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Ramirez-Falcon M, Suarez-Pajes E, Flores C. Defining the Differential Corticosteroid Response Basis from Multiple Omics Approaches. Int J Mol Sci 2024; 25:13611. [PMID: 39769372 PMCID: PMC11679800 DOI: 10.3390/ijms252413611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
Since their discovery, corticosteroids have been widely used in the treatment of several diseases, including asthma, acute lymphoblastic leukemia, chronic obstructive pulmonary disease, and many other conditions. However, it has been noted that some patients develop undesired side effects or even fail to respond to treatment. The reasons behind this have not yet been fully elucidated. This poses a significant challenge to effective treatment that needs to be addressed urgently. Recent genomic, transcriptomic, and other omics-based approximations have begun to shed light into the genetic factors influencing interindividual variability in corticosteroid efficacy and its side effects. Here, we comprehensively revise the recent literature on corticosteroid response in various critical and chronic diseases, with a focus on omics approaches, and highlight existing knowledge gaps where further investigation is urgently needed.
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Affiliation(s)
- Melody Ramirez-Falcon
- Research Unit, Hospital Universitario Ntra. Sra. de Candelaria, Instituto de Investigación Sanitaria de Canarias, 38010 Santa Cruz de Tenerife, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Eva Suarez-Pajes
- Research Unit, Hospital Universitario Ntra. Sra. de Candelaria, Instituto de Investigación Sanitaria de Canarias, 38010 Santa Cruz de Tenerife, Spain
| | - Carlos Flores
- Research Unit, Hospital Universitario Ntra. Sra. de Candelaria, Instituto de Investigación Sanitaria de Canarias, 38010 Santa Cruz de Tenerife, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Genomics Division, Instituto Tecnológico y de Energías Renovables, Granadilla de Abona, 38600 Santa Cruz de Tenerife, Spain
- Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, 35450 Las Palmas de Gran Canaria, Spain
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2
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Gasmi A, Noor S, Menzel A, Khanyk N, Semenova Y, Lysiuk R, Beley N, Bolibrukh L, Gasmi Benahmed A, Storchylo O, Bjørklund G. Potential Drugs in COVID-19 Management. Curr Med Chem 2024; 31:3245-3264. [PMID: 37461346 DOI: 10.2174/0929867331666230717154101] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 05/27/2023] [Accepted: 06/05/2023] [Indexed: 11/18/2023]
Abstract
The SARS-CoV-2 virus first emerged in China in December 2019 and quickly spread worldwide. Despite the absence of a vaccination or authorized drug specifically developed to combat this infection, certain medications recommended for other diseases have shown potential effectiveness in treating COVID-19, although without definitive confirmation. This review aims to evaluate the existing literature on the efficacy of these medications against COVID-19. The review encompasses various potential treatments, including antiviral medications, anti-malaria and anti-rheumatic drugs, vaccines, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), antipyretic and analgesic medicines, antiparasitic drugs, and statins. The analysis also addresses the potential benefits and drawbacks of these medications, as well as their effects on hypertension and diabetes. Although these therapies hold promise against COVID-19, further research, including suitable product production or clinical testing, is needed to establish their therapeutic efficacy.
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Affiliation(s)
- Amin Gasmi
- Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
| | - Sadaf Noor
- Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan
| | | | - Nataliia Khanyk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
- CONEM Ukraine Life Science Research Group, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Yuliya Semenova
- Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Roman Lysiuk
- Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
- CONEM Ukraine Life Science Research Group, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Nataliya Beley
- I. Ya. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
| | | | | | - Olha Storchylo
- Medical Chemistry Department, Odessa National Medical University, Odesa, Ukraine
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway
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Alroqi A, Abaalkhail MB, Albuhayjan N, Alorainy J, Jomah M, Alromaih S, Binkhamis K. Evaluation of Chronic Rhinosinusitis Symptoms' Severity Following COVID-19 Infection: A Retrospective Analysis. Cureus 2023; 15:e38517. [PMID: 37288207 PMCID: PMC10241694 DOI: 10.7759/cureus.38517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2023] [Indexed: 06/09/2023] Open
Abstract
Objectives This study aims to compare the severity of chronic rhinosinusitis (CRS) symptoms pre- and post-COVID-19 infection and estimate the impact of the COVID-19 pandemic on the use of intranasal corticosteroids (ICS) among adult CRS patients. Methods This was an observational retrospective cohort study conducted at King Abdulaziz University Hospital, Riyadh, Saudi Arabia, between July 2022 and October 2022. Adult CRS patients with sino-nasal outcomes test-22 (SNOT-22) scores documented prior to March 2020, marking the occurrence of Saudi Arabia's initial reported case of COVID-19, were requested to complete the SNOT-22 questionnaire following COVID-19 infection. A comparison was subsequently made between the two scores obtained. Results The study enrolled a total of 33 patients, with 16 assigned to the control group and 17 with a history of COVID-19 infection. The mean age of the patients was 43 years, and the majority (52%) were males. Statistical analysis did not reveal any statistically significant differences in the total SNOT-22 scores or domain-level scores between the two groups. Furthermore, the use of ICS during the COVID-19 pandemic did not show any significant associations, except for patients with asthma, where 80% of them used ICS during the pandemic (p=0.0073). Conclusion There was no statistically significant disparity observed in the SNOT-22 scores between patients who tested positive for COVID-19 and those who did not. The use of corticosteroids during the COVID-19 pandemic was found to be more prevalent in this study compared to previous studies conducted before the pandemic, particularly among patients with asthma. The use of ICS during the pandemic was not associated with the presence of polyps, functional endoscopic sinus surgery (FESS), allergic rhinitis, or eczema.
