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1
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Lu W, Yang X, Wang B. Carbon monoxide potentiates the effect of corticosteroids in suppressing inflammatory responses in cell culture. Bioorg Med Chem 2025; 120:118092. [PMID: 39904198 DOI: 10.1016/j.bmc.2025.118092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 01/24/2025] [Accepted: 01/27/2025] [Indexed: 02/06/2025]
Abstract
Inflammation is a pathology implicated in a wide range of human diseases. Recent years have seen tremendous progress in developing new types of anti-inflammatory agents for the treatment of inflammation of various origins. However, each has its own strengths and weaknesses. The very fact that there needs to have multiple types of anti-inflammatory agents underlines the complexity of inflammatory diseases and conditions, their molecular origins, and their treatment. Such complexity dictates the need to search for new approaches with improved potency and efficacy as well as reduced side effects. For these reasons, we are interested in exploring the possibility of generating synergy between carbon monoxide (CO), an endogenously produced cytoprotective agent, and known anti-inflammatory agents. Herein, we report the potentiating actions of CO on the anti-inflammatory effects of cortisone and dexamethasone as demonstrated in their ability to suppress the expression of TNF-α and IL-6 induced by either LPS or the S protein of SARS-CoV-2. Such effects are reflected in the substantially increased potency as well efficacy, when the efficacy of the corticosteroid alone does not allow for complete suppression of the expression of these cytokines. Further, increased attenuation of p65 phosphorylation is at least part of the molecular mechanism for the observed potentiating effects. We hope our work will stimulate a high level of activity along the same direction, leading to anti-inflammatory strategies with improved potency and efficacy and reduced side effects.
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Affiliation(s)
- Wen Lu
- Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA
| | - Xiaoxiao Yang
- Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA
| | - Binghe Wang
- Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
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2
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Li W, Gao M, Hao Y, Chi H, Yu J. Beneficial effect of sequential treatment with high-dose steroids and short-course oral glucocorticoids in patients with severe influenza virus-associated pneumonia. Sci Rep 2024; 14:25023. [PMID: 39443650 PMCID: PMC11499680 DOI: 10.1038/s41598-024-76400-2] [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: 06/21/2024] [Accepted: 10/14/2024] [Indexed: 10/25/2024] Open
Abstract
Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.
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Affiliation(s)
- Wei Li
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Mingyue Gao
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Yuqiu Hao
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Hao Chi
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Jinyan Yu
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China.
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3
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Riyaz Tramboo S, Elkhalifa AM, Quibtiya S, Ali SI, Nazir Shah N, Taifa S, Rakhshan R, Hussain Shah I, Ahmad Mir M, Malik M, Ramzan Z, Bashir N, Ahad S, Khursheed I, Bazie EA, Mohamed Ahmed E, Elderdery AY, Alenazy FO, Alanazi A, Alzahrani B, Alruwaili M, Manni E, E. Hussein S, Abdalhabib EK, Nabi SU. The critical impacts of cytokine storms in respiratory disorders. Heliyon 2024; 10:e29769. [PMID: 38694122 PMCID: PMC11058722 DOI: 10.1016/j.heliyon.2024.e29769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 04/15/2024] [Accepted: 04/15/2024] [Indexed: 05/03/2024] Open
Abstract
Cytokine storm (CS) refers to the spontaneous dysregulated and hyper-activated inflammatory reaction occurring in various clinical conditions, ranging from microbial infection to end-stage organ failure. Recently the novel coronavirus involved in COVID-19 (Coronavirus disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been associated with the pathological phenomenon of CS in critically ill patients. Furthermore, critically ill patients suffering from CS are likely to have a grave prognosis and a higher case fatality rate. Pathologically CS is manifested as hyper-immune activation and is clinically manifested as multiple organ failure. An in-depth understanding of the etiology of CS will enable the discovery of not just disease risk factors of CS but also therapeutic approaches to modulate the immune response and improve outcomes in patients with respiratory diseases having CS in the pathogenic pathway. Owing to the grave consequences of CS in various diseases, this phenomenon has attracted the attention of researchers and clinicians throughout the globe. So in the present manuscript, we have attempted to discuss CS and its ramifications in COVID-19 and other respiratory diseases, as well as prospective treatment approaches and biomarkers of the cytokine storm. Furthermore, we have attempted to provide in-depth insight into CS from both a prophylactic and therapeutic point of view. In addition, we have included recent findings of CS in respiratory diseases reported from different parts of the world, which are based on expert opinion, clinical case-control research, experimental research, and a case-controlled cohort approach.
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Affiliation(s)
- Shahana Riyaz Tramboo
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Ahmed M.E. Elkhalifa
- Department of Public Health, College of Health Sciences, Saudi Electronic University, Riyadh, 11673, Saudi Arabia
- Department of Haematology, Faculty of Medical Laboratory Sciences, University of El Imam El Mahdi, Kosti, 1158, Sudan
| | - Syed Quibtiya
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Medical College, Srinagar, 190011, Jammu & Kashmir, India
| | - Sofi Imtiyaz Ali
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Naveed Nazir Shah
- Department of Chest Medicine, Govt. Medical College, Srinagar, 191202, Jammu & Kashmir, India
| | - Syed Taifa
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Rabia Rakhshan
- Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu & Kashmir, 190006, India
| | - Iqra Hussain Shah
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Muzafar Ahmad Mir
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Masood Malik
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Zahid Ramzan
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Nusrat Bashir
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Shubeena Ahad
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
| | - Ibraq Khursheed
- Department of Zoology, Central University of Kashmir, 191201, Nunar, Ganderbal, Jammu & Kashmir, India
| | - Elsharif A. Bazie
- Pediatric Department, Faculty of Medicine, University of El Imam El Mahdi, Kosti, 1158, Sudan
| | - Elsadig Mohamed Ahmed
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha, 61922, Saudi Arabia
- Department of Clinical Chemistry, Faculty of Medical Laboratory Sciences, University of El Imam El Mahdi, Kosti, 1158, Sudan
| | - Abozer Y. Elderdery
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Fawaz O. Alenazy
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Awadh Alanazi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Badr Alzahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Muharib Alruwaili
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Emad Manni
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Sanaa E. Hussein
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Ezeldine K. Abdalhabib
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia
| | - Showkat Ul Nabi
- Preclinical Research Laboratory, Department of Clinical Veterinary Medicine, Ethics & Jurisprudence, Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir), Srinagar, J&K, 190006, India
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4
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Azargoonjahromi A. Role of the SARS-CoV-2 Virus in Brain Cells. Viral Immunol 2024; 37:61-78. [PMID: 38315740 DOI: 10.1089/vim.2023.0116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2024] Open
Abstract
COVID-19, caused by the SARS-CoV-2 virus, can have neurological effects, including cognitive symptoms like brain fog and memory problems. Research on the neurological effects of COVID-19 is ongoing, and factors such as inflammation, disrupted blood flow, and damage to blood vessels may contribute to cognitive symptoms. Notably, some authors and existing evidence suggest that the SARS-CoV-2 virus can enter the central nervous system through different routes, including the olfactory nerve and the bloodstream. COVID-19 infection has been associated with neurological symptoms such as altered consciousness, headaches, dizziness, and mental disorders. The exact mechanisms and impact on memory formation and brain shrinkage are still being studied. This review will focus on pathways such as the olfactory nerve and blood-brain barrier disruption, and it will then highlight the interactions of the virus with different cell types in the brain, namely neurons, astrocytes, oligodendrocytes, and microglia.
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Affiliation(s)
- Ali Azargoonjahromi
- Researcher in Neuroscience, Shiraz University of Medical Sciences, Shiraz, Iran
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5
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Davulcu CD, Karaismailoğlu B, Ozsahin MK, Davutluoglu E, Akbaba D, Terzi E, Ünlü MC. Autologous bone plug-sliding with core decompression and bone marrow aspirate concentrate application: a joint-preserving surgical technique for corticosteroid-induced osteonecrosis of femoral head. Acta Orthop Belg 2023; 89:603-608. [PMID: 38205748 DOI: 10.52628/89.4.10669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
This study aimed to describe a surgical procedure for the management of corticosteroid-induced osteonecrosis of the femoral head (ONFH) and report its clinical results. The technique included harvesting a bone plug from the lateral femoral neck, core decompression, and bone marrow aspirate concentrate (BMAC) application; the procedure was completed by press-fit insertion of the autologous bone plug in the debrided area. Autologous bone plug-sliding with core decompression and bone marrow concentrate aspirate application provides good clinical outcomes in the management of ONFH. A retrospective review was performed using records of patients operated on between October 2019 and June 2021. Only patients with Ficat-Arlet stage-2 ONFH, who underwent the procedure described, were included. Twenty- nine hips (18 patients) were included and evaluated clinically and radiologically. Clinical evaluation included the Harris hip score (HHS) and Visual analogue scale (VAS) for pain, while radiological evaluation included direct radiographs. The average age was 39.8 years (± 11.7, range: 24-65 years). The average follow-up was 13.5 months (± 3.4, range: 8-19 months). There were improvements in the VAS pain and Harris hip scores in all patients. Average HHS increased from 61.90 to 87.45 (p < 0.001), while the average VAS pain score decreased from 7.14 to 3.27 (p < 0.001). No complications were encountered in any of the patients during the follow-up. None of the patients had femoral head collapse on the latest radiograph or required total hip replacement. The combination of the novel autologous bone plug-sliding method with conventional regenerative methods is a successful treatment choice for ONFH.
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Rabaan AA, Alenazy MF, Alshehri AA, Alshahrani MA, Al-Subaie MF, Alrasheed HA, Al Kaabi NA, Thakur N, Bouafia NA, Alissa M, Alsulaiman AM, AlBaadani AM, Alhani HM, Alhaddad AH, Alfouzan WA, Ali BMA, Al-Abdulali KH, Khamis F, Bayahya A, Al Fares MA, Sharma M, Dhawan M. An updated review on pathogenic coronaviruses (CoVs) amid the emergence of SARS-CoV-2 variants: A look into the repercussions and possible solutions. J Infect Public Health 2023; 16:1870-1883. [PMID: 37839310 DOI: 10.1016/j.jiph.2023.09.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 10/17/2023] Open
Abstract
SARS-CoV-2, responsible for COVID-19, shares 79% and 50% of its identity with SARS-CoV-1 and MERS-CoV, respectively. It uses the same main cell attachment and entry receptor as SARS-CoV-1, which is the ACE-2 receptor. However, key residues in the receptor-binding domain of its S-protein seem to give it a stronger affinity for the receptor and a better ability to hide from the host immune system. Like SARS-CoV-1 and MERS-CoV, cytokine storms in critically ill COVID-19 patients cause ARDS, neurological pathology, multiorgan failure, and increased death. Though many issues remain, the global research effort and lessons from SARS-CoV-1 and MERS-CoV are hopeful. The emergence of novel SARS-CoV-2 variants and subvariants raised serious concerns among the scientific community amid the emergence of other viral diseases like monkeypox and Marburg virus, which are major concerns for healthcare settings worldwide. Hence, an updated review on the comparative analysis of various coronaviruses (CoVs) has been developed, which highlights the evolution of CoVs and their repercussions.
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Affiliation(s)
- Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan.
| | - Maha Fahad Alenazy
- Department of Physiology, College of Medicine, King Khalid university hospital, King Saud University, Riyadh 4545, Saudi Arabia
| | - Ahmad A Alshehri
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
| | - Mohammed Abdulrahman Alshahrani
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia
| | - Maha F Al-Subaie
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; Research Center, Dr. Sulaiman Alhabib Medical Group, Riyadh 13328, Saudi Arabia; Department of Infectious Diseases, Dr. Sulaiman Alhabib Medical Group, Riyadh 13328, Saudi Arabia
| | - Hayam A Alrasheed
- Department of pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia; Pharmacy Department, King Abdullah Bin Abdulaziz University Hospital, Riyadh 11671, Saudi Arabia
| | - Nawal A Al Kaabi
- Sheikh Khalifa Medical City, Abu Dhabi Health Services Company (SEHA), Abu Dhabi, 51900, United Arab Emirates; College of Medicine and Health Science, Khalifa University, Abu Dhabi 127788, United Arab Emirates
| | - Nanamika Thakur
- University Institute of Biotechnology, Department of Biotechnology, Chandigarh University, Mohali 140413, India
| | - Nabiha A Bouafia
- Infection prevention and control centre of Excellence, Prince Sultan Medical Military City, Riyadh 12233, Saudi Arabia
| | - Mohammed Alissa
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | | | - Abeer M AlBaadani
- Internal Medicine Department, Infectious Disease Division, London health science Center, London, Ontario N6G0X2, Canada
| | - Hatem M Alhani
- Department of Pediatric Infectious Disease, Maternity and Children Hospital, Dammam 31176, Saudi Arabia; Department of Infection Control, Maternity and Children Hospital, Dammam 31176, Saudi Arabia; Preventive Medicine and Infection Prevention and Control Department, Directorate of Ministry of Health, Dammam 32245, Saudi Arabia
| | - Ali H Alhaddad
- Assistant Agency for Hospital Affairs, Ministry of Health, Riyadh 12382, Saudi Arabia
| | - Wadha A Alfouzan
- Department of Microbiology, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait; Microbiology Unit, Department of Laboratories, Farwania Hospital, Farwania 85000, Kuwait
| | - Batool Mohammed Abu Ali
- Infectious disease section, Department of internal medicine, King Fahad Hospital Hofuf, Hofuf 36365, Saudi Arabia
| | - Khadija H Al-Abdulali
- Nursing Department, Home health care, Qatif Health Network, Qatif 31911, Saudi Arabia
| | - Faryal Khamis
- Infection Diseases unit, Department of Internal Medicine, Royal Hospital, Muscat 1331, Oman
| | - Ali Bayahya
- Microbiology Department, Alqunfudah General Hospital, Alqunfudah 28813, Saudi Arabia
| | - Mona A Al Fares
- Department of Internal Medicine, King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia.
| | - Manish Sharma
- University Institute of Biotechnology, Department of Biotechnology, Chandigarh University, Mohali 140413, India
| | - Manish Dhawan
- Department of Microbiology, Punjab Agricultural University, Ludhiana 141004, India; Trafford College, Altrincham, Manchester WA14 5PQ, UK.
