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Oba S, Hosoya T, Kawata D, Komiya Y, Iwai H, Koike R, Miyamoto S, Kanno T, Ainai A, Suzuki T, Hasegawa H, Yasuda S. Iguratimod, a promising therapeutic agent for COVID-19 that attenuates excessive inflammation in mouse models. Eur J Pharmacol 2025; 996:177537. [PMID: 40147575 DOI: 10.1016/j.ejphar.2025.177537] [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: 11/27/2024] [Revised: 03/18/2025] [Accepted: 03/20/2025] [Indexed: 03/29/2025]
Abstract
In severe COVID-19 patients, excessive inflammation can lead to multiorgan dysfunction. Current anti-inflammatory treatments like glucocorticoids partially improve the outcomes, while immune systems are compromised. We have identified that SARS-CoV-2-infected obese mice were a good model of the cytokine storm seen in COVID-19. Here, we revealed that iguratimod (IGU), an approved agent for rheumatoid arthritis, improved survival by attenuating inflammation with minimal immune suppression. In this study, C57BL/6 mice were fed a high-fat diet (HFD) or a normal-fat diet (NFD) for ten weeks before being infected with a mouse-adapted SARS-CoV-2. IGU significantly improved survival rates and reduced lung inflammation in HFD-fed mice, with minimal impact on interferon-induced genes and viral load. Meanwhile, dexamethasone (DEX) did not improve survival, while it suppressed various immune reactions with different mechanisms to IGU. Interestingly, IGU-treated mice had fewer SARS-CoV-2 positive cells in the lung, although viral replication was comparable to the control mice. Neither IGU nor DEX inhibited the SARS-CoV-2 infection in Vero-E6 cells, unlike the antiviral agent, remdesivir. Of note, IGU was effective prophylactically and therapeutically in HFD mice, and showed beneficial effects in NFD-fed mice with a lethal dose exposure of SARS-CoV-2. We demonstrated that IGU could be a promising treatment for severe COVID-19, especially in obese patients, by fine-tuning inflammation without compromising antiviral immunity. This study supports the possibility of drug repositioning for IGU COVID-19 beyond autoimmune diseases.
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Affiliation(s)
- Seiya Oba
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan; Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Tadashi Hosoya
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan; Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan.
| | - Daisuke Kawata
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan; Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Yoji Komiya
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan; Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Hideyuki Iwai
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan; Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Ryuji Koike
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan
| | - Sho Miyamoto
- Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Takayuki Kanno
- Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Akira Ainai
- Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Tadaki Suzuki
- Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan
| | - Hideki Hasegawa
- WHO Collaborating Centre for Reference and Research on Influenza, Tokyo, Japan; Research Center for Influenza and Respiratory Virus, National Institute of Infectious Diseases, Tokyo, Japan
| | - Shinsuke Yasuda
- Department of Rheumatology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
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Petry J, Shoykhet M, Weiser T, Griesbaum L, Bashiri Dezfouli A, Verschoor A, Wollenberg B. SARS-CoV-2 S1 protein induces IgG-mediated platelet activation and is prevented by 1.8-cineole. Biomed Pharmacother 2025; 187:118100. [PMID: 40306177 DOI: 10.1016/j.biopha.2025.118100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 04/12/2025] [Accepted: 04/24/2025] [Indexed: 05/02/2025] Open
Abstract
COVID-19 patients face an increased risk of thromboembolic complications, yet the exact pathophysiological role of platelets in the disease remains unclear. Considering the multifaceted nature of COVID-19 symptoms, including platelet hyperactivation and inflammation, the development of compounds that simultaneously target both represents a promising therapeutic strategy. The monoterpene 1.8-cineole (CNL-1976) is known for its anti-inflammatory and anti-aggregatory effects. Thus, understanding the mechanism behind platelet hyperactivation and the effect of 1.8-cineole during COVID-19 is crucial when aiming for a reduction of disease severity. In this study, we investigated the mechanism of platelet activation triggered by the SARS-CoV-2 S1 spike protein (S1). Utilizing S1-coupled beads, we discovered that platelet activation and aggregation were dependent on plasma components, particularly S1-specific IgG antibodies. The formation of immune complexes through IgG binding to S1 facilitated the crosslinking of the platelet expressed FcγRIIa receptor, initiating platelet activation and aggregation, as well as formation of platelet-leukocyte aggregates (PLAs). Importantly, treatment with 1.8-cineole significantly inhibited S1-bead-induced platelet activity and PLA formation. These findings strongly suggest that antibody-mediated platelet activation via FcγRIIa directly contributes to the well-recognized prothrombotic environment during COVID-19. Moreover, our data indicate that 1.8-cineole can serve as a potential therapeutic compound, alleviating platelet-driven thromboinflammatory complications associated with COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC).
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Affiliation(s)
- Julie Petry
- Technical University of Munich, School of Medicine and Health, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Germany
| | - Maria Shoykhet
- Technical University of Munich, School of Medicine and Health, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Germany
| | - Tobias Weiser
- Technical University of Munich, School of Medicine and Health, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Germany
| | - Lena Griesbaum
- Technical University of Munich, School of Medicine and Health, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Germany
| | - Ali Bashiri Dezfouli
- Technical University of Munich, School of Medicine and Health, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Germany; Central Institute for Translational Cancer Research, Technical University of Munich (TranslaTUM), Department of Radiation Oncology, TUM University Hospital, Germany
| | - Admar Verschoor
- Technical University of Munich, School of Medicine and Health, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Germany; University of Lübeck, Department of Dermatology, University Clinic Schleswig-Holstein (UKSH), Germany
| | - Barbara Wollenberg
- Technical University of Munich, School of Medicine and Health, Department of Otorhinolaryngology, Head and Neck Surgery, TUM University Hospital, Germany.
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Xue L, Qi Y, Zou Y. Short-term safety and efficacy of aspirin in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials. PeerJ 2025; 13:e19466. [PMID: 40416616 PMCID: PMC12103164 DOI: 10.7717/peerj.19466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Accepted: 04/23/2025] [Indexed: 05/27/2025] Open
Abstract
Objective Coagulation activation and inflammatory derangements are key characteristics of coronavirus disease 2019 (COVID-19). Aspirin therapy in patients with COVID-19 remains uncertain due to conflicting evidence regarding its ability to balance anti-inflammatory and antithrombotic benefits against potential bleeding risks in the context of COVID-19-associated coagulopathy. This study aimed to compare the clinical safety and efficacy of aspirin in patients with COVID-19 in randomized controlled trials (RCTs). Methods In the present systematic review and meta-analysis, the Medline, Embase, and Cochrane Library databases were searched for RCTs from database inception to January 13, 2023. Data were independently extracted and screened by two authors using structured data collection forms based on published reports. Results were calculated using odds ratios (ORs) and 95% confidence intervals (CIs) with the Mantel-Haenszel method. Quality was assessed using the Cochrane Risk of Bias tool. The main outcomes were short-term all-cause mortality, bleeding events and any thrombosis events. This meta-analysis was registered on PROSPERO. Results A total of 922 studies were identified. Finally, six RCTs with low risk of bias were pooled in the analysis. The results showed that aspirin use was not associated with a reduction in all-cause mortality (OR = 0.95, 95% CI [0.88-1.03], I2 = 0%) or the risk of any thrombosis (RR 0.88, 95% CI [0.77-1.01], I2 = 0%), but aspirin use was associated with a higher risk of bleeding (OR 1.72, 95% CI [1.32-2.24], I2 = 0%). No obvious risk of bias was found among the included RCTs for the primary outcome. Conclusion Routine low-dose aspirin use does not reduce the risk of short-term mortality and risk of any thrombosis but increases the risk of bleeding. The data does not support the use of low-dose aspirin in patients with COVID-19.