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Affiliation(s)
- Ahmad Alroqi
- Otolaryngology-Head & Neck Surgery, King Saud University, Riyadh, SAU
| | | | - Nawaf Albuhayjan
- Otolaryngology-Head & Neck Surgery, King Saud University, Riyadh, SAU
| | - Jehad Alorainy
- Otolaryngology-Head & Neck Surgery, King Saud University, Riyadh, SAU
| | - Mohammed Jomah
- Otolaryngology-Head & Neck Surgery, King Saud University, Riyadh, SAU
| | - Saud Alromaih
- Otolaryngology-Head & Neck Surgery, King Saud University, Riyadh, SAU
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Usman M, Khadka S, Saleem M, Rasheed H, Kunwar B, Ali M. Pharmacometrics: A New Era of Pharmacotherapy and Drug Development in Low- and Middle-Income Countries. Adv Pharmacol Pharm Sci 2023; 2023:3081422. [PMID: 36925562 PMCID: PMC10014156 DOI: 10.1155/2023/3081422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 02/04/2023] [Accepted: 02/25/2023] [Indexed: 03/09/2023] Open
Abstract
Pharmacotherapy, in many cases, is practiced at a suboptimal level of performance in low- and middle-income countries (LMICs) although stupendous amounts of data are available regularly. The process of drug development is time-consuming, costly, and is also associated with loads of hurdles related to the safety concerns of the compounds. This review was conducted with the objective to emphasize the role of pharmacometrics in pharmacotherapy and the drug development process in LMICs for rational drug therapy. Pharmacometrics is widely applied for the rational clinical pharmacokinetic (PK) practice through the population pharmacokinetic (popPK) modeling and physiologically based pharmacokinetic (PBPK) modeling approach. The scope of pharmacometrics practice is getting wider day by day with the untiring efforts of pharmacometricians. The basis for pharmacometrics analysis is the computer-based modeling and simulation of pharmacokinetics/pharmacodynamics (PK/PD) data supplemented by characterization of important aspects of drug safety and efficacy. Pharmacometrics can be considered an invaluable tool not only for new drug development with maximum safety and efficacy but also for dose optimization in clinical settings. Due to the convenience of using sparse and routine patient data, a significant advantage exists in this regard for LMICs which would otherwise lag behind in clinical trials.
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Affiliation(s)
- Muhammad Usman
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Sitaram Khadka
- Shree Birendra Hospital, Nepalese Army Institute of Health Sciences, Kathmandu, Nepal
| | - Mohammad Saleem
- Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan
| | - Huma Rasheed
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Bimal Kunwar
- Nobel College, Pokhara University, Kathmandu, Nepal
| | - Moshin Ali
- Faculty of Pharmaceutical Sciences, Govt. College University, Faisalabad, Pakistan
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Comparison of Different Antiviral Regimens in the Treatment of Patients with Severe COVID-19: A Retrospective Cohort. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020260. [PMID: 36837462 PMCID: PMC9962820 DOI: 10.3390/medicina59020260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/21/2023] [Accepted: 01/26/2023] [Indexed: 02/03/2023]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disorders, with disease severity ranging from asymptomatic to critical manifestations. The current retrospective study compared the efficacies of different antiviral regimens used in patients suffering from severe COVID-19 disease from 19 January 2020 to December 2021 in a single center in Saudi Arabia. In total, 188 patients were enrolled in the current study, including 158 patients treated with different antiviral regimens, and 30 who did not receive any antiviral treatment. Different antiviral regimens, including favipiravir, remdesivir, oseltamivir, favipiravir/remdesivir, and favipiravir/oseltamivir were adopted. The effects of using different antivirals and antibiotics on the survival rate were evaluated, as well as the presence of comorbidities. Among all severely affected patients, 39/188 (20.7%) survived. Both age and comorbidities, including diabetes and hypertension, were significantly correlated with high case fatality following SARS-CoV-2 infection. Remdesivir alone and the combination of favipiravir and remdesivir increased the survival rate. Surprisingly, both imipenem and linezolid helped in the deterioration of disease outcome in the patients. A negative correlation was detected between increased mortality and the use of favipiravir and the use of either imipenem or linezolid. Among the compared antiviral regimens used in the treatment of severe COVID-19, remdesivir was found to be an effective antiviral that reduces COVID-19 case fatality. Antibiotic treatment using imipenem and/or linezolid should be carefully re-evaluated.
