risk of severe illness of COVID-19.
AIM To find out the relationship between cardiovascular comorbidities and severe illness of COVID-19.
METHODS The clinical data of 140 COVID-19 patients treated from January 22, 2020 to March 3, 2020 at our hospital were retrospectively collected. The clinical characteristics were compared between patients with mild illness and those with severe illness.
RESULTS There were 75 male patients and 65 female patients (53.6% vs 46.4%). The mean age was 45.4 ± 14.6 years (range, 2-85 years). Most of the patients had mild illness (n = 114, 81.4%) and 26 patients had severe illness (18.6%). The most common symptom was fever (n = 110, 78.6%), followed by cough (n = 82, 58.6%) and expectoration (n = 51, 36.4%). Eight patients were asymptomatic but were positive for severe acute respiratory syndrome coronavirus 2 RNA. Patients with severe illness were significantly more likely to be hypertensive than those with mild illness [(10/26, 38.4%) vs (22/114, 19.3%), P = 0.036]. The levels of lactate dehydrogenase were significantly higher in the severe illness group than in the mild illness group (299.35 ± 68.82 vs 202.94 ± 63.87, P < 0.001). No patient died in either the severe illness or the mild illness group.
CONCLUSION Hypertension and elevated levels of lactate dehydrogenase may be associated with severe illness of COVID-19.
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Affiliation(s)
- Zhen-Mu Jin
- Department of Rheumatology, Immunology and Allergy, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Ji-Chan Shi
- Department of Infectious Diseases, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Mo Zheng
- Department of Rheumatology, Immunology and Allergy, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Que-Lu Chen
- Department of Radiology, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Yue-Ying Zhou
- Department of Infectious Diseases, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Fang Cheng
- Department of Infectious Diseases, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Jing Cai
- Department of Infectious Diseases, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Xian-Gao Jiang
- Department of Infectious Diseases, Wenzhou Central Hospital, The Second Affiliated Hospital of Shanghai University, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
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Atif M, Naz F, Akhtar J, Imran M, Saleem S, Akram J, Imran M, Ullah MI. From Molecular Pathology of COVID 19 to Nigella Sativum as a Treatment Option: Scientific Based Evidence of Its Myth or Reality. Chin J Integr Med 2022; 28:88-95. [PMID: 34586557 PMCID: PMC8479716 DOI: 10.1007/s11655-021-3311-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/10/2021] [Indexed: 11/06/2022]
Abstract
COVID-19 virus is a causative agent of viral pandemic in human beings which specifically targets respiratory system of humans and causes viral pneumonia. This unusual viral pneumonia is rapidly spreading to all parts of the world, currently affecting about 105 million people with 2.3 million deaths. Current review described history, genomic characteristics, replication, and pathogenesis of COVID-19 with special emphasis on Nigella sativum (N. sativum) as a treatment option. N. sativum seeds are historically and religiously used over the centuries, both for prevention and treatment of different diseases. This review summarizes the potential role of N. sativum seeds against COVID-19 infection at levels of in silico, cell lines and animal models.
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Affiliation(s)
- Muhammad Atif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, 75471, Saudi Arabia
| | - Farrah Naz
- Department of Microbiology, Government College University, Faisalabad, 38000, Pakistan
| | - Junaid Akhtar
- Department of Microbiology, University of Health Sciences, Lahore, 54600, Pakistan
- Department of Allied Health Sciences, Sargodha Medical College, University of Sargodha, Sargodha, 40100, Pakistan
| | - Muhammad Imran
- Department of Microbiology, University of Health Sciences, Lahore, 54600, Pakistan
| | - Sidrah Saleem
- Department of Microbiology, University of Health Sciences, Lahore, 54600, Pakistan
| | - Javed Akram
- University of Health Sciences, Lahore, 54600, Pakistan
| | - Muhammad Imran
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Lahore, 54590, Pakistan.
| | - Muhammad Ikram Ullah
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, 75471, Saudi Arabia
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Comparisons of treatment protocols for SARS-COV-2 in early pandemic: Single center experience ın Turkey. JOURNAL OF CONTEMPORARY MEDICINE 2022. [DOI: 10.16899/jcm.1009652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Rabby MII, Hossain F, Islam MA, Islam AS, Akhi IJ, Akter F. Impact of supplemental vitamins and natural honey for treatment of COVID-19: A review. BRAZ J PHARM SCI 2022. [DOI: 10.1590/s2175-97902022e20607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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Borujerdi R, Adeli SH, Mohammadbeigi A, Aliasl F, Asghari A, Hormati A, Dehnavi HM, Hoseini F, Asghari M. Effects of Iranian Polyherbal Syrup (Zufa syrup) on oxygen saturation and clinical symptoms in suspected patients with COVID-19: a triple-blinded, randomized, placebo-controlled trial. Med Gas Res 2021; 12:44-50. [PMID: 34677151 PMCID: PMC8562395 DOI: 10.4103/2045-9912.325991] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) pandemic has caused an urgent need for investigating potential treatments. Traditional medicine offers many potential remedies that have been historically used and have the advantage of bypassing the cultural obstacles in the practice of medicine. We aimed to investigate the efficacy of Zufa syrup in the treatment of suspected patients with mild to moderate symptoms of COVID-19. This triple-blind randomized controlled trial recruited patients with evidence of COVID-19 on chest computed tomography without an indication of hospital admission from March 2020 until April 2020. Participants were assessed by a physician and completed a pre-specified form to assess the duration and severity of symptoms. Patients were randomized to receive Zufa syrup (a combination of herbal medicines: Nepetabracteata, Ziziphus jujube, Glycyrrhizaglabra, Ficuscarica, Cordia myxa, Papaver somniferum, Fennel, Adiantumcapillusveneris, Viola, Viper‘s-buglosses, Lavender, Iris, and sugar) or identical-looking placebo syrup at a dose of 7.5 mL (one tablespoon) every 4 hours for 10 days. After applying the eligibility criteria, 116 patients (49.1% male) were randomized to trial arms with a mean age of 44.3. During the follow-up, Cough, dyspnea, headache, myalgia, anorexia, anxiety, and insomnia improved gradually in both groups, and showed no difference between Zufa syrup and placebo. Oxygen saturation and pulse rate had stable trends throughout the follow-up and were similar between study arms. No patient required hospital admission or supplemental oxygen therapy during the study period. To conclude, in patients with mild to moderate symptoms of COVID-19, Zufa syrup did not show any difference in symptomatology over a 10 days’ period when compared with placebo. Due to potential effects of medicinal plants in the treatment of respiratory infections, further studies are warranted to clarify their role in COVID-19. The study was approved by the Ethics Committee of the Qom University of Medical Science (Ethics committee reference number IR.MUQ.REC.1398.165) on March 10, 2020 and was registered in Iranian Clinical Trial Center (approval ID: IRCT20200404046934N1) on April 13, 2020.
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Affiliation(s)
- Razieh Borujerdi
- Department of Persian Medicine, School of Persian Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Seyed Hasan Adeli
- Department of Internal Medicine, School of Medicine, Spiritual Health Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Abolfazl Mohammadbeigi
- Department of Epidemiology and Biostatistics, School of Health, Qom University of Medical Sciences, Qom, Iran
| | - Fatemeh Aliasl
- Department of Persian Medicine, School of Persian Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Akram Asghari
- Department of Internal Medicine, School of Medicine, Spiritual Health Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Ahmad Hormati
- Gastroenterology and Hepatology Disease Research Center, Qom University of Medical Science, Qom, Iran
| | - Hosein Moradi Dehnavi
- Department of Persian Medicine, School of Persian Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Farhad Hoseini
- Department of Internal Medicine, School of Medicine, Spiritual Health Research Center, Qom University of Medical Sciences, Qom, Iran
| | - Majid Asghari
- Department of Persian Medicine, School of Persian Medicine, Qom University of Medical Sciences, Qom, Iran
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12
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Ding W, Nayak J, Swapnarekha H, Abraham A, Naik B, Pelusi D. Fusion of intelligent learning for COVID-19: A state-of-the-art review and analysis on real medical data. Neurocomputing 2021; 457:40-66. [PMID: 34149184 PMCID: PMC8206574 DOI: 10.1016/j.neucom.2021.06.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/02/2021] [Accepted: 06/11/2021] [Indexed: 12/11/2022]
Abstract
The unprecedented surge of a novel coronavirus in the month of December 2019, named as COVID-19 by the World Health organization has caused a serious impact on the health and socioeconomic activities of the public all over the world. Since its origin, the number of infected and deceased cases has been growing exponentially in almost all the affected countries of the world. The rapid spread of the novel coronavirus across the world results in the scarcity of medical resources and overburdened hospitals. As a result, the researchers and technocrats are continuously working across the world for the inculcation of efficient strategies which may assist the government and healthcare system in controlling and managing the spread of the COVID-19 pandemic. Therefore, this study provides an extensive review of the ongoing strategies such as diagnosis, prediction, drug and vaccine development and preventive measures used in combating the COVID-19 along with technologies used and limitations. Moreover, this review also provides a comparative analysis of the distinct type of data, emerging technologies, approaches used in diagnosis and prediction of COVID-19, statistics of contact tracing apps, vaccine production platforms used in the COVID-19 pandemic. Finally, the study highlights some challenges and pitfalls observed in the systematic review which may assist the researchers to develop more efficient strategies used in controlling and managing the spread of COVID-19.
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Affiliation(s)
- Weiping Ding
- School of Information Science and Technology, Nantong University, China
| | - Janmenjoy Nayak
- Aditya Institute of Technology and Management (AITAM), India
| | - H Swapnarekha
- Aditya Institute of Technology and Management (AITAM), India
- Veer Surendra Sai University of Technology, India
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13
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Baral PK, Yin J, James MNG. Treatment and prevention strategies for the COVID 19 pandemic: A review of immunotherapeutic approaches for neutralizing SARS-CoV-2. Int J Biol Macromol 2021; 186:490-500. [PMID: 34237371 PMCID: PMC8256663 DOI: 10.1016/j.ijbiomac.2021.07.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/02/2021] [Accepted: 07/02/2021] [Indexed: 12/19/2022]
Abstract
Researchers from the world over are working to create prophylactic and therapeutic interventions to combat the COVID-19 global healthcare crisis. The current therapeutic options against the COVID-19 include repurposed drugs aimed at targets other than virus-specific proteins. Antibody-based therapeutics carry a lot of promise, and there are several of these candidates for COVID-19 treatment currently being investigated in the preclinical and clinical research stages around the world. The viral spike protein (S protein) appears to be the main target of antibody development candidates, with the majority being monoclonal antibodies. Several antibody candidates targeting the SARS-CoV-2 S protein include LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. These neutralizing antibodies will treat COVID-19 and possibly future coronavirus infections. Future studies should focus on effective immune-therapeutics and immunomodulators with the purpose of developing specific, affordable, and cost-effective prophylactic and treatment regimens to fight the COVID-19 globally.
