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Hussaini H, Rogers S, Kataria S, Uddin K, Mohamed KH, Mohamed AS, Tariq F, Ahmad S, Awais A, Ahmed Z, Chukwurah A, Khan A. COVID-19-Induced Seizures: A Meta-Analysis of Case Series and Retrospective Cohorts. Cureus 2022; 14:e28633. [PMID: 36196331 PMCID: PMC9524720 DOI: 10.7759/cureus.28633] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2022] [Indexed: 11/30/2022] Open
Abstract
The adverse events and complications of coronavirus disease 2019 (COVID-19) continue to challenge the medical profession despite the worldwide vaccination against the severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. Other than typical respiratory manifestations, COVID-19 also presents a wide range of neurological manifestations. This article underlines the pooled incidence of COVID-19-induced seizures in patients with epilepsy and without epilepsy. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, we conducted a bibliographical search, and an initial search revealed 1,375 articles. In total, 21 articles were included in the final analysis by following the inclusion criteria. A total of 11,526 patients from 21 published articles that met the predetermined search criteria were included. The median age of the patients was 61.9 years, of whom 51.5% were males. A total of 255 patients presented with seizures as the first manifestation of COVID-19 with a prevalence of 2.2% (95% confidence interval = 0.05-0.24, p < 0.01) (I2 = 97%), of which 71 patients had previously been diagnosed with epilepsy. Among patients with epilepsy, 49 patients had seizures as an initial presentation of SARA-CoV-2 with an incidence of 72% (0.54-0.85, p = 0.1) (I2 = 34). Although the incidence of COVID-19-induced seizures is not high compared to other neurological manifestations, seizure incidence in epileptic patients with COVID-19 is remarkably high. New-onset seizures in any patient should be considered a presentation of COVID-19 in the absence of other causative factors.
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Tahsini Tekantapeh S, Ghojazadeh M, Ghamari AA, Mohammadi A, Soleimanpour H. Therapeutic and anti-inflammatory effects of baricitinib on mortality, ICU transfer, clinical improvement, and CRS-related laboratory parameters of hospitalized patients with moderate to severe COVID-19 pneumonia: a systematic review and meta-analysis. Expert Rev Respir Med 2022; 16:1109-1132. [PMID: 35981253 DOI: 10.1080/17476348.2022.2114899] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
BACKGROUND Due to the high incidence and mortality of the worldwide COVID-19 pandemic, beneficial effects of effective antiviral and anti-inflammatory drugs used in other diseases, especially rheumatic diseases, were observed in the treatment of COVID-19. METHODS Clinical and laboratory parameters of eight included cohort studies and five Randomized Control Trials between the baricitinib group and the control group were analyzed on the first day of admission and days 7, 14, and 28 during hospitalization. RESULTS According to the meta-analysis result of eight included cohort studies with 2088 patients, the Pooled Risk Ratios were 0.46 (P<0.001) for mortality, 6.14 (P< 0.001) for hospital discharge, and the mean differences of 76.78 (P< 0.001) for PaO2/FiO2 ratio was -47.32 (P= 0.02) for CRP, in the baricitinib group vs. control group on the seventh or fourteenth day of the treatment compared to the first day. Based on the meta-analysis of five RCT studies with 11825 patients, the pooled RR was 0.84 (P= 0.001) for mortality and 1.07 (P= 0.014) for patients' recovery. The mean differences were -0.80 (P<0.001) for hospitalization days, -0.51(P= 0.33) for time to recovery in the baricitinib group vs. control group. CONCLUSIONS Baricitinib prescription is strongly recommended in moderate to severe COVID-19. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number: CRD42021254541.
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Affiliation(s)
| | - Morteza Ghojazadeh
- Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Akbar Ghamari
- Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aida Mohammadi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Soleimanpour
- Road Traffic Injury research center, Tabriz university of medical sciences, Tabriz, Iran
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Punekar M, Kshirsagar M, Tellapragada C, Patil K. Repurposing of antiviral drugs for COVID-19 and impact of repurposed drugs on the nervous system. Microb Pathog 2022; 168:105608. [PMID: 35654381 PMCID: PMC9160731 DOI: 10.1016/j.micpath.2022.105608] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 04/11/2022] [Accepted: 05/28/2022] [Indexed: 12/19/2022]
Abstract
The recent pandemic, Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has devastated humanity and is continuing to threaten us. Due to the high transmissibility of this pathogen, researchers are still trying to cope with the treatment and prevention of this disease. Few of them were successful in finding cure for COVID-19 by including repurposed drugs in the treatment. In such pandemic situations, when it is nearly impossible to design and implement a new drug target, previously designed antiviral drugs could help against novel viruses, referred to as drug repurposing/redirecting/repositioning or re-profiling. This review describes the current landscape of the repurposing of antiviral drugs for COVID-19 and the impact of these drugs on our nervous system. In some cases, specific antiviral therapy has been notably associated with neurological toxicity, characterized by peripheral neuropathy, neurocognitive and neuropsychiatric effects within the central nervous system (CNS).