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Elekhnawy E, Negm WA, El-Sherbeni SA, Zayed A. Assessment of drugs administered in the Middle East as part of the COVID-19 management protocols. Inflammopharmacology 2022; 30:1935-1954. [PMID: 36018432 PMCID: PMC9411846 DOI: 10.1007/s10787-022-01050-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 08/03/2022] [Indexed: 02/06/2023]
Abstract
The pandemic spread of coronavirus (COVID-19) has been reported first at the end of 2019. It continues disturbing various human aspects with multiple pandemic waves showing more fatal novel variants. Now Egypt faces the sixth wave of the pandemic with controlled governmental measures. COVID-19 is an infectious respiratory disease-causing mild to moderate illness that can be progressed into life-threatening complications based on patients- and variant type-related factors. The symptoms vary from dry cough, fever to difficulty in breathing that required urgent hospitalization. Most countries have authorized their national protocols for managing manifested symptoms and thus lowering the rate of patients' hospitalization and boosting the healthcare systems. These protocols are still in use even with the development and approval of several vaccines. These protocols were instructed to aid home isolation, bed rest, dietary supplements, and additionally the administration of antipyretic, steroids, and antiviral drugs. The current review aimed to highlight the administered protocols in the Middle East, namely in Egypt and the Kingdom of Saudi Arabia demonstrating how these protocols have shown potential effectiveness in treating patients and saving many soles.
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Affiliation(s)
- Engy Elekhnawy
- Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Elguish Street (Medical Campus), Tanta, 31527 Egypt
| | - Walaa A. Negm
- Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Elguish Street (Medical Campus), Tanta, 31527 Egypt
| | - Suzy A. El-Sherbeni
- Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Elguish Street (Medical Campus), Tanta, 31527 Egypt
| | - Ahmed Zayed
- Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Elguish Street (Medical Campus), Tanta, 31527 Egypt
- Institute of Bioprocess Engineering, Technical University of Kaiserslautern, Gottlieb-Daimler-Straße 49, 67663 Kaiserslautern, Germany
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Jou E, Zhou AK, Ho JSY, Thahir A. Perioperative use of intra-articular steroids during the COVID-19 pandemic. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY & TRAUMATOLOGY : ORTHOPEDIE TRAUMATOLOGIE 2022; 32:1225-1235. [PMID: 34468841 PMCID: PMC8408365 DOI: 10.1007/s00590-021-03105-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 08/23/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE There are growing concerns with the widely used glucocorticoids during the Coronavirus disease-19 (COVID-19) pandemic due to the associated immunosuppressive effects, which may increase the risk of COVID-19 infection and worsen COVID-19 patient outcome. Heavily affecting orthopaedics, the pandemic led to delay and cancellation of almost all surgical cases, and procedures including perioperative intra-articular corticosteroid injections (ICIs) saw similar decreases. However, the benefits of ICI treatments during the pandemic may outweigh these potential risks, and their continued use may be warranted. METHODS A literature search was conducted, and all relevant articles including original articles and reviews were identified and considered in full for inclusion, and analysed with expert opinion. Epidemiological statistics and medical guidelines were consulted from relevant authorities. RESULTS ICIs allow a targeted approach on the affected joint and are effective in reducing pain while improving functional outcome and patient quality-of-life. ICIs delay the requirement for surgery, accommodating for the increased healthcare burden during the pandemic, while reducing postoperative hospital stay, bringing significant financial benefits. However, ICIs can exert systemic effects and suppress the immune system. ICIs may increase the risk of COVID-19 infection and reduce the efficacy of COVID-19 vaccinations, leading to important public health implications. CONCLUSION Perioperative ICI treatments may bring significant, multifaceted benefits during the pandemic. However, ICIs increase the risk of infection, and perioperative COVID-19 is associated with mortality. The use of ICIs during the COVID-19 pandemic should therefore be considered carefully on an individual patient basis, weighing the associated risks and benefits.
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Affiliation(s)
- Eric Jou
- School of Clinical Medicine, University of Cambridge, Cambridge, UK.
- MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
| | | | | | - Azeem Thahir
- School of Clinical Medicine, University of Cambridge, Cambridge, UK
- Department of Trauma and Orthopaedic Surgery, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Ferreira-da-Silva R, Ribeiro-Vaz I, Morato M, Junqueira Polónia J. A comprehensive review of adverse events to drugs used in COVID-19 patients: Recent clinical evidence. Eur J Clin Invest 2022; 52:e13763. [PMID: 35224719 PMCID: PMC9111855 DOI: 10.1111/eci.13763] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 02/16/2022] [Accepted: 02/20/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND Since the breakthrough of the pandemic, several drugs have been used to treat COVID-19 patients. This review aims to gather information on adverse events (AE) related to most drugs used in this context. METHODS We performed a literature search to find articles that contained information about AE in COVID-19 patients. We analysed and reviewed the most relevant studies in the Medline (via PubMed), Scopus and Web of Science. The most frequent AE identified were grouped in our qualitative analysis by System Organ Class (SOC), the highest level of the MedDRA medical terminology for each of the drugs studied. RESULTS The most frequent SOCs among the included drugs are investigations (n = 7 drugs); skin and subcutaneous tissue disorders (n = 5 drugs); and nervous system disorders, infections and infestations, gastrointestinal disorders, hepatobiliary disorders, and metabolism and nutrition disorders (n = 4 drugs). Other SOCs also emerged, such as general disorders and administration site conditions, renal and urinary disorders, vascular disorders and cardiac disorders (n = 3 drugs). Less frequent SOC were eye disorders, respiratory, thoracic and mediastinal disorders, musculoskeletal and connective tissue disorders, and immune system disorders (n = 2 drugs). Psychiatric disorders, and injury, poisoning and procedural complications were also reported (n = 1 drug). CONCLUSIONS Some SOCs seem to be more frequent than others among the COVID-19 drugs included, although neither of the studies included reported causality analysis. For that purpose, further clinical studies with robust methodologies, as randomised controlled trials, should be designed and performed.
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Affiliation(s)
- Renato Ferreira-da-Silva
- Porto Pharmacovigilance Centre, INFARMED, I.P, University of Porto, Porto, Portugal.,Department of Community Medicine, Health Information and Decision, University of Porto, Porto, Portugal.,CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Inês Ribeiro-Vaz
- Porto Pharmacovigilance Centre, INFARMED, I.P, University of Porto, Porto, Portugal.,Department of Community Medicine, Health Information and Decision, University of Porto, Porto, Portugal.,CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Manuela Morato
- LAQV/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, University of Porto, Porto, Portugal
| | - Jorge Junqueira Polónia
- Porto Pharmacovigilance Centre, INFARMED, I.P, University of Porto, Porto, Portugal.,CINTESIS - Center for Health Technology and Services Research, Porto, Portugal.,Department of Medicine, University of Porto, Porto, Portugal
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Dwivedi S, Choudhary P, Gupta A, Singh S. The cross-talk between mucormycosis, steroids and diabetes mellitus amidst the global contagion of COVID-19. Crit Rev Microbiol 2022; 49:318-333. [PMID: 35324372 DOI: 10.1080/1040841x.2022.2052795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Mucormycosis is an opportunistic fungal disease that targets individuals having an impaired immune system due to a wide array of risk factors including HIV-AIDS, immunosuppressive therapy, diabetes mellitus, etc. The current explosive outbreak of coronavirus disease 2019 (COVID-19) has become the latest threat to such patients who are already susceptible to secondary infections. Physiological outcomes of COVID-19 end up in a cascade of grave alterations to the immunological profile and irreparable harm to their respiratory passage, heart and kidneys. Corticosteroidal treatment facilitates faster recovery and alleviates the adverse pathological effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But clinical reports lend this approach a darker perspective especially if these patients have pre-existing diabetes mellitus. The mucormycotic fungal genera belonging to the order Mucorales not only survive but thrive under the comorbidity of COVID-19 and diabetes, often staying undetected until they have inflicted irreversible damage. Steroidal usage has been noted to be a common thread in the sudden spurt in secondary fungal infections among COVID-19 cases. Once considered a rare occurrence, mucormycosis has now acquired a notoriously lethal status in mainstream medical hierarchy. We set out to investigate whether corticosteroidal therapy against COVID-19 emboldens the development of mucormycosis. We also assess the conditions brought forth by steroidal usage and uncontrolled progression of diabetes in COVID-19 cases and their effect on the susceptibility towards mucormycosis.
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Affiliation(s)
- Shrey Dwivedi
- Department of Applied Science, Indian Institute of Information Technology, Allahabad, India
| | - Princy Choudhary
- Department of Applied Science, Indian Institute of Information Technology, Allahabad, India
| | - Ayushi Gupta
- Department of Applied Science, Indian Institute of Information Technology, Allahabad, India
| | - Sangeeta Singh
- Department of Applied Science, Indian Institute of Information Technology, Allahabad, India
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Faour WH, Choaib A, Issa E, Choueiry FE, Shbaklo K, Alhajj M, Sawaya RT, Harhous Z, Alefishat E, Nader M. Mechanisms of COVID-19-induced kidney injury and current pharmacotherapies. Inflamm Res 2022; 71:39-56. [PMID: 34802072 PMCID: PMC8606168 DOI: 10.1007/s00011-021-01520-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/31/2021] [Accepted: 11/01/2021] [Indexed: 01/08/2023] Open
Abstract
The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.