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Hassan AAA, Khalifa AA. Femoral head avascular necrosis in COVID-19 survivors: a systematic review. Rheumatol Int 2023; 43:1583-1595. [PMID: 37338665 PMCID: PMC10348993 DOI: 10.1007/s00296-023-05373-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 06/13/2023] [Indexed: 06/21/2023]
Abstract
The current systematic review aimed to document published cases of femoral head avascular necrosis (FHAVN) post-COVID-19, to report the COVID-19 disease characteristics and management patients received, and to evaluate how the FHAVN were diagnosed and treated among various reports. A systematic literature review was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through a comprehensive English literature search on January 2023 through four databases (Embase, PubMed, Cochrane Library, and Scopus), including studies reporting on FHAVN post-COVID-19. Fourteen articles were included, ten (71.4%) were case reports, and four (28.6%) case series reported on 104 patients having a mean age of 42.2 ± 11.7 (14:74) years, in which 182 hip joints were affected. In 13 reports, corticosteroids were used during the COVID-19 management plan for a mean of 24.8 ± 11 (7:42) days, with a mean prednisolone equivalent dose of 1238.5 ± 492.8 (100:3520) mg. A mean of 142.1 ± 107.6 (7:459) days passed between COVID-19 diagnosis and FHAVN detection, and most of the hips were stage II (70.1%), and concomitant septic arthritis was present in eight (4.4%) hips. Most hips (147, 80.8%) were treated non-surgically, of which 143 (78.6%) hips received medical treatment, while 35 (19.2%) hips were surgically managed, 16 (8.8%) core decompression, 13 (7.1%) primary THA, five (2.7%) staged THA and three (1.6%) had first stage THA (debridement and application of antibiotic-loaded cement spacer). The outcomes were acceptable as regards hip function and pain relief. Femoral head avascular necrosis post-COVID-19 infection is a real concern, primarily attributed to corticosteroid usage, besides other factors. Early suspicion and detection are mandatory, as conservative management lines are effective during early stages with acceptable outcomes. However, surgical intervention was required for progressive collapse or patients presented in the late stage.
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Affiliation(s)
| | - Ahmed A. Khalifa
- Orthopedic Department, Qena Faculty of Medicine, South Valley University, Kilo 6 Qena-Safaga Highway, Qena, Egypt
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Sun J. A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases. JOURNAL OF INTEGRATIVE MEDICINE 2023:S2095-4964(23)00046-8. [PMID: 37349214 DOI: 10.1016/j.joim.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 05/12/2023] [Indexed: 06/24/2023]
Abstract
The prognosis of infectious diseases is determined by host-pathogen interactions. Control of pathogens has been the central dogma of treating infectious diseases in modern medicine, but the pathogen-directed medicine is facing significant challenges, including a lack of effective antimicrobials for newly emerging pathogens, pathogen drug resistance, and drug side effects. Here, a mathematic equation (termed equation of host-pathogen interactions, HPI-Equation) is developed to dissect the key variables of host-pathogen interactions. It shows that control of pathogens does not necessarily lead to host recovery. Instead, a combination of promoting a host's power of self-healing and balancing immune responses provides the best benefit for host. Moreover, the HPI-Equation elucidates the scientific basis of traditional Chinese medicine (TCM), a host-based medicine that treats infectious diseases by promoting self-healing power and balancing immune responses. The importance of self-healing power elucidated in the HPI-Equation is confirmed by recent studies that the tolerance mechanism, which is discovered in plants and animals and conceptually similar to self-healing power, improves host survival without directly attacking pathogens. In summary, the HPI-Equation describes host-pathogen interactions with mathematical logic and precision; it translates the ancient wisdoms of TCM into apprehensible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine.
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Affiliation(s)
- Jianjun Sun
- Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, TX 79968, USA.
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Raghav PK, Mann Z, Ahluwalia SK, Rajalingam R. Potential treatments of COVID-19: Drug repurposing and therapeutic interventions. J Pharmacol Sci 2023; 152:1-21. [PMID: 37059487 PMCID: PMC9930377 DOI: 10.1016/j.jphs.2023.02.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 01/31/2023] [Accepted: 02/10/2023] [Indexed: 02/17/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is caused when Spike-protein (S-protein) present on the surface of SARS-CoV-2 interacts with human cell surface receptor, Angiotensin-converting enzyme 2 (ACE2). This binding facilitates SARS-CoV-2 genome entry into the human cells, which in turn causes infection. Since the beginning of the pandemic, many different therapies have been developed to combat COVID-19, including treatment and prevention. This review is focused on the currently adapted and certain other potential therapies for COVID-19 treatment, which include drug repurposing, vaccines and drug-free therapies. The efficacy of various treatment options is constantly being tested through clinical trials and in vivo studies before they are made medically available to the public.
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Affiliation(s)
- Pawan Kumar Raghav
- Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
| | | | - Simran Kaur Ahluwalia
- Amity Institute of Biotechnology, Amity University, Sector-125, Noida, Uttar Pradesh, India
| | - Raja Rajalingam
- Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA
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10
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Muthu S, Jeyaraman M, Selvaraj P, Jeyaraman N, Potty AG, Gupta A. Dose-Response Meta-Analysis of Corticosteroid Effects in SARS Outbreak: A Model for Risk Stratification and Screening Strategy for Osteonecrosis of Femoral Head Post-Corticosteroid Therapy for COVID-19. Life (Basel) 2023; 13:907. [PMID: 37109436 PMCID: PMC10143798 DOI: 10.3390/life13040907] [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: 02/02/2023] [Revised: 03/14/2023] [Accepted: 03/27/2023] [Indexed: 04/01/2023] Open
Abstract
Corticosteroids (CS) have been used in the management regimens for COVID-19 disease to mitigate the cytokine storm and ill effects of the pulmonary inflammatory cascade. With the rampant use of CS, clinicians started reporting the occurrence of osteonecrosis of the femoral head (OFH). In this systematic review, we aim to analyze the literature and identify the definitive cumulative dose and duration of CS needed for the development of OFH based on the SARS model and generate a risk-based screening recommendation for OFH in convalescent COVID-19 patients to facilitate early identification and management. An electronic database search was conducted until December 2022 in PubMed, Web of Science, Embase, and CNKI (China Knowledge Resource Integrated Database). Studies involving CS therapy and osteonecrosis data in SARS patients were included. Three authors independently extracted the data from the included studies and a dose-response meta-analysis was performed for various doses and duration of CS utilized in the included studies. We selected 12 articles with 1728 patients in the analysis. The mean age was 33.41 (±4.93) years. The mean dosage of CS administered was 4.64 (±4.7) g which was administered for a mean duration of 29.91 (±12.3) days. The risk of osteonecrosis increases at pooled OR of 1.16 (95% CI 1.09-1.23, p < 0.001) per 2.0 g increase in the cumulative dose of CS usage. Similarly, the risk increases at pooled OR of 1.02 (95% CI 1.01-1.03, p < 0.001) per 5 days of increase in the cumulative duration of CS usage. A cumulative dosage of 4 g and a duration of 15 days were determined as the critical cut-off for the non-linear dose-response relationship observed. Appropriate and frequent screening of these individuals at regular intervals would help in the identification of the disease at an early stage in order to treat them appropriately.
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Affiliation(s)
- Sathish Muthu
- Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624003, Tamil Nadu, India
| | - Madhan Jeyaraman
- Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Dr. MGR Educational and Research Institute, ACS Medical College and Hospital, Chennai 600056, Tamil Nadu, India
- South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045, USA
| | - Preethi Selvaraj
- Department of Community Medicine, Dr. MGR Educational and Research Institute, Faculty of Medicine, Sri Lalithambigai Medical College and Hospital, Chennai 600095, Tamil Nadu, India
| | - Naveen Jeyaraman
- Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
- Department of Orthopaedics, Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth, Chengalpet 603108, Tamil Nadu, India
| | - Anish G. Potty
- South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045, USA
| | - Ashim Gupta
- South Texas Orthopaedic Research Institute (STORI Inc.), Laredo, TX 78045, USA
- Future Biologics, Lawrenceville, GA 30043, USA
- Regenerative Orthopaedics, Noida 201301, Uttar Pradesh, India
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11
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Zhu Y, Chen D, Zhu Y, Ge X, Li Z, Miao H. Clinical observation of glucocorticoid therapy for critically ill patients with COVID-19 pneumonia. J Int Med Res 2023; 51:3000605221149292. [PMID: 36843426 PMCID: PMC9972059 DOI: 10.1177/03000605221149292] [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] [Indexed: 02/28/2023] Open
Abstract
OBJECTIVE We aimed to investigate the clinical effects of intravenous glucocorticoid (GC) therapy for severe COVID-19 pneumonia. METHODS Seventy-two patients hospitalized with severe COVID-19 pneumonia who were discharged or died between 5 January 2020 and 3 March 2020 at Huangshi Infectious Disease Hospital were included. Patients were divided into a treatment group (GC group) and non-treatment group (non-GC group) according to whether they had received GCs within 7 days of hospital admission. RESULTS There was no significant difference between groups for Acute Physiology and Chronic Health Evaluation (APACHE) II score and 28-day survival rate. The rate of invasive mechanical ventilation was higher in the GC group than in the non-GC group. On day 7 after admission, the GC group had shorter fever duration and higher white blood cell count than the non-GC group. In subgroup analysis by age and severity, there was no significant difference in 28-day survival rate and other indicators. Compared with those in the non-GC group, patients in the GC group more frequently required admission to the intensive care unit. CONCLUSION In the present study, we found no significant improvement in patients with severe COVID-19 pneumonia treated with GCs within 7 days of admission.
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Affiliation(s)
- Yingjie Zhu
- Department of Emergency/Critical Care Medicine, Children's
Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, China
| | - Dongmei Chen
- Department of Emergency/Critical Care Medicine, Children's
Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, China
| | - Yanfang Zhu
- Department of Critical Care Medicine, Huangshi Hospital of TCM
(Infectious Disease Hospital), 12 Guangchang Road, Huangshi, China
| | - Xuhua Ge
- Department of Emergency/Critical Care Medicine, Children's
Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, China
| | - Zhuo Li
- Department of Emergency/Critical Care Medicine, Children's
Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, China
| | - Hongjun Miao
- Department of Emergency/Critical Care Medicine, Children's
Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, China,Hongjun Miao, Children's Hospital of
Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, China.
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12
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Gong X, Khan A, Wani MY, Ahmad A, Duse A. COVID-19: A state of art on immunological responses, mutations, and treatment modalities in riposte. J Infect Public Health 2023; 16:233-249. [PMID: 36603376 PMCID: PMC9798670 DOI: 10.1016/j.jiph.2022.12.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 12/25/2022] [Accepted: 12/26/2022] [Indexed: 12/31/2022] Open
Abstract
Over the last few years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) unleashed a global public health catastrophe that had a substantial influence on human physical and mental health, the global economy, and socio-political dynamics. SARS-CoV-2 is a respiratory pathogen and the cause of ongoing COVID-19 pandemic, which testified how unprepared humans are for pandemics. Scientists and policymakers continue to face challenges in developing ideal therapeutic agents and vaccines, while at the same time deciphering the pathology and immunology of SARS-CoV-2. Challenges in the early part of the pandemic included the rapid development of diagnostic assays, vaccines, and therapeutic agents. The ongoing transmission of COVID-19 is coupled with the emergence of viral variants that differ in their transmission efficiency, virulence, and vaccine susceptibility, thus complicating the spread of the pandemic. Our understanding of how the human immune system responds to these viruses as well as the patient groups (such as the elderly and immunocompromised individuals) who are often more susceptible to serious illness have both been aided by this epidemic. COVID-19 causes different symptoms to occur at different stages of infection, making it difficult to determine distinct treatment regimens employed for the various clinical phases of the disease. Unsurprisingly, determining the efficacy of currently available medications and developing novel therapeutic strategies have been a process of trial and error. The global scientific community collaborated to research and develop vaccines at a neck-breaking speed. This review summarises the overall picture of the COVID-19 pandemic, different mutations in SARS-CoV-2, immune response, and the treatment modalities against SARS-CoV-2.
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Affiliation(s)
- Xiaolong Gong
- Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Amber Khan
- Department of Clinical Haematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Mohmmad Younus Wani
- Department of Chemistry, College of Science, University of Jeddah, P.O. Box 80327, Jeddah 21589, Kingdom of Saudi Arabia
| | - Aijaz Ahmad
- Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Division of Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, South Africa,Corresponding author at: Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Adriano Duse
- Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Division of Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, South Africa
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13
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Moreno G, Ruiz-Botella M, Martín-Loeches I, Gómez Álvarez J, Jiménez Herrera M, Bodí M, Armestar F, Marques Parra A, Estella Á, Trefler S, Jorge García R, Murcia Paya J, Vidal Cortes P, Díaz E, Ferrer R, Albaya-Moreno A, Socias-Crespi L, Bonell Goytisolo J, Sancho Chinesta S, Loza A, Forcelledo Espina L, Pozo Laderas J, deAlba-Aparicio M, Sánchez Montori L, Vallverdú Perapoch I, Hidalgo V, Fraile Gutiérrez V, Casamitjana Ortega A, Martín Serrano F, Nieto M, Blasco Cortes M, Marín-Corral J, Solé-Violán J, Rodríguez A, on behalf COVID-19 SEMICYUC Working Group. A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients. Med Intensiva 2023; 47:23-33. [PMID: 36272908 PMCID: PMC9579897 DOI: 10.1016/j.medine.2021.10.016] [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: 07/04/2021] [Accepted: 10/02/2021] [Indexed: 11/06/2022]
Abstract
OBJECTIVE To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN A secondary analysis derived from multicenter, observational study. SETTING Critical Care Units. PATIENTS Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.