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Affiliation(s)
- Liwen Xue
- Department of Pathology and Pathophysiology, School of Basic Medicine, Kunming Medical University, Kunming, China
| | - Yuhan Qi
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
- Division of Vascular Surgery Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yingying Zou
- Department of Pathology and Pathophysiology, School of Basic Medicine, Kunming Medical University, Kunming, China
- Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan Province, China
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Becker RC, Tantry US, Khan M, Gurbel PA. The COVID-19 thrombus: distinguishing pathological, mechanistic, and phenotypic features and management. J Thromb Thrombolysis 2025; 58:15-49. [PMID: 39179952 PMCID: PMC11762605 DOI: 10.1007/s11239-024-03028-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2024] [Indexed: 08/26/2024]
Abstract
A heightened risk for thrombosis is a hallmark of COVID-19. Expansive clinical experience and medical literature have characterized small (micro) and large (macro) vessel involvement of the venous and arterial circulatory systems. Most events occur in patients with serious or critical illness in the hyperacute (first 1-2 weeks) or acute phases (2-4 weeks) of SARS-CoV-2 infection. However, thrombosis involving the venous, arterial, and microcirculatory systems has been reported in the subacute (4-8 weeks), convalescent (> 8-12 weeks) and chronic phases (> 12 weeks) among patients with mild-to-moderate illness. The purpose of the current focused review is to highlight the distinguishing clinical features, pathological components, and potential mechanisms of venous, arterial, and microvascular thrombosis in patients with COVID-19. The overarching objective is to better understand the proclivity for thrombosis, laying a solid foundation for screening and surveillance modalities, preventive strategies, and optimal patient management.
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Affiliation(s)
- Richard C Becker
- Cardiovascular Center, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
| | - Udaya S Tantry
- Sinai Center for Thrombosis Research and Drug Development, Baltimore, USA
| | - Muhammad Khan
- Division of General Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, USA
| | - Paul A Gurbel
- Sinai Center for Thrombosis Research and Drug Development, Baltimore, USA
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Mallah N, Visos-Varela I, Takkouche B, Bugarín-González R, Piñeiro-Lamas M, Herdeiro T, Zapata-Cachafeiro M, Rodríguez-Fernández A, Salgado-Barreira A, Figueiras A. The role of traditional NSAIDs and selective COX-2 inhibitors on COVID-19 outcomes: a real-world data study. Inflammopharmacology 2024; 32:3697-3705. [PMID: 39312097 PMCID: PMC11550288 DOI: 10.1007/s10787-024-01568-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 08/31/2024] [Indexed: 11/10/2024]
Abstract
The relation between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and severity of COVID-19 has been the subject to debate since the outbreak of the pandemic. Despite speculations about the possible harmful or protective effects, the position currently most supported by the scientific community is that there is no association between use of NSAIDs and COVID-19 outcomes. With the aim of contributing to increase the body of evidence on this issue, we conducted a case-control study using real-world data to investigate the association between prior use of NSAIDs, by active ingredient and type (traditional NSAIDs and selective COX-2 inhibitors), and important COVID-19-related outcomes, including susceptibility, PCR + patient progression, and hospitalisation. Our findings suggest that, in general, the use of traditional NSAIDs is not associated with any adverse COVID-19 outcome. However, we observed a possible association between diclofenac and a higher risk of PCR + patient progression. Our results also suggest that selective COX-2 inhibitors might be related with a reduction in the risk of PCR + patient progression. These results suggest that, with the possible exception of diclofenac, the use of NSAIDs should not be advised against for relief of symptoms in patients with COVID-19. In addition, they support the importance of continue to investigate the treatment potential of selective COX-2 inhibitors in the management of COVID-19, something that could have significant implications for the treatment of this disease and other viral infections.
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Affiliation(s)
- Narmeen Mallah
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Institute of Health Research of Santiago de Compostela de Compostela, Santiago de Compostela, Spain
- WHO Collaborating Centre for Vaccine Safety, Santiago de Compostela, Spain
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, C/ San Francisco s/n, 15782, Santiago de Compostela, Spain
| | - Irene Visos-Varela
- Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Institute of Health Research of Santiago de Compostela de Compostela, Santiago de Compostela, Spain.
- WHO Collaborating Centre for Vaccine Safety, Santiago de Compostela, Spain.
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, C/ San Francisco s/n, 15782, Santiago de Compostela, Spain.
| | - Bahi Takkouche
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, C/ San Francisco s/n, 15782, Santiago de Compostela, Spain
- Institute of Health Research of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Rosendo Bugarín-González
- Centro de Salud de Monforte de Lemos, Área Sanitaria de Lugo, A Mariña e Monforte de Lemos, SERGAS, Monforte de Lemos, Lugo, Spain
| | - María Piñeiro-Lamas
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain
| | - Teresa Herdeiro
- Department of Medical Sciences, iBiMED-Institute of Biomedicine, University of Aveiro, Aveiro, Portugal
| | - Maruxa Zapata-Cachafeiro
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, C/ San Francisco s/n, 15782, Santiago de Compostela, Spain
- Institute of Health Research of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Almudena Rodríguez-Fernández
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, C/ San Francisco s/n, 15782, Santiago de Compostela, Spain
- Institute of Health Research of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Angel Salgado-Barreira
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, C/ San Francisco s/n, 15782, Santiago de Compostela, Spain
- Institute of Health Research of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Adolfo Figueiras
- Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Santiago de Compostela, C/ San Francisco s/n, 15782, Santiago de Compostela, Spain
- Institute of Health Research of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
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Karcioglu O, Akman C, Ozturk GA. Prothrombotic state and thrombotic events in COVID-19 pandemic period, including portal vein and splenic artery thromboses. World J Clin Cases 2024; 12:6595-6603. [PMID: 39600474 PMCID: PMC11514335 DOI: 10.12998/wjcc.v12.i33.6595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 08/02/2024] [Accepted: 08/23/2024] [Indexed: 09/27/2024] Open
Abstract
This editorial article is intended to perform a discussion on the manuscript entitled "Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient: A case report and review of literature" written by Abramowitz et al. The article focuses on the diagnostic processes in a 77-year-old-male patient with a simultaneous portal vein and splenic artery thrombosis accompanying coronavirus disease 2019 (COVID-19). The authors postulated that splanchnic thrombosis should be on the list of differential diagnoses in a patient presenting with abdominal pain in presence of a COVID-19 infection. The tendency for venous and arterial thrombosis in COVID-19 patients is encountered, largely attributed to hypercoagulopathy. In general, venous thromboembolism mostly manifest as deep vein thrombosis (DVT), pulmonary embolism (PE) or catheter-related thromboembolic events. Acute PE, DVT, cerebrovascular events and myocardial infarction are seen as the most common thromboembolic complications in COVID-19 patients. COVID-19-associated hemostatic abnormalities include mild thrombocytopenia and increased D-dimer level. Similar to other coagulopathies, the treatment of the underlying condition is the mainstay. Addition of antiplatelet agents can be considered in critically ill patients at low bleeding risk, not on therapeutic anticoagulation, and receiving gastric acid suppression Early administration of antithrombotic drugs will have a beneficial effect in both the prevention and treatment of thrombotic events, especially in non-ambulatory patients. Low molecular weight heparin (LMWH) should be started if there is no contraindication, including in non-critical patients who are at risk of hospitalization LMWH (enoxaparin) is preferred to standard heparin.
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Affiliation(s)
- Ozgur Karcioglu
- Department of Emergency Medicine, University of Health Sciences, Istanbul Education and Research Hospital, Istanbul 34140, Bakırkoy, Türkiye
| | - Canan Akman
- Department of Emergency Medicine, Canakkale Onsekiz Mart University, Canakkale 17000, Çanakkale, Türkiye
| | - Göksu Afacan Ozturk
- Department of Emergency Medicine, Istanbul Aydin University, Istanbul 34295, Kucukcekmece, Istanbul, Türkiye
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Aseman-Bashiz E, Sayyaf H. Sonoelectrochemical degradation of aspirin in aquatic medium using ozone and peroxymonosulfate activated with FeS 2 nanoparticles. JOURNAL OF CONTAMINANT HYDROLOGY 2024; 267:104419. [PMID: 39270599 DOI: 10.1016/j.jconhyd.2024.104419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 08/17/2024] [Accepted: 08/30/2024] [Indexed: 09/15/2024]
Abstract
The catalytic performance of nano-FeS2 in the sonoelectrochemical activation of peroxymonosulfate (PMS) and ozone to remove aspirin (ASP) was studied for the first time. The crystal structure and Fe bonds in the catalyst were confirmed through XRD and FTIR analysis. Within 30 min, ASP (TOC) was removed by 99.2 % (81.6 %) and 98.6 % (77.4 %) in nano-FeS2/PMS and nano-FeS2/O3 sonoelectrochemical systems, respectively. Water anions, especially (almost 50 %), had an inhibitory effect on ASP removal. The probes confirmed that SO4•-and HO• were the key to ASP degradation in nano-FeS2/PMS and nano-FeS2/O3 systems, respectively. The effective activation of oxidants due to the ideal distribution of Fe2+ by catalyst was the main mechanism of ASP removal, in which electric current (EC) and ultrasound (US) played a crucial role through the recycling of Fe ions, dissolution and cleaning of the catalyst. LC-MS analysis identified thirteen byproducts in the ASP degradation pathways. The energy consumption of the proposed sonoelectrochemical systems was lower than previous similar systems. This study presented economic and sustainable hybrid systems for pharmaceutical wastewater remediation.