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Affiliation(s)
- Wissam H Faour
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon.
| | - Ali Choaib
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Elio Issa
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Francesca El Choueiry
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Khodor Shbaklo
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Maryline Alhajj
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Ramy Touma Sawaya
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Zeina Harhous
- Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Eman Alefishat
- Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman, Jordan
| | - Moni Nader
- Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi, United Arab Emirates.
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
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11
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Alrashed F, Battat R, Abdullah I, Charabaty A, Shehab M. Impact of medical therapies for inflammatory bowel disease on the severity of COVID-19: a systematic review and meta-analysis. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000774. [PMID: 34725056 PMCID: PMC8561831 DOI: 10.1136/bmjgast-2021-000774] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 10/15/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND During COVID-19 pandemic, the safety of medical therapies for inflammatory bowel disease (IBD) in relation to COVID-19 has emerged as an area of concern. This study aimed to evaluate the association between IBD therapies and severe COVID-19 outcomes. METHOD We performed a systematic review and meta-analysis of all published studies from December 2019 to August 2021 to identify studies that reported severe COVID-19 outcomes in patients on current IBD therapies including 5-aminosalicylic acid (5-ASA), immunomodulators, corticosteroids, biologics, combination therapy, or tofacitinib. RESULTS Twenty-two studies were identified. Corticosteroids (risk ratio (RR) 1.91 (95% CI 1.25 to 2.91, p=0.003)) and 5-ASA (RR 1.50 (95% CI 1.17 to 1.93, p=0.001)) were associated with increased risk of severe COVID-19 outcomes in patients with IBD patients. However, possible confounders for 5-ASA use were not controlled for. Sub-analysis showed that corticosteroids increased the risk of intensive care unit (ICU) admission but not mortality. Immunomodulators alone (RR 1.18 (95% CI 0.87 to 1.59, p=0.28)) or in combination with anti-TNFs ((RR 0.96 (95% CI 0.80 to 1.15, p=0.63)), tofacitinib (RR 0.81 (95% CI 0.49 to 1.33, p=0.40)) and vedolizumab ((RR 1.02 (95% CI 0.79 to 1.31, p=0.89)) were not associated with severe disease. Anti-TNFs (RR 0.47 (95% CI 0.40 to 0.54, p<0.00001)) and ustekinumab (RR 0.55 (95% CI 0.43 to 0.72, p<0.00001)) were associated with decreased risk of severe COVID-19. CONCLUSION In patients with IBD, the risk of severe COVID-19 is higher among patients receiving corticosteroids. Corticosteroid use was associated with ICU admission but not mortality. The risk is also higher among patients receiving 5-ASAs. However, patient-level data were lacking and insufficient data existed for meta-regression analyses to adjust for confounding. Vedolizumab, tofacitinib, and immunomodulators alone or in combination with anti-TNF were not associated with severe disease. Anti-TNFs, and ustekinumab were associated with favourable outcomes.
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Affiliation(s)
- Fatema Alrashed
- Pharmacy Practice, MCPHS University, Boston, Massachusetts, USA
| | - Robert Battat
- Department of Medicine, Weill Cornell Medical College, New York, New York, USA
| | - Israa Abdullah
- Department of Pharmacy Practice, Kuwait University, Kuwait, Kuwait
| | - Aline Charabaty
- Division of gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Mohammad Shehab
- Department of Internal Medicine, Kuwait University, Kuwait, Kuwait
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Xu X, Reitsma S, Wang DY, Fokkens WJ. Highlights in the advances of chronic rhinosinusitis. Allergy 2021; 76:3349-3358. [PMID: 33948955 DOI: 10.1111/all.14892] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/15/2021] [Accepted: 04/26/2021] [Indexed: 12/27/2022]
Abstract
Chronic rhinosinusitis (CRS) is a complex upper airway inflammatory disease with a broad spectrum of clinical variants. As our understanding of the disease pathophysiology evolves, so too does our philosophy towards the approach and management of CRS. Endotyping is gaining favour over phenotype-based classifications, owing to its potential in prognosticating disease severity and delivering precision treatment. Endotyping is especially useful in challenging CRS with nasal polyposis cases, for whom novel treatment options such as biologicals are now available. The latest European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2020) reflects these changes with updated rhinosinusitis classifications and new integrated care pathways. With the coronavirus disease 2019 (COVID-19) pandemic, physicians and rhinologists have to balance the responsibility of managing their patients' upper airway while adequately protecting themselves from droplet and aerosol transmission. This review summarises the key updates from EPOS2020, endotype-based classification and biomarkers. The role of biologicals in CRS and the lessons we can draw from their use in severe asthma will be examined. Finally, the principles of CRS management during COVID-19 will also be discussed.