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Affiliation(s)
- G. Moreno
- ICU, Hospital Universitario Joan XXIII/URV/IISPV, Tarragona, Spain
| | - M. Ruiz-Botella
- Tarragona Health Data Research Working Group (THeDaR) – ICU Hospital Universitario Joan XXIII, Tarragona, Spain
| | - I. Martín-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, Dublin, Ireland
| | - J. Gómez Álvarez
- Tarragona Health Data Research Working Group (THeDaR) – ICU Hospital Universitario Joan XXIII, Tarragona, Spain
| | | | - M. Bodí
- ICU, Hospital Universitario Joan XXIII/URV/IISPV, Tarragona, Spain,CIBERES/CIBERESUCICOVID
| | - F. Armestar
- ICU, Hospital Universitario German Trias i Pujol, Badalona, Spain
| | | | - Á. Estella
- ICU, Hospital Universitario de Jerez, Jerez de la Frontera, Spain
| | - S. Trefler
- ICU, Hospital Universitario Joan XXIII/URV/IISPV, Tarragona, Spain
| | | | | | - P. Vidal Cortes
- UCI, Complejo Hospitalario Universitario de Ourense, Orense, Spain
| | - E. Díaz
- UCI, Hospital Parc Taulí/UAB/CIBERES, Barcelona, Spain
| | - R. Ferrer
- UCI, Hospital Universitario Vall d’Hebron, Barcelona, Spain
| | | | - L. Socias-Crespi
- UCI, Hospital Universitario Son Llátzer, Palma de Mallorca, Spain
| | | | | | - A. Loza
- ICU, Hospital Universitario Nuestra Señora de Valme, Sevilla, Spain
| | - L. Forcelledo Espina
- ICU, Hospital Central de Asturias, Grupo de Investigación de Microbiología Traslacional del ISPA, Oviedo, Spain
| | | | | | | | | | - V. Hidalgo
- ICU, Hospital Complejo Asistencial de Segovia, Segovia, Spain
| | | | - A.M. Casamitjana Ortega
- UCI, Complejo Hospitalario Universitario Insular – Materno Infantil, Las Palmas de Gran Canaria, Spain
| | | | - M. Nieto
- UCI, Hospital Clínico San Carlos, Madrid, Spain
| | | | - J. Marín-Corral
- ICU, Hospital del Mar/GREPAC – IMIM, Barcelona, Spain,Division of Pulmonary Diseases & Critical Care Medicine, UTH San Antonio, San Antonio, TX, USA
| | - J. Solé-Violán
- ICU, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - A. Rodríguez
- ICU, Hospital Universitario Joan XXIII/URV/IISPV, Tarragona, Spain,CIBERES/CIBERESUCICOVID,Corresponding author
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14
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Isnardi CA, Roberts K, Saurit V, Petkovic I, Báez RM, Quintana R, Tissera Y, Ornella S, D.Angelo Exeni ME, Pisoni CN, Castro Coello VV, Berbotto G, Haye Salinas MJ, Velozo E, Reyes Torres ÁA, Tanten R, Zelaya MD, Gobbi C, Alonso CG, de los Ángeles Severina M, Vivero F, Paula A, Cogo AK, Alle G, Pera M, Nieto RE, Cosatti M, Asnal C, Pereira D, Albiero JA, Savio VG, Maldonado FN, Gamba MJ, Germán NF, Baños A, Gallino Yanzi J, Gálvez Elkin MS, Morbiducci JS, Martire MV, Maldonado Ficco H, Schmid MM, Villafañe Torres JA, de los Ángeles Correa M, Medina MA, Cusa MA, Scafati J, Agüero SE, Lloves Schenone NM, Soriano ER, Graf C, Pons-Estel BA, Gomez G, Landi M, De la Vega MC, Pons-Estel GJ, the S. A. R.–COVID Registry Investigators SauritVeronicaPetkovicIngridBaezRoberto MiguelPons-EstelGuillermoTisseraYohanaOrnellaSofíaExeniIda ElenaPisoniCeciliaCastro CoelloVanessaBerbottoGuillermoHaye SalinasMaria JezabelVelozoEdsonReyes TorresAlvaro AndresTantenRominaZelayaMarcos DavidGobbiCarlaAlonsoCarla GimenaSeverinaMariaViveroFlorenciaAlbaPaulaCogoKarinaAlleGelsominaPeraMarianaNietoRominaCosattiMicaelaAsnalCeciliaPereiraDoraAlbieroJuan AlejandroSavioVerónica GabrielaMaldonadoFederico NicolasGambaMaria JulietaGermánNoeliaBañosAndreaGallino YanziJosefinaGálvez ElkinMaria SoledadMorbiducciJulieta SilvanaMartireMaría VictoriaMaldonado FiccoHernanSchmidMaria MarcelaVillafaneJaimede los Angeles CorreaMariaMedinaMaría AlejandraCusaMaría AlejandraScafatiJuliaAgüeroSantiago EduardoLloves SchenoneNicolás MartínRojas TesselIvana RominaPerez AlaminoRodolfoMercéAixa LuciaDe la VegaMariaBellomioVerónicaCarlevarisLeandroMarecoJonatan MarcosFigueroaRosa MaríaLazaroMaria AliciaGarcíaMercedesQuagliaMaria IsabelGonzález LuceroLucianaTakashimaLorenaWernerMarina LauraRisueñoFabianCucchiaroNatalia LiliBertoliAnaPendonGiselaRodriguez GilGustavo FabiánFinucci CuriPabloRaitiLauraVaraAndrea Belen GomezCasallaLucianaPiccoEugeniaMuñozLeila MarianaCalvoMaria ElenaCastrillónDiana MarcelaGómezCatalinaCórdobaMercedes CeciliaGómezCamila Rosario ReyesRoldánBrian ManasesAmitranoCristinaMatellanCarlaSoares de SouzaSidneyRodriguezFlorenciaAeschlimannCarolinaJuarezVicenteGrafCésarMauriMarianela ElianaRomeoCeciliaNovattiElisaTamboreneaMaria NataliaPaniegoRaúlViolaMalenaCosentinoVanesaPetruzzeliSandraBedranZaida NoemiMoyanoSebastiánBarbichTatianaContiSilvanaMaldiniCarlaAlonsoMaria DanielaBorgiaMaría VictoriaLedesmaAna CarolinaMartinMaria LuzKislukBorisPinedaSusana IsabelHerscovichNatalia AgustinaIbañez ZurloLeticiaTraliceElda RossellaVasquezDora LiaMoralesNataliaDíazMónica PatriciaMolina MerinoHernan ArielGalloRosanaTomasJessica LucianaAlbaAnibalGómezGracielaSubilsGiselaTestiAdrianaVernaGiseleBedoyaMaria EugeniaYohenaVictorGuagliononeDeboraRebakJonathan EliseoCroceMaria MercedesDieguezCarolinaGuinsburgMaraCatalán PelletSantiagoMaidPabloPortaSabrinaQuagliatoNorberto JavierDe La Vega FernandezSabrina SolangeBuschiazzoEmilioVelasco ZamoraJosé LuisPérez RodríguezMaría SilvinaPaniegoFederico MartinMamani OrtegaMaria LourdesBetancurGraciela VanesaSerranoRosaCastaños MenescardiMaria SolRetamozoCinthyaGoizuetaCeciliaQuinterosAnaAbadieFernandaCarrilloIgnacioGuzzantiFernanda. Sociodemographic and clinical factors associated with poor COVID-19 outcomes in patients with rheumatic diseases: data from the SAR-COVID Registry. Clin Rheumatol 2023; 42:563-578. [PMID: 36201124 PMCID: PMC9535223 DOI: 10.1007/s10067-022-06393-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/29/2023]
Abstract
BACKGROUND/OBJECTIVE This study aims to describe the course and to identify poor prognostic factors of SARS-CoV-2 infection in patients with rheumatic diseases. METHODS Patients ≥ 18 years of age, with a rheumatic disease, who had confirmed SARS-CoV-2 infection were consecutively included by major rheumatology centers from Argentina, in the national, observational SAR-COVID registry between August 13, 2020 and July 31, 2021. Hospitalization, oxygen requirement, and death were considered poor COVID-19 outcomes. RESULTS A total of 1915 patients were included. The most frequent rheumatic diseases were rheumatoid arthritis (42%) and systemic lupus erythematosus (16%). Comorbidities were reported in half of them (48%). Symptoms were reported by 95% of the patients, 28% were hospitalized, 8% were admitted to the intensive care unit (ICU), and 4% died due to COVID-19. During hospitalization, 9% required non-invasive mechanical ventilation (NIMV) or high flow oxygen devices and 17% invasive mechanical ventilation (IMV). In multivariate analysis models, using poor COVID-19 outcomes as dependent variables, older age, male gender, higher disease activity, treatment with glucocorticoids or rituximab, and the presence of at least one comorbidity and a greater number of them were associated with worse prognosis. In addition, patients with public health insurance and Mestizos were more likely to require hospitalization. CONCLUSIONS In addition to the known poor prognostic factors, in this cohort of patients with rheumatic diseases, high disease activity, and treatment with glucocorticoids and rituximab were associated with worse COVID-19 outcomes. Furthermore, patients with public health insurance and Mestizos were 44% and 39% more likely to be hospitalized, respectively. STUDY REGISTRATION This study has been registered in ClinicalTrials.gov under the number NCT04568421. Key Points • High disease activity, and treatment with glucocorticoids and rituximab were associated with poor COVID-19 outcome in patients with rheumatic diseases. • Some socioeconomic factors related to social inequality, including non-Caucasian ethnicity and public health insurance, were associated with hospitalization due to COVID-19.
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Affiliation(s)
- Carolina A. Isnardi
- Present Address: Unidad de Investigación de la Sociedad Argentina de Reumatología, Buenos Aires, Argentina
| | - Karen Roberts
- Present Address: Unidad de Investigación de la Sociedad Argentina de Reumatología, Buenos Aires, Argentina
| | - Verónica Saurit
- grid.413199.70000 0001 0368 1276Hospital Privado Universitario de Córdoba, Córdoba, Argentina
| | | | - Roberto M. Báez
- Hospital Francisco López Lima, General Roca, Río Negro, Argentina
| | - Rosana Quintana
- Present Address: Centro Regional de Enfermedades Autoinmunes Y Reumáticas, Rosario, Argentina
| | - Yohana Tissera
- grid.497623.dPresent Address: Hospital Córdoba, Córdoba, Argentina
| | - Sofía Ornella
- HIGA San Martín de La Plata, La Plata, Buenos Aires, Argentina
| | | | - Cecilia N. Pisoni
- grid.418248.30000 0004 0637 5938CEMIC—Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina
| | | | - Guillermo Berbotto
- Hospital Escuela Eva Perón, Sanatorio Británico, Granadero Baigorria; Rosario, Santa Fe, Argentina
| | - María J. Haye Salinas
- grid.441659.b0000 0001 2201 7776CEMMA, Universidad Nacional de La Rioja, La Rioja, Argentina
| | - Edson Velozo
- grid.441666.70000 0001 2284 8908Sanatorio y Universidad Adventista del Plata, Libertador San Martín, Entre Ríos, Argentina
| | - Álvaro A. Reyes Torres
- grid.414775.40000 0001 2319 4408Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Romina Tanten
- grid.414775.40000 0001 2319 4408Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Carla Gobbi
- grid.10692.3c0000 0001 0115 2557Cátedra de Clínica Médica I, Hospital Córdoba, FCM, UNC, Córdoba, Argentina
| | | | | | | | - Alba Paula
- Hospital Materno-Neonatal, Córdoba, Argentina
| | - Adriana K. Cogo
- Hospital Interzonal Luis Guemes, Haedo; Hospital San Juan de Dios, Castelar, Buenos Aires, Argentina
| | - Gelsomina Alle
- grid.414775.40000 0001 2319 4408Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Mariana Pera
- Hospital Ángel C Padilla, San Miguel de Tucumán, Tucumán, Argentina
| | | | - Micaela Cosatti
- grid.418248.30000 0004 0637 5938CEMIC—Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina
| | | | | | | | | | | | | | | | - Andrea Baños
- Fundación CIDEA, Ciudad Autónoma de Buenos Aires, Sindicato Empleados de Junín, Junín, Buenos Aires, Argentina
| | | | | | | | | | | | | | | | - Maria de los Ángeles Correa
- grid.419103.eInstituto de Rehabilitación Psicofísica, Instituto de Diagnóstico E Investigaciones Metabólicas, Buenos Aires, Argentina
| | | | | | - Julia Scafati
- HIGA San Martín de La Plata, La Plata, Buenos Aires, Argentina
| | - Santiago E. Agüero
- Centro de Rehabilitación Dr Mauricio Figueroa, Artrosport Catamarca, San Fernando del Valle de Catamarca, Catamarca, Argentina
| | | | - Enrique R. Soriano
- grid.414775.40000 0001 2319 4408Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Cesar Graf
- Sociedad Argentina de Reumatología, Buenos Aires, Argentina
| | - Bernardo A. Pons-Estel
- Present Address: Centro Regional de Enfermedades Autoinmunes Y Reumáticas, Rosario, Argentina
| | - Gimena Gomez
- Present Address: Unidad de Investigación de la Sociedad Argentina de Reumatología, Buenos Aires, Argentina
| | - Margarita Landi
- Present Address: Unidad de Investigación de la Sociedad Argentina de Reumatología, Buenos Aires, Argentina
| | | | - Guillermo J. Pons-Estel
- Present Address: Unidad de Investigación de la Sociedad Argentina de Reumatología, Buenos Aires, Argentina
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A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients. Med Intensiva 2023; 47:23-33. [PMID: 34720310 PMCID: PMC8547942 DOI: 10.1016/j.medin.2021.10.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/02/2021] [Indexed: 01/04/2023]
Abstract
Objective To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design A secondary analysis derived from multicenter, observational study. Setting Critical Care Units. Patients Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions Corticosteroids vs. no corticosteroids. Main variables of interest Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.