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Affiliation(s)
- Pravas Kumar Baral
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Jiang Yin
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Michael N G James
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
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14
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Nimgampalle M, Devanathan V, Saxena A. Screening of Chloroquine, Hydroxychloroquine and its derivatives for their binding affinity to multiple SARS-CoV-2 protein drug targets. J Biomol Struct Dyn 2021; 39:4949-4961. [PMID: 32579059 PMCID: PMC7332874 DOI: 10.1080/07391102.2020.1782265] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 06/09/2020] [Indexed: 02/06/2023]
Abstract
Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities' world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time screening was performed for some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through in silico approaches. For the purpose of the study, some essential viral proteins and enzymes were selected that are implicated in SARS-CoV-2 replication and multiplication as putative drug targets. Chloroquine, Hydroxychloroquine, and some of their chemically synthesized derivatives, taken from earlier published studies were selected as drug molecules. We have conducted molecular docking and related studies between Chloroquine and its derivatives and SARS-CoV-2 viral proteins, and the findings show that both Chloroquine and Hydroxychloroquine can bind to specific structural and non-structural proteins implicated in the pathogenesis of SARS-CoV-2 infection with different efficiencies. Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. These findings bring into light another possible mechanism of action of Chloroquine and Hydroxychloroquine and also pave the way for further drug repurposing and remodeling.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Mallikarjuna Nimgampalle
- Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati, India
| | - Vasudharani Devanathan
- Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati, India
| | - Ambrish Saxena
- Center for Sponsored Research and Consultancy, Indian Institute of Technology (IIT) Tirupati, Tirupati, India
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15
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Drug repurposing for COVID-19 using computational screening: Is Fostamatinib/R406 a potential candidate? Methods 2021; 203:564-574. [PMID: 34455072 PMCID: PMC8390099 DOI: 10.1016/j.ymeth.2021.08.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/17/2021] [Accepted: 08/24/2021] [Indexed: 12/11/2022] Open
Abstract
With the gradual increase in the COVID-19 mortality rate, there is an urgent need for an effective drug/vaccine. Several drugs like Remdesivir, Azithromycin, Favirapir, Ritonavir, Darunavir, etc., are put under evaluation in more than 300 clinical trials to treat COVID-19. On the other hand, several vaccines like Pfizer-BioNTech, Moderna, Johnson & Johnson's Janssen, Sputnik V, Covishield, Covaxin, etc., also evolved from the research study. While few of them already gets approved, others show encouraging results and are still under assessment. In parallel, there are also significant developments in new drug development. But, since the approval of new molecules takes substantial time, drug repurposing studies have also gained considerable momentum. The primary agent of the disease progression of COVID-19 is SARS-CoV2/nCoV, which is believed to have ~89% genetic resemblance with SARS-CoV, a coronavirus responsible for the massive outbreak in 2003. With this hypothesis, Human-SARS-CoV protein interactions are used to develop an in-silico Human-nCoV network by identifying potential COVID-19 human spreader proteins by applying the SIS model and fuzzy thresholding by a possible COVID-19 FDA drugs target-based validation. At first, the complete list of FDA drugs is identified for the level-1 and level-2 spreader proteins in this network, followed by applying a drug consensus scoring strategy. The same consensus strategy is involved in the second analysis but on a curated overlapping set of key genes/proteins identified from COVID-19 symptoms. Validation using subsequent docking study has also been performed on COVID-19 potential drugs with the available major COVID-19 crystal structures whose PDB IDs are: 6LU7, 6M2Q, 6W9C, 6M0J, 6M71 and 6VXX. Our computational study and docking results suggest that Fostamatinib (R406 as its active promoiety) may also be considered as one of the potential candidates for further clinical trials in pursuit to counter the spread of COVID-19.
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16
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Gour A, Manhas D, Bag S, Gorain B, Nandi U. Flavonoids as potential phytotherapeutics to combat cytokine storm in SARS-CoV-2. Phytother Res 2021; 35:4258-4283. [PMID: 33786876 PMCID: PMC8250405 DOI: 10.1002/ptr.7092] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 02/22/2021] [Accepted: 03/12/2021] [Indexed: 01/08/2023]
Abstract
Emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, COVID-19, has become the global panic since December 2019, which urges the global healthcare professionals to identify novel therapeutics to counteract this pandemic. So far, there is no approved treatment available to control this public health issue; however, a few antiviral agents and repurposed drugs support the patients under medical supervision by compromising their adverse effects, especially in emergency conditions. Only a few vaccines have been approved to date. In this context, several plant natural products-based research studies are evidenced to play a crucial role in immunomodulation that can prevent the chances of infection as well as combat the cytokine release storm (CRS) generated during COVID-19 infection. In this present review, we have focused on flavonoids, especially epicatechin, epigallocatechin gallate, hesperidin, naringenin, quercetin, rutin, luteolin, baicalin, diosmin, ge nistein, biochanin A, and silymarin, which can counteract the virus-mediated elevated levels of inflammatory cytokines leading to multiple organ failure. In addition, a comprehensive discussion on available in silico, in vitro, and in vivo findings with critical analysis has also been evaluated, which might pave the way for further development of phytotherapeutics to identify the potential lead candidatetoward effective and safe management of the SARS-CoV-2 disease.
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Affiliation(s)
- Abhishek Gour
- PK‐PD, Toxicology and Formulation DivisionCSIR‐Indian Institute of Integrative MedicineJammuIndia
- Academy of Scientific and Innovative Research (AcSIR)GhaziabadUttar PradeshIndia
| | - Diksha Manhas
- PK‐PD, Toxicology and Formulation DivisionCSIR‐Indian Institute of Integrative MedicineJammuIndia
- Academy of Scientific and Innovative Research (AcSIR)GhaziabadUttar PradeshIndia
| | - Swarnendu Bag
- Proteomics DivisionCSIR‐Institute of Genomics and Integrative BiologyNew DelhiIndia
| | - Bapi Gorain
- School of Pharmacy, Faculty of Health and Medical SciencesTaylor's UniversitySubang JayaMalaysia
| | - Utpal Nandi
- PK‐PD, Toxicology and Formulation DivisionCSIR‐Indian Institute of Integrative MedicineJammuIndia
- Academy of Scientific and Innovative Research (AcSIR)GhaziabadUttar PradeshIndia
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17
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Huang J, Qian C, Bian T, Chu M, Yin W, Pang Y, Bai J, Huang Y. A retrospective analysis from a single center for 60 COVID-19 patients with asymptomatic, mild to moderate, and severe conditions in Wuxi, China. Medicine (Baltimore) 2021; 100:e26748. [PMID: 34397716 PMCID: PMC8322555 DOI: 10.1097/md.0000000000026748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 07/08/2021] [Indexed: 01/19/2023] Open
Abstract
The aim of this study was to retrospectively analyze the clinical data of COVID-19 patients with different severity during February 2020 in Wuxi, China.The present retrospective study included a total of 60 cases who were diagnosed as COVID-19 patients and hospitalized in the Wuxi Fifth People's Hospital during February 2020 to March 2020. Among all patients 14 cases were asymptomatic, 25 cases were with mild stage, 13 cases were with moderate stage, and 8 cases were with severe stage. Basic clinical data as well as clinical characteristics, including temperature, respiratory rate, heart rate, blood gas analysis data, whole blood test data, and the prognosis condition, were collected and analyzed. Statistical analysis was conducted in different severity stage patients.Among the patients, the median temperature gradually increased from the asymptomatic to the severe patients and the median age increased from the mild to the severe patients with statistical difference. The hospitalization duration was the highest in severe patients. Higher heart rate, as well as lower oxygen partial pressure and oxygenation index were observed in severe patients than the other groups. Besides, higher CRP and globulin levels after admission were found in severe patients, and were gradually increased from the asymptomatic patients to the severe patients. On the contrary, the lymphocyte ratio and count was significant lower in severe patients. We also observed higher D-Dimer levels in the severe patients and the difference was statistical. Among all patients, 2 cases (3.33%) died and other patients were all cured after treatment.Statistical difference was mainly found mainly in age, hospitalization duration, temperature, CRP levels, O2 partial pressure and oxygenation index, globulin, lymphocyte ratio, and D-Dimer in patients with different severity. The higher CRP levels, lower O2 partial pressure and oxygenation index, higher globulin, lower lymphocyte ratio, and higher D-Dimer might be associated with the patients' severity.
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18
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Mamo A, Hassen MM, Adem A, Teferu Z, Kumbi M, Husen A, Solomon D, Lette A, Hailu S, Sinba E, Abduletif AM, Kassim J, Walle G, Atlaw D. Knowledge, attitude, and utilization of drugs toward COVID-19 pandemic among Bale Zone residents, Southeast Ethiopia. SAGE Open Med 2021; 9:20503121211034384. [PMID: 34367639 PMCID: PMC8312174 DOI: 10.1177/20503121211034384] [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: 04/01/2021] [Accepted: 07/05/2021] [Indexed: 12/24/2022] Open
Abstract
Background: Coronavirus disease is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2, which poses therapeutic dilemmas. Some suggestions for drug treatment seem problematic. Beliefs about the causes of health problems are determinants of treatment seeking decisions. Hence, one of the alternatives for the solution of health problems is employing traditional medicine to prevent coronavirus disease 19. Objective: To assess the knowledge, attitude, and utilization of drugs toward the coronavirus disease 19 pandemic among Bale zone residents. Methods: Community-based cross-sectional study was conducted among the Bale Zone population from May 30 to June 30, 2020. Eight hundred fifty-four participants were selected using a single population formula, and a multistage sampling technique was employed. Data were analyzed using SPSS version 25.0. Descriptive and binary logistic regression was used to analyze the outcomes. A p value ⩽ 0.05 was considered statistically significant. Results: Out of the total 854 respondents, about 534 (62.5%) got information about coronavirus disease 19 from TV/radio. More than two-thirds (71.9%) of the respondents have known that severe acute respiratory syndrome coronavirus 2 has no curative drugs, and 65.4% had a more appropriate attitude toward overall drug use in coronavirus disease 19. Level of education and, attitude towards drug use were singnificantly associated with knowledge of drugs, source of information about coronavirus disease 19 and having good practice were significantly associated with atittude toward drug utilization. Conclusion: One out of two study participants have good knowledge regarding drugs to the coronavirus disease 19 pandemic. Illiterate people in the community were identified to have poor knowledge about drugs, hence community educuation program is important to improve the knowledge about drugs towards the coronavirus disease 19 pandemic.