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Affiliation(s)
- Xinni Xu
- Department of Otolaryngology ‐ Head & Neck Surgery National University Hospital Singapore Singapore
| | - Sietze Reitsma
- Department of Otorhinolaryngology Amsterdam University Medical Centers, location AMC Amsterdam The Netherlands
| | - De Yun Wang
- Department of Otolaryngology, Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore
| | - Wytske J. Fokkens
- Department of Otorhinolaryngology Amsterdam University Medical Centers, location AMC Amsterdam The Netherlands
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13
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Abstract
Pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced COVID-19 implied the presence of excessive proinflammatory cytokines and chemokines in patients causing significant morbidity and mortality. To diminish systemic hyper inflammation, a few physicians and researchers have utilized corticosteroids. Corticosteroid implementation has increased after the publication of interim guidelines regarding corticosteroid use in COVID-19 patients by WHO, despite the remaining controversies regarding long-term side effects and disease progression capability of corticosteroids. In different studies, the implementation of corticosteroids on COVID-19 patients revealed controversial results, which require further intensive research. This review will present the current outcomes and possibilities of using corticosteroids to treat COVID-19 patients.
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14
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Ashktorab H, Folake A, Pizuorno A, Oskrochi G, Oppong-Twene P, Tamanna N, Mehdipour Dalivand M, Umeh LN, Moon ES, Kone AM, Banson A, Federman C, Ramos E, Awoyemi EO, Wonni BJ, Otto E, Maskalo G, Velez AO, Rankine S, Thrift C, Ekwunazu C, Scholes D, Chirumamilla LG, Ibrahim ME, Mitchell B, Ross J, Curtis J, Kim R, Gilliard C, Mathew J, Laiyemo A, Kibreab A, Lee E, Sherif Z, Shokrani B, Aduli F, Brim H. COVID-19 among African Americans and Hispanics: Does gastrointestinal symptoms impact the outcome? World J Clin Cases 2021; 9:8374-8387. [PMID: 34754847 PMCID: PMC8554449 DOI: 10.12998/wjcc.v9.i28.8374] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 07/19/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) disproportionately affected African Americans (AA) and Hispanics (HSP). AIM To analyze the significant effectors of outcome in African American patient population and make special emphasis on gastrointestinal (GI) symptoms, laboratory values and comorbidities. METHODS We retrospectively evaluated the medical records of 386 COVID-19 positive patients admitted at Howard University Hospital between March and May 2020. We assessed the symptoms, including the GI manifestations, comorbidities, and mortality, using logistic regression analysis. RESULTS Of these 386 COVID-19 positive patients, 257 (63.7%) were AAs, 102 (25.3%) HSP, and 26 (6.45%) Whites. There were 257 (63.7%) AA, 102 (25.3%) HSP, 26 (6.45%) Whites. The mean age was 55.6 years (SD = 18.5). However, the mean age of HSP was the lowest (43.7 years vs 61.2 for Whites vs 60 for AAs). The mortality rate was highest among the AAs (20.6%) and lowest among HSP (6.9%). Patients with shortness of breath (SOB) (OR2 = 3.64, CI = 1.73-7.65) and elevated AST (OR2 = 8.01, CI = 3.79-16.9) elevated Procalcitonin (OR2 = 8.27, CI = 3.95-17.3), AST (OR2 = 8.01, CI = 3.79-16.9), ferritin (OR2 = 2.69, CI = 1.24-5.82), and Lymphopenia (OR2 = 2.77, CI = 1.41-5.45) had a high mortality rate. Cough and fever were common but unrelated to the outcome. Hypertension and diabetes mellitus were the most common comorbidities. Glucocorticoid treatment was associated with higher mortality (OR2 = 5.40, CI = 2.72-10.7). Diarrhea was prevalent (18.8%), and GI symptoms did not affect the outcome. CONCLUSION African Americans in our study had the highest mortality as they consisted of an older population and comorbidities. Age is the most important factor along with SOB in determining the mortality rate. Overall, elevated liver enzymes, ferritin, procalcitonin and C-reactive protein were associated with poor prognosis. GI symptoms did not affect the outcome. Glucocorticoids should be used judiciously, considering the poor outcomes associated with it. Attention should also be paid to monitor liver function during COVID-19, especially in AA and HSP patients with higher disease severity.