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16
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Promoting self‐healing power and balancing immune response: a holistic, effective strategy of traditional Chinese medicine in treating COVID‐19. PHARMACOLOGICAL RESEARCH. MODERN CHINESE MEDICINE 2022; 5:100199. [PMCID: PMC9674391 DOI: 10.1016/j.prmcm.2022.100199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/15/2022] [Accepted: 11/18/2022] [Indexed: 06/24/2023]
Abstract
The COVID-19 pandemic is a serious challenge to human medicines. Modern medicine (MM) has been excellent in identifying the virus, sequencing its mutants, and monitoring the pandemic progress. However, due to lack of effective antivirals in the first two years of the pandemic, MM treated COVID-19 mainly by conventional supportive care with limited efficacy. In China, traditional Chinese medicine (TCM) has been actively participating the control of COVID-19, and the combination of TCM and conventional supportive care has shown better efficacies than the conventional care alone. Purpose: Clinical studies have shown that TCM treats COVID-19 through a holistic action, such as repairing organ injuries, anti-inflammation, immunoregulation and antiviral activities, etc. However, it is not clear how TCM is able to achieve these effects, and the scientific interpretation of TCM theories is lacking. This review aims to elucidate the scientific basis underlying TCM theories in the context of host-pathogen interaction and provide a working model for TCM in treating infectious diseases. Procedure: This review focuses on the essential components of host-pathogen interaction and performs an in-depth analysis of current literatures, including TCM theories and clinical studies as well as the most recent findings of tolerance (self-healing) mechanism in biomedical sciences. Conclusion: TCM treats COVID-19 through a holistic regulation of host responses, particularly by promoting patients’ self-healing power and balancing immune responses. Compared to the pathogen-centered MM, the host-centered TCM doesn't require specific antivirals and has less side-effects and drug resistance. This review provides a scientific insight into the mechanism of TCM and sheds a light on the prospective integration of TCM and MM for future challenges.
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Shah SMI, Yasmin F, Memon RS, Jatoi NN, Savul IS, Kazmi S, Monawwer SA, Zafar MDB, Asghar MS, Tahir MJ, Lee KY. COVID-19 and myasthenia gravis: A review of neurological implications of the SARS-COV-2. Brain Behav 2022; 12:e2789. [PMID: 36306401 PMCID: PMC9759145 DOI: 10.1002/brb3.2789] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 09/10/2022] [Accepted: 09/24/2022] [Indexed: 11/11/2022] Open
Abstract
INTRODUCTION This review highlights the potential mechanisms of neuromuscular manifestation of COVID-19, especially myasthenia gravis (MG). METHODS An extensive literature search was conducted by two independent investigators using PubMed/MEDLINE and Google Scholar from its inception to December 2020. RESULTS Exacerbations of clinical symptoms in patients of MG who were treated with some commonly used COVID-19 drugs has been reported, with updated recommendations of management of symptoms of neuromuscular disorders. Severe acute respiratory syndrome coronavirus 2 can induce the immune response to trigger autoimmune neurological disorders. CONCLUSIONS Further clinical studies are warranted to indicate and rather confirm if MG in the setting of COVID-19 can pre-existent subclinically or develop as a new-onset disease.
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Affiliation(s)
| | - Farah Yasmin
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Roha Saeed Memon
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Nadia Nazir Jatoi
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Ilma Saleh Savul
- Department of Internal Medicine, St. Joseph Medical Center, Houston, Texas, USA
| | - Sana Kazmi
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | | | - Muhammad Daim Bin Zafar
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | | | | | - Ka Yiu Lee
- Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden
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18
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Abadi B, Aarabi Jeshvaghani AH, Fathalipour H, Dehghan L, Rahimi Sirjani K, Forootanfar H. Therapeutic Strategies in the Fight against COVID-19: From Bench to Bedside. IRANIAN JOURNAL OF MEDICAL SCIENCES 2022; 47:517-532. [PMID: 36380976 PMCID: PMC9652495 DOI: 10.30476/ijms.2021.92662.2396] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Revised: 11/17/2021] [Accepted: 12/10/2021] [Indexed: 06/16/2023]
Abstract
In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China. This virus rapidly spread worldwide and was declared a global pandemic by the World Health Organization (WHO) in March 2020. High incidence, long incubation period, and diverse clinical signs of the disease posed a huge challenge globally. The efforts of health systems have been focused on repurposing existing drugs or developing innovative therapies to reduce the morbidity and mortality associated with SARS-CoV-2. In addition, most of the large pharmaceutical companies are intensely working on vaccine development to swiftly deliver safe and effective vaccines to prevent further spread of the virus. In this review, we will discuss the latest data on therapeutic strategies undergoing clinical trials. Additionally, we will provide a summary of vaccines currently under development.
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Affiliation(s)
- Banafshe Abadi
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Brain Cancer Research Core, Universal Scientific Education and Research Network, Tehran, Iran
| | | | - Hadis Fathalipour
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Leili Dehghan
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Hamid Forootanfar
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
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19
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El-Saber Batiha G, Al-Gareeb AI, Saad HM, Al-kuraishy HM. COVID-19 and corticosteroids: a narrative review. Inflammopharmacology 2022; 30:1189-1205. [PMID: 35562628 PMCID: PMC9106274 DOI: 10.1007/s10787-022-00987-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 03/30/2022] [Indexed: 02/06/2023]
Abstract
It has been reported that corticosteroid therapy was effective in the management of severe acute respiratory syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), and recently in coronavirus disease 2019 (COVID-19). Corticosteroids are potent anti-inflammatory drugs that mitigate the risk of acute respiratory distress syndrome (ARDS) in COVID-19 and other viral pneumonia, despite a reduction of viral clearance; corticosteroids inhibit the development of cytokine storm and multi-organ damage. The risk-benefit ratio should be assessed for critical COVID-19 patients. In conclusion, corticosteroid therapy is an effective way in the management of COVID-19, it reduces the risk of complications primarily acute lung injury and the development of ARDS. Besides, corticosteroid therapy mainly dexamethasone and methylprednisolone are effective in reducing the severity of COVID-19 and associated comorbidities such as chronic obstructive pulmonary diseases (COPD), rheumatoid arthritis, and inflammatory bowel disease (IBD).
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Affiliation(s)
- Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511 AlBeheira Egypt
| | - Ali I. Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyiah University, Baghdad, Iraq
| | - Hebatallah M. Saad
- Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, 51744 Matrouh Egypt
| | - Hayder M. Al-kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyiah University, Baghdad, Iraq
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20
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Peter L, Wendering DJ, Schlickeiser S, Hoffmann H, Noster R, Wagner DL, Zarrinrad G, Münch S, Picht S, Schulenberg S, Moradian H, Mashreghi MF, Klein O, Gossen M, Roch T, Babel N, Reinke P, Volk HD, Amini L, Schmueck-Henneresse M. Tacrolimus-resistant SARS-CoV-2-specific T cell products to prevent and treat severe COVID-19 in immunosuppressed patients. Mol Ther Methods Clin Dev 2022; 25:52-73. [PMID: 35252469 PMCID: PMC8882037 DOI: 10.1016/j.omtm.2022.02.012] [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: 02/16/2022] [Accepted: 02/25/2022] [Indexed: 12/15/2022]
Abstract
Solid organ transplant (SOT) recipients receive therapeutic immunosuppression that compromises their immune response to infections and vaccines. For this reason, SOT patients have a high risk of developing severe coronavirus disease 2019 (COVID-19) and an increased risk of death from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Moreover, the efficiency of immunotherapies and vaccines is reduced due to the constant immunosuppression in this patient group. Here, we propose adoptive transfer of SARS-CoV-2-specific T cells made resistant to a common immunosuppressant, tacrolimus, for optimized performance in the immunosuppressed patient. Using a ribonucleoprotein approach of CRISPR-Cas9 technology, we have generated tacrolimus-resistant SARS-CoV-2-specific T cell products from convalescent donors and demonstrate their specificity and function through characterizations at the single-cell level, including flow cytometry, single-cell RNA (scRNA) Cellular Indexing of Transcriptomes and Epitopes (CITE), and T cell receptor (TCR) sequencing analyses. Based on the promising results, we aim for clinical validation of this approach in transplant recipients. Additionally, we propose a combinatory approach with tacrolimus, to prevent an overshooting immune response manifested as bystander T cell activation in the setting of severe COVID-19 immunopathology, and tacrolimus-resistant SARS-CoV-2-specific T cell products, allowing for efficient clearance of viral infection. Our strategy has the potential to prevent severe COVID-19 courses in SOT or autoimmunity settings and to prevent immunopathology while providing viral clearance in severe non-transplant COVID-19 cases.
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Affiliation(s)
- Lena Peter
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Einstein Center for Regenerative Therapies at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Désirée Jacqueline Wendering
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Stephan Schlickeiser
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Henrike Hoffmann
- Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Rebecca Noster
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Dimitrios Laurin Wagner
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Transfusion Medicine, Charitéplatz 1, 10117 Berlin, Germany
| | - Ghazaleh Zarrinrad
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Einstein Center for Regenerative Therapies at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Sandra Münch
- Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Samira Picht
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Sarah Schulenberg
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Einstein Center for Regenerative Therapies at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Hanieh Moradian
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Institute of Active Polymers, Helmholtz-Zentrum Hereon, Kantstr. 55, 14513 Teltow, Germany.,Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
| | - Mir-Farzin Mashreghi
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany
| | - Oliver Klein
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany
| | - Manfred Gossen
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Institute of Active Polymers, Helmholtz-Zentrum Hereon, Kantstr. 55, 14513 Teltow, Germany
| | - Toralf Roch
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany.,Center for Translational Medicine, Immunology, and Transplantation, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Hölkeskampring 40, 44625 Herne, Germany
| | - Nina Babel
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany.,Center for Translational Medicine, Immunology, and Transplantation, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Hölkeskampring 40, 44625 Herne, Germany
| | - Petra Reinke
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Hans-Dieter Volk
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.,Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Institute of Medical Immunology, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Leila Amini
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Michael Schmueck-Henneresse
- Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Charitéplatz 1, 10117 Berlin, Germany.,Berlin Center for Advanced Therapies (BeCAT) at Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
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21
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Liu Y, Zhou T, Hu J, Jin S, Wu J, Guan X, Wu Y, Cui J. Targeting Selective Autophagy as a Therapeutic Strategy for Viral Infectious Diseases. Front Microbiol 2022; 13:889835. [PMID: 35572624 PMCID: PMC9096610 DOI: 10.3389/fmicb.2022.889835] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 03/29/2022] [Indexed: 12/13/2022] Open
Abstract
Autophagy is an evolutionarily conserved lysosomal degradation system which can recycle multiple cytoplasmic components under both physiological and stressful conditions. Autophagy could be highly selective to deliver different cargoes or substrates, including protein aggregates, pathogenic proteins or superfluous organelles to lysosome using a series of cargo receptor proteins. During viral invasion, cargo receptors selectively target pathogenic components to autolysosome to defense against infection. However, viruses not only evolve different strategies to counteract and escape selective autophagy, but also utilize selective autophagy to restrict antiviral responses to expedite viral replication. Furthermore, several viruses could activate certain forms of selective autophagy, including mitophagy, lipophagy, aggrephagy, and ferritinophagy, for more effective infection and replication. The complicated relationship between selective autophagy and viral infection indicates that selective autophagy may provide potential therapeutic targets for human infectious diseases. In this review, we will summarize the recent progress on the interplay between selective autophagy and host antiviral defense, aiming to arouse the importance of modulating selective autophagy as future therapies toward viral infectious diseases.
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Affiliation(s)
- Yishan Liu
- Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Tao Zhou
- Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
| | - Jiajia Hu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shouheng Jin
- Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
| | - Jianfeng Wu
- Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiangdong Guan
- Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yaoxing Wu
- Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jun Cui
- Ministry of Education (MOE) Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
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22
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Yoo W, Lee W, Kim HN, Jeong J, Park HH, Ahn JH, Jung D, Lee J, Kim JS, Lee SW, Cho WS, Kim S. Nanodiamond as a Cytokine Sponge in Infectious Diseases. Front Bioeng Biotechnol 2022; 10:862495. [PMID: 35445003 PMCID: PMC9014093 DOI: 10.3389/fbioe.2022.862495] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 03/15/2022] [Indexed: 11/25/2022] Open
Abstract
Cytokine release syndrome (CRS) is a systemic inflammatory response resulting in overexpression of cytokines in serum and tissues, which leads to multiple-organ failure. Due to rapid aggravation of symptoms, timely intervention is paramount; however, current therapies are limited in their capacity to address CRS. Here, we find that the intravenous injection of highly purified detonation-synthesized nanodiamonds (DND) can act as a therapeutic agent for treating CRS by adsorbing inflammatory cytokines. Highly purified DNDs successfully inactivated various key cytokines in plasma from CRS patients with pneumonia, septic shock, and coronavirus disease 2019 pandemic (COVID-19). The intravenous injection of the DND samples in a mouse sepsis model by cecal ligation and puncture significantly improved survival rates and prevented tissue damage by reducing the circulating inflammatory cytokines. The results of this study suggest that the clinical application of highly purified DND can provide survival benefits for CRS patients by adsorbing inflammatory cytokines.