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Affiliation(s)
- Ayele Mamo
- Pharmacy Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Mesud M Hassen
- Pharmacy Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Ahmednur Adem
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Zinash Teferu
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Musa Kumbi
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Abduljewad Husen
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Damtew Solomon
- Anatomy Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Abate Lette
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Sintayew Hailu
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Edao Sinba
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Abdushakur M Abduletif
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Jeylan Kassim
- Public Health Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
| | - Gashaw Walle
- Biomedical Department, College of Health Science, Debre Tabor University, Debre Tabor, Ethiopia
| | - Daniel Atlaw
- Anatomy Department, Madda Walabu University Goba Referral Hospital, Bale-Goba, Ethiopia
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19
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Chen Q, Leaman R, Allot A, Luo L, Wei CH, Yan S, Lu Z. Artificial Intelligence in Action: Addressing the COVID-19 Pandemic with Natural Language Processing. Annu Rev Biomed Data Sci 2021; 4:313-339. [PMID: 34465169 DOI: 10.1146/annurev-biodatasci-021821-061045] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The COVID-19 (coronavirus disease 2019) pandemic has had a significant impact on society, both because of the serious health effects of COVID-19 and because of public health measures implemented to slow its spread. Many of these difficulties are fundamentally information needs; attempts to address these needs have caused an information overload for both researchers and the public. Natural language processing (NLP)-the branch of artificial intelligence that interprets human language-can be applied to address many of the information needs made urgent by the COVID-19 pandemic. This review surveys approximately 150 NLP studies and more than 50 systems and datasets addressing the COVID-19 pandemic. We detail work on four core NLP tasks: information retrieval, named entity recognition, literature-based discovery, and question answering. We also describe work that directly addresses aspects of the pandemic through four additional tasks: topic modeling, sentiment and emotion analysis, caseload forecasting, and misinformation detection. We conclude by discussing observable trends and remaining challenges.
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Affiliation(s)
- Qingyu Chen
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
| | - Robert Leaman
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
| | - Alexis Allot
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
| | - Ling Luo
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
| | - Chih-Hsuan Wei
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
| | - Shankai Yan
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
| | - Zhiyong Lu
- National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
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20
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Meikle CKS, Creeden JF, McCullumsmith C, Worth RG. SSRIs: Applications in inflammatory lung disease and implications for COVID-19. Neuropsychopharmacol Rep 2021; 41:325-335. [PMID: 34254465 PMCID: PMC8411309 DOI: 10.1002/npr2.12194] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 05/17/2021] [Accepted: 07/02/2021] [Indexed: 12/15/2022] Open
Abstract
Selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory properties that may have clinical utility in treating severe pulmonary manifestations of COVID-19. SSRIs exert anti-inflammatory effects at three mechanistic levels: (a) inhibition of proinflammatory transcription factor activity, including NF-κB and STAT3; (b) downregulation of lung tissue damage and proinflammatory cell recruitment via inhibition of cytokines, including IL-6, IL-8, TNF-α, and IL-1β; and (c) direct suppression inflammatory cells, including T cells, macrophages, and platelets. These pathways are implicated in the pathogenesis of COVID-19. In this review, we will compare the pathogenesis of lung inflammation in pulmonary diseases including COVID-19, ARDS, and chronic obstructive pulmonary disease (COPD), describe the anti-inflammatory properties of SSRIs, and discuss the applications of SSRIS in treating COVID-19-associated inflammatory lung disease.
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Affiliation(s)
- Claire Kyung Sun Meikle
- Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Justin Fortune Creeden
- Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.,Department of Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Cheryl McCullumsmith
- Department of Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Randall G Worth
- Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
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21
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Fatmi S, Taouzinet L, Skiba M, Iguer-Ouada M. The Use of Cyclodextrin or its Complexes as a Potential Treatment Against the 2019 Novel Coronavirus: A Mini-Review. Curr Drug Deliv 2021; 18:382-386. [PMID: 32940180 DOI: 10.2174/1567201817666200917124241] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/08/2020] [Accepted: 08/18/2020] [Indexed: 11/22/2022]
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 has spread rapidly since its discovery in December 2019 in the Chinese province of Hubei, reaching this day all the continents. This scourge is, unfortunately, in lineage with various dangerous outbreaks such as Ebola, Cholera, Spanish flu, American seasonal flu. Until today, the best solution for the moment remains prevention (Social distancing, hand disinfection, use of masks, partial or total sanitary containment, etc.); there is also the emergence of drug treatment (research and development, clinical trials, use on patients). Recent reviews emphasized the role of membrane lipids in the infectivity mechanism of SARS-COV-2. Cholesterol-rich parts of cell membranes serve as docking places of host cells for the viruses. Coronavirus 2 is a member of a virus family with lipid envelope that fuses with host cell through endocytosis, internalizing its components in the cell. In vitro cell models have shown that depletion of cholesterol by cyclodextrin, and particularly methyl beta cyclodextrin disturb the host cell membrane lipid composition this way, reducing the attachment of the virus to the protein receptors. This review aims to summarize the state of the art of research concerning the use of cyclodextrin or its complexes as a potential treatment against this new virus and update work already published.
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Affiliation(s)
- Sofiane Fatmi
- Department of Processes Engineering, Faculty of Technology, Technology Pharmaceutical Laboratory, Université de Bejaia, 06000, Bejaia, Algeria
| | - Lamia Taouzinet
- Department of Processes Engineering, Faculty of Technology, Technology Pharmaceutical Laboratory, Université de Bejaia, 06000, Bejaia, Algeria
| | - Mohamed Skiba
- Technology Pharmaceutical and Bio Pharmaceutics Laboratory, UFR Medicine and Pharmacy, Rouen University, 22 Blvd. Gambetta, 76183, Rouen, France
| | - Mokrane Iguer-Ouada
- Faculty of Nature and Life Sciences, Associated Laboratory in Marine Ecosystems and Aquaculture, Université de Bejaia, 06000, Bejaia, Algeria
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22
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Lyu X, Hu J, Xu X, Xianyu Y, Dong W. Factors influencing risk perception and nosocomial infection prevention practices of frontline nurses during the COVID-19 pandemic. BMC Nurs 2021; 20:78. [PMID: 34001128 PMCID: PMC8127227 DOI: 10.1186/s12912-021-00591-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 04/19/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND During the coronavirus disease 2019 (COVID-19) pandemic, exploring factors influencing nosocomial infection among frontline nurses may provide evidence to optimize prevention strategies in hospitals. METHOD A large-scale online questionnaire survey of nurses' state-trait anxiety, job burnout, risk perception, workplace safety perception, knowledge about nosocomial infection, and preventive practices was conducted with 2795 frontline nurses working in the COVID-19 wards of six hospitals in Hubei Province, China, from February 1 to April 1, 2020. The questionnaire data were analyzed using the structural equation modeling (SEM) method to reveal the mechanisms influencing nurses' risk perception and preventive practices related to nosocomial COVID-19 infection. RESULTS A model of the factors that influence nurses' risk perception and preventive practices regarding nosocomial COVID-19 infection was established. The model verified hypotheses regarding the impact of nurses' risk perception and preventive practices. Notably, the hypothesis that risk perception has an impact on nurses' preventive practices regarding nosocomial infection is not valid. Moreover, different marital and educational conditions are associated with significant differences in the impact of state anxiety on the execution of preventive practices, the impact of workplace safety perceptions on risk perception, and the impact of workplace safety perceptions on the execution of preventive practices. The effect of state anxiety on preventive practices differed significantly with different durations of work experience. CONCLUSIONS According to the results of the influencing factor model, promoting the quality of training on nosocomial infection, meliorating workplace safety, and conducting timely and effective psychological interventions would aid in improving nurses' preventive practices. Meliorating workplace safety and easing state anxiety would be beneficial to reduce nurses' risk perception. These strategies are conducive to the optimization of policies for preventing nosocomial COVID-19 infections and similar infectious diseases.
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Affiliation(s)
- Xiaoguang Lyu
- The Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jiming Hu
- School of Information Management, Wuhan University, Wuhan, China
| | - Xin Xu
- The General Medicine Ward, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yunyan Xianyu
- The Nursing Department, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Weiguo Dong
- The Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
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Barabanov MА, Martyanov GS, Pestov AV. Biological activity and synthesis of 5,6-dihydroxyindole-2-carboxylic acid - biosynthetic precursor of melanins (microreview). Chem Heterocycl Compd (N Y) 2021; 57:417-419. [PMID: 34007085 PMCID: PMC8118682 DOI: 10.1007/s10593-021-02918-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 02/05/2021] [Indexed: 01/25/2023]
Abstract
The microreview considers the biological activity and methods of obtaining natural melanin pigments and their biosynthetic precursor 5,6-dihydroxyindole-2-carboxylic acid. The key methods for the synthesis of 5,6-dihydroxyindole-2-carboxylic acid, published over the past 8 years (2012–2020), are presented.
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Affiliation(s)
- Mikhail А Barabanov
- Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22/20 Sofyi Kovalevskoi St, Yekaterinburg, 620108 Russia
| | - Georgii S Martyanov
- Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22/20 Sofyi Kovalevskoi St, Yekaterinburg, 620108 Russia
| | - Alexander V Pestov
- Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22/20 Sofyi Kovalevskoi St, Yekaterinburg, 620108 Russia.,Ural Federal University named after the first President of Russia B. N. Yeltsin, 28 Mira St, Yekaterinburg, 620078 Russia
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24
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Ağagündüz D, Çelik MN, Çıtar Dazıroğlu ME, Capasso R. Emergent Drug and Nutrition Interactions in COVID-19: A Comprehensive Narrative Review. Nutrients 2021; 13:1550. [PMID: 34064534 PMCID: PMC8147951 DOI: 10.3390/nu13051550] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/26/2021] [Accepted: 04/28/2021] [Indexed: 01/08/2023] Open
Abstract
Coronaviruses are a large family of viruses that are known to cause respiratory tract infections ranging from colds to more severe diseases, such as Middle East Respiratory Syndrome (MERS) and the Severe Acute Respiratory Syndrome (SARS). New Coronavirus Disease 2019 (COVID-19), which led to deaths as well as social and economic disruptions, is an ongoing worldwide pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Currently, there is no approved treatment for COVID-19. Hence, only supportive care has been approved by the World Health Organization (WHO) for now. Pharmacological agents used for the adjunctive treatment of COVID-19 following the current literature and clinical experiences include antiviral, anti-inflammatory, and anti-malaria drugs, and other traditional or untraditional treatments. However, it has been reported that the use of these drugs may have some negative effects and comorbidities. Moreover, the current data have indicated that the risk of drug-drug interactions may also be high in polypharmacy cases, especially in elderly people, some comorbidity situations, and intensive care unit (ICU) patients. It is highly possible that these situations can not only increase the risk of drug-drug interactions but also increase the risk of food/nutrition-drug interactions and affect the nutritional status. However, this issue has not yet been entirely discussed in the literature. In this review, current information on the possible mechanisms as well as pharmacokinetic and pharmacodynamic effects of some pharmacological agents used in the treatment of COVID-19 and/or their secondary interactions with nutrition were evaluated and some future directions were given.
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Affiliation(s)
- Duygu Ağagündüz
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Emek, Ankara 06490, Turkey; (M.N.Ç.); (M.E.Ç.D.)
| | - Menşure Nur Çelik
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Emek, Ankara 06490, Turkey; (M.N.Ç.); (M.E.Ç.D.)
| | - Merve Esra Çıtar Dazıroğlu
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Emek, Ankara 06490, Turkey; (M.N.Ç.); (M.E.Ç.D.)