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Affiliation(s)
- Hassan Ashktorab
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Adeleye Folake
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Antonio Pizuorno
- Faculty of Medicine, La Universidad del Zulia, Maracaibo 4002, Zulia, Venezuela
| | - Gholamreza Oskrochi
- College of Engineering and Technology, American University of Middle East Kuwait, Egaila 54200, Kuwait
| | - Philip Oppong-Twene
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Nuri Tamanna
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Maryam Mehdipour Dalivand
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Lisa N Umeh
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Esther S Moon
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Abdoul Madjid Kone
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Abigail Banson
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Cassandra Federman
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Edward Ramos
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Eyitope Ola Awoyemi
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Boubini Jones Wonni
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Eric Otto
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Guttu Maskalo
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Alexandra Ogando Velez
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Sheldon Rankine
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Camelita Thrift
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Chiamaka Ekwunazu
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Derek Scholes
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Lakshmi Gayathri Chirumamilla
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Mohd Elmugtaba Ibrahim
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Brianna Mitchell
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Jillian Ross
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Julencia Curtis
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Rachel Kim
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Chandler Gilliard
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Joseph Mathew
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Adeyinka Laiyemo
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Angesum Kibreab
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Edward Lee
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Zaki Sherif
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
- Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC 20060, United States
| | - Babak Shokrani
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Farshad Aduli
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC 20060, United States
| | - Hassan Brim
- Pathology and Cancer Center, Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC 20060, United States
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15
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Iturricastillo G, Ávalos Pérez-Urría E, Couñago F, Landete P. Scientific evidence in the COVID-19 treatment: A comprehensive review. World J Virol 2021; 10:217-228. [PMID: 34631473 PMCID: PMC8474978 DOI: 10.5501/wjv.v10.i5.217] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/12/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
In December 2019, cases of unknown origin pneumonia appeared in Wuhan, China; the causal agent of this pneumonia was a new virus of the coronaviridae family called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). According to the clinical severity, symptoms and response to the different treatments, the evolution of the disease is divided in three phases. We analysed the most used treatments for coronavirus disease 2019 and the phase in which they are supposed to be effective. In the viral phase, remdesivir has demonstrated reduction in recovery time but no mortality reduction. Other drugs proposed for viral phase such as convalescent plasma and lopinavir/ritonavir did not demonstrate to be effective. In the inflammatory phase, corticosteroids demonstrated reduction of 28-d mortality in patients who needed oxygen, establishing that a corticosteroid regimen should be part of the standard treatment of critically ill patients. There are other immunosuppressive and immunomodulatory treatments such as anakinra, sarilumab, tocilizumab, colchicine or baricitinib that are being studied. Other treatments that were proposed at the beginning, like hydroxichloroquine or azithromycin, demonstrated no efficacy and increased mortality when combined.
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Affiliation(s)
- Gorane Iturricastillo
- Department of Pulmonology, Hospital Universitario de La Princesa, Madrid 28006, Spain
| | | | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón 28223, Spain
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
- Department of Radiation Oncology Universidad Europea de Madrid, Madrid 28670, Spain
| | - Pedro Landete
- Department of Pulmonology, Hospital Universitario de La Princesa, Madrid 28006, Spain
- Department of Pulmonology, Universidad Autónoma de Madrid, Madrid 28049, Spain
- Department of Pulmonology, Instituto Investigación Princesa, Madrid 28006, Spain
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16
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Baslilar S, Saylan B. Patients with hypertension hospitalized with COVID-19 pneumonia using angiotensinconverting enzyme inhibitors and angiotensin II receptor blockers or other antihypertensives: retrospective analysis of 435 patients. Ann Saudi Med 2021; 41:268-273. [PMID: 34618609 PMCID: PMC8497007 DOI: 10.5144/0256-4947.2021.268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension (HT). Whether the use of these drugs increases the infectivity of novel coronavirus and results in an additional risk for morbidity and mortality of COVID-19 is a matter of interest. OBJECTIVES Assess the effect of ACEI/ARBs compared with other hypertensives on the clinical course and outcome in COVID-19 pneumonia. DESIGN Retrospective. SETTINGS Tertiary care hospital. PATIENTS AND METHODS We collected data on adult inpatients with COVID-19 pneumonia using ACEI/ARBs versus other antihypertensives between 15 March 2020, and 15 February 2021. MAIN OUTCOME MEASURES Severity, clinical course, mortality, and time to PCR negativity between patients using ACEI/ARBs and other antihypertensives. SAMPLE SIZE 435 RESULTS: ACEI/ARBs were used by 203 patients (46.6%) (median age: 71 [41-94] years), while 232 patients (53.4%) were using other antihypertensives (median age: 69 [22-93] years, P=.645 vs age of ACEI/ARB users). There were no statistically significant differences between the ACEI/ARBs users and non-users in the number of patients admitted to intensive care (65 cases [32%] vs. 74 cases [31.9%], P=.978), the median duration of stay in hospital (8 [1-54] days vs.7 [1-55] days, P=.806) the median duration of ICU stay (8 [1-40] days vs. 6 [1-25] days), and the mortality rate (48 cases [23.6%] vs. 61 [26.3%], P=.525). While the median days before transfer to the ICU was shorter in ACE/ARBI non-users (2 [1-15] days vs. 3 [1-21] days, P=.02), the difference was not important clinically. The median time to PCR negativity was similar in ACEI/ARBs users and non-users (13 [7-34] days for users and 13 [5-45] days for non-users), (P=.083). CONCLUSIONS ACEI/ARB use is probably unrelated to poor prognosis in COVID-19 pneumonia inpatients. ACEI/ARBs did not prolong the time to PCR negativity. We conclude that using ACEI/ARBs probably does not increase the infectivity of SARS-CoV-2. LIMITATIONS Pharmacological therapies were not discussed in detail. The use of corticosteroids may affect the time to PCR negativity. We could not analyze the effect of obesity because of a lack of data. CONFLICT OF INTEREST None.