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Affiliation(s)
- Elham Aseman-Bashiz
- Environmental Health Engineering Lecturer, Alifard (SANICH) Institute of Applied Nscience and Technology, Hashtgerd, Alborz, Iran; National Water and Wastewater Engineering Company, Department of Supervision of Wastewater Operation, Tehran, Iran
| | - Hossein Sayyaf
- Environmental Health Engineering Lecturer, Alifard (SANICH) Institute of Applied Nscience and Technology, Hashtgerd, Alborz, Iran; Department of Environmental Health Engineering, Tehran University of Medical Sciences, Health Assistant Department, South Tehran Health Center, Tehran, Iran.
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8
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Park S, Je NK, Kim DW, Park M, Heo J. Current status and clinical outcomes of pharmacotherapies according to SARS-CoV-2 mutations in patients with mild-to-moderate COVID-19: a retrospective single center study. BMC Infect Dis 2024; 24:871. [PMID: 39223456 PMCID: PMC11370261 DOI: 10.1186/s12879-024-09765-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND During the pandemic period, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated, leading to changes in the disease's severity and the therapeutic effect of drugs accordingly. This study aimed to present the actual use of therapeutics and clinical outcomes based on the prevalence of each variant using real-world data. METHODS We analyzed the electronic medical records of adult patients admitted to Busan Medical Center after confirming coronavirus disease 2019 (COVID-19) from February 1, 2020, to June 30, 2022. Patients with mild-to-moderate COVID-19 who were at a high risk of disease progression were selected as study subjects, and the time period was classified according to the variants as ancestral strain, Delta variant, or Omicron variant. We compared drug use status and clinical outcomes by time period. RESULTS Among all 3,091 patients, corticosteroids were the most commonly used therapy (56.0%), being used most frequently in the Delta variant (93.0%), followed by the Omicron variant (42.9%) and ancestral strain (21.2%). Regdanvimab accounted for the majority of therapeutic use in the Delta variant (82.9%) and ancestral strain (76.8%), whereas remdesivir was most frequently used during the Omicron variant period (68.9%). The composite outcomes of death or disease aggravation were ranked in the order of the Delta variant, Omicron variant, and ancestral strain (14.5, 11.9, and 6.0%, respectively, P < 0.001). CONCLUSION Regdanvimab was primarily used during the ancestral strain period, regdanvimab plus corticosteroids during the Delta variant period, and remdesivir during the Omicron variant period. The rate of death or disease aggravation was highest in the Delta variant, followed by the Omicron variant and the ancestral strain.
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Affiliation(s)
- Susin Park
- College of Pharmacy, Kyungsung University, Busan, Republic of Korea
| | - Nam Kyung Je
- College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Dong Wan Kim
- Division of Pulmonology, Department of Internal Medicine, Good Moonhwa Hospital, Busan, Republic of Korea
| | - Miran Park
- Division of Pulmonology, Department of Internal Medicine, Busan Medical Center, Busan, Republic of Korea
| | - Jeonghun Heo
- Division of Pulmonology, Department of Internal Medicine, Maryknoll Hospital, 121, Junggu-Ro, Jung-Gu, Busan, 48972, Republic of Korea.
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Aboelghar SM, Hegazy MA, Wagdy HA. Eco-Friendly Synchronous Spectrofluorimetric Method for Simultaneous Determination of Remdesivir and Acetyl Salicylic Acid in Spiked Human Plasma. J Fluoresc 2024:10.1007/s10895-024-03851-1. [PMID: 39150458 DOI: 10.1007/s10895-024-03851-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/15/2024] [Indexed: 08/17/2024]
Abstract
Remdesivir and acetyl salicylic acid are often co-administered medications in the treatment of COVID-19, specifically targeting the viral infection and thromboembolism associated with the condition. Hence, it is essential to establish a technique that enables the concurrent quantification of these pharmaceutical compounds in plasma while also keeping environmentally friendly methods. Accordingly, the aim of this work is to simultaneously determine remdesivir and acetyl salicylic acid through a bioanalytical validated synchronous spectrofluorimetric method with applying principles of green chemistry. Since, the two drugs showed severe overlap after excitation at 242.0 nm, 284.0 nm for remdesivir and acetyl salicylic acid, respectively. The overlap was effectively overcome by using synchronous mode with a wavelength difference (Δλ) of 160.0 nm for remdesivir and 100.0 nm for acetyl salicylic acid. Different parameters have been optimized such as Δλ, solvent, pH and surfactant. A linear calibration was obtained over the concentration range 0.01-4.00 µg/mL for remdesivir and 0.01-3.00 µg/mL for acetyl salicylic acid and the method was precise and accurate. The method was successfully used for the investigation of pharmaceutical formulation and the quantification of the maximum plasma concentration (Cmax) of the two drugs. The method has been evaluated as an excellent green analytical method based on three greenness assessment tools.
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Affiliation(s)
- Sohair M Aboelghar
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, P.O. Box 43, El-Sherouk City, Cairo, 11837, Egypt
- Health Research Center of Excellence, Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Egypt
| | - Maha A Hegazy
- Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr-El-Aini Street, Cairo, 11562, Egypt.
| | - Hebatallah A Wagdy
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, P.O. Box 43, El-Sherouk City, Cairo, 11837, Egypt
- Health Research Center of Excellence, Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Egypt
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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10
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Inokuchi T, Homma T, Kitasato Y, Akiyama M, Chikasue A, Nishii Y, Ban S, Adachi T, Sonezaki A, Masuda H, Kamei H, Takenaka M, Tanaka M, Okamoto M, Hoshino T. Oral Colchicine and Low-Dose Aspirin Combination Therapy for Non-elderly, Non-severe, Early Time From Onset, Adult Outpatients with Coronavirus Disease 2019 (COVID-19) during "The Fifth Pandemic Wave" in Japan. Kurume Med J 2024; 70:39-45. [PMID: 38508737 DOI: 10.2739/kurumemedj.ms7012003] [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: 03/22/2024]
Abstract
BACKGROUND Treatment with antiviral drugs for non-severe, early time from onset, adult outpatients with Coronavirus Disease 2019 (COVID-19) had not been established in 2021. However, some new variants of SARS-CoV-2 had caused rapid exacerbation and hospitalization among non-elderly outpatients with COVID-19, contributing to widespread crises within healthcare systems. METHODS From July to October 2021, we urgently assessed a therapeutic program using oral colchicine (1.0 mg loading dose, followed approximately half a day later by 0.5 mg twice daily for 5 days, and then 0.5 mg once daily for 4 days) and low-dose aspirin (100 mg once daily for 10 days), for non-elderly, non-severe, early time from onset, adult outpatients with COVID-19. To verify its effectiveness, we set loxoprofen as a control arm, and com parison of these two arms was performed. The primary outcomes were hospitalization, criticality, and death rates. RESULTS Thirty-eight patients (23 receiving colchicine and low-dose aspirin [CA]; 15 receiving loxoprofen [LO]) were evaluated. Hospitalization rate was lower in the CA group (1/23; 4.3%) than in the LO group (2/15; 13.3%); however, no significant difference was found between the two groups (p=0.34). No critical cases, deaths, or severe adverse events were found in either group. CONCLUSIONS Our CA regimen did not show superiority over LO treatment. However, our clinical experience should be recorded as part of community health care activities carried out in Kurume City against the unprece dented COVID-19 pandemic.