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Naples, Italy
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25
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Mortara A, Mazzetti S, Margonato D, Delfino P, Bersano C, Catagnano F, Lauriola M, Grosso P, Perseghin G, Ippoliti G. Compassionate use of ruxolitinib in patients with SARS-Cov-2 infection not on mechanical ventilation: Short-term effects on inflammation and ventilation. Clin Transl Sci 2021; 14:1062-1068. [PMID: 33403775 PMCID: PMC8212747 DOI: 10.1111/cts.12971] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/21/2020] [Accepted: 11/20/2020] [Indexed: 12/15/2022] Open
Abstract
Ruxolitinib is an anti-inflammatory drug that inhibits the Janus kinase-signal transducer (JAK-STAT) pathway on the surface of immune cells. The potential targeting of this pathway using JAK inhibitors is a promising approach in patients affected by coronavirus disease 2019 (COVID-19). Ruxolitinib was provided as a compassionate use in patients consecutively admitted to our institution for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria were oxygen saturation less than or equal to 92%, signs of interstitial pneumonia, and no need of mechanical ventilation. Patients received 5 mg b.i.d. of ruxolitinib for 15 days, data were collected at baseline and on days 4, 7, and 15 during treatment. Two main targets were identified, C-reactive protein (CRP) and PaO2 /FiO2 ratio. In the 31 patients who received ruxolitinib, symptoms improved (dyspnea scale) on day 7 in 25 of 31 patients (80.6%); CRP decreased progressively from baseline (79.1 ± 73.4 mg/dl) to day 15 (18.6 ± 33.2, p = 0.022). In parallel with CRP, PO2/FiO2 ratio increased progressively during the 3 steps from 183 ± 95 to 361 ± 144 mmHg (p < 0.001). In those patients with a reduction of polymerase chain reaction less than or equal to 80%, delta increase of the PO2/FiO2 ratio was significantly more pronounced (129 ± 118 vs. 45 ± 35 mmHg, p = 0.02). No adverse side effects were recorded during treatment. In patients hospitalized for COVID-19, compassionate-use of ruxolitinib determined a significant reduction of biomarkers of inflammation, which was associated with a more effective ventilation and reduced need for oxygen support. Data on ruxolitinib reinforces the hypothesis that targeting the hyperinflammation state, may be of prognostic benefit in patients with SARS-CoV-2 infection. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Some evidence suggest that patients affected by coronavirus disease 2019 (COVID-19) present an exuberant inflammatory response represented by a massive production of type I interferons and different pro-inflammatory cytokines. Nonetheless, as for the present, there are no proven therapeutic agents for COVID-19, in particular anti-inflammatory and antiviral, with a significant and reproducible positive clinical response. WHAT QUESTION DID THIS STUDY ADDRESS? Targeted therapeutic management of pro-inflammatory pathways appears to be a promising strategy against COVID-19, and ruxolitinib, due to its established broad and fast anti-inflammatory effect, appears to be a promising candidate worthy of focused investigations in this field. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Ruxolitinib rapidly reduces the systemic inflammation, which accompanies the disease, thereby improving respiratory function and the need of oxygen support. This effect may contribute to avoid progression of the disease and the use of invasive ventilation. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Data on ruxolitinib contributes the reinforcement of the hypothesis that it is crucial to counteract the early hyperinflammation state, particularly of the lungs, induced by COVID-19 infection.
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Affiliation(s)
- Andrea Mortara
- Department of Clinical CardiologyPoliclinico di MonzaMonzaItaly
| | - Simone Mazzetti
- Department of Clinical CardiologyPoliclinico di MonzaMonzaItaly
| | - Davide Margonato
- Department of Clinical CardiologyPoliclinico di MonzaMonzaItaly
- Department of CardiologyUniversity of PaviaPaviaItaly
| | - Pietro Delfino
- Department of Clinical CardiologyPoliclinico di MonzaMonzaItaly
| | - Chiara Bersano
- Department of Clinical CardiologyPoliclinico di MonzaMonzaItaly
| | - Francesco Catagnano
- Department of Clinical CardiologyPoliclinico di MonzaMonzaItaly
- Department of CardiologyUniversity of PaviaPaviaItaly
| | | | - Paolo Grosso
- Department of Anaesthesiology and Intensive CarePoliclinico di MonzaMonzaItaly
| | - Gianluca Perseghin
- Department of Medicine and RehabilitationPoliclinico di MonzaUniversità degli Studi di Milano BicoccaMonzaItaly
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Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19. Molecules 2021; 26:molecules26082214. [PMID: 33921378 PMCID: PMC8069104 DOI: 10.3390/molecules26082214] [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: 01/25/2021] [Revised: 03/31/2021] [Accepted: 04/02/2021] [Indexed: 11/17/2022] Open
Abstract
To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38–7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein’s binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.
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iResponse: An AI and IoT-Enabled Framework for Autonomous COVID-19 Pandemic Management. SUSTAINABILITY 2021. [DOI: 10.3390/su13073797] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
SARS-CoV-2, a tiny virus, is severely affecting the social, economic, and environmental sustainability of our planet, causing infections and deaths (2,674,151 deaths, as of 17 March 2021), relationship breakdowns, depression, economic downturn, riots, and much more. The lessons that have been learned from good practices by various countries include containing the virus rapidly; enforcing containment measures; growing COVID-19 testing capability; discovering cures; providing stimulus packages to the affected; easing monetary policies; developing new pandemic-related industries; support plans for controlling unemployment; and overcoming inequalities. Coordination and multi-term planning have been found to be the key among the successful national and global endeavors to fight the pandemic. The current research and practice have mainly focused on specific aspects of COVID-19 response. There is a need to automate the learning process such that we can learn from good and bad practices during pandemics and normal times. To this end, this paper proposes a technology-driven framework, iResponse, for coordinated and autonomous pandemic management, allowing pandemic-related monitoring and policy enforcement, resource planning and provisioning, and data-driven planning and decision-making. The framework consists of five modules: Monitoring and Break-the-Chain, Cure Development and Treatment, Resource Planner, Data Analytics and Decision Making, and Data Storage and Management. All modules collaborate dynamically to make coordinated and informed decisions. We provide the technical system architecture of a system based on the proposed iResponse framework along with the design details of each of its five components. The challenges related to the design of the individual modules and the whole system are discussed. We provide six case studies in the paper to elaborate on the different functionalities of the iResponse framework and how the framework can be implemented. These include a sentiment analysis case study, a case study on the recognition of human activities, and four case studies using deep learning and other data-driven methods to show how to develop sustainability-related optimal strategies for pandemic management using seven real-world datasets. A number of important findings are extracted from these case studies.
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Caracciolo M, Correale P, Mangano C, Foti G, Falcone C, Macheda S, Cuzzola M, Conte M, Falzea AC, Iuliano E, Morabito A, Caraglia M, Polimeni N, Ferrarelli A, Labate D, Tescione M, Di Renzo L, Chiricolo G, Romano L, De Lorenzo A. Efficacy and Effect of Inhaled Adenosine Treatment in Hospitalized COVID-19 Patients. Front Immunol 2021; 12:613070. [PMID: 33815368 PMCID: PMC8012541 DOI: 10.3389/fimmu.2021.613070] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 02/24/2021] [Indexed: 01/08/2023] Open
Abstract
Lack of specific antiviral treatment for COVID-19 has resulted in long hospitalizations and high mortality rate. By harnessing the regulatory effects of adenosine on inflammatory mediators, we have instituted a new therapeutic treatment with inhaled adenosine in COVID-19 patients, with the aim of reducing inflammation, the onset of cytokine storm, and therefore to improve prognosis. The use of inhaled adenosine in COVID19 patients has allowed reduction of length of stay, on average 6 days. This result is strengthened by the decrease in SARS-CoV-2 positive days. In treated patients compared to control, a clear improvement in PaO2/FiO2 was observed together with a reduction in inflammation parameters, such as the decrease of CRP level. Furthermore, the efficacy of inhaled exogenous adenosine led to an improvement of the prognosis indices, NLR and PLR. The treatment seems to be safe and modulates the immune system, allowing an effective response against the viral infection progression, reducing length of stay and inflammation parameters.
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Affiliation(s)
- Massimo Caracciolo
- Unit of Post-Surgery Intensive Therapy (USDO), Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Pierpaolo Correale
- Medical Oncology Unit, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Carmelo Mangano
- Unit of Infectious Disease, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Giuseppe Foti
- Unit of Infectious Disease, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Carmela Falcone
- Unit of Radiology, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Sebastiano Macheda
- Unit of Intensive Care Medicine and Anaesthesia, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Maria Cuzzola
- Microbiology Unit, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Marco Conte
- Microbiology Unit, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | | | - Eleonora Iuliano
- Medical Oncology Unit, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | | | - Michele Caraglia
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Biogem Scarl, Institute of Genetic Research, Laboratory of Precision and Molecular Oncology, Ariano Irpino, Italy
| | - Nicola Polimeni
- Unit of Intensive Care Medicine and Anaesthesia, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Anna Ferrarelli
- Unit of Radiology, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Demetrio Labate
- Unit of Intensive Care Medicine and Anaesthesia, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Marco Tescione
- Unit of Intensive Care Medicine and Anaesthesia, Grand Metropolitan Hospital, Reggio Calabria, Italy
| | - Laura Di Renzo
- Section of Clinical Nutrition and Nutrigenomics, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Gaetano Chiricolo
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
| | - Lorenzo Romano
- PhD School of Applied Medical, Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Antonino De Lorenzo
- Section of Clinical Nutrition and Nutrigenomics, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
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Zafri NM, Afroj S, Nafi IM, Hasan MMU. A content analysis of newspaper coverage of COVID-19 pandemic for developing a pandemic management framework. Heliyon 2021; 7:e06544. [PMID: 33758786 PMCID: PMC7973064 DOI: 10.1016/j.heliyon.2021.e06544] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/08/2021] [Accepted: 03/15/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The emergence of COVID-19 pandemic has not only shaken the global health sector, but also almost every other sector, including economic and education sectors. Newspapers are performing a significant role by featuring the news of COVID-19 from its very onset. The temporal fluctuation of COVID-19 related key themes presented in newspaper articles and the findings obtained from them could offer an effective lesson in dealing with future epidemics and pandemics. AIM AND METHOD This paper intends to develop a pandemic management framework through an automated content analysis of local newspaper coverage of COVID-19 pandemic in Bangladesh. To fulfill the aim, 7,209 newspaper articles are assembled and analyzed from three popular local newspapers named "bdnews24.com", "New Age", and "Prothom Alo English" over the period from January 1, 2020 to October 31, 2020. RESULTS Twelve key topics are identified: origin and outbreak of COVID-19, response of healthcare system, impact on economy, impact on lifestyle, government assistance to the crisis, regular updates, expert opinions, pharmaceutical measures, non-pharmaceutical measures, updates on vaccines, testing facilities, and local unusual activities within the system. Based on the identified topics, their timeline of discussion, and information flow in each topic, a four-stage pandemic management framework is developed for epidemic and pandemic management in future. The stages are preparedness, response, recovery, and mitigation. CONCLUSION This research would provide insights into stage-wise response to any biological hazard and contribute ideas to endure future outbreaks.