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Affiliation(s)
- Madhura Punekar
- ICMR National Institute of Virology, 20-A, P B No 11, Dr Ambedkar Road, Pune, 411001, Maharashtra, India.
| | - Manas Kshirsagar
- Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, the Netherlands.
| | - Chaitanya Tellapragada
- Division of Clinical Microbiology, Department of Laboratory Medicine (LABMED), Karolinska Institutet, Solnavägen 1, 171 77, Stockholm, Sweden.
| | - Kanchankumar Patil
- ICMR National Institute of Virology, 20-A, P B No 11, Dr Ambedkar Road, Pune, 411001, Maharashtra, India.
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Plassmeyer M, Alpan O, Corley MJ, Premeaux TA, Lillard K, Coatney P, Vaziri T, Michalsky S, Pang APS, Bukhari Z, Yeung ST, Evering TH, Naughton G, Latterich M, Mudd P, Spada A, Rindone N, Loizou D, Ulrik Sønder S, Ndhlovu LC, Gupta R. Caspases and therapeutic potential of caspase inhibitors in moderate-severe SARS-CoV-2 infection and long COVID. Allergy 2022; 77:118-129. [PMID: 33993490 PMCID: PMC8222863 DOI: 10.1111/all.14907] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND COVID-19 can present with lymphopenia and extraordinary complex multiorgan pathologies that can trigger long-term sequela. AIMS Given that inflammasome products, like caspase-1, play a role in the pathophysiology of a number of co-morbid conditions, we investigated caspases across the spectrum of COVID-19 disease. MATERIALS & METHODS We assessed transcriptional states of multiple caspases and using flow cytometry, the expression of active caspase-1 in blood cells from COVID-19 patients in acute and convalescent stages of disease. Non-COVID-19 subject presenting with various comorbid conditions served as controls. RESULTS Single-cell RNA-seq data of immune cells from COVID-19 patients showed a distinct caspase expression pattern in T cells, neutrophils, dendritic cells, and eosinophils compared with controls. Caspase-1 was upregulated in CD4+ T-cells from hospitalized COVID-19 patients compared with unexposed controls. Post-COVID-19 patients with lingering symptoms (long-haulers) also showed upregulated caspase-1activity in CD4+ T-cells that ex vivo was attenuated with a select pan-caspase inhibitor. We observed elevated caspase-3/7levels in red blood cells from COVID-19 patients compared with controls that was reduced following caspase inhibition. DISCUSSION Our preliminary results suggest an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Further clinical correlations of caspase expression in different stages of COVID-19 will be needed. CONCLUSION Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19.
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Affiliation(s)
| | | | - Michael J. Corley
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Thomas A. Premeaux
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | | | | | | | | | - Alina P. S. Pang
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Zaheer Bukhari
- S.U.N.Y. Downstate Health Sciences University Brooklyn NY USA
| | - Stephen T. Yeung
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Teresa H. Evering
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | | | | | - Philip Mudd
- Department of Emergency Medicine Washington University School of Medicine Saint Louis MO USA
| | | | | | | | | | - Lishomwa C. Ndhlovu
- Department of Medicine Division of Infectious Diseases Weill Cornell Medicine New York City NY USA
| | - Raavi Gupta
- S.U.N.Y. Downstate Health Sciences University Brooklyn NY USA
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Abu-El-Rub E, Khasawneh RR, Almahasneh F, Altaany Z, Bataineh N, Zegallai H, Sekaran S. Mesenchymal stem cells and COVID-19: What they do and what they can do. World J Stem Cells 2021; 13:1318-1337. [PMID: 34630865 PMCID: PMC8474724 DOI: 10.4252/wjsc.v13.i9.1318] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 06/15/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) pandemic has exhausted the health systems in many countries with thousands cases diagnosed daily. The currently used treatment guideline is to manage the common symptoms like fever and cough, but doesn't target the virus itself or halts serious complications arising from this viral infection. Currently, SARS-CoV-2 exhibits many genetic modulations which have been associated with the appearance of highly contagious strains. The number of critical cases of COVID-19 increases markedly, and many of the infected people die as a result of respiratory failure and multiple organ dysfunction. The regenerative potential of mesenchymal stem cells (MSCs) has been extensively studied and confirmed. The impressive immunomodulation and anti-inflammatory activity of MSCs have been recognized as a golden opportunity for the treatment of COVID-19 and its associated complications. Moreover, MSCs regenerative and repairing abilities have been corroborated by many studies with positive outcomes and high recovery rates. Based on that, MSCs infusion could be an effective mechanism in managing and stemming the serious complications and multiple organ failure associated with COVID-19. In the present review, we discuss the commonly reported complications of COVID-19 viral infection and the established and anticipated role of MSCs in managing these complications.