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Affiliation(s)
| | - Tomoki Homma
- Kurume Physicians Association (Kurume Naikaikai)
- Homma Cardiovascular Clinic
| | - Yasuhiko Kitasato
- Kurume Physicians Association (Kurume Naikaikai)
- JCHO Kurume General Hospital
| | | | | | - Yuuya Nishii
- JCHO Kurume General Hospital
- Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine
| | - Shigeki Ban
- Kurume Physicians Association (Kurume Naikaikai)
- Ban Clinic
| | - Takeki Adachi
- Kurume Physicians Association (Kurume Naikaikai)
- Adachi Clinic
| | | | | | | | | | | | | | - Tomoaki Hoshino
- Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine
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11
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Collamore G, DiCorcia MJ, Nagpal Y, Fiedler L, Garone MA, DeMets DL, Maki DG, Hennekens CH. Guidance for Healthcare Providers on Newest Guidelines for Over-the-Counter Drug Treatment of Mild Symptoms of COVID-19. Am J Med 2024; 137:490-493. [PMID: 38490308 DOI: 10.1016/j.amjmed.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 03/04/2024] [Indexed: 03/17/2024]
Abstract
On January 18, 2024, the US Centers for Disease Control and Prevention issued their most recent guidelines for over-the-counter drugs for coronavirus disease 2019 (COVID-19). Specifically, the organization stated that "Most people with COVID-19 have mild illness and can recover at home. You can treat symptoms with over-the-counter medicines, such as acetaminophen (Tylenol) or ibuprofen (Motrin, Advil), to help you feel better." In this review we consider the contributions of different types of evidence and conclude that healthcare providers should make individual clinical judgments for each of their patients in the selection of over-the-counter drugs to treat symptoms of COVID-19. This judgment should be based on the entire benefit to risk profile of the patient. It is our belief that the individual healthcare provider knows far more about each of his or her patients than anyone, including expert members of guideline committees. Their astute and judicious individual clinical decision-making for each individual patient based on all these considerations has the potential to do far more good than harm.
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Affiliation(s)
- Gage Collamore
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton
| | - Mark J DiCorcia
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton
| | - Yash Nagpal
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton
| | - Lawrence Fiedler
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton
| | - Michael A Garone
- Inova Fair Oaks Hospital, Chantilly, Virginia; George Washington University Hospital, Washington, DC
| | - David L DeMets
- University of Wisconsin School of Medicine and Public Health, Madison
| | - Dennis G Maki
- University of Wisconsin School of Medicine and Public Health, Madison
| | - Charles H Hennekens
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton.
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12
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Vinod P, Krishnappa V, Rathell W, Amir S, Sundil S, Dogbey G, Patel H, Herzog W. Effect of Aspirin Use on the Adverse Outcomes in Patients Hospitalized for COVID-19. Cardiol Res 2024; 15:179-188. [PMID: 38994222 PMCID: PMC11236346 DOI: 10.14740/cr1645] [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: 03/31/2024] [Accepted: 05/02/2024] [Indexed: 07/13/2024] Open
Abstract
Background Coronavirus disease 2019 (COVID-19) triggers multiple components of the immune system and causes inflammation of endothelial walls across vascular beds, resulting in respiratory failure, arterial and venous thrombosis, myocardial injury, and multi-organ failure leading to death. Early in the COVID-19 pandemic, aspirin was suggested for the treatment of symptomatic individuals, given its analgesic, antipyretic, anti-inflammatory, anti-thrombotic, and antiviral effects. This study aimed to evaluate the association of aspirin use with various clinical outcomes in patients hospitalized for COVID-19. Methods This was a retrospective study involving patients aged ≥ 18 years and hospitalized for COVID-19 from March 2020 to October 2020. Primary outcomes were acute cardiovascular events (ST elevation myocardial infarction (STEMI), type 1 non-ST elevation myocardial infarction (NSTEMI), acute congestive heart failure (CHF), and acute stroke) and death. Secondary outcomes were respiratory failure, need for mechanical ventilation, and acute deep vein thrombosis (DVT)/pulmonary embolism (PE). Results Of 376 patients hospitalized for COVID-19, 128 were taking aspirin. Significant proportions of native Americans were hospitalized for COVID-19 in both aspirin (22.7%) and non-aspirin (24.6%) groups. Between aspirin and non-aspirin groups, no significant differences were found with regard to mechanical ventilator support (21.1% vs. 15.3%, P = 0.16), acute cardiovascular events (7.8% vs. 5.2%, P = 0.32), acute DVT/PE (3.9% vs. 5.2%, P = 0.9), readmission rate (13.3% vs. 12.9%, P = 0.91) and mortality (23.4% vs. 20.2%, P = 0.5); however, the median duration of mechanical ventilation was significantly shorter (7 vs. 9 days, P = 0.04) and median length of hospitalization was significantly longer (5.5 vs. 4 days, P = 0.01) in aspirin group compared to non-aspirin group. Conclusion No significant differences were found in acute cardiovascular events, acute DVT/PE, mechanical ventilator support, and mortality rate between hospitalized COVID-19 patients who were taking aspirin compared to those not taking aspirin. However, larger studies are required to confirm our findings.
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Affiliation(s)
- Poornima Vinod
- Department of Internal Medicine, University of North Carolina Health Southeastern, Lumberton, NC, USA
- Department of Medicine, Campbell University, Buies Creek, NC, USA
| | - Vinod Krishnappa
- Department of Internal Medicine, University of North Carolina Health Southeastern, Lumberton, NC, USA
| | - William Rathell
- Department of Internal Medicine, University of North Carolina Health Southeastern, Lumberton, NC, USA
| | - Saira Amir
- Department of Nephrology, University of Maryland, Baltimore, MD, USA
| | - Subrina Sundil
- Department of Nephrology, East Carolina University, Greenville, NC, USA
| | - Godwin Dogbey
- Campbell University School of Osteopathic Medicine, Buies Creek, NC, USA
| | - Hiten Patel
- Department of Cardiology, University of North Carolina Health Southeastern, Lumberton, NC, USA
| | - William Herzog
- Department of Cardiology, University of North Carolina Health Southeastern, Lumberton, NC, USA
- Department of Cardiology, Duke University, Durham, NC, USA
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13
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Lei S, Lei X, Chen M, Pan Y. Drug Repositioning Based on Deep Sparse Autoencoder and Drug-Disease Similarity. Interdiscip Sci 2024; 16:160-175. [PMID: 38103130 DOI: 10.1007/s12539-023-00593-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 11/03/2023] [Accepted: 11/06/2023] [Indexed: 12/17/2023]
Abstract
Drug repositioning is critical to drug development. Previous drug repositioning methods mainly constructed drug-disease heterogeneous networks to extract drug-disease features. However, these methods faced difficulty when we are using structurally simple models to deal with complex heterogeneous networks. Therefore, in this study, the researchers introduced a drug repositioning method named DRDSA. The method utilizes a deep sparse autoencoder and integrates drug-disease similarities. First, the researchers constructed a drug-disease feature network by incorporating information from drug chemical structure, disease semantic data, and existing known drug-disease associations. Then, we learned the low-dimensional representation of the feature network using a deep sparse autoencoder. Finally, we utilized a deep neural network to make predictions on new drug-disease associations based on the feature representation. The experimental results show that our proposed method has achieved optimal results on all four benchmark datasets, especially on the CTD dataset where AUC and AUPR reached 0.9619 and 0.9676, respectively, outperforming other baseline methods. In the case study, the researchers predicted the top ten antiviral drugs for COVID-19. Remarkably, six out of these predictions were subsequently validated by other literature sources.
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Affiliation(s)
- Song Lei
- School of Computer Science, Shaanxi Normal University, Xi'an, 710119, China
| | - Xiujuan Lei
- School of Computer Science, Shaanxi Normal University, Xi'an, 710119, China.
| | - Ming Chen
- College of Information Science and Engineering, Hunan Normal University, Changsha, 410081, China
| | - Yi Pan
- Faculty of Computer Science and Control Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
- Shenzhen Key Laboratory of Intelligent Bioinformatics, Shenzhen Institute of Advanced Technology, Shenzhen, 518055, China.
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14
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Duo H, Jin M, Yang Y, Baheti R, Feng Y, Fu Z, Jiang Y, Zheng L, Wan J, Pan H. Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis. PLoS One 2024; 19:e0297628. [PMID: 38300975 PMCID: PMC10833506 DOI: 10.1371/journal.pone.0297628] [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: 03/25/2023] [Accepted: 01/09/2024] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. METHODS Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI. RESULTS Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments. CONCLUSION According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.