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Affiliation(s)
- Wonbeak Yoo
- Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea
| | - Wonhwa Lee
- Department of Chemistry, Sungkyunkwan University, Suwon, South Korea
| | - Hong Nam Kim
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea
| | - Jiyoung Jeong
- Department of Health Sciences, The Graduate School of Dong-A University, Busan, South Korea
| | - Hee Ho Park
- Department of Bioengineering, Hanyang University, Seoul, South Korea
| | - June Hong Ahn
- Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, South Korea
| | - Dana Jung
- Department of Health Sciences, The Graduate School of Dong-A University, Busan, South Korea
| | - Juheon Lee
- Department of Health Sciences, The Graduate School of Dong-A University, Busan, South Korea
| | - Ji-su Kim
- Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, South Korea
| | - Seung Whan Lee
- Institute of Plasma Technology Research, Korea Institute of Fusion Energy, Gunsan-si, South Korea
- *Correspondence: Seung Whan Lee, ; Wan-Seob Cho, ; Seokho Kim,
| | - Wan-Seob Cho
- Department of Health Sciences, The Graduate School of Dong-A University, Busan, South Korea
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, South Korea
- *Correspondence: Seung Whan Lee, ; Wan-Seob Cho, ; Seokho Kim,
| | - Seokho Kim
- Department of Health Sciences, The Graduate School of Dong-A University, Busan, South Korea
- Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, South Korea
- *Correspondence: Seung Whan Lee, ; Wan-Seob Cho, ; Seokho Kim,
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23
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Najjar M, Albuaini S, Fadel M, Aljbawi A, Mohsen F, Sulaiman S, Koudsi A. COVID-19 Disease in Syrian Patients With Cancer: Clinical Manifestations, Laboratory Findings, Treatment, and Outcomes. JCO Glob Oncol 2022; 8:e2100283. [PMID: 35230875 PMCID: PMC8887951 DOI: 10.1200/go.21.00283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 11/16/2021] [Accepted: 01/24/2022] [Indexed: 12/15/2022] Open
Abstract
PURPOSE This study aims to describe the clinical manifestations, laboratory findings, treatment, and outcomes of patients with cancer with COVID-19 infection in Syria. The primary objective was to identify the overall survival (OS) time, and the secondary objectives were to identify factors associated with severe COVID-19 infection. METHODS This multicenter retrospective study was undertaken at four hospitals in Damascus, Syria, between March 28, 2020, and March 29, 2021. Data extracted from medical records included clinical manifestations, radiologic findings, laboratory results, treatment, and outcomes. Survival analysis was done by using the Kaplan-Meier method and Cox regression model for follow-up and anticancer treatment patients to study the effect on OS time. The effects of potential risk factors of developing severe COVID-19 were studied by multivariable logistic regression. RESULTS Of 114 patients included, 61 (53.51%) were male. Smokers represented 29 (25.44%), and 63 (55.26%) patients had a history of coexisting chronic diseases. The most common cancer type was breast cancer 17 (14.91%). Sixty-eight (59.65%) patients were receiving anticancer treatment within 1 month of being diagnosed with COVID-19 infection and 46 (40.35%) were outpatient follow-ups. Multiple logistic regression analysis showed that comorbidities (odds ratio: 2.814, P = .044) and anticancer treatment (odds ratio: 8.790, P < .05) were risk factors linked to severe to critical COVID-19 infection. OS time was 245 (95% CI, 217.96 to 272.47) days, lower among patients with cancer with COVID-19 infection receiving anticancer treatment compared with follow-up patients (P value < .05). CONCLUSION Patients with cancer with COVID-19 infection receiving anticancer treatment had a lower OS time. It may be worth considering stopping anticancer treatment in patients with cancer with COVID-19 when possible in search of better outcomes.
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Affiliation(s)
- Michel Najjar
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Sara Albuaini
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Mohammad Fadel
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Ahmed Aljbawi
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Fatema Mohsen
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Seham Sulaiman
- Department of Internal Medicine, Faculty of Medicine, Damascus University, Damascus, Syria
- Department of Internal Medicine, Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Abir Koudsi
- Department of Family and Community Medicine, Faculty of Medicine, Damascus University, Damascus, Syria
- Department of Family and Community Medicine, Faculty of Medicine, Syrian Private University, Damascus, Syria
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24
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Ghaleb N, Bulkhi A, Al-Qurashi E, Touman A, Aldobyany A, Alsaggaf R, Mabar H, Murtaza N, Rajab A. Clinical characteristics and risk factors for mortality of hospitalized cancer patients with COVID-2019 in Mecca, Saudi Arabia. Ann Thorac Med 2022; 17:220-228. [DOI: 10.4103/atm.atm_91_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/09/2022] [Indexed: 11/04/2022] Open
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25
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Peng Z, Su L, Yang C, Zhang J, Dou R, Sun Z, Yang J, He L, Jiang N, Huang R, Yuan F, Xiao G, Gan Q, Lu Q. Corticosteroids Utilization in the Management of Critically Ill Coronavirus Disease-2019 Pneumonia. JOURNAL OF TRANSLATIONAL CRITICAL CARE MEDICINE 2022. [PMCID: PMC9070587 DOI: 10.4103/jtccm.jtccm-d-21-00011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Tsagkaris C, Bilal M, Aktar I, Aboufandi Y, Tas A, Aborode AT, Suvvari TK, Ahmad S, Shkodina A, Phadke R, Emhamed MS, Baig AA, Alexiou A, Ashraf GM, Kamal MA. Cytokine Storm and Neuropathological Alterations in Patients with Neurological Manifestations of COVID-19. Curr Alzheimer Res 2022; 19:641-657. [PMID: 36089786 DOI: 10.2174/1567205019666220908084559] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 07/09/2022] [Accepted: 07/22/2022] [Indexed: 11/22/2022]
Abstract
The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines, such as TNF-α, IFN-γ, IL-6 IL-8, IL- 10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients may persist even after apparent recovery from infection. Biomarker studies on CSF and plasma and serum from COVID-19 patients have also shown a high level of IL-6, intrathecal IgG, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and tau protein. Emerging evidence on the matter has established the concept of COVID-19-associated neuroinflammation, in the context of COVID-19-associated cytokine storm. While the short-term implications of this condition are extensively documented, its longterm implications are yet to be understood. The association of the aforementioned cytokines with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, may increase COVID-19 patients' risk of developing neurodegenerative diseases. Analysis of proinflammatory cytokines and CSF biomarkers in patients with COVID-19 can contribute to the early detection of the disease's exacerbation, monitoring the neurological implications of the disease and devising risk scales, and identifying treatment targets.
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Affiliation(s)
| | - Muhammad Bilal
- College of Pharmacy, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan
| | - Irem Aktar
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Ahmet Tas
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | | | - Tarun Kumar Suvvari
- Faculty of Medicine, Dr. NTR University of Health Sciences, Vijayawada, India
| | - Shoaib Ahmad
- Department of Medical Sciences, Punjab Medical College, Faisalabad, Pakistan
- Faisalabad Medical University, Faisalabad, Pakistan
| | - Anastasiia Shkodina
- Department of Neurological Diseases With Neurosurgery and Medical Genetics, Poltava State Medical University, Poltava, Ukraine
| | - Rachana Phadke
- School of Medicine, Indira Gandhi Government Medical College, Nagpur, India
| | | | - Atif Amin Baig
- Faculty of Medicine, Sultan Zainal Abidin University, Kuala Terengganu, Malaysia
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia
- AFNP Med Austria, Wien 1010, Austria
| | - Ghulam Md Ashraf
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, University City, Sharjah 27272, United Arab Emirates
| | - Mohammad Amjad Kamal
- West China School of Nursing /Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Enzymoics, 7 Peterlee Place, Novel Global Community Educational Foundation, Hebersham, NSW, Australia
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Benalia A, Environment and Health Research Laboratory (LRES), Faculty of Medicine, University of Djillali Liabes, Sidi Bel Abbès, Algeria, Abdeldjebar H, Badji TE, Centre de Recherche Scientifique et Technique en Analyses Physico Chimiques, Bou Ismail, Algeria, Laboratoire Physico-Chimie des Matériaux Avancés(LPCMA), Faculté des sciences exactes, Sidi Bèl Abbès, Algeria. Computational Docking Study of Calanolides as Potential Inhibitors of SARS-CoV-2 Main Protease. FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY 2022. [DOI: 10.17721/fujcv10i1p48-59] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Despite the nationwide effort provided to combat the COVID-19 pandemic, we have yet to approve a specific antiviral treatment against the SARS-CoV-2. We have studied the molecular interactions between two anti-HIV-1 natural drugs, +(-) calanolide A and -(-) calanolide B, and the active site of 3CLpro through a computational docking method. Our promising results show that the two compounds of this study are potential inhibitors of the SARS-CoV-2 3CLpro through strong binding to its catalytic dyad. Considering its progress in clinical trials as an anti-HIV-1 treatment, we suggest that +(-) calanolide A is a good candidate for the treatment of COVID-19.
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Mairpady Shambat S, Gómez-Mejia A, Schweizer TA, Huemer M, Chang CC, Acevedo C, Bergada-Pijuan J, Vulin C, Hofmaenner DA, Scheier TC, Hertegonne S, Parietti E, Miroshnikova N, Wendel Garcia PD, Hilty MP, Buehler PK, Schuepbach RA, Brugger SD, Zinkernagel AS. Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19. PLoS Pathog 2022; 18:e1010176. [PMID: 35007290 PMCID: PMC8782468 DOI: 10.1371/journal.ppat.1010176] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 01/21/2022] [Accepted: 12/06/2021] [Indexed: 02/06/2023] Open
Abstract
COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU stay and ventilation-days in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients.
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Affiliation(s)
- Srikanth Mairpady Shambat
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Alejandro Gómez-Mejia
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Tiziano A. Schweizer
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Markus Huemer
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Chun-Chi Chang
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Claudio Acevedo
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Judith Bergada-Pijuan
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Clément Vulin
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Daniel A. Hofmaenner
- Institute of Intensive Care, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Thomas C. Scheier
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Sanne Hertegonne
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Elena Parietti
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Nataliya Miroshnikova
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Pedro D. Wendel Garcia
- Institute of Intensive Care, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Matthias P. Hilty
- Institute of Intensive Care, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Philipp Karl Buehler
- Institute of Intensive Care, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Reto A. Schuepbach
- Institute of Intensive Care, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Silvio D. Brugger
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Annelies S. Zinkernagel
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
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Balaz D, Wikman-Jorgensen PE, Galvañ VG, Rubio-Rivas M, de Miguel Campo B, López MN, Caleya JFL, Huelgas RG, Fontán PMP, Bailón MM, Fernández-Garcés M, Cruz AF, García GMG, Rhyman N, Corral-Gudino L, Rodríguez-Mancheño AL, De La Chica MN, García AT, Alcalá JN, Jiménez PD, Trallero LER, Casanova PC, Núñez-Cortés JM, Casas-Rojo JM, on behalf of the SEMI-COVID-19 Network. Evolution of the Use of Corticosteroids for the Treatment of Hospitalised COVID-19 Patients in Spain between March and November 2020: SEMI-COVID National Registry. J Clin Med 2021; 10:4610. [PMID: 34640628 PMCID: PMC8509849 DOI: 10.3390/jcm10194610] [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] [Received: 09/03/2021] [Revised: 10/01/2021] [Accepted: 10/04/2021] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. MATERIAL AND METHODS A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID-19 Registry from March to November 2020. RESULTS CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236-996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation CONCLUSIONS Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation
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Affiliation(s)
- David Balaz
- Department of Internal Medicine, Hospital Universitario San Juan de Alicante, 03550 Alicante, Spain
- Department of Clinical Medicine, Faculty of Medicine, Miguel Hernández University, 03202 Alicante, Spain
| | - Philip Erick Wikman-Jorgensen
- Department of Internal Medicine, Hospital Universitario San Juan de Alicante, 03550 Alicante, Spain
- Department of Clinical Medicine, Faculty of Medicine, Miguel Hernández University, 03202 Alicante, Spain
| | - Vicente Giner Galvañ
- Department of Internal Medicine, Hospital Universitario San Juan de Alicante, 03550 Alicante, Spain
- Department of Clinical Medicine, Faculty of Medicine, Miguel Hernández University, 03202 Alicante, Spain
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Conselleria de Sanitat, 46010 Valencia, Spain
| | - Manuel Rubio-Rivas
- Department of Internal Medicine, Hospital Universitario de Bellvitge, 08907 Barcelona, Spain;
| | - Borja de Miguel Campo
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain;
| | | | | | - Ricardo Gómez Huelgas
- Department of Internal Medicine, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain;
| | | | - Manuel Méndez Bailón
- Department of Internal Medicine, Hospital Clínico San Carlos, 28040 Madrid, Spain;
| | - Mar Fernández-Garcés
- Department of Internal Medicine, Hospital Universitario Dr. Peset, 46017 Valencia, Spain;
| | - Ana Fernández Cruz
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain;
| | - Gema María García García
- Department of Internal Medicine, Complejo Hospitalario Universitario de Badajoz, 06010 Badajoz, Spain;
| | - Nicolás Rhyman
- Department of Internal Medicine, Hospital Moisès Broggi, Sant Joan Despí, 08970 Barcelona, Spain;
| | - Luis Corral-Gudino
- Department of Internal Medicine, Hospital Universitario Río Hortega, 47012 Valladolid, Spain;
| | | | | | | | - José Nicolás Alcalá
- Department of Internal Medicine, Hospital de Pozoblanco, 14400 Córdoba, Spain;
| | - Pablo Díaz Jiménez
- Department of Internal Medicine, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain;
| | | | - Pere Comas Casanova
- Department of Internal Medicine, Hospital Comarcal de Blanes, 17300 Girona, Spain;
| | | | - José-Manuel Casas-Rojo
- Department of Internal Medicine, Hospital Infanta Cristina University Hospital, 28981 Madrid, Spain;
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Chong WH, Saha BK, Chopra A. Does COVID-19 pneumonia signify secondary organizing pneumonia?: A narrative review comparing the similarities between these two distinct entities. Heart Lung 2021; 50:667-674. [PMID: 34098237 PMCID: PMC8164344 DOI: 10.1016/j.hrtlng.2021.04.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/07/2021] [Accepted: 04/12/2021] [Indexed: 12/16/2022]
Abstract
Multiple observational studies have described the similarities between COVID-19 pneumonia and organizing pneumonia (OP). These two entities clinically manifest with mild and subacute respiratory symptoms, often with a delayed diagnosis due to the atypical ARDS and silent hypoxemia presentation. Radiological features are often indistinguishable between the two. With the increase in antemortem lung biopsies and autopsies being performed, more histopathological findings of OP and its variant, acute fibrinous and organizing pneumonia (AFOP), are being diagnosed. These entities are known complications of viral infections as a delayed immunological process, explaining the favorable response to corticosteroids. Clinicians should be vigilant to diagnose this under-recognized entity of secondary OP in people with COVID-19 when clinical deterioration occurs, especially with compatible radiologic findings and recent cessation of corticosteroids. Despite the proven benefits of corticosteroids in treating COVID-19, treatment approaches can be more effective as OP often requires higher doses and a more prolonged therapy duration for remission and preventing relapses. The purpose of our narrative review is to compare the similarities between COVID-19 pneumonia and OP, emphasizing the clinical, radiological, and histopathological features based on the evidence available in the literature.