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Affiliation(s)
- Seyma Baslilar
- From the Department of Pulmonology, Umraniye Training and Research Hospital, Istanbul, Turkey
| | - Bengu Saylan
- From the Department of Pulmonology, Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey
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17
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Cheng B, Ma J, Yang Y, Shao T, Zhao B, Zeng L. Systemic Corticosteroid Administration in Coronavirus Disease 2019 Outcomes: An Umbrella Meta-Analysis Incorporating Both Mild and Pulmonary Fibrosis-Manifested Severe Disease. Front Pharmacol 2021; 12:670170. [PMID: 34122093 PMCID: PMC8187793 DOI: 10.3389/fphar.2021.670170] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 04/30/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Effective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. The real role of corticosteroid use in COVID-19 has long been of interest and is disputable. Methods: We aimed to quantitatively reevaluate the efficacy of corticosteroids on COVID-19. Databases were searched for eligible meta-analyses/systematic reviews with available outcome data. For each association, we estimated the summary effect size with fixed- and random-effects models, 95% confidence intervals, and 95% prediction intervals. Heterogeneity, Egger’s test, evidence of small-study effects and excess significance bias, and subgroup analyses were rigorously evaluated. Results: Intended outcomes of 12 eligible studies were mortality, clinical improvement, hospitalization, mechanical ventilation (MV), adverse events (AEs), intensive care unit (ICU) stay, hospital stay, virus clearance time (VCT), and negative conversion. Corticosteroid administration was associated with a 27% risk reduction in MV [hazard ratio (HR): 0.73 (0.64–0.83)] and a 20% reduction in mortality of critically ill/severe COVID-19 patients [HR: 0.80 (0.65–0.98)]. Interestingly, shorter ICU stays and, conversely, potentially longer hospital stays, a longer VCT, and a longer time to negative conversion were associated with corticosteroid use. There was no significant impact of different corticosteroid doses on mortality. Only one study showed slightly excess significant bias. Caution should be applied given the weak nature of the evidence, and it has been confirmed by sensitivity analyses too. Conclusion: This umbrella study found benefits from corticosteroids on MV and especially the mortality of critically ill/severe patients with shorter ICU stays but prolonged hospital stays and VCT. The benefits and harms should be reevaluated and balanced before corticosteroids are cautiously prescribed in clinical practice.
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Affiliation(s)
- Bin Cheng
- Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jinxiu Ma
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yani Yang
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Tingting Shao
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Binghao Zhao
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Linxiang Zeng
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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18
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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: 46] [Impact Index Per Article: 11.5] [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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19
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Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Anti-Inflammatory Effects of Amantadine and Memantine: Possible Therapeutics for the Treatment of Covid-19? J Pers Med 2020; 10:jpm10040217. [PMID: 33182350 PMCID: PMC7712421 DOI: 10.3390/jpm10040217] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/04/2020] [Accepted: 11/06/2020] [Indexed: 12/15/2022] Open
Abstract
We have reviewed current data on the anti-inflammatory effects of amantadine and memantine in clinical and in vivo models of inflammation, and we propose that these effects have potential interest for the treatment of the SARS-CoV-2 infection (COVID-19 disease). To that end, we performed a literature search using the PubMed Database from 1966 up to October 31 2020, crossing the terms “amantadine” and “memantine” with “inflammation” and “anti-inflammatory”. Amantadine and/or memantine have shown anti-inflammatory effects in chronic hepatitis C, in neuroinflammation induced by sepsis and by lipopolysaccharides, experimental models of multiple sclerosis, spinal cord injury, and respiratory diseases. Since the inflammatory response is one of the main pathogenetic mechanisms in the progression of the SARS-CoV-2 infection, anti-inflammatory effects of amantadine and memantine could be hypothetically useful in the treatment of this condition. This potential utility deserves further research.
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Affiliation(s)
- Félix Javier Jiménez-Jiménez
- Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, E-28500 Madrid, Spain;
- Correspondence: ; Tel.: +34-636968395
| | - Hortensia Alonso-Navarro
- Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, E-28500 Madrid, Spain;
| | - Elena García-Martín
- University Institute of Molecular Pathology Biomarkers, UNEx. ARADyAL Instituto de Salud Carlos III, E-10071 Cáceres, Spain; (E.G.-M.); (J.A.G.A.)
| | - José A. G. Agúndez
- University Institute of Molecular Pathology Biomarkers, UNEx. ARADyAL Instituto de Salud Carlos III, E-10071 Cáceres, Spain; (E.G.-M.); (J.A.G.A.)
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