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Affiliation(s)
- Niaz Mahmud Zafri
- Department of Urban and Regional Planning, Bangladesh University of Engineering and Technology (BUET), Dhaka 1000, Bangladesh
| | - Sadia Afroj
- Department of Urban and Regional Planning, Bangladesh University of Engineering and Technology (BUET), Dhaka 1000, Bangladesh
| | - Imtiaz Mahmud Nafi
- Department of Electrical and Electronic Engineering, Islamic University of Technology (IUT), Gazipur 1704, Bangladesh
| | - Md. Musleh Uddin Hasan
- Department of Urban and Regional Planning, Bangladesh University of Engineering and Technology (BUET), Dhaka 1000, Bangladesh
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Kandasamy M. NF-κB signalling as a pharmacological target in COVID-19: potential roles for IKKβ inhibitors. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2021; 394:561-567. [PMID: 33394134 PMCID: PMC7780215 DOI: 10.1007/s00210-020-02035-5] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022]
Abstract
Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the functions of the immune cells and alters the gene expression profile of different cytokines in response to various pathogenic stimuli, while many proinflammatory factors have been known to induce NF-κB signalling cascade. Besides, NF-κB has been known to potentiate the production of reactive oxygen species (ROS) leading to apoptosis in various tissues in many diseases and viral infections. Though the reports on the involvement of the NF-κB signalling pathway in COVID-19 are limited, the therapeutic benefits of NF-κB inhibitors including dexamethasone, a synthetic form of glucocorticoid, have increasingly been realized. Considering the fact, the abnormal activation of the NF-κB resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might be associated with the pathogenic profile of immune cells, cytokine storm and multiorgan defects. Thus, the pharmacological inactivation of the NF-κB signalling pathway can strongly represent a potential therapeutic target to treat the symptomatology of COVID-19. This article signifies pharmacological blockade of the phosphorylation of inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ), a key downstream effector of NF-κB signalling, for a therapeutic consideration to attenuate COVID-19.
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Affiliation(s)
- Mahesh Kandasamy
- Laboratory of Stem Cells and Neuroregeneration, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India.
- Faculty Recharge Programme, University Grants Commission (UGC-FRP), New Delhi, India.
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Musyuni P, Aggarwal G, Nagpal M, Goyal RK. A Case Study: Analysis of Patents on Coronaviruses and Covid-19 for Technological Assessment and Future Research. Curr Pharm Des 2021; 27:423-439. [PMID: 32693757 DOI: 10.2174/1381612826666200720233947] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 07/01/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Protecting intellectual property rights are important and particularly pertinent for inventions that are an outcome of rigorous research and development. While the grant of patents is subject to establishing novelty and inventive step, it further indicates the technological development and is helpful for researchers working in the same technical domain. The aim of the present research work is to map the existing work through an analysis of patent literature in the field of Coronaviruses (CoV), particularly COVID-19 (2019-nCoV). CoV is a large family of viruses known to cause illness in humans and animals, particularly known for causing respiratory infections, as evidenced in earlier times, such as in MERS i.e., Middle East Respiratory Syndrome; and SRS i.e., Severe Acute Respiratory Syndrome. A recently identified novel-coronavirus, known as COVID-19, has caused pandemic situations across the globe. OBJECTIVE To expand the analysis of patents related to CoV and 2019-nCoV, an evaluation has been conducted by patenting trends of particular strains of identified CoV diseases by present legal status, main concerned countries via the earliest priority years and its assignee types and inventors of identified relevant patents. The global patent documents were analyzed to check the scope of claims along with focuses and trends of the published patent documents for the entire CoV family, including 2019-nCoV through the present landscape. METHODS To extract the results, the Derwent Innovation database was used by a combination of different keystrings. Approximately 3800 patents were obtained and further scrutinized and analyzed. The present write-up also discusses the recent progress of patent applications in a period of the year 2010 to 2020 (present) along with the recent developments in India for the treatment options for CoV and 2019-nCoV. RESULTS Present analysis showed that key areas of the inventions were the vaccines and diagnostic kits apart from the composition for the treatment of CoV. It was also observed that no specific vaccine treatments are available for the treatment of 2019-nCov; however, developing novel chemical or biological drugs and kits for early diagnosis, prevention, and disease management is the primary governing topic among the patented inventions. The present study also indicates potential research opportunities for the future, particularly to combat 2019-nCoV. CONCLUSION The present paper analyzes the existing patents in the field of Coronaviruses and 2019-nCoV and suggests a way forward for the effective contribution in this upcoming research area. From the trend analysis, an increase in the filing of the overall trend of patent families was observed for a period of 2010 to the current year. This multifaceted analysis of identified patent literature provides an understanding of the focuses on present ongoing research and a grey area in terms of the trends of technological innovations in disease management in patients with CoV and 2019-nCoV. Furthermore, the findings and outcome of the present study offer insights for the proposed research and innovation opportunities and provide actionable information in order to facilitate policymakers, academia, research-driven institutes and also investors to make better decisions regarding programmed steps for research and development for the diagnosis, treatment and taking preventive measures for CoV and 2019-nCoV. The present article also emphasizes the need for future development and the role of academia and collaboration with industry for speedy research with a rationale.
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Affiliation(s)
- Pankaj Musyuni
- Delhi Pharmaceutical Sciences and Research University, New Delhi-110017, India
| | - Geeta Aggarwal
- Delhi Pharmaceutical Sciences and Research University, New Delhi-110017, India
| | - Manju Nagpal
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Ramesh K Goyal
- Delhi Pharmaceutical Sciences and Research University, New Delhi-110017, India
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Molecular designing, crystal structure determination and in silico screening of copper(II) complexes bearing 8-hydroxyquinoline derivatives as anti-COVID-19. Bioorg Chem 2021; 110:104772. [PMID: 33676041 PMCID: PMC7902223 DOI: 10.1016/j.bioorg.2021.104772] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 02/06/2021] [Accepted: 02/22/2021] [Indexed: 12/16/2022]
Abstract
The pandemic by COVID-19 is hampering everything on the earth including physical and mental health, daily life and global economy. At the moment, there are no defined drugs, while few vaccines are available in the market to combat SARS-CoV-2. Several organic molecules were designed and tested against the virus but they did not show promising activity. In this work we designed two copper complexes from the ligands analogues with chloroquine and hydroxychloroquine. Both the ligands and complexes were well characterized by using various spectroscopic, thermal and X-ray diffraction techniques. Both the complexes as well as ligands were screened through in silico method with the chloroquine and hydroxychloroquine which essentially proved pivotal for successful understanding towards the target protein and their mechanism of action. The results indicated that the balanced hydrophobic and polar groups in the complexes favor their binding in the active site of the viral ADP-ribose-1 monophosphatase enzyme over the parent organic molecules.
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Wong NA, Saier MH. The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis. Int J Mol Sci 2021; 22:1308. [PMID: 33525632 PMCID: PMC7865831 DOI: 10.3390/ijms22031308] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/21/2021] [Accepted: 01/22/2021] [Indexed: 02/07/2023] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.
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Affiliation(s)
- Nicholas A. Wong
- Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA
| | - Milton H. Saier
- Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA
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Mouffouk C, Mouffouk S, Mouffouk S, Hambaba L, Haba H. Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CL pro and PL pro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2). Eur J Pharmacol 2021; 891:173759. [PMID: 33249077 PMCID: PMC7691142 DOI: 10.1016/j.ejphar.2020.173759] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 11/01/2020] [Accepted: 11/23/2020] [Indexed: 12/12/2022]
Abstract
The novel coronavirus outbreak (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the actual greatest global public health crisis. The lack of efficacious drugs and vaccines against this viral infection created a challenge for scientific researchers in order to find effective solutions. One of the promising therapeutic approaches is the search for bioactive molecules with few side effects that display antiviral properties in natural sources like medicinal plants and vegetables. Several computational and experimental studies indicated that flavonoids especially flavonols and their derivatives constitute effective viral enzyme inhibitors and possess interesting antiviral activities. In this context, the present study reviews the efficacy of many dietary flavonols as potential antiviral drugs targeting the SARS-CoV-2 enzymes and proteins including Chymotrypsin-Like Protease (3CLpro), Papain Like protease (PLpro), Spike protein (S protein) and RNA-dependent RNA polymerase (RdRp), and also their ability to interact with the angiotensin-converting enzyme II (ACE2) receptor. The relationship between flavonol structures and their SARS-CoV-2 antiviral effects were discussed. On the other hand, the immunomodulatory, the anti-inflammatory and the antiviral effects of secondary metabolites from this class of flavonoids were reported. Also, their bioavailability limitations and toxicity were predicted.
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Affiliation(s)
- Chaima Mouffouk
- Faculty of Nature and Life Sciences, Department of Organisms, University of Batna 2, Algeria.
| | - Soumia Mouffouk
- Laboratory of Chemistry and Environmental Chemistry (L.C.C.E), Department of Chemistry, Faculty of Sciences of the Matter, University of Batna 1, 05000, Batna, Algeria
| | - Sara Mouffouk
- Faculty of Nature and Life Sciences, Department of Organisms, University of Batna 2, Algeria
| | - Leila Hambaba
- Faculty of Nature and Life Sciences, Department of Organisms, University of Batna 2, Algeria
| | - Hamada Haba
- Laboratory of Chemistry and Environmental Chemistry (L.C.C.E), Department of Chemistry, Faculty of Sciences of the Matter, University of Batna 1, 05000, Batna, Algeria
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Goud PT, Bai D, Abu-Soud HM. A Multiple-Hit Hypothesis Involving Reactive Oxygen Species and Myeloperoxidase Explains Clinical Deterioration and Fatality in COVID-19. Int J Biol Sci 2021; 17:62-72. [PMID: 33390833 PMCID: PMC7757048 DOI: 10.7150/ijbs.51811] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Multi-system involvement and rapid clinical deterioration are hallmarks of coronavirus disease 2019 (COVID-19) related mortality. The unique clinical phenomena in severe COVID-19 can be perplexing, and they include disproportionately severe hypoxemia relative to lung alveolar-parenchymal pathology and rapid clinical deterioration, with poor response to O2 supplementation, despite preserved lung mechanics. Factors such as microvascular injury, thromboembolism, pulmonary hypertension, and alteration in hemoglobin structure and function could play important roles. Overwhelming immune response associated with "cytokine storms" could activate reactive oxygen species (ROS), which may result in consumption of nitric oxide (NO), a critical vasodilation regulator. In other inflammatory infections, activated neutrophils are known to release myeloperoxidase (MPO) in a natural immune response, which contributes to production of hypochlorous acid (HOCl). However, during overwhelming inflammation, HOCl competes with O2 at heme binding sites, decreasing O2 saturation. Moreover, HOCl contributes to several oxidative reactions, including hemoglobin-heme iron oxidation, heme destruction, and subsequent release of free iron, which mediates toxic tissue injury through additional generation of ROS and NO consumption. Connecting these reactions in a multi-hit model can explain generalized tissue damage, vasoconstriction, severe hypoxia, and precipitous clinical deterioration in critically ill COVID-19 patients. Understanding these mechanisms is critical to develop therapeutic strategies to combat COVID-19.