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Affiliation(s)
- Woon H Chong
- Department of Pulmonary and Critical Care Medicine, Albany Medical Center, 43 New Scotland Avenue, Albany 12208, New York, USA.
| | - Biplab K Saha
- Department of Pulmonary and Critical Care, Ozarks Medical Center, West Plains, Missouri, USA
| | - Amit Chopra
- Department of Pulmonary and Critical Care Medicine, Albany Medical Center, 43 New Scotland Avenue, Albany 12208, New York, USA
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Mslati H, Gentile F, Perez C, Cherkasov A. Comprehensive Consensus Analysis of SARS-CoV-2 Drug Repurposing Campaigns. J Chem Inf Model 2021; 61:3771-3788. [PMID: 34313439 PMCID: PMC8340583 DOI: 10.1021/acs.jcim.1c00384] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Indexed: 01/18/2023]
Abstract
The current COVID-19 pandemic has elicited extensive repurposing efforts (both small and large scale) to rapidly identify COVID-19 treatments among approved drugs. Herein, we provide a literature review of large-scale SARS-CoV-2 antiviral drug repurposing efforts and highlight a marked lack of consistent potency reporting. This variability indicates the importance of standardizing best practices-including the use of relevant cell lines, viral isolates, and validated screening protocols. We further surveyed available biochemical and virtual screening studies against SARS-CoV-2 targets (Spike, ACE2, RdRp, PLpro, and Mpro) and discuss repurposing candidates exhibiting consistent activity across diverse, triaging assays and predictive models. Moreover, we examine repurposed drugs and their efficacy against COVID-19 and the outcomes of representative repurposed drugs in clinical trials. Finally, we propose a drug repurposing pipeline to encourage the implementation of standard methods to fast-track the discovery of candidates and to ensure reproducible results.
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Affiliation(s)
- Hazem Mslati
- Vancouver Prostate Centre, University of
British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6,
Canada
| | - Francesco Gentile
- Vancouver Prostate Centre, University of
British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6,
Canada
| | - Carl Perez
- Vancouver Prostate Centre, University of
British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6,
Canada
| | - Artem Cherkasov
- Vancouver Prostate Centre, University of
British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6,
Canada
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Sargazi S, Sheervalilou R, Rokni M, Shirvaliloo M, Shahraki O, Rezaei N. The role of autophagy in controlling SARS-CoV-2 infection: An overview on virophagy-mediated molecular drug targets. Cell Biol Int 2021; 45:1599-1612. [PMID: 33818861 PMCID: PMC8251464 DOI: 10.1002/cbin.11609] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 03/22/2021] [Accepted: 04/01/2021] [Indexed: 12/16/2022]
Abstract
Autophagy-dependent cell death is a prominent mechanism that majorly contributes to homeostasis by maintaining the turnover of organelles under stressful conditions. Several viruses, including coronaviruses (CoVs), take advantage of cellular autophagy to facilitate their own replication. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-coronavirus (β-CoVs) that mediates its replication through a dependent or independent ATG5 pathway using specific double-membrane vesicles that can be considered as similar to autophagosomes. With due attention to several mutations in NSP6, a nonstructural protein with a positive regulatory effect on autophagosome formation, a potential correlation between SARS-CoV-2 pathogenesis mechanisms and autophagy can be expected. Certain medications, albeit limited in number, have been indicated to negatively regulate autophagy flux, potentially in a way similar to the inhibitory effect of β-CoVs on the process of autophagy. However, there is no conclusive evidence to support their direct antagonizing effect on CoVs. Off-target accumulation of a major fraction of FDA-approved autophagy modulating drugs may result in adverse effects. Therefore, medications that have modulatory effects on autophagy could be considered as potential lead compounds for the development of new treatments against this virus. This review discusses the role of autophagy/virophagy in controlling SARS-CoV-2, focusing on the potential therapeutic implications.
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Affiliation(s)
- Saman Sargazi
- Cellular and Molecular Research Center, Resistant Tuberculosis InstituteZahedan University of Medical SciencesZahedanIran
| | | | - Mohsen Rokni
- Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA)Universal Scientific Education and Research Network (USERN)TehranIran
| | - Milad Shirvaliloo
- Student Research CommitteeTabriz University of Medical SciencesTabrizIran
- Faculty of MedicineTabriz University of Medical SciencesTabrizIran
| | - Omolbanin Shahraki
- Pharmacology Research CenterZahedan University of Medical SciencesZahedanIran
| | - Nima Rezaei
- Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA)Universal Scientific Education and Research Network (USERN)TehranIran
- Research Center for Immunodeficiencies, Children's Medical CenterTehran University of Medical SciencesTehranIran
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Comparison of Associations Between Glucocorticoids Treatment and Mortality in COVID-19 Patients and SARS Patients: A Systematic Review and Meta-Analysis. Shock 2021; 56:215-228. [PMID: 33555845 DOI: 10.1097/shk.0000000000001738] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The response to glucocorticoids treatment may be different between coronavirus disease 2019 (Covid-19) and severe acute respiratory syndrome (SARS). METHODS In this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, ClinicalTrials.gov, International Clinical Trials Registry Platform from 2002 to October 7, 2020. We used fixed-effects and random-effects models to compute the risk ratio of death in the group receiving glucocorticoids treatment and the control group for COVID-19 and SARS, respectively. RESULTS Ten trials and 71 observational studies, with a total of 45,935 patients, were identified. Glucocorticoids treatment was associated with decreased all-cause mortality both in COVID-19 (risk ratio, 0.88; 95% confidence interval, 0.82-0.94; I2 = 26%) and SARS (0.48; 0.29-0.79; 10%), based on high-quality evidence, as well as decreased all-cause mortality-including composite outcome of COVID-19 (0.89; 0.82-0.98; 0%). In subgroup analyses, all-cause mortality was significantly lower among COVID-19 patients being accompanied by severe ARDS but not mild ARDS, taking low-dose or pulse glucocorticoids, being critically severe but not only severe, being of critical severity and old but not young, being of critical severity and men but not women, non-early taking glucocorticoids, taking dexamethasone or methylprednisolone, and with the increased inflammatory state; but for SARS, lower mortality was observed among those who were taking medium-high dose glucocorticoids, being severe or critically severe, early taking glucocorticoids, and taking methylprednisolone or prednisolone. CONCLUSIONS Glucocorticoids treatment reduced mortality in COVID-19 and SARS patients of critical severity; however, different curative effects existed between the two diseases among subpopulations, mainly regarding sex- and age-specific effects, optimal doses, and use timing of glucocorticoids.
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Lu L, Huang J, Deng X, Sun X, Dong J. Application of glucocorticoids in patients with novel coronavirus infection: From bench to bedside. TRADITIONAL MEDICINE AND MODERN MEDICINE 2021. [DOI: 10.1142/s257590002030009x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Glucocorticoids (GCs) have potential anti-inflammatory and immunosuppressive effects. There is plenty of controversy about the application of glucocorticoids in the treatment of coronavirus disease 2019 (COVID-19). This paper briefly summarizes the mechanism of glucocorticoids and their receptors and clinical applications in COVID-19. Through reviewing the current literature, our aim is to have a deeper understanding of the mechanism of GCs and their clinical applications, so as to find possible ways to enhance their efficacy and reduce drug resistance or side effects.
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Affiliation(s)
- Linwei Lu
- Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, P. R. China
- Qingpu Chinese Medicine Hospital, Institutes of Integrative Medicine, Fudan University, Shanghai, P. R. China
| | - Jianhua Huang
- Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, P. R. China
- Qingpu Chinese Medicine Hospital, Institutes of Integrative Medicine, Fudan University, Shanghai, P. R. China
| | - Xiaohong Deng
- Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, P. R. China
- Qingpu Chinese Medicine Hospital, Institutes of Integrative Medicine, Fudan University, Shanghai, P. R. China
| | - Xianjun Sun
- Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, P. R. China
- Qingpu Chinese Medicine Hospital, Institutes of Integrative Medicine, Fudan University, Shanghai, P. R. China
| | - Jingcheng Dong
- Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, P. R. China
- Qingpu Chinese Medicine Hospital, Institutes of Integrative Medicine, Fudan University, Shanghai, P. R. China
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35
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Yuen KCJ, Mortensen MJ, Azadi A, Fonkem E, Findling JW. Rethinking the management of immune checkpoint inhibitor-related adrenal insufficiency in cancer patients during the COVID-19 pandemic. Endocrinol Diabetes Metab 2021; 4:e00246. [PMID: 34268454 PMCID: PMC8250331 DOI: 10.1002/edm2.246] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 02/15/2021] [Accepted: 02/20/2021] [Indexed: 12/12/2022] Open
Abstract
Introduction The coronavirus disease 2019 (COVID-19) is currently a major pandemic challenge, and cancer patients are at a heightened risk of severity and mortality from this infection. In recent years, immune checkpoint inhibitor (ICI) use to treat multiple cancers has increased in oncology, but equally has raised the question of whether ICI therapy and its side-effects is harmful or beneficial during this pandemic. Methods A combination of published literature in PubMed between January 2010 and December 2020, recommended guidelines in non-cancer patients, and clinical experience was utilized to outline recommendations on glucocorticoid timing and dosing regimens in ICI-treated patients presenting with AI during this COVID-19 pandemic. Results The potential immune interaction between ICIs and COVID-19 require major consideration because these agents act at the intersection between effective cancer immunotherapy and increasing patient susceptibility, severity and complications from the SARS-CoV-2 sepsis. Furthermore, ICI use can induce autoimmune adrenal insufficiency (AI) that further increases infection susceptibility. Thus, ICI-treated cancer patients with AI may be at greater risk of COVID-19 infection. Glucocorticoids are the cornerstone for replacement therapy, and for treatment and mitigation of adrenal crisis and relief of mass effects in ICI-related hypophysitis. High-dose glucocorticoids have also been used with cytotoxic chemotherapy as part of cancer treatment, and iatrogenic AI may arise after glucocorticoid discontinuation that increases the risk of adrenal crisis. Furthermore, in patients who develop the "long COVID-19" syndrome, when to discontinue glucocorticoid therapy becomes crucial to avoid unnecessary prolongation of therapy and the development of iatrogenic hypercortisolemia. Conclusion During the COVID-19 pandemic, much of cancer care have been impacted and an important clinical question is how to optimally manage ICI-related AI during these unprecedented times. Herein, we suggest practical recommendations on the timing and dosing regimens of glucocorticoids in different clinical scenarios of ICI-treated cancer patients presenting with AI during this COVID-19 pandemic.
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Affiliation(s)
- Kevin C. J. Yuen
- Departments of Neuroendocrinology and NeurosurgeryBarrow Neurological InstituteUniversity of Arizona College of Medicine and Creighton School of MedicinePhoenixArizonaUSA
| | | | - Amir Azadi
- Departments of Neurology and Neuro‐OncologyBarrow Neurological Institute/Ivy Brain Center at PhoenixSt. Joseph’s Hospital and Medical CenterPhoenixArizonaUSA
| | - Ekokobe Fonkem
- Departments of Neurology and Neuro‐OncologyBarrow Neurological Institute/Ivy Brain Center at PhoenixSt. Joseph’s Hospital and Medical CenterPhoenixArizonaUSA
| | - James W. Findling
- Division of Endocrinology and Molecular MedicineMedical College of WisconsinMilwaukeeWisconsinUSA
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Ripon MAR, Bhowmik DR, Amin MT, Hossain MS. Role of arachidonic cascade in COVID-19 infection: A review. Prostaglandins Other Lipid Mediat 2021; 154:106539. [PMID: 33592322 PMCID: PMC7882227 DOI: 10.1016/j.prostaglandins.2021.106539] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 02/01/2021] [Accepted: 02/08/2021] [Indexed: 02/06/2023]
Abstract
The World Health Organization has described the 2019 Coronavirus disease caused by an influenza-like virus called SARS-CoV-2 as a pandemic. Millions of people worldwide are already infected by this virus, and severe infection causes hyper inflammation, thus disrupting lung function, exacerbating breath difficulties, and death. Various inflammatory mediators bio-synthesized through the arachidonic acid pathway play roles in developing cytokine storms, injuring virus-infected cells. Since pro-inflammatory eicosanoids, including prostaglandins, and leukotrienes, are key brokers for physiological processes such as inflammation, fever, allergy, and pain but, their function in COVID-19 is not well defined. This study addresses eicosanoid's crucial role through the arachidonic pathway in inflammatory cascading and recommends using bioactive lipids, NSAIDs, steroids, cell phospholipase A2 (cPLA2) inhibitors, and specialized pro-resolving mediators (SPMs) to treat COVID-19 disease. The role of soluble epoxide hydrolase inhibitors (SEHIs) in promoting the activity of epoxyeicosatrienoic acids (EETs) and 17-hydroxide-docosahexaenoic acid (17-HDHA) is also discussed. Additional research that assesses the eicosanoid profile in COVID-19 patients or preclinical models generates novel insights into coronavirus-host interaction and inflammation regulation.