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Affiliation(s)
- Hong Duo
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China
| | - Mengying Jin
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yanwei Yang
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Rewaan Baheti
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yujia Feng
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zirui Fu
- College of Agriculture and Life Science, University of Wisconsin Madison, Madison, Wisconsin, United States of America
| | - Yuyue Jiang
- University of California, Santa Barbara/ UC Santa Barbara, Santa Barbara, California, United States of America
| | - Lanzhuoying Zheng
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jing Wan
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Huaqin Pan
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
- Clinical Research Center for Critical Care Medicine of Hubei Province, Wuhan, China
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15
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Constantinescu-Bercu A, Lobiuc A, Căliman-Sturdza OA, Oiţă RC, Iavorschi M, Pavăl NE, Șoldănescu I, Dimian M, Covasa M. Long COVID: Molecular Mechanisms and Detection Techniques. Int J Mol Sci 2023; 25:408. [PMID: 38203577 PMCID: PMC10778767 DOI: 10.3390/ijms25010408] [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: 11/28/2023] [Revised: 12/25/2023] [Accepted: 12/26/2023] [Indexed: 01/12/2024] Open
Abstract
Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction.
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Affiliation(s)
- Adela Constantinescu-Bercu
- Department of Biomedical Sciences, Faculty of Medicine and Biological Sciences, “Ştefan cel Mare” University of Suceava, 720229 Suceava, Romania; (A.C.-B.); (O.A.C.-S.); (M.I.); (N.-E.P.); (M.C.)
| | - Andrei Lobiuc
- Department of Biomedical Sciences, Faculty of Medicine and Biological Sciences, “Ştefan cel Mare” University of Suceava, 720229 Suceava, Romania; (A.C.-B.); (O.A.C.-S.); (M.I.); (N.-E.P.); (M.C.)
| | - Olga Adriana Căliman-Sturdza
- Department of Biomedical Sciences, Faculty of Medicine and Biological Sciences, “Ştefan cel Mare” University of Suceava, 720229 Suceava, Romania; (A.C.-B.); (O.A.C.-S.); (M.I.); (N.-E.P.); (M.C.)
- Suceava Emergency Clinical County Hospital, 720224 Suceava, Romania
| | - Radu Cristian Oiţă
- Integrated Center for Research, Development and Innovation for Advanced Materials, Nanotechnologies, Manufacturing and Control Distributed Systems (MANSiD), Ştefan cel Mare University of Suceava, 720229 Suceava, Romania; (R.C.O.); (I.Ș.); (M.D.)
| | - Monica Iavorschi
- Department of Biomedical Sciences, Faculty of Medicine and Biological Sciences, “Ştefan cel Mare” University of Suceava, 720229 Suceava, Romania; (A.C.-B.); (O.A.C.-S.); (M.I.); (N.-E.P.); (M.C.)
| | - Naomi-Eunicia Pavăl
- Department of Biomedical Sciences, Faculty of Medicine and Biological Sciences, “Ştefan cel Mare” University of Suceava, 720229 Suceava, Romania; (A.C.-B.); (O.A.C.-S.); (M.I.); (N.-E.P.); (M.C.)
| | - Iuliana Șoldănescu
- Integrated Center for Research, Development and Innovation for Advanced Materials, Nanotechnologies, Manufacturing and Control Distributed Systems (MANSiD), Ştefan cel Mare University of Suceava, 720229 Suceava, Romania; (R.C.O.); (I.Ș.); (M.D.)
| | - Mihai Dimian
- Integrated Center for Research, Development and Innovation for Advanced Materials, Nanotechnologies, Manufacturing and Control Distributed Systems (MANSiD), Ştefan cel Mare University of Suceava, 720229 Suceava, Romania; (R.C.O.); (I.Ș.); (M.D.)
- Department of Computers, Electronics and Automation, Ştefan cel Mare University of Suceava, 720229 Suceava, Romania
| | - Mihai Covasa
- Department of Biomedical Sciences, Faculty of Medicine and Biological Sciences, “Ştefan cel Mare” University of Suceava, 720229 Suceava, Romania; (A.C.-B.); (O.A.C.-S.); (M.I.); (N.-E.P.); (M.C.)
- Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91711, USA
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16
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Abdelouahed M, Yateem D, Fredericks S. Fc γRIIa - dependent platelet activation identified in COVID-19 vaccine-induced immune thrombotic thrombocytopenia-, heparin-induced thrombocytopenia, streptokinase- and anisoylated plasminogen-streptokinase activator complex-induced platelet activation. Front Cardiovasc Med 2023; 10:1282637. [PMID: 38034388 PMCID: PMC10684751 DOI: 10.3389/fcvm.2023.1282637] [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: 08/24/2023] [Accepted: 10/30/2023] [Indexed: 12/02/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), which was caused by the coronavirus - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was globally responsible for remarkable morbidity and mortality. Several highly effective vaccines for COVID-19 were developed and disseminated worldwide within an unprecedented timescale. Rare but dangerous clotting and thrombocytopenia events, and subsequent coagulation abnormalities, have been reported after massive vaccination against SARS-CoV-2. Soon after their global rollout, reports of a morbid clinical syndrome following vaccination with adenovirus-DNA-based vaccines appeared. In the spring of 2021, reports of a novel, rare and morbid clinical syndrome, with clinically devastating and fatal complication after vaccination with adenovirus-based coronavirus vaccines (Janssen/Johnson & Johnson and Astra-Zeneca vaccines) led to a brief suspension of their use by several countries. Those complications were associated with unusual cerebral and splanchnic venous thrombosis, and circulating autoantibodies directed against anti-platelet factor 4 (PF4), a protein secreted from platelets, leading to the designation: Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT). The reported VITT incidence remains very low and does not affect the overall benefit of immunization, however, if left untreated, VITT can be debilitating or even fatal. VITT resembled specific adverse drugs' reactions that also involved the production of autoantibodies and subsequent abnormal platelet activation through platelet FcγRIIa. These unusual but well-documented drug reactions were heparin-induced thrombocytopenia (HIT), streptokinase- (SK), and anisoylated plasminogen-streptokinase activator complex- (APSAC) associated with platelet-activating antibodies. There was considerable overlapping of clinical features between VITT, COVID-19 and these adverse drugs' reactions. We review the phenomenon of VITT against the backdrop of shared and common mechanisms that underlie HIT-, SK-, and APSAC-platelet FcγRIIa-dependent platelet activation. An understanding of VITT's pathogenesis may be achieved by comparing and contrasting VITT-, HIT-, SK- and APSAC-induced platelet activation mechanisms, their respective physiopathology and similarities. Discussing these conditions in parallel provides insight into complex immunological disorders and diseases associated with abnormal hemostasis and thrombosis in particular.
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Affiliation(s)
- Mustapha Abdelouahed
- Department of Medical Sciences and Education, Boston University School of Medicine, Boston, MA, United States
| | - Dana Yateem
- School of Medicine, The Royal College of Surgeons in Ireland, Medical University of Bahrain, Al Sayh, Muharraq Governorate, Bahrain
| | - Salim Fredericks
- School of Medicine, The Royal College of Surgeons in Ireland, Medical University of Bahrain, Al Sayh, Muharraq Governorate, Bahrain
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17
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Dalbeni A, Susca N, Daidone M, Rossi I, Giontella A, Cimellaro A, Talerico G, Pietrangelo A, Sesti G, Zaccone V, Villani R. Low dose aspirin and clinical outcomes in patients with SARS-CoV-2 pneumonia: a propensity score-matched cohort analysis from the National SIMI‑COVID‑19 Registry. Intern Emerg Med 2023; 18:2311-2319. [PMID: 37751084 DOI: 10.1007/s11739-023-03432-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 09/11/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND SARS- CoV-2 virus has had dramatic consequences worldwide being able to cause acute respiratory distress syndrome (ARDS), massive thrombosis and pulmonary embolism and, finally, patients' death. In COVID-19 infection, platelets have a procoagulant phenotype that can cause thrombosis in the pulmonary and systemic vascular network. Aspirin is a well-known anti-platelet drug widely used for the prevention of cardiovascular events and systematic reviews suggest a possible benefit of low-dose aspirin (LDA) use in the prevention and treatment of ARDS in patients with COVID-19 infection. However, several studies are available in the literature which do not support any benefits and no association with the patients' outcome. Therefore, currently available data are inconclusive. MATERIALS AND PATIENTS Data from the nationwide cohort multicenter study of the Italian Society of Internal Medicine (SIMI) were analyzed. We conducted a propensity score-matched cohort analysis to investigate the impact of chronic assumption of LDA on mortality of adult COVID-19 patients admitted in Internal Medicine Units (IMU). Data from 3044 COVID-19 patients who referred to 41 Italian hospitals between February 3rd to May 8th 2020 were analyzed. A propensity score-matched analysis was conducted using the following variables: age, sex, hypertension, hyperlipidemia diabetes, atrial fibrillation, cerebrovascular disease, COPD, CKD and stratified upon LDA usage, excluding anticoagulant treatment. After matching, 380 patients were included in the final analysis (190 in LDA group and 190 in no-LDA group). RESULTS 66.2% were male, median age was 77 [70-83]. 34.8% of the population died during the hospitalization. Cardiovascular diseases were not significantly different between the groups. After comparison of LDA and no-LDA subgroups, we didn't record a significant difference in mortality rate (35.7% vs 33.7%) duration of hospital stay and ICU admission. In a logistic regression model, age (OR 1.05; 95% CI 1.01-1.09), FiO2 (OR 1.024; 95% CI 1.03-1.04) and days between symptoms onset and hospitalization (OR 0.93; 95% CI 0.87-0.99) were the only variables independently associated with death.
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Affiliation(s)
- A Dalbeni
- Section General Medicine C and Liver Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Verona, University of Verona, Verona, Italy
| | - N Susca
- Department of Biomedical Sciences and Human Oncology, "Aldo Moro" University of Bari Medical School, 70124, Bari, Italy
| | - M Daidone
- Internal Medicine and Stroke Care Ward. Department of Health Promotion, Maternal and Infant Care, Internal Medicine and Medical Specialties, "G. D'Alessandro", University of Palermo, Piazza delle Cliniche N.2, Palermo, Italy
| | - I Rossi
- Department of Medicine and Aging Sciences, Clinica Medica" Institute, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy
| | - A Giontella
- Section General Medicine C and Liver Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Verona, University of Verona, Verona, Italy
| | - A Cimellaro
- Internal Medicine Unit, Pugliese-Ciaccio, Hospital, 88100, Catanzaro, Italy
| | - G Talerico
- Internal Medicine Unit, Policlinico Casilino, Rome, Italy
| | - A Pietrangelo
- Internal Medicine Unit, Department of Surgical and Medical Sciences for Children and Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - G Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00189, Rome, Italy
| | - V Zaccone
- Department of Emergency Medicine, Internal and Sub-Intensive Medicine, Azienda Ospedaliero-Universitaria "Ospedali Riuniti", 60166, Ancona, Italy.
| | - R Villani
- Liver Unit, Centro Universitario per la Ricerca e la Cura delle Epatopatie (C.U.R.E.), Università di Foggia, 71100, Foggia, Italy
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18
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Tang SW, Helmeste DM, Leonard BE. COVID-19 as a polymorphic inflammatory spectrum of diseases: a review with focus on the brain. Acta Neuropsychiatr 2023; 35:248-269. [PMID: 36861428 DOI: 10.1017/neu.2023.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
There appear to be huge variations and aberrations in the reported data in COVID-19 2 years now into the pandemic. Conflicting data exist at almost every level and also in the reported epidemiological statistics across different regions. It is becoming clear that COVID-19 is a polymorphic inflammatory spectrum of diseases, and there is a wide range of inflammation-related pathology and symptoms in those infected with the virus. The host's inflammatory response to COVID-19 appears to be determined by genetics, age, immune status, health status and stage of disease. The interplay of these factors may decide the magnitude, duration, types of pathology, symptoms and prognosis in the spectrum of COVID-19 disorders, and whether neuropsychiatric disorders continue to be significant. Early and successful management of inflammation reduces morbidity and mortality in all stages of COVID-19.
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Affiliation(s)
- Siu Wa Tang
- Department of Psychiatry, University of California, Irvine, Irvine, CA, USA
- Institute of Brain Medicine, Hong Kong, China
| | - Daiga Maret Helmeste
- Department of Psychiatry, University of California, Irvine, Irvine, CA, USA
- Institute of Brain Medicine, Hong Kong, China
| | - Brian E Leonard
- Institute of Brain Medicine, Hong Kong, China
- Department of Pharmacology, National University of Ireland, Galway, Ireland
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19
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Laughey W, Lodhi I, Pennick G, Smart L, Sanni O, Sandhu S, Charlesworth B. Ibuprofen, other NSAIDs and COVID-19: a narrative review. Inflammopharmacology 2023; 31:2147-2159. [PMID: 37603158 PMCID: PMC10518289 DOI: 10.1007/s10787-023-01309-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 07/31/2023] [Indexed: 08/22/2023]
Abstract
At the start of the coronavirus disease 2019 (COVID-19) pandemic (March 2020), there was speculation that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, used to manage some of the symptoms of COVID-19, could increase the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and negatively impact clinical outcomes. In the absence of any robust mechanistic and clinical evidence, this speculation led to confusion about the safety of ibuprofen, contributing to the so-called 'infodemic' surrounding COVID-19. A wealth of evidence has been generated in subsequent years, and this narrative review aims to consider the body of in vitro and in vivo research, observational studies, systematic reviews and meta-analyses on the use of NSAIDs, including ibuprofen, in COVID-19. Overall, the direction of evidence supports that NSAIDs do not increase susceptibility to infection, nor worsen disease outcomes in patients with COVID-19. Neither do they impact the immune response to COVID-19 vaccines. There is no basis to limit the use of NSAIDs, and doing so may deprive patients of effective self-care measures to control symptoms.
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Affiliation(s)
- William Laughey
- Reckitt Health Care UK Ltd, Hull, UK.
- Hull York Medical School, University of York, York, UK.
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20
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Zhao J, Xu X, Gao Y, Yu Y, Li C. Crosstalk between Platelets and SARS-CoV-2: Implications in Thrombo-Inflammatory Complications in COVID-19. Int J Mol Sci 2023; 24:14133. [PMID: 37762435 PMCID: PMC10531760 DOI: 10.3390/ijms241814133] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 08/14/2023] [Accepted: 08/22/2023] [Indexed: 09/29/2023] Open
Abstract
The SARS-CoV-2 virus, causing the devastating COVID-19 pandemic, has been reported to affect platelets and cause increased thrombotic events, hinting at the possible bidirectional interactions between platelets and the virus. In this review, we discuss the potential mechanisms underlying the increased thrombotic events as well as altered platelet count and activity in COVID-19. Inspired by existing knowledge on platelet-pathogen interactions, we propose several potential antiviral strategies that platelets might undertake to combat SARS-CoV-2, including their abilities to internalize the virus, release bioactive molecules to interfere with viral infection, and modulate the functions of immune cells. Moreover, we discuss current and potential platelet-targeted therapeutic strategies in controlling COVID-19, including antiplatelet drugs, anticoagulants, and inflammation-targeting treatments. These strategies have shown promise in clinical settings to alleviate the severity of thrombo-inflammatory complications and reduce the mortality rate among COVID-19 patients. In conclusion, an in-depth understanding of platelet-SARS-CoV-2 interactions may uncover novel mechanisms underlying severe COVID-19 complications and could provide new therapeutic avenues for managing this disease.
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Affiliation(s)
| | | | | | - Yijing Yu
- School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; (J.Z.); (X.X.); (Y.G.)
| | - Conglei Li
- School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; (J.Z.); (X.X.); (Y.G.)
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21
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Ram MD, Umer M, Trada IJ, Khan SJ, Imran L, Rehan T, Hassan W, Zafar F, Razak S, Laeeq T, Aijaz P, Majid Z. The Role of Anticoagulants and Antiplatelets in Reducing Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis of Studies Reporting Adjusted Data. Cureus 2023; 15:e45749. [PMID: 37872904 PMCID: PMC10590480 DOI: 10.7759/cureus.45749] [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] [Accepted: 09/22/2023] [Indexed: 10/25/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels. Therefore, we aim to investigate if anticoagulants (AC) and antiplatelet (AP) therapy play a role in mitigating COVID-19 and its associated thrombosis along with its effect on the mortality rate, the need for mechanical ventilation, and the risk of hospital admission. Electronic databases were searched from their inception to July 19, 2022. The studies were divided into two groups: Group A (any dose of AC/AP versus no AC/AP) and Group B (therapeutic dose of AC (tAC)/AP versus prophylactic dose of AC (pAC)/AP). Review Manager (RevMan) version 5.4.1 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used for all statistical analyses. Adjusted data ratios were extracted from all included studies and pooled using the random effects model. A total of 33 studies were taken for the analysis of two groups (Group A: 285,065 COVID-19-positive patients, Group B: 2,421 COVID-19-positive patients). Overall analysis in Group A showed that the AC/AP group had a low risk of mortality in COVID-19 patients compared to the control group (risk ratio (RR): 0.77, 95% confidence interval (CI): 0.69-0.86). There was no significant difference in the need for mechanical ventilation (RR: 0.80, 95% CI: 0.60-1.08) and hospital admission (RR: 1.12, 95% CI: 0.78-1.59) between the AC/AP and no AC/AP group. Alongside, in Group B, tAC/AP did not demonstrate a significant decrease in mortality as compared to pAC/AP (RR: 0.62, 95% CI: 0.37-1.06). Treatment with AC and AP drugs can significantly decrease the mortality rate in COVID-19-infected patients, while AC also significantly reduces the need for mechanical ventilation.
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Affiliation(s)
| | - Muhammed Umer
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | | | | | - Laiba Imran
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Tayyaba Rehan
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Warda Hassan
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Faiqa Zafar
- General Surgery, New York Institute of Osteopathic Medicine, New York, USA
| | - Sufyan Razak
- Oncology, Johns Hopkins University School of Medicine, Baltimore, USA
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
| | - Tooba Laeeq
- Internal Medicine, Kirk Kerkorian School of Medicine at University of Nevada, Las Vegas (UNLV), Las Vegas, USA
| | - Parisa Aijaz
- Internal Medicine, Charleston Area Medical Center, Charleston, USA
| | - Zainab Majid
- Internal Medicine, Dow University of Health Sciences, Karachi, PAK
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22
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Szilveszter M, Pál S, Simon-Szabó Z, Akácsos-Szász OZ, Moldován M, Réger B, Dénes L, Faust Z, Tilinca MC, Nemes-Nagy E. The Management of COVID-19-Related Coagulopathy: A Focus on the Challenges of Metabolic and Vascular Diseases. Int J Mol Sci 2023; 24:12782. [PMID: 37628963 PMCID: PMC10454092 DOI: 10.3390/ijms241612782] [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: 07/01/2023] [Revised: 08/07/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
The course of COVID-19 is highly dependent on the associated cardiometabolic comorbidities of the patient, which worsen the prognosis of coronavirus infection, mainly due to systemic inflammation, endothelium dysfunction, and thrombosis. A search on the recent medical literature was performed in five languages, using the PubMed, Embase, Cochrane, and Google Scholar databases, for the review of data regarding the management of patients with a high risk for severe COVID-19, focusing on the associated coagulopathy. Special features of COVID-19 management are presented, based on the underlying conditions (obesity, diabetes mellitus, and cardiovascular diseases), emphasizing the necessity of a modern, holistic approach to thromboembolic states. The latest findings regarding the most efficient therapeutic approaches are included in the article, offering guidance for medical professionals in severe, complicated cases of SARS-CoV-2 infection. We can conclude that severe COVID-19 is closely related to vascular inflammation and intense cytokine release leading to hemostasis disorders. Overweight, hyperglycemia, cardiovascular diseases, and old age are important risk factors for severe outcomes of coronavirus infection, involving a hypercoagulable state. Early diagnosis and proper therapy in complicated SARS-CoV-2-infected cases could reduce mortality and the need for intensive care during hospitalization in patients with cardiometabolic comorbidities.
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Affiliation(s)
- Mónika Szilveszter
- Clinic of Plastic Surgery, Mureș County Emergency Hospital, 540136 Târgu-Mureș, Romania;
| | - Sándor Pál
- Department of Transfusion Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary;
| | - Zsuzsánna Simon-Szabó
- Department of Pathophysiology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania
| | - Orsolya-Zsuzsa Akácsos-Szász
- Doctoral School, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
| | - Mihály Moldován
- Klinik für Suchttherapie, ZtP Winnenden-Haus der Gesundheit, 73525 Schwäbisch Gümund, Germany;
| | - Barbara Réger
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary;
| | - Lóránd Dénes
- Department of Anatomy and Embryology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
| | - Zsuzsanna Faust
- Department of Transfusion Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary;
| | - Mariana Cornelia Tilinca
- Department of Internal Medicine I, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
| | - Enikő Nemes-Nagy
- Department of Chemistry and Medical Biochemistry, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
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23
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Kumar S, Basu M, Ghosh P, Pal U, Ghosh MK. COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery. Genes Dis 2023; 10:1402-1428. [PMID: 37334160 PMCID: PMC10079314 DOI: 10.1016/j.gendis.2022.12.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 12/07/2022] [Accepted: 12/16/2022] [Indexed: 06/17/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the complicated disease COVID-19. Clinicians are continuously facing huge problems in the treatment of patients, as COVID-19-specific drugs are not available, hence the principle of drug repurposing serves as a one-and-only hope. Globally, the repurposing of many drugs is underway; few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical trials. Here in this review, our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs, the potential mechanism of actions, and the current clinical trial status of various drugs which are under repurposing since early 2020. At last, we briefly proposed the probable pharmacological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines.
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Affiliation(s)
- Sunny Kumar
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector–V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India
| | - Malini Basu
- Department of Microbiology, Dhruba Chand Halder College, Dakshin Barasat, West Bengal 743372, India
| | - Pratyasha Ghosh
- Department of Economics, Bethune College, University of Calcutta, Kolkata 700006, India
| | - Uttam Pal
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector–V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India
| | - Mrinal K. Ghosh
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector–V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India
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24
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Alhawiti NM, Alhawiti JM, Alshalan SD, Alotaibi BA, Khobrani AY. Clinical Outcomes of Anticoagulant Therapy in COVID-19 Patients with Pre-Existing Cardiovascular Diseases: A Systematic Review. Infect Drug Resist 2023; 16:3767-3775. [PMID: 37337574 PMCID: PMC10277005 DOI: 10.2147/idr.s410374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 05/25/2023] [Indexed: 06/21/2023] Open
Abstract
The COVID-19 infection caused by SARS-CoV-2 is a healthcare crisis that has led to unparalleled disruption and has impacted healthcare services, leading to significant morbidity and mortality in the worldwide population. Insufficient data on the management of COVID-19 complications such as hypercoagulability and the controversy about the benefits of anticoagulant therapy are major challenges encountered by clinicians, especially for patients with pre-existing cardiovascular diseases (CVD), and are still debatable. Therefore, we endeavored to conduct a systematic review to assess the clinical outcomes of prior anticoagulant therapy in patients with COVID-19 having pre-existing CVD. Electronic searches of the PubMed database and EBSCO Information Services were carried out, and all relevant articles were employed. Seven articles with data from 21,989 subjects were included. Despite the promised clinical outcomes of anticoagulant therapy, the results of the current systematic review indicated insignificant improvements in the reduction of mortality rate or ICU admission among patients with COVID-19 having pre-existing CVD. Furthermore, direct oral anticoagulant (DOAC) were favored over vitamin K antagonists (VKAs) due to better action and less side effects. In conclusion, the findings are controversial as we did not statistically analyze the results. The data showed inconsistent information with no clear effect of anticoagulant use before patient hospitalization or decreasing COVID-19 severity, particularly in those with CVD. Further studies including randomized controlled trials are required to describe the best course as well as optimal dose of anticoagulant use in the treatment of patients with COVID-19, particularly those with comorbidities such as CVD.