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Affiliation(s)
- Pravin T Goud
- Division of Reproductive Endocrinology and Infertility & California IVF Fertility Center, Department of Obstetrics and Gynecology, University of California Davis, Sacramento, CA, 95833, USA
- California Northstate University Medical College, Elk Grove, CA, 95757, USA
| | - David Bai
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Husam M Abu-Soud
- Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, 48201, USA
- Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
- Department of Microbiology, Immunology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, 48201, USA
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Mohamed MS, Moulin TC, Schiöth HB. Sex differences in COVID-19: the role of androgens in disease severity and progression. Endocrine 2021; 71:3-8. [PMID: 33179220 PMCID: PMC7657570 DOI: 10.1007/s12020-020-02536-6] [Citation(s) in RCA: 127] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 10/24/2020] [Indexed: 12/31/2022]
Abstract
PURPOSE Throughout the SARS-CoV2 pandemic, multiple reports show higher percentages of hospitalization, morbidity, and mortality among men than women, indicating that men are more affected by COVID-19. The pathophysiology of this difference is yet not established, but recent studies suggest that sex hormones may influence the viral infectivity process. Here, we review the current evidence of androgen sensitivity as a decisive factor for COVID-19 disease severity. METHODS Relevant literature investigating the role of androgens in COVID-19 was assessed. Further, we describe several drugs suggested as beneficial for COVID-19 treatment related to androgen pathways. Lastly, we looked at androgen sensitivity as a predictor for COVID-19 progression and ongoing clinical trials on androgen suppression therapies as a line of treatment. RESULTS SARS-COV2 virus spike proteins utilize Transmembrane protease serine 2 (TMPRSS2) for host entry. Androgen receptors are transcription promoters for TMPRSS2 and can, therefore, facilitate SARS-COV2 entry. Variants in the androgen receptor gene correlate with androgen sensitivity and are implicated in diseases like androgenetic alopecia and prostate cancer, conditions that have been associated with worse COVID-19 outcomes and hospitalization. CONCLUSION Androgen's TMPRSS2-mediated actions might explain both the low fatalities observed in prepubertal children and the differences between sexes regarding SARS-COV2 infection. Androgen sensitivity may be a critical factor in determining COVID-19 disease severity, and sensitivity tests can, therefore, help in predicting patient outcomes.
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Affiliation(s)
- Mohamed S Mohamed
- Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala, Sweden
| | - Thiago C Moulin
- Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
| | - Helgi B Schiöth
- Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala, Sweden
- Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia
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Lambert WC, Alhatem A, Lambert MW, Schwartz RA. What we have learned from the COVID-19 pandemic: Time to think outside the box, maybe far outside. Clin Dermatol 2021; 39:107-117. [PMID: 33972037 PMCID: PMC7834261 DOI: 10.1016/j.clindermatol.2020.12.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The coronavirus disease 2019 pandemic has had a profound effect on our lives and careers; this presentation explores some of the lessons we have learned from it and others that it may yet teach us. Socioeconomic effects have been profound, not all of them favorable. Travel and meeting activities, as well as many other activities, have been severely restricted. Social unrest has become intense, and it may have questionable political consequences, as the United States is undergoing a contested election result.
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Affiliation(s)
- W Clark Lambert
- Department of Dermatology, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
| | - Albert Alhatem
- Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Muriel W Lambert
- Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Robert A Schwartz
- Department of Dermatology, Rutgers New Jersey Medical School, Newark, New Jersey, USA; Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
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Pathogenetic Substantiation of Therapeutic and Preventive Measures in Severe Coronavirus Infection. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2020. [DOI: 10.2478/sjecr-2020-0043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Abstract
The basis of coronavirus disease is an infectious process, accompanied by a varying degree of activity of pathological processes. Based on the study of the pathological course of infection, modern approaches to the treatment and prevention of complications of coronavirus infection are presented. The main strategic pathogenetic direction in the creation of effective programs for the treatment of COVID-19, as well as the prevention of fatal complications, should be a set of measures enhancing permissive regulatory influences and events. Endothelium, being a source of inflammatory mediators and a transducer of their regulatory effects on the vascular tone, is involved in the development and alternation of vascular reactions, changing the volume of perfusion. The main mechanism for the development of endothelial dysfunction and damage is associated with an imbalance between the generation of reactive oxygen species and the power of the antioxidant defense system. Any measures to protect the endothelium, reducing the severity of microcirculatory disorders and hypoxia, will have a therapeutic and preventive effect on fatal complications. In this regard, in the treatment of COVID-19, the use of synthetic gas transport preparations based on perfluorocarbon nanodispersed emulsions with a clinical effect directed at once to several patho-genetic links underlying the progression of COVID-19 disease can be quite effective. The necessity of a comprehensive effect on pathogenesis using sanogenetic principles of treatment, allowing influencing the speed and time of onset of resolution of inflammation, which can reduce the number of complications and deaths of the disease, is substantiated.
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Godman B, Haque M, Islam S, Iqbal S, Urmi UL, Kamal ZM, Shuvo SA, Rahman A, Kamal M, Haque M, Jahan I, Islam MZ, Hossain MM, Munzur-E-Murshid, Kumar S, Charan J, Bhatt R, Dutta S, Abhayanand JP, Sharma Y, Saleem Z, Phuong TNT, Kwon HY, Kurdi A, Wale J, Sefah I. Rapid Assessment of Price Instability and Paucity of Medicines and Protection for COVID-19 Across Asia: Findings and Public Health Implications for the Future. Front Public Health 2020; 8:585832. [PMID: 33381485 PMCID: PMC7767884 DOI: 10.3389/fpubh.2020.585832] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/15/2020] [Indexed: 12/15/2022] Open
Abstract
Background: Countries have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE), with some countries adopting preventative strategies earlier than others. However, there has been considerable controversy surrounding some treatments. This includes hydroxychloroquine where the initial hype and misinformation lead to shortages, price rises and suicides. Price rises and shortages have also been seen for PPE. Such activities can have catastrophic effects on patients where there are high co-payment levels and issues of affordability. Consequently, there is a need to investigate this further. Objective: Assess changes in the availability, utilization and prices of relevant medicines and PPE during the pandemic among a range of Asian countries. Our approach: Narrative literature review combined with interviews among community pharmacists to assess changes in consumption, prices and shortages of medicines and PPE from the beginning of March 2020 until end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: 308 pharmacists took part from five Asian countries. There was an appreciable increase in the utilization of antimicrobials in Pakistan (in over 88% of pharmacies), with lower increases or no change in Bangladesh, India, Malaysia and Vietnam. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries, as well as limited price rises for antimicrobials in India, Malaysia and Vietnam, although greater price rises seen for analgesics and vitamin C/immune boosters. Appreciable price increases were also seen for PPE across some countries. Conclusion: Encouraging to see increases in utilization of vitamins/immune boosters and PPE. However, increases in the utilization and prices of antimicrobials is a concern that needs addressing alongside misinformation and any unintended consequences from the pandemic. Community pharmacists can play a key role in providing evidence-based advice, helping to moderate prices, as well as helping address some of the unintended consequences of the pandemic.
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Affiliation(s)
- Brian Godman
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
- Division of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
- School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria, South Africa
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
| | - Mainul Haque
- Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, Malaysia
| | - Salequl Islam
- Department of Microbiology, Jahangirnagar University, Dhaka, Bangladesh
| | - Samiul Iqbal
- Department of Orthodontics, Faculty of Dentistry, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Umme Laila Urmi
- Department of Microbiology, Jahangirnagar University, Dhaka, Bangladesh
| | - Zubair Mahmood Kamal
- Integrated Sleep Disorders Center, McGuire VAMC/VCU Health, Richmond, VA, United States
| | | | - Aminur Rahman
- Finance & Account Division, Grameen Euglena, Dhaka, Bangladesh
| | - Mustafa Kamal
- Al-Manar Hospital Ltd., Modern Hospital Cumilla Ltd., Dhaka, Bangladesh
| | - Monami Haque
- Human Resource Department, Square Toiletries Limited, Rupayan Center, Dhaka, Bangladesh
| | - Iffat Jahan
- Department of Physiology, Eastern Medical College, Comilla, Bangladesh
| | - Md. Zakirul Islam
- Department of Pharmacology, Eastern Medical College, Comilla, Bangladesh
| | | | - Munzur-E-Murshid
- WISH2ACTION Project, Handicap International, Kurigram, Bangladesh
| | - Santosh Kumar
- Department of Periodontology and Implantology, Karnavati University, Gandhinagar, India
| | - Jaykaran Charan
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India
| | - Rohan Bhatt
- Department of Pediatric Dentistry, Karnavati University, Gandhinagar, India
| | - Siddhartha Dutta
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India
| | | | - Yesh Sharma
- Department of Conservative Dentistry and Endodontics, Rajasthan University of Health Sciences, Jaipur, India
| | - Zikria Saleem
- Department of Pharmacy Practice, Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
| | - Thuy Nguyen Thi Phuong
- Pharmaceutical Administration & PharmacoEconomics, Hanoi University of Pharmacy, Hanoi, Vietnam
| | - Hye-Young Kwon
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
- College of Pharmacy, Seoul National University, Seoul, South Korea
| | - Amanj Kurdi
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
- Department of Pharmacology, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Janney Wale
- Independent Consumer Advocate, Brunswick, VIC, Australia
| | - Israel Sefah
- Ghana Health Service, Keta Municipal Hospital, Pharmacy Department, Keta, Ghana
- University of Health and Allied Sciences, School of Pharmacy, Pharmacy Practice Department, Volta Region, Ghana
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Yen YF, Tsai YF, Su VYF, Chan SY, Yu WR, Ho H, Hou CM, Chen CC, Woung LC, Huang SJ. Use and Cost-Effectiveness of a Telehealth Service at a Centralized COVID-19 Quarantine Center in Taiwan: Cohort Study. J Med Internet Res 2020; 22:e22703. [PMID: 33259324 PMCID: PMC7735809 DOI: 10.2196/22703] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 11/17/2020] [Accepted: 11/30/2020] [Indexed: 12/31/2022] Open
Abstract
Background Telehealth is a recommended method for monitoring the progression of nonsevere infections in patients with COVID-19. However, telehealth has not been widely implemented to monitor SARS-CoV-2 infection in quarantined individuals. Moreover, studies on the cost-effectiveness of quarantine measures during the COVID-19 pandemic are scarce. Objective In this cohort study, we aimed to use telehealth to monitor COVID-19 infections in 217 quarantined Taiwanese travelers and to analyze the cost-effectiveness of the quarantine program. Methods Travelers were quarantined for 14 days at the Taiwan Yangmingshan quarantine center and monitored until they were discharged. The travelers’ clinical symptoms were evaluated twice daily. A multidisciplinary medical team used the telehealth system to provide timely assistance for ill travelers. The cost of the mandatory quarantine was calculated according to data from the Ministry of Health and Welfare of Taiwan. Results All 217 quarantined travelers tested negative for SARS-CoV-2 upon admission to the quarantine center. During the quarantine, 28/217 travelers (12.9%) became ill and were evaluated via telehealth. Three travelers with fever were hospitalized after telehealth assessment, and subsequent tests for COVID-19 were negative for all three patients. The total cost incurred during the quarantine was US $193,938, which equated to US $894 per individual. Conclusions Telehealth is an effective instrument for monitoring COVID-19 infection in quarantined travelers and could help provide timely disease management for people who are ill. It is imperative to screen and quarantine international travelers for SARS-CoV-2 infection to reduce the nationwide spread of COVID-19.
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Affiliation(s)
- Yung-Feng Yen
- Section of Infectious Diseases, Taipei City Hospital, Yangming Branch, Taipei City, Taiwan.,Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.,Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.,University of Taipei, Taipei, Taiwan
| | - Yi-Fan Tsai
- Department of Nursing, Taipei City Hospital Yangming Branch, Taipei, Taiwan
| | - Vincent Yi-Fong Su
- Department of Internal Medicine, Taipei City Hospital Yangming Branch, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shang-Yih Chan
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.,University of Taipei, Taipei, Taiwan.,Department of Internal Medicine, Taipei City Hospital Yangming Branch, Taipei, Taiwan
| | - Wen-Ruey Yu
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsuan Ho
- University of Taipei, Taipei, Taiwan
| | | | - Chu-Chieh Chen
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - Lin-Chung Woung
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.,Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan
| | - Sheng-Jean Huang
- Department of Neurosurgery, Taipei City Hospital, Taipei, Taiwan.,Department of Surgery, Medical College, National Taiwan University Hospital, Taipei, Taiwan
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Talaie H, Hosseini SM, Nazari M, Fakhri Y, Mousavizadeh A, Vatanpour H, Firoozfar A. Is there any potential management against COVID-19? A systematic review and meta-analysis. Daru 2020; 28:765-777. [PMID: 32812187 PMCID: PMC7434334 DOI: 10.1007/s40199-020-00367-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 08/07/2020] [Indexed: 12/19/2022] Open
Abstract
PURPOSE A recent survey has shown that the COVID-19 pandemic has culminated in dramatical and critical treatment particularly in acute infected patients. In fact, this systematic review-meta-analysis was directly pertained to estimation at the efficient value of some clinical managements to confront the COVID-19 infection. METHODS Pubmed, Embase, Scopus, Cochrane, and Scholar databases were searched from inception to July 1, 2020, to identify studies reporting the current treatment process and medications (e.g. hydroxychloroquine, antiviral therapy, convalescent plasma, and immunomodulatory agents) for COVID-19. A random-effects model meta-analysis was performed to calculate the relative risk (RR) with 95% confidence intervals (CI). The outcomes of this study were the frequency of negative conversion cases, clinical improvements, mechanical ventilation demand, intensive care unit (ICU) entry, and mortality. The standard treatment refers to the published guidelines and specialist experience which varies in different articles, and the proposed treatment refers to the kind of interest suggested in the included studies. RESULTS A number of 45 articles met the eligibility criteria (out of 6793 articles). Among them, 26 articles involving 3263 patients were included in quantitative analysis. Anti-COVID-19 interventions could significantly increase clinical improvement (RR 1.17, 95% CI 1.08-1.27; I2 = 49.8%) and reduce the mortality rate (RR 0.58, 95% CI 0.35-0.95; I2 = 74.8%). Although in terms of negative conversion, ICU entry, and mechanical ventilation demand, clinical intervention had no beneficial effect. The clinical effect of immunomodulatory agents (especially tocilizumab and anakinra) was noticeable compared to other medications with RR of 0.22 (95% CI 0.09-0.53; I2 = 40.9%) for mortality and 1.25 (95% CI 1.07-1.46; I2 = 45.4%) for clinical improvement. Moreover, Antivirals (RR 1.13, 95% CI 1.01-1.26; I2 = 47.0%) and convalescent plasma therapy (RR 1.41, 95% CI 1.01-1.98; I2 = 66.6%) had significant beneficial effects on clinical improvement. CONCLUSION Based on our findings, all the included interventions significantly declined the mortality and enhanced clinical improvements with no effect on negative conversion and mechanical ventilation demand. Especially, immunomodulators and plasma therapy showed favorable outcomes. An evaluation on the efficacy of proposed treatment against COVID-19.
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Affiliation(s)
- Haleh Talaie
- Toxicological Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Kamali Avenue, south Karegar Street, Tehran, 1333631151, Iran.
- Department of Infectious and Tropical diseases, Loghman-Hakim Hospital, Shahid Behesht University of Medical Sciences, Tehran, Iran.
| | - Sayed Masoud Hosseini
- Departments of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Nazari
- Toxicological Research Center, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Kamali Avenue, south Karegar Street, Tehran, 1333631151, Iran
| | - Yadollah Fakhri
- Infectious and Tropical Diseases Research Center, Hormozgan Heath Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Atieh Mousavizadeh
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hossein Vatanpour
- Departments of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Firoozfar
- Anatomy and Physiology Department, Gharmsar University, Gharmsar, Iran
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Khoubnasabjafari M, Amanlou M, Dehpour A, Jouyban A. A Rapid Strategy for Repurposing Drugs for COVID-19. PHARMACEUTICAL SCIENCES 2020. [DOI: 10.34172/ps.2020.76] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Affiliation(s)
- Maryam Khoubnasabjafari
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Amanlou
- Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Dehpour
- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Abolghasem Jouyban
- Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Lopes N, Vernuccio F, Costantino C, Imburgia C, Gregoretti C, Salomone S, Drago F, Lo Bianco G. An Italian Guidance Model for the Management of Suspected or Confirmed COVID-19 Patients in the Primary Care Setting. Front Public Health 2020; 8:572042. [PMID: 33330317 PMCID: PMC7732472 DOI: 10.3389/fpubh.2020.572042] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
An outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 started in China's Hubei province at the end of 2019 has rapidly become a pandemic. In Italy, a great number of patients was managed in primary care setting and the role of general practitioners and physicians working in the first-aid emergency medical service has become of utmost importance to coordinate the network between the territory and hospitals during the pandemic. Aim of this manuscript is to provide a guidance model for the management of suspected, probable, or confirmed cases of SARS-CoV-2 infection in the primary care setting, from diagnosis to treatment, applying also the recommendations of the Italian Society of General Medicine. Moreover, this multidisciplinary contribution would analyze and synthetize the preventive measures to limit the spread of SARS-CoV-2 infection in the general population as well as the perspective for vaccines.
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Affiliation(s)
- Noemi Lopes
- Provincial Health Authority of Palermo, Palermo, Italy
| | - Federica Vernuccio
- Centro Neurolesi Bonino Pulejo Istituto di Ricovero e Cura a Carattere Scientifico - Scientific Institutes of Hospitalization and Care (IRCCS), Messina, Italy
- Department of Science for Health Promotion and Mother to Child Care, University of Palermo, Palermo, Italy
- Section of Radiology - Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Claudio Costantino
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Excellence Specialties “G. D'Alessandro”, University of Palermo, Palermo, Italy
| | - Claudia Imburgia
- Infectious Disease Unit, National Relevance Hospital Trust, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Civico Di Cristina e Benfratelli, Palermo, Italy
| | - Cesare Gregoretti
- Department of Surgical, Oncological, and Stomatological Sciences, University of Palermo, Palermo, Italy
- Anesthesiology and Pain Department, Fondazione Istituto G. Giglio, Cefalù, Italy
| | - Salvatore Salomone
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Giuliano Lo Bianco
- Anesthesiology and Pain Department, Fondazione Istituto G. Giglio, Cefalù, Italy
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
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Rivera-Izquierdo M, Valero-Ubierna MDC, R-delAmo JL, Fernández-García MÁ, Martínez-Diz S, Tahery-Mahmoud A, Rodríguez-Camacho M, Gámiz-Molina AB, Barba-Gyengo N, Gámez-Baeza P, Cabrero-Rodríguez C, Guirado-Ruiz PA, Martín-Romero DT, Láinez-Ramos-Bossini AJ, Sánchez-Pérez MR, Mancera-Romero J, García-Martín M, Martín-delosReyes LM, Martínez-Ruiz V, Jiménez-Mejías E. Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality. MEDICINA CLINICA (ENGLISH ED.) 2020; 155:375-381. [PMID: 33072869 PMCID: PMC7546238 DOI: 10.1016/j.medcle.2020.06.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 06/24/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND OBJECTIVES In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, Hazard Ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox Regression models. RESULTS The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.
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Affiliation(s)
- Mario Rivera-Izquierdo
- Servicio de Medicina Preventiva y Salud Pública, Hospital Universitario Clínico San Cecilio, Granada, Spain
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, Spain
- Instituto Biosanitario de Granada, Granada, Spain
| | | | - Juan Luis R-delAmo
- Servicio de Neurología, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | | | - Silvia Martínez-Diz
- Servicio de Medicina Preventiva y Salud Pública, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - Arezu Tahery-Mahmoud
- Servicio de Psiquiatría, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | | | | | - Nicolás Barba-Gyengo
- Servicio de Neumología, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | - Pablo Gámez-Baeza
- Servicio de Neumología, Hospital Universitario Clínico San Cecilio, Granada, Spain
| | | | | | | | | | - María Rosa Sánchez-Pérez
- Cátedra de Docencia e Investigación en Medicina de Familia "SEMERGEN-UGR", Universidad de Granada, Granada, Spain
| | - José Mancera-Romero
- Cátedra de Docencia e Investigación en Medicina de Familia "SEMERGEN-UGR", Universidad de Granada, Granada, Spain
| | - Miguel García-Martín
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, Spain
- Instituto Biosanitario de Granada, Granada, Spain
- CIBER de Epidemiología y Salud Pública de España, Madrid, Spain
| | - Luis Miguel Martín-delosReyes
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, Spain
- Programa de Doctorado en Medicina Clínica y Salud Pública, Universidad de Granada, Granada, Spain
- CIBER de Epidemiología y Salud Pública de España, Madrid, Spain
| | - Virginia Martínez-Ruiz
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, Spain
- Instituto Biosanitario de Granada, Granada, Spain
- CIBER de Epidemiología y Salud Pública de España, Madrid, Spain
| | - Eladio Jiménez-Mejías
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, Spain
- Instituto Biosanitario de Granada, Granada, Spain
- Cátedra de Docencia e Investigación en Medicina de Familia "SEMERGEN-UGR", Universidad de Granada, Granada, Spain
- CIBER de Epidemiología y Salud Pública de España, Madrid, Spain
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Rivera-Izquierdo M, Valero-Ubierna MDC, R-delAmo JL, Fernández-García MÁ, Martínez-Diz S, Tahery-Mahmoud A, Rodríguez-Camacho M, Gámiz-Molina AB, Barba-Gyengo N, Gámez-Baeza P, Cabrero-Rodríguez C, Guirado-Ruiz PA, Martín-Romero DT, Láinez-Ramos-Bossini AJ, Sánchez-Pérez MR, Mancera-Romero J, García-Martín M, Martín-delosReyes LM, Martínez-Ruiz V, Jiménez-Mejías E. Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality. Med Clin (Barc) 2020; 155:375-381. [PMID: 32773165 PMCID: PMC7346829 DOI: 10.1016/j.medcli.2020.06.025] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 06/20/2020] [Accepted: 06/24/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND OBJECTIVES In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, hazard ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox regression models. RESULTS The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.
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Affiliation(s)
- Mario Rivera-Izquierdo
- Servicio de Medicina Preventiva y Salud Pública, Hospital Universitario Clínico San Cecilio, Granada, España; Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, España; Instituto Biosanitario de Granada, Granada, España
| | | | - Juan Luis R-delAmo
- Servicio de Neurología, Hospital Universitario Clínico San Cecilio, Granada, España
| | | | - Silvia Martínez-Diz
- Servicio de Medicina Preventiva y Salud Pública, Hospital Universitario Clínico San Cecilio, Granada, España
| | - Arezu Tahery-Mahmoud
- Servicio de Psiquiatría, Hospital Universitario Clínico San Cecilio, Granada, España
| | | | | | - Nicolás Barba-Gyengo
- Servicio de Neumología, Hospital Universitario Clínico San Cecilio, Granada, España
| | - Pablo Gámez-Baeza
- Servicio de Neumología, Hospital Universitario Clínico San Cecilio, Granada, España
| | | | | | | | | | - María Rosa Sánchez-Pérez
- Cátedra de Docencia e Investigación en Medicina de Familia «SEMERGEN-UGR», Universidad de Granada, Granada, España
| | - José Mancera-Romero
- Cátedra de Docencia e Investigación en Medicina de Familia «SEMERGEN-UGR», Universidad de Granada, Granada, España
| | - Miguel García-Martín
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, España; Instituto Biosanitario de Granada, Granada, España; CIBER de Epidemiología y Salud Pública de España, Madrid, España
| | - Luis Miguel Martín-delosReyes
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, España; Programa de Doctorado en Medicina Clínica y Salud Pública, Universidad de Granada, Granada, España; CIBER de Epidemiología y Salud Pública de España, Madrid, España.
| | - Virginia Martínez-Ruiz
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, España; Instituto Biosanitario de Granada, Granada, España; CIBER de Epidemiología y Salud Pública de España, Madrid, España
| | - Eladio Jiménez-Mejías
- Departamento de Medicina Preventiva y Salud Pública, Universidad de Granada, Granada, España; Instituto Biosanitario de Granada, Granada, España; Cátedra de Docencia e Investigación en Medicina de Familia «SEMERGEN-UGR», Universidad de Granada, Granada, España; CIBER de Epidemiología y Salud Pública de España, Madrid, España
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Giuliani F, Gualdi G, Amerio P. Effect of immunosuppressive drugs in immune-mediated inflammatory disease during the coronavirus pandemic. Dermatol Ther 2020; 33:e14204. [PMID: 32829511 PMCID: PMC7461363 DOI: 10.1111/dth.14204] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023]
Abstract
The safety of immunosuppressive treatment in patients with Immune-Mediated Inflammatory Diseases (IMIDs) during the Coronavirus pandemic is questioned and it is utmost important for public health. We searched studies trough MEDLINE/EMBASE database, including patient with IMID, undergoing immunosuppressive treatment with a positive diagnosis for SARS-CoV 2. We included 11 studies for the descriptive analysis and 10 studies for the pooled analysis, with a total population of 57 and 53 IMID-affected SARS-CoV-positive patients respectively. Overall no death was reported; 16 patients were hospitalized (30.2%) and only two cases were admitted to Intensive Care Unit (ICU) (3.8%). We found a significant association between the risk of hospitalization and older age (P .03), obesity (P .02), and presence of multi-comorbidity (P .03). No significant association was found between the risk of hospitalization and the use of biological or conventional DMARDs (respectively P .32 and .26), neither when they are used combined (P .85). We found consistent results in the sub-analysis of Psoriasis: 10 patients were hospitalized (31.3%) and only one case was admitted to Intensive Care Unit (ICU) (3.1%) Particular attention should be placed for patients with older age, obesity and multi-comorbidity that are at higher risk of hospitalization.
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Affiliation(s)
- Federica Giuliani
- Clinical Research Center—CAST, Center for Advanced Science and Technology“G. d'Annunzio” FoundationChietiItaly
| | - Giulio Gualdi
- Clinical Research Center—CAST, Center for Advanced Science and Technology“G. d'Annunzio” FoundationChietiItaly
- Dermatologic Clinic, Department of Medicine and Ageing Science“G. d'Annunzio” UniversityChietiItaly
| | - Paolo Amerio
- Clinical Research Center—CAST, Center for Advanced Science and Technology“G. d'Annunzio” FoundationChietiItaly
- Dermatologic Clinic, Department of Medicine and Ageing Science“G. d'Annunzio” UniversityChietiItaly
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Kumar D, Chauhan G, Kalra S, Kumar B, Gill MS. A perspective on potential target proteins of COVID-19: Comparison with SARS-CoV for designing new small molecules. Bioorg Chem 2020; 104:104326. [PMID: 33142431 PMCID: PMC7524440 DOI: 10.1016/j.bioorg.2020.104326] [Citation(s) in RCA: 15] [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: 06/15/2020] [Revised: 09/25/2020] [Accepted: 09/26/2020] [Indexed: 02/08/2023]
Abstract
SARS-CoV-2 (COVID-19) epidemic has created an unprecedented medical and economic crisis all over the world. SARS-CoV-2 is found to have more contagious character as compared to MERS-CoV and is spreading in a very fast manner all around the globe. It has affected over 31 million people all over the world till date. This virus shares around 80% of genome similarity with SARS-CoV. In this perspective, we have explored three major targets namely; SARS-CoV-2 spike (S) protein, RNA dependent RNA polymerase, and 3CL or Mpro Protease for the inhibition of SARS-CoV-2. These targets have attracted attention of the medicinal chemists working on computer-aided drug design in developing new small molecules that might inhibit these targets for combating COVID-19 disease. Moreover, we have compared the similarity of these target proteins with earlier reported coronavirus (SARS-CoV). We have observed that both the coronaviruses share around 80% similarity in their amino acid sequence. The key amino acid interactions which can play a crucial role in designing new small molecule inhibitors against COVID-19 have been reported in this perspective. Authors believe that this study will help the medicinal chemists to understand the key amino acids essential for interactions at the active site of target proteins in SARS-CoV-2, based on their similarity with earlier reported viruses. In this review, we have also described the lead molecules under various clinical trials for their efficacy against COVID-19.
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Affiliation(s)
- Devendra Kumar
- Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, G.T Road, Moga, Punjab 142001, India
| | - Gaurav Chauhan
- School of Engineering and Sciences, Tecnologico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, 64849 Monterrey, Nuevo León, Mexico
| | - Sourav Kalra
- Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research, SAS Nagar, Sector 67, Mohali, Punjab 160062, India
| | - Bhupinder Kumar
- Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, G.T Road, Moga, Punjab 142001, India.
| | - Manjinder Singh Gill
- Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research, SAS Nagar, Sector 67, Mohali, Punjab 160062, India.
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Gomides A, Ferreira G, Kakehasi A, Lacerda M, Marques C, Mota L, Paiva E, Pileggi G, Provenza J, Reis-Neto E, Sampaio V, Xavier R, Pinheiro M. Impact of Chronic Use of Antimalarials on SARS-CoV-2 Infection in Patients With Immune-Mediated Rheumatic Diseases: Protocol for a Multicentric Observational Cohort Study. JMIR Res Protoc 2020; 9:e23532. [PMID: 32924956 PMCID: PMC7575340 DOI: 10.2196/23532] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/07/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
Background COVID-19, caused by the virus SARS-CoV-2, has brought extensive challenges to the scientific community in recent months. Several studies have been undertaken in an attempt to minimize the impact of the disease worldwide. Although new knowledge has been quickly disseminated, including viral mechanisms, pathophysiology, and clinical findings, there is a lack of information on the effective pharmacological management of this disease. In vitro studies have shown some benefits related to the use of antimalarials (chloroquine and hydroxychloroquine) for inhibiting SARS-CoV-2. However, the data from open clinical trials on COVID-19 patients are controversial. Objective We present the protocol for a research project that compares the potential protective effect of antimalarials in preventing moderate-to-severe forms of COVID-19 in two groups: (1) patients treated chronically with antimalarials for rheumatic diseases and (2) other members of the patients’ household who have not been diagnosed with rheumatic diseases and are not taking antimalarials. Methods This is a 24-week, prospective, observational cohort study comprising patients from public and private health services across Brazil, who chronically use antimalarials for the treatment of immune-mediated rheumatic diseases, osteoarthritis, or chikungunya-related arthropathy. A total of six sequential phone interviews were scheduled during the COVID-19 outbreak in five different regions of Brazil. Information regarding social, epidemiological, and demographic data, as well as details about rheumatic diseases, antimalarials, comorbidities, and concomitant medication, is being recorded using a specific online form in the REDCap database. Symptoms suggestive of COVID-19, including fever, cough, dyspnea, anosmia, and dysgeusia, are being self-reported and collected via phone interviews. Our main outcomes are hospitalization, need of intensive care unit, and death. Results Recruitment began at the end of March 2020, and the inclusion was done during an 8-week period (from March 29 to May 17) with a total of 10,443 individuals enrolled at baseline, 5166 of whom have rheumatic diseases, from 23 tertiary rheumatology centers across 97 Brazilian cities. Data analysis is scheduled to begin after all inclusion data have been collected. Conclusions This study, which includes a large sample of chronic antimalarial users, will allow us to explore whether SARS-CoV-2 infection may be associated with immune-mediated rheumatic diseases and long-term antimalarial usage. Trial Registration Brazilian Registry of Clinical Trials RBR–9KTWX6; http://www.ensaiosclinicos.gov.br/rg/RBR-9ktwx6/ International Registered Report Identifier (IRRID) DERR1-10.2196/23532
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Affiliation(s)
- Ana Gomides
- University Center of Brasília, Brasília, Brazil
| | - Gilda Ferreira
- Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | | | | | - Licia Mota
- University of Brasília, Brasília, Brazil
| | | | | | - José Provenza
- Sociedade Brasileira de Reumatologia, São Paulo, Brazil
| | | | | | - Ricardo Xavier
- Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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Pawełczyk A, Zaprutko L. Anti-COVID drugs: repurposing existing drugs or search for new complex entities, strategies and perspectives. Future Med Chem 2020; 12:1743-1757. [PMID: 32698626 PMCID: PMC7377048 DOI: 10.4155/fmc-2020-0204] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 07/14/2020] [Indexed: 12/15/2022] Open
Abstract
At the end of 2019, a novel virus causing severe acute respiratory syndrome to spread globally. There are currently no effective drugs targeting SARS-CoV-2. In this study, based on the analysis of numerous references and selected methods of computational chemistry, the strategy of integrative structural modification of small molecules with antiviral activity into potential active complex molecules has been presented. Proposed molecules have been designed based on the structure of triterpene oleanolic acid and complemented by structures characteristic of selected anti-COVID therapy assisted drugs. Their pharmaceutical molecular parameters and the preliminary bioactivity were calculated and predicted. The results of the above analyses show that among the designed complex substances there are potential antiviral agents directed mainly on SARS-CoV-2.
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Affiliation(s)
- Anna Pawełczyk
- Poznan University of Medical Sciences, Department of Organic Chemistry, Grunwaldzka 6, Poznań 60-780, Poland
| | - Lucjusz Zaprutko
- Poznan University of Medical Sciences, Department of Organic Chemistry, Grunwaldzka 6, Poznań 60-780, Poland
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