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Affiliation(s)
- Md Abdur Rahman Ripon
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Dipty Rani Bhowmik
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Mohammad Tohidul Amin
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Mohammad Salim Hossain
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
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Chen Y, Guo L, Jiao Y, Fan F, Liu J, Chen M, Yuan H, Lin L, Wang Y. Imaging features of COVID-19: What we can learn from SARS and MERS (Review). Exp Ther Med 2021; 21:356. [PMID: 33732329 PMCID: PMC7903420 DOI: 10.3892/etm.2021.9787] [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: 06/11/2020] [Accepted: 12/11/2020] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly infectious type of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly become a global pandemic. COVID-19, SARS and Middle East respiratory syndrome (MERS) are all caused by members of the Coronaviridae family. As expected, emerging genetic and clinical evidence from patients with COVID-19 has indicated that the pathway of infection is similar to that of SARS and MERS. Additionally, much like SARS and MERS, chest imaging serves an important role in the diagnosis, management and follow-up of patients with COVID-19. Although these related viruses present a similar pneumonic pathogenesis, the imaging results have distinguishable features. The current review evaluated the imaging results of patients with SARS and MERS and explored the potential similarities and differences among patients with COVID-19, SARS and MERS at early, progressive, severe and recovery stages, with the aim of improving our understanding of SARS-CoV-2 infections by comparing the features of COVID-19 images with those of SARS and MERS. The current review assessed whether imaging results had implications for the administration of corticosteroids as treatment for COVID-19. Whether corticosteroids can inhibit inflammatory cytokine storms and reduce the mortality of patients with viral pneumonia remains controversial. However, his review may help radiologists and clinicians to identify viral pneumonia and guide appropriate COVID-19 treatment.
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Affiliation(s)
- Yuanbin Chen
- Department of Respiratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine and Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
| | - Liya Guo
- Department of Respiratory Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, P.R. China
| | - Yiqing Jiao
- Department of Respiratory Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, P.R. China
| | - Feiting Fan
- Department of Respiratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine and Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
| | - Jian Liu
- Department of Respiratory Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, P.R. China
| | - Ming Chen
- Department of Radiology, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui 236000, P.R. China
| | - Huaiping Yuan
- Department of Radiology, Fuyang Hospital of Anhui Medical University, Fuyang, Anhui 236000, P.R. China
| | - Lin Lin
- Department of Respiratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine and Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
| | - Yuguang Wang
- Department of Respiratory Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, P.R. China
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Tariq R, Khalid UA, Kanwal S, Adnan F, Qasim M. Photodynamic Therapy: A Rational Approach Toward COVID-19 Management. JOURNAL OF EXPLORATORY RESEARCH IN PHARMACOLOGY 2021; 000:000-000. [DOI: 10.14218/jerp.2020.00036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Zhang S, Wang C, Shi L, Xue Q. Beware of Steroid-Induced Avascular Necrosis of the Femoral Head in the Treatment of COVID-19-Experience and Lessons from the SARS Epidemic. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:983-995. [PMID: 33692615 PMCID: PMC7939498 DOI: 10.2147/dddt.s298691] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/19/2021] [Indexed: 01/08/2023]
Abstract
Summary The recent outbreak of coronavirus disease 2019 (COVID-19) has become a global epidemic. Corticosteroids have been widely used in the treatment of severe acute respiratory syndrome (SARS), and the pathological findings seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are very similar to those observed in severe acute respiratory syndrome-related coronavirus (SARS-CoV) infection. However, the long-term use of corticosteroids (especially at high doses) is associated with potentially serious adverse events, particularly steroid-induced avascular necrosis of the femoral head (SANFH). In today’s global outbreak, whether corticosteroid therapy should be used, the dosage and duration of treatment, and ways for the prevention, early detection, and timely intervention of SANFH are some important issues that need to be addressed. This review aims to provide a reference for health care providers in COVID-19 endemic countries and regions. Article Focus Hormones are a double-edged sword. This review aims to provide a reference for health care providers in coronavirus disease 2019 (COVID-19) endemic countries and regions, especially with respect to the pros and cons of corticosteroid use in the treatment of patients with COVID-19. Key Messages In today’s global outbreak, whether corticosteroid therapy should be used, the dosage and duration of treatment, and ways for the prevention, early detection, and timely intervention of SANFH are some important issues that need to be addressed. Strengths and Limitations Since SARS was mainly prevalent in China at that time, many evidences in this paper came from the reports of Chinese scholars. There is a bias in the selection of data, which may ignore the differences in environment, race, living habits, medical level and so on. SANFH may be the result of multiple factors. Whether the virus itself is an independent risk factor for SANFH has not been confirmed. In this paper, through literature retrieval, some reference opinions on glucocorticoid usage, diagnosis and treatment of SANFH are given. However, due to the lack of large-scale research data support, it can not be used as the gold standard for the above problems.
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Affiliation(s)
- Shenqi Zhang
- Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China.,Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.,Department of Joint and Sports Medicine, Zaozhuang Municipal Hospital Affiliated to Jining Medical University, Shandong, People's Republic of China
| | - Chengbin Wang
- Department of Joint and Sports Medicine, Zaozhuang Municipal Hospital Affiliated to Jining Medical University, Shandong, People's Republic of China
| | - Lei Shi
- Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China
| | - Qingyun Xue
- Department of Orthopedics, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China.,Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
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40
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Ye ZW, Yuan S, Chan JFW, Zhang AJ, Yu CY, Ong CP, Yang D, Chan CCY, Tang K, Cao J, Poon VKM, Chan CCS, Cai JP, Chu H, Yuen KY, Jin DY. Beneficial effect of combinational methylprednisolone and remdesivir in hamster model of SARS-CoV-2 infection. Emerg Microbes Infect 2021; 10:291-304. [PMID: 33538646 PMCID: PMC7919885 DOI: 10.1080/22221751.2021.1885998] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Effective treatments for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Dexamethasone has been shown to confer survival benefits to certain groups of hospitalized patients, but whether glucocorticoids such as dexamethasone and methylprednisolone should be used together with antivirals to prevent a boost of SARS-CoV-2 replication remains to be determined. Here, we show the beneficial effect of methylprednisolone alone and in combination with remdesivir in the hamster model of SARS-CoV-2 infection. Treatment with methylprednisolone boosted RNA replication of SARS-CoV-2 but suppressed viral induction of proinflammatory cytokines in human monocyte-derived macrophages. Although methylprednisolone monotherapy alleviated body weight loss as well as nasal and pulmonary inflammation, viral loads increased and antibody response against the receptor-binding domain of spike protein attenuated. In contrast, a combination of methylprednisolone with remdesivir not only prevented body weight loss and inflammation, but also dampened viral protein expression and viral loads. In addition, the suppressive effect of methylprednisolone on antibody response was alleviated in the presence of remdesivir. Thus, combinational anti-inflammatory and antiviral therapy might be an effective, safer and more versatile treatment option for COVID-19. These data support testing of the efficacy of a combination of methylprednisolone and remdesivir for the treatment of COVID-19 in randomized controlled clinical trials.
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Affiliation(s)
- Zi-Wei Ye
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Shuofeng Yuan
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Jasper Fuk-Woo Chan
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Anna Jinxia Zhang
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Ching-Yun Yu
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong
| | - Chon Phin Ong
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong
| | - Dong Yang
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Chris Chun-Yiu Chan
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Kaiming Tang
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Jianli Cao
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Vincent Kwok-Man Poon
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Chris Chung-Sing Chan
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Jian-Piao Cai
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Hin Chu
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Kwok-Yung Yuen
- State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong
| | - Dong-Yan Jin
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong
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Rebold N, Holger D, Alosaimy S, Morrisette T, Rybak M. COVID-19: Before the Fall, An Evidence-Based Narrative Review of Treatment Options. Infect Dis Ther 2021; 10:93-113. [PMID: 33495967 PMCID: PMC7831619 DOI: 10.1007/s40121-021-00399-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 01/08/2021] [Indexed: 12/21/2022] Open
Abstract
The 2019 novel coronavirus (COVID-19) has quickly become one of the most dire international pandemic crises since the 1918 Spanish flu. Evidence for COVID-19 pharmacological therapies has shown rapid growth and a diverse array of results, but an assessment of the value of each piece of evidence must be reinforced. This article aims to review utilized therapies, the evidence level supporting these therapies, as well as drugs under investigation for the treatment of COVID-19. Primary scrutinized therapies include antiviral regimens, such as remdesivir, hydroxychloroquine/chloroquine, lopinavir/ritonavir, immunomodulating drugs, such as corticosteroids and interleukin (IL) inhibitors, and other therapies including convalescent plasma. Only one therapy, dexamethasone, has shown a mortality benefit in randomized controlled trials and summarized evidence for other therapies show limited positive results. Reviewing these therapies in a historical way shows how limited evidence can drive therapy decisions. A broad summary of available evidence can assist clinicians in a return to hierarchical assessments of evidence which can lead to safer patient outcomes, improved distribution of resources, and better targets for appropriate therapy decisions.
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Affiliation(s)
- Nicholas Rebold
- Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA
| | - Dana Holger
- Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA
| | - Sara Alosaimy
- Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA
| | - Taylor Morrisette
- Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA
| | - Michael Rybak
- Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
- Department of Pharmacy, Detroit Receiving Hospital, Detroit, MI, USA.
- Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, MI, USA.
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42
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Guo Y, Chen Y, Li Y. Glucocorticoids Should Be Used With Caution in Patients With SARS-CoV-2. Front Med (Lausanne) 2021; 8:564943. [PMID: 33718395 PMCID: PMC7943439 DOI: 10.3389/fmed.2021.564943] [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: 05/23/2020] [Accepted: 02/01/2021] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, and the use of glucocorticoids in clinical practice is controversial. Our clinical experiences with glucocorticoid treatment suggested that, while use was effective in some cases, in other cases, glucocorticoid were ineffective and even resulted in immunosuppression that could lead to deterioration. Therefore, glucocorticoids should be used with caution in patients with SARS-CoV-2.
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Affiliation(s)
- Yong Guo
- Department of Critical Care Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yan Chen
- Department of Clinical Pharmocology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yingchuan Li
- Department of Critical Care Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Department of Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Hirawat R, Saifi MA, Godugu C. Targeting inflammatory cytokine storm to fight against COVID-19 associated severe complications. Life Sci 2021; 267:118923. [PMID: 33358906 PMCID: PMC7831473 DOI: 10.1016/j.lfs.2020.118923] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 12/09/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023]
Abstract
Such testing and trying time probably never seen before in the human history. The novel coronavirus disease abbreviated as COVID-19 is the ongoing health crisis which entered into human life in late December 2019. The ease of transmission between humans and the undetectability in early stage makes COVID-19 frightening and unprecedented. The disease is characterised by pneumonia progressing to breathing difficulty, acute respiratory distress syndrome (ARDS) and multi-organ failure. Clinical studies suggest excessive release of inflammatory mediators leads to cytokine storm, a phenomenon which appears to be potentially life-threatening in COVID-19. Across the globe, when the world authorities are grappling to contain the virus, our review provides a glimpse on structure, pathophysiology of the virus and further sheds light on various clinical complications associated with the disease in order to open up/raise new horizons to explore various possible theoretical targets for COVID-19. The review also portrays a question and debates: Can targeting cytokine storm can be a feasible approach to combat COVID-19?
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Affiliation(s)
- Rishabh Hirawat
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Mohd Aslam Saifi
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Chandraiah Godugu
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
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Li Y, Li J, Ke J, Jiao N, Zhu L, Shen L, Chen L, Jiang Z, Cheng S, Huang Y, Zou Y, Zhu R, Yan G. Adverse Outcomes Associated With Corticosteroid Use in Critical COVID-19: A Retrospective Multicenter Cohort Study. Front Med (Lausanne) 2021; 8:604263. [PMID: 33634148 PMCID: PMC7900536 DOI: 10.3389/fmed.2021.604263] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 01/21/2021] [Indexed: 12/15/2022] Open
Abstract
Corticosteroid is commonly used to reduce damage from inflammatory reactions in coronavirus disease 2019 (COVID-19). We aim to determine the outcomes of corticosteroid use in critically ill COVID-19 patients. Ninety six critically ill patients, hospitalized in 14 hospitals outside Wuhan from January 16 to March 30, 2020 were enrolled in this study. Among 96 critical patients, 68 were treated with corticosteroid (CS group), while 28 were not treated with corticosteroids (non-CS group). Multivariable logistic regression were performed to determine the possible correlation between corticosteroid use and the treatment outcomes. Forty-six (68%) patients in the CS group died compared to six (21%) of the non-CS group. Corticosteroid use was also associated with the development of ARDS, exacerbation of pulmonary fibrosis, longer hospital stay and virus clearance time. On admission, no difference in laboratory findings between the CS and the non-CS group was observed. After corticosteroid treatment, patients treated with corticosteroids were associated with higher counts of white blood cells, neutrophils, neutrophil-to-lymphocyte ratio, alanine aminotransferase level and Sequential Organ Failure Assessment score. In conclusion, corticosteroid use in critically ill COVID-19 patients was associated with a much higher case fatality rate. Frequent incidence of liver injury and multi-organ failure in corticosteroid treated patients may have contributed to the adverse outcomes. The multi-organ failure is likely caused by more persistent SARS-CoV-2 infection and higher viral load, due to the inhibition of immune surveillance by corticosteroid.