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Affiliation(s)
- Naif M Alhawiti
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center (KAIMRC), Riyadh, Kingdom of Saudi Arabia
| | - Jamal M Alhawiti
- College of Medicine, Al Jouf University, Riyadh, Kingdom of Saudi Arabia
| | - Saif D Alshalan
- College of Medicine, Al Jouf University, Riyadh, Kingdom of Saudi Arabia
| | - Badi A Alotaibi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center (KAIMRC), Riyadh, Kingdom of Saudi Arabia
| | - Ahmad Y Khobrani
- Emergency Department, King Abdullah Bin Abdulaziz University Hospital, Princess Norah University, Riyadh, Kingdom of Saudi Arabia
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25
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Harahsheh AS, Portman MA, Khoury M, Elias MD, Lee S, Lin J, McCrindle BW. Management of Multisystem Inflammatory Syndrome in Children: Decision-Making Regarding a New Condition in the Absence of Clinical Trial Data. Can J Cardiol 2023; 39:803-814. [PMID: 36455760 PMCID: PMC9705008 DOI: 10.1016/j.cjca.2022.11.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 11/30/2022] Open
Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a new illness that evolved during the COVID-19 pandemic with initial reports of severe disease including use of extracorporeal membrane oxygenation and death. Institutions rapidly assembled task forces to develop treatment algorithms. At the national/international levels, collaboratives and associations assembled consensus writing groups to draft guidelines. These guidelines and algorithms were initially on the basis of expert opinion and small case series. Some groups used the Delphi approach, and the resultant guidelines often mimicked those for other conditions that resembled MIS-C, like Kawasaki disease (KD). For instance, intravenous immunoglobulin (IVIG), a known effective treatment for KD, was recommended for MIS-C. Early in the pandemic many favoured IVIG over steroids as first-line therapy. As evidence evolved so did some guidelines, which now endorse the dual use of IVIG with steroids as first-line therapy. In contrast, withholding immunotherapy became an option for some MIS-C patients with mild symptoms. Herein, we review guidelines and discuss the evidence informing early recommendations, how this has evolved, the role and limitations of expert opinion and observational data, and the importance of leveraging existing research infrastructures, such as the intensive care unit collaborative (Overcoming COVID-19 surveillance registry), and the International Kawasaki Disease Registry. Finally, we discuss strategies to rapidly develop, deploy, and adapt clinical trials evaluating the treatment of such rare conditions in children, which might include alternatives to conventional clinical trial design. The emergence of MIS-C during the COVID-19 pandemic has highlighted unmet needs regarding research of a new condition.
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Affiliation(s)
- Ashraf S Harahsheh
- Division of Cardiology, Department of Pediatrics, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | | | - Michael Khoury
- Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada
| | - Matthew D Elias
- Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Simon Lee
- The Heart Center at Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Justin Lin
- Labatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Brian W McCrindle
- Labatt Family Heart Centre, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
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26
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Tobi M, Bluth MH, Rossi NF, Demian E, Talwar H, Tobi YY, Sochacki P, Levi E, Lawson M, McVicker B. In the SARS-CoV-2 Pandora Pandemic: Can the Stance of Premorbid Intestinal Innate Immune System as Measured by Fecal Adnab-9 Binding of p87:Blood Ferritin, Yielding the FERAD Ratio, Predict COVID-19 Susceptibility and Survival in a Prospective Population Database? Int J Mol Sci 2023; 24:7536. [PMID: 37108697 PMCID: PMC10145175 DOI: 10.3390/ijms24087536] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/03/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility.
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Affiliation(s)
- Martin Tobi
- Research and Development Service, Detroit VAMC, 4747 John R Street, Detroit, MI 48602, USA
| | - Martin H. Bluth
- Blood Transfusion and Donor Services, Department of Pathology, Maimonides Medical Center, 4802 10th Avenue, Brooklyn, NY 11219, USA
- School of Medicine, Wayne State University, 540 E Canfield St, Detroit, MI 48201, USA
| | - Noreen F. Rossi
- Research and Development Service, Detroit VAMC, 4747 John R Street, Detroit, MI 48602, USA
- Division of Nephrology, Department of Physiology, School of Medicine, Wayne State University, 540 E. Canfield Ave., Detroit, MI 48201, USA
| | - Ereny Demian
- Department of Internal Medicine, Pennsylvania State University College of Medicine, 700 HMC Cres Rd., Hershey, PA 17033, USA
| | - Harvinder Talwar
- Research and Development Service, Detroit VAMC, 4747 John R Street, Detroit, MI 48602, USA
- School of Medicine, Wayne State University, 540 E Canfield St, Detroit, MI 48201, USA
| | - Yosef Y. Tobi
- Department of Thoracic Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
| | - Paula Sochacki
- Department of Pathology, Detroit VAMC, 4747 John R Street, Detroit, MI 48602, USA
| | - Edi Levi
- Research and Development Service, Detroit VAMC, 4747 John R Street, Detroit, MI 48602, USA
| | - Michael Lawson
- Division of Gastroenterology and Hepatology, University of California at Sacramento, Sacramento, CA 95819, USA
| | - Benita McVicker
- Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
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27
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Vilaplana-Carnerero C, Giner-Soriano M, Dominguez À, Morros R, Pericas C, Álamo-Junquera D, Toledo D, Gallego C, Redondo A, Grau M. Atherosclerosis, Cardiovascular Disease, and COVID-19: A Narrative Review. Biomedicines 2023; 11:biomedicines11041206. [PMID: 37189823 DOI: 10.3390/biomedicines11041206] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/12/2023] [Accepted: 04/17/2023] [Indexed: 05/17/2023] Open
Abstract
Atherosclerosis is a chronic inflammatory and degenerative process that mainly occurs in large- and medium-sized arteries and is morphologically characterized by asymmetric focal thickenings of the innermost layer of the artery, the intima. This process is the basis of cardiovascular diseases (CVDs), the most common cause of death worldwide. Some studies suggest a bidirectional link between atherosclerosis and the consequent CVD with COVID-19. The aims of this narrative review are (1) to provide an overview of the most recent studies that point out a bidirectional relation between COVID-19 and atherosclerosis and (2) to summarize the impact of cardiovascular drugs on COVID-19 outcomes. A growing body of evidence shows that COVID-19 prognosis in individuals with CVD is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with CVD after COVID-19. The most common treatments for CVD may influence COVID-19 outcomes. Thus, their implication in the infection process is briefly discussed in this review. A better understanding of the link among atherosclerosis, CVD, and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients.
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Affiliation(s)
- Carles Vilaplana-Carnerero
- Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), 08007 Barcelona, Spain
- Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- School of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
| | - Maria Giner-Soriano
- Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), 08007 Barcelona, Spain
- School of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
| | - Àngela Dominguez
- Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Biomedical Research Consortium in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Rosa Morros
- Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), 08007 Barcelona, Spain
- Biomedical Research Consortium in Infectious Diseases (CIBERINFEC), 28029 Madrid, Spain
- Department of Pharmacology, Therapeutics and Toxicology, School of Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
| | - Carles Pericas
- Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Epidemiology Service, Public Health Agency of Barcelona (ASPB), 08023 Barcelona, Spain
| | - Dolores Álamo-Junquera
- Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Quality, Process and Innovation Direction, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
- Health Services Research Group, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
| | - Diana Toledo
- Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Biomedical Research Consortium in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
| | - Carmen Gallego
- Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- Methodology, Quality and Medical Care Assessment Department, Direcció d'Atenció Primària Metropolitana Sud, Catalan Institute of Health (ICS), 08908 Barcelona, Spain
| | - Ana Redondo
- Hospital Universitario Bellvitge, Catalan Institute of Health (ICS), 08907 Barcelona, Spain
| | - María Grau
- Biomedical Research Consortium in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
- Serra Húnter Fellow, Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain
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28
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Kankaria R, Sanina C, Gabr M, Wiley J, Bortnick AE. Extracardiac Prothrombotic Effects of COVID-19. Heart Fail Clin 2023; 19:213-220. [PMID: 36863813 PMCID: PMC9973540 DOI: 10.1016/j.hfc.2022.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/04/2023]
Abstract
COVID-19 infection triggers a heightened inflammatory response which in turn, increases thrombosis and thromboembolism. Microvascular thrombosis has been detected in various tissue beds which may account for some of the multi-system organ dysfunction associated with COVID-19. Additional research is needed to understand which prophylactic and therapeutic drug regimens are best for the prevention and treatment of thrombotic complications of COVID-19.
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Affiliation(s)
- Rohan Kankaria
- Albert Einstein College of Medicine, Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA
| | - Cristina Sanina
- Albert Einstein College of Medicine, Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Medicine, Division of Cardiology, Montefiore Medical Center, 111 E 210th Street, Bronx