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Affiliation(s)
- Ejlal Abu-El-Rub
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg R2H2A6, Canada
- Department of Physiology and Pathophysiology, Basic Medical Sciences, Yarmouk University, IRBID 21163, Jordan.
| | - Ramada R Khasawneh
- Department of Anatomy and Histology, Basic Medical Sciences, Yarmouk University, IRBID 21163, Jordan
| | - Fatimah Almahasneh
- Department of Physiology and Pharmacology, Basic Medical Sciences, Yarmouk University, IRBID 21163, Jordan
| | - Zaid Altaany
- Department of Biochemistry and Genetics, Basic Medical Sciences, Yarmouk University, IRBID 21163, Jordan
| | - Nesreen Bataineh
- Department of Pathology, Basic Medical Sciences, Yarmouk University, IRBID 21163, Jordan
| | - Hana Zegallai
- Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg R2H2A6, Canada
| | - Saravanan Sekaran
- Department of Pharmacology, Saveetha Dental College and Hospitals to be University, Chennai 600077, India
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Sarmast ST, Mohamed AS, Amar Z, Sarwar S, Ahmed Z. A Case of Acute Encephalitis in COVID-19 Patient: A Rare Complication. Cureus 2021; 13:e15636. [PMID: 34306848 PMCID: PMC8279905 DOI: 10.7759/cureus.15636] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/14/2021] [Indexed: 12/17/2022] Open
Abstract
Coronavirus disease 19 (COVID-19) is a respiratory disease, has a variable presentation, and neurological involvement in COVID-19 is not widely reported. We report a rare case of acute encephalitis in a COVID-19 patient presented with fever, dry cough, and dyspnea. She had a fever, tachypnea, and tachycardia. On auscultation, she had scattered wheezing in both lung fiends. Chest X-ray revealed small infiltrates in the lower lobe of both lungs. A nasopharyngeal swab for the COVID-19 polymerase chain reaction was positive. Later on, she developed sudden onset confusion accompanied by restlessness and visual hallucinations. Neurological examination revealed an altered level of consciousness, slight trembling of the limbs, psychomotor restlessness, and poor speech with no signs of meningeal irritation. Magnetic resonance imaging of the brain revealed diffuse hyperintense signals. A possible diagnosis of acute encephalitis was made due to concurrent COVID-19 infection and lack of other findings suggesting a diagnosis other than COVID-19. She was treated with azithromycin, tocilizumab, and methylprednisolone. Her condition started improving gradually.
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Affiliation(s)
- Shah T Sarmast
- Neurology, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | | | - Zain Amar
- Medicine, Isra University Hospital Hyderabad, Hyderabad, PAK
| | - Sobia Sarwar
- Neurology, Independent Medical College, Faisalabad, PAK
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Ehsan P, Haseeb M, Khan Z, Rehan A, Singh R. Coronavirus Disease 2019 Pneumonia and Acute Pancreatitis in a Young Girl. Cureus 2021; 13:e15374. [PMID: 34249527 PMCID: PMC8249145 DOI: 10.7759/cureus.15374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2021] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 pneumonia and acute pancreatitis are rarely reported in patients with coronavirus disease 2019 (COVID-19). We present the case of a 13-year-old girl who presented with nausea, vomiting, and abdominal pain for the last two days, along with a cough for the last week. She had a fever and tachycardia. Lung examination revealed reduced breath sounds, and abdominal examination showed tenderness in the epigastrium. COVID-19 polymerase chain reaction was positive, and her serum chemistry revealed elevated serum amylase and lipase. Abdominal computed tomography revealed diffuse inflammation of the pancreas with peripancreatic edema, and chest X-ray demonstrated diffuse infiltrates and pneumonic patches in both lungs. Her initial management included bowel rest, intravenous fluids, intravenous remdesivir, and azithromycin with supplemental oxygen based on the provisional diagnosis of COVID-19 pneumonia and acute pancreatitis. Her abdominal symptoms started improving, and dexamethasone was added to her regimen due to her worsened respiratory condition. She was symptom-free on day seven except for a mild cough. She was discharged on day eight with follow-up.
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Affiliation(s)
- Paghunda Ehsan
- Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | | | - Zaraq Khan
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Aiman Rehan
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
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AL‐Rasheedi M, Alhazmi Y, Almaqwashi N, Mateq Ali A, Kardam A, Sharaf M, Haider KH. Corticosteroid therapy for 2019-nCoV-infected patients: A case series of eight mechanically ventilated patients. Clin Case Rep 2021; 9:e04066. [PMID: 34084491 PMCID: PMC8142400 DOI: 10.1002/ccr3.4066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 02/18/2021] [Accepted: 03/05/2021] [Indexed: 01/16/2023] Open
Abstract
High-dose short-term corticosteroid therapy is effective and produces favorable clinical outcome in patients with severe 2019-nCoV infection who are candidates for mechanical ventilation with close monitor/ing for the adverse effect of corticosteroids.
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Affiliation(s)
| | - Yasir Alhazmi
- Clinical Pharmacy DepartmentKing Faisal Medical CityAbhaSaudi Arabia
| | - Nouf Almaqwashi
- Clinical Pharmacy Department College of PharmacyQassim UniversityBuraidahSaudi Arabia
| | - Alreshidi Mateq Ali
- Medical Laboratory SciencesSulaiman AlRajhi UniversityAlbukairyahSaudi Arabia
| | - Abdulaziz Kardam
- Clinical Pharmacy DepartmentKing Faisal Medical CityAbhaSaudi Arabia
| | - Mohammod Sharaf
- Albukairyah General HospitalMinistry of HealthAlbukairyahSaudi Arabia
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Chan SW. Current and Future Direct-Acting Antivirals Against COVID-19. Front Microbiol 2020; 11:587944. [PMID: 33262747 PMCID: PMC7688518 DOI: 10.3389/fmicb.2020.587944] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 10/23/2020] [Indexed: 01/18/2023] Open
Abstract
The coronavirus disease of 2019 (COVID-19) has caused an unprecedented global crisis. The etiological agent is a new virus called the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). As of October, 2020 there have been 45.4 million confirmed cases with a mortality rate of 2.6% globally. With the lack of a vaccine and effective treatments, the race is on to find a cure for the virus infection using specific antivirals. The viral RNA-dependent RNA polymerase, proteases, spike protein-host angiotensin-converting enzyme 2 binding and fusion have presented as attractive targets for pan-coronavirus and broad spectrum direct-acting antivirals (DAAs). This review presents a perspective on current re-purposing treatments and future DAAs.
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Makarov V, Riabova O, Ekins S, Pluzhnikov N, Chepur S. The past, present and future of RNA respiratory viruses: influenza and coronaviruses. Pathog Dis 2020; 78:ftaa046. [PMID: 32860686 PMCID: PMC7499567 DOI: 10.1093/femspd/ftaa046] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 08/25/2020] [Indexed: 12/12/2022] Open
Abstract
Influenza virus and coronaviruses continue to cause pandemics across the globe. We now have a greater understanding of their functions. Unfortunately, the number of drugs in our armory to defend us against them is inadequate. This may require us to think about what mechanisms to address. Here, we review the biological properties of these viruses, their genetic evolution and antiviral therapies that can be used or have been attempted. We will describe several classes of drugs such as serine protease inhibitors, heparin, heparan sulfate receptor inhibitors, chelating agents, immunomodulators and many others. We also briefly describe some of the drug repurposing efforts that have taken place in an effort to rapidly identify molecules to treat patients with COVID-19. While we put a heavy emphasis on the past and present efforts, we also provide some thoughts about what we need to do to prepare for respiratory viral threats in the future.
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Affiliation(s)
- Vadim Makarov
- Federal Research Center Fundamentals of Biotechnology of the Russian Academy of Sciences, 33-2 Leninsky Prospect, Moscow 119071, Russia
| | - Olga Riabova
- Federal Research Center Fundamentals of Biotechnology of the Russian Academy of Sciences, 33-2 Leninsky Prospect, Moscow 119071, Russia
| | - Sean Ekins
- Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, NC 27606, USA
| | - Nikolay Pluzhnikov
- State Research Institute of Military Medicine of the Ministry of Defence of the Russian Federation, St Petersburg 195043, Russia
| | - Sergei Chepur
- State Research Institute of Military Medicine of the Ministry of Defence of the Russian Federation, St Petersburg 195043, Russia
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