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Affiliation(s)
- Yichen Li
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Li
- The Third Clinical Medical College of Yangtze University, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, China
| | - Jia Ke
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Na Jiao
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Putuo People's Hospital, Department of Bioinformatics, Tongji University, Shanghai, China
| | - Lixin Zhu
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lihan Shen
- Department of Critical Care Medicine, Dongguan People's Hospital, Southern Medical University, Dongguan, China
| | - Lei Chen
- Department of Critical Care Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhiqiang Jiang
- School of Medicine, Sun Yat-sen University, Shenzhen, China
| | - Sijing Cheng
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- School of Medicine, Sun Yat-sen University, Shenzhen, China
| | - Yibo Huang
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yifeng Zou
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ruixin Zhu
- Putuo People's Hospital, Department of Bioinformatics, Tongji University, Shanghai, China
| | - Guangjun Yan
- The Third Clinical Medical College of Yangtze University, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou, China
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Akbas EM, Akbas N. COVID-19, adrenal gland, glucocorticoids, and adrenal insufficiency. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021; 165:1-7. [PMID: 33542545 DOI: 10.5507/bp.2021.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 01/21/2021] [Indexed: 01/08/2023] Open
Abstract
The current Coronavirus disease outbreak requires that physicians work in collaboration with other physicians especially in intensive care and emergency units. To fight against this new disease, whose pathogenesis, effects, and results have not been clearly demonstrated, especially in patients with the pre-existing chronic disease, requires special expertise and perspectives. Due to the need for dynamic glucocorticoid treatment at different stages of the disease in patients with adrenal insufficiency, the existence of reports indicating that "coronavirus disease 2019" also affects the adrenal reserve, and the use of glucocorticoids also in advanced stages in patients with Coronavirus disease require this issue to be emphasized with precision. Herein, treatment of the pre-existing adrenal insufficiency in patients with actual Coronavirus disease and the effects of the this critical disease on the adrenal gland have been reviewed.
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Affiliation(s)
- Emin Murat Akbas
- Erzincan Binali Yildirim University, School of Medicine, Mengucek Gazi Training and Research Hospital, Department of Endocrinology, Erzincan, Turkey
| | - Nergis Akbas
- Mengucek Gazi Training and Research Hospital, Department of Obesity, Biochemistry, Erzincan, Turkey
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Choudhary J, Dheeman S, Sharma V, Katiyar P, Karn SK, Sarangi MK, Chauhan AK, Verma G, Baliyan N. Insights of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) pandemic: a current review. Biol Proced Online 2021; 23:5. [PMID: 33526007 PMCID: PMC7849622 DOI: 10.1186/s12575-020-00141-5] [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: 10/15/2020] [Accepted: 12/25/2020] [Indexed: 01/08/2023] Open
Abstract
COVID-19, a pandemic of the 21st century caused by novel coronavirus SARS-CoV-2 was originated from China and shallowed world economy and human resource. The medical cures via herbal treatments, antiviral drugs, and vaccines still in progress, and studying rigorously. SARS-CoV-2 is more virulent than its ancestors due to evolution in the spike protein(s), mediates viral attachment to the host's membranes. The SARS-CoV-2 receptor-binding spike domain associates itself with human angiotensin-converting enzyme 2 (ACE-2) receptors. It causes respiratory ailments with irregularities in the hepatic, nervous, and gastrointestinal systems, as reported in humans suffering from COVID-19 and reviewed in the present article. There are several approaches, have been put forward by many countries under the world health organization (WHO) recommendations and some trial drugs were introduced for possible treatment of COVID-19, such as Lopinavir or Ritonavir, Arbidol, Chloroquine (CQ), Hydroxychloroquine (HCQ) and most important Remdesivir including other like Tocilizumab, Oritavancin, Chlorpromazine, Azithromycin, Baricitinib, etc. RT-PCR is the only and early detection test available besides the rapid test kit (serodiagnosis) used by a few countries due to unreasonable causes. Development of vaccine by several leader of pharmaceutical groups still under trial or waiting for approval for mass inoculation. Management strategies have been evolved by the recommendations of WHO, specifically important to control COVID-19 situations, in the pandemic era. This review will provide a comprehensive collection of studies to support future research and enhancement in our wisdom to combat COVID-19 pandemic and to serve humanity.
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Affiliation(s)
- Jyoti Choudhary
- Department of Microbiology, Chinmaya Degree College (Hemwati Nandan Bahuguna Garhwal University, Srinagar, Garhwal, Uttarakhand), Haridwar, Uttarakhand 249401 India
- Department of Botany and Microbiology, Gurukula Kangri Deemed to be University, Haridwar, Uttarakhand 249404 India
| | - Shrivardhan Dheeman
- Department of Microbiology, School of Life Sciences, Sardar Bhagwan Singh University, Dehradun, Uttarakhand 248161 India
| | - Vipin Sharma
- Department of Pharmaceuticals Sciences, Faculty of Ayurvedic and Medicinal Sciences, Gurukula Kangri Deemed to be University, Haridwar, Uttarakhand 249404 India
| | - Prashant Katiyar
- Department of Botany and Microbiology, Gurukula Kangri Deemed to be University, Haridwar, Uttarakhand 249404 India
| | - Santosh Kumar Karn
- Deaprtment of Biotechnology and Biochemistry, School of Life Sciences, Sardar Bhagwan Singh University, Dehradun, Uttarakhand 248161 India
| | - Manoj Kumar Sarangi
- Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences and Technology, Sardar Bhagwan Singh University, Dehradun, Uttarakhand 248161 India
| | - Ankit Kumar Chauhan
- Department of Botany and Microbiology, Gurukula Kangri Deemed to be University, Haridwar, Uttarakhand 249404 India
- Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, 110001 India
| | - Gaurav Verma
- Deaprtment of Microbiology, Shri Dev Suman Subharti Medical College, Ras Bihari Bose Subharti University, Dehradun, Uttarakhand 248001 India
| | - Nitin Baliyan
- Department of Botany and Microbiology, Gurukula Kangri Deemed to be University, Haridwar, Uttarakhand 249404 India
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47
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Asrani P, Hassan MI. SARS-CoV-2 mediated lung inflammatory responses in host: targeting the cytokine storm for therapeutic interventions. Mol Cell Biochem 2021; 476:675-687. [PMID: 33064288 PMCID: PMC7563911 DOI: 10.1007/s11010-020-03935-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 10/07/2020] [Indexed: 02/07/2023]
Abstract
The recent exposure of novel coronavirus strain, severe acute respiratory syndrome (SARS-CoV-2) has spread to different countries at an alarming rate. Faster transmission rate and genetic modifications have provoked scientists to search for an immediate solution. With an increasing death rate, it becomes important to throw some light on the life cycle of the virus and its associated pathogenesis in the form of lung inflammation through cytokine storm (CS) production. This paper highlights the different stages of viral-mediated inflammatory responses in the host respiratory system. Previously, known anti-inflammatory drugs and therapeutic strategies that might show potential in controlling the CS of Coronavirus disease-2019 (COVID-19) is also mentioned in this study. Our critical analysis provides insights into the inflammation cycle induced in the lungs by early virus replication, downregulation and shedding of angiotensin-converting enzyme 2 (ACE2), and in the CS production. Identification of suitable targets within the inflammatory pathways for devising the therapeutic strategies useful in controlling the prognosis of COVID-19 finds a special mention in this article. However, antibody-dependent enhancement is the key aspect to consider before testing any drug/compound for therapeutic purposes. Our in-depth analysis would provide similarities and differences between the inflammatory responses induced by SARS-CoV and SARS-CoV-2, providing an excellent avenue to further look at how earlier outbreaks of coronaviruses were controlled and where new steps are required?
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Affiliation(s)
- Purva Asrani
- Division of Biochemistry, Indian Agricultural Research Institute, New Delhi, 110012, India
| | - Md Imtaiyaz Hassan
- Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
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Liang MY, Chen P, He M, Tang J, Li H, He XL, Zhou YY, Feng SW, Xue YE, Liu Y, Ma YL, Zhang JC. Corticosteroids Treatment of Patients with Coronavirus Disease 2019: A Propensity Score Matching Study. Curr Med Sci 2021; 41:24-30. [PMID: 33582901 PMCID: PMC7881915 DOI: 10.1007/s11596-021-2313-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 02/01/2021] [Indexed: 12/25/2022]
Abstract
The role of corticosteroids in the treatment of Coronavirus disease 2019 (COVID-19) is controversial. In the present study, we evaluated the effects of adjuvant corticosteroids treatment on the outcome of patients with COVID-19 (n=966), using Propensity Score Matching to adjust for potential differences between the corticosteroids group (n=289) and the non-corticosteroids group (n=677). Analysis of data without adjusting differences in baseline characteristics indicated that the proportion of mechanical ventilation and the mortality was higher in the corticosteroids treatment group in total or severe/critical patients. The duration of viral shedding was longer in the non-corticosteroids treatment group in total or general/mild patients. After adjusting the difference between the corticosteroids and non-corticosteroids treatment group, the analysis revealed that the use of corticosteroids had no effect on the duration of viral shedding, in-hospital mortality or 28-day mortality.
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Affiliation(s)
- Meng-yuan Liang
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Ping Chen
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Miao He
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Jian Tang
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Hui Li
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Xin-liang He
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Ya-ya Zhou
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Si-wei Feng
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Yu-e Xue
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Yao Liu
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Yan-ling Ma
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Jian-chu Zhang
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
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Xu X, Jiang W, Chen L, Xu Z, Zhang Q, Zhu M, Ye P, Li H, Yu L, Zhou X, Zhou C, Chen X, Zheng X, Xu K, Cai H, Zheng S, Jiang W, Wu X, Li D, Chen L, Luo Q, Wang Y, Qu J, Li Y, Zheng W, Jiang Y, Tang L, Xiang C, Li L. Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: An exploratory clinical trial. Clin Transl Med 2021; 11:e297. [PMID: 33634996 PMCID: PMC7839959 DOI: 10.1002/ctm2.297] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 01/07/2021] [Accepted: 01/11/2021] [Indexed: 01/08/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID-19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID-19, especially for severe and critical patients. Menstrual blood-derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty-four patients were enrolled from January to April 2020 in a multicenter, open-label, nonrandomized, parallel-controlled exploratory trial. Twenty-six patients received allogeneic, menstrual blood-derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1-month period following MSC infusion. Safety was measured using the frequency of treatment-related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC-based therapy may serve as a promising alternative method for treating severe and critical COVID-19.
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Affiliation(s)
- Xiaowei Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Wanli Jiang
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Lijun Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Zhenyu Xu
- Innovative Precision Medicine (IPM) GroupHangzhouZhejiangP. R. China
| | - Qiang Zhang
- Innovative Precision Medicine (IPM) GroupHangzhouZhejiangP. R. China
| | - Mengfei Zhu
- Shulan (Hangzhou) Hospital, Zhejiang Shuren University Shulan International Medical CollegeHangzhouZhejiangP. R. China
| | - Peng Ye
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Hang Li
- Innovative Precision Medicine (IPM) GroupHangzhouZhejiangP. R. China
| | - Liang Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Xiaoyang Zhou
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Chenliang Zhou
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Xiaobei Chen
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Xiaoqin Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Kaijin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Hongliu Cai
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Shufa Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Wubian Jiang
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Xiaojun Wu
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Dong Li
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Lu Chen
- Innovative Precision Medicine (IPM) GroupHangzhouZhejiangP. R. China
| | - Qingqing Luo
- Innovative Precision Medicine (IPM) GroupHangzhouZhejiangP. R. China
| | - Yingyan Wang
- Innovative Precision Medicine (IPM) GroupHangzhouZhejiangP. R. China
| | - Jingjing Qu
- Department of Respiratory DiseaseThoracic Disease CentreThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Yifei Li
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Wendi Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Yingan Jiang
- Department of Infectious DiseasesRenmin Hospital of Wuhan UniversityWuhanHebeiP.R. China
| | - Lingling Tang
- Shulan (Hangzhou) Hospital, Zhejiang Shuren University Shulan International Medical CollegeHangzhouZhejiangP. R. China
| | - Charlie Xiang
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangP. R. China
- Shulan (Hangzhou) Hospital, Zhejiang Shuren University Shulan International Medical CollegeHangzhouZhejiangP. R. China
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50
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Thepmankorn P, Bach J, Lasfar A, Zhao X, Souayah S, Chong ZZ, Souayah N. Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations. Cytokine 2021; 138:155404. [PMID: 33360025 PMCID: PMC7832981 DOI: 10.1016/j.cyto.2020.155404] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 12/05/2020] [Accepted: 12/07/2020] [Indexed: 02/07/2023]
Abstract
The new coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can trigger a hyperinflammatory state characterized by elevated cytokine levels known as hypercytokinemia or cytokine storm, observed most often in severe patients. Though COVID-19 is known to be a primarily respiratory disease, neurological complications affecting both the central and peripheral nervous systems have also been reported. This review discusses potential routes of SARS-CoV-2 neuroinvasion and pathogenesis, summarizes reported neurological sequelae of COVID-19, and examines how aberrant cytokine levels may precipitate these complications. Clarification of the pathogenic mechanisms of SARS-CoV-2 is needed to encourage prompt diagnosis and optimized care. In particular, identifying the presence of cytokine storm in patients with neurological COVID-19 manifestations will facilitate avenues for treatment. Future investigations into aberrant cytokine levels in COVID-19 patients with neurological symptoms as well as the efficacy of cytokine storm-targeting treatments will be critical in elucidating the pathogenic mechanisms and effective treatments of COVID-19.
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Affiliation(s)
- Parisorn Thepmankorn
- Department of Neurology, Rutgers New Jersey Medical School, Newark, NJ, United States
| | - John Bach
- Department of Physical Medicine and Rehab, Rutgers New Jersey Medical School, Newark, NJ, United States
| | - Ahmed Lasfar
- Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, United States
| | - Xilin Zhao
- Department of Microbiology, Biochemistry, & Molecular Genetics, Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, NJ, United States; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
| | - Sami Souayah
- Department of Neurology, Rutgers New Jersey Medical School, Newark, NJ, United States
| | - Zhao Zhong Chong
- Department of Neurology, Rutgers New Jersey Medical School, Newark, NJ, United States
| | - Nizar Souayah
- Department of Neurology, Rutgers New Jersey Medical School, Newark, NJ, United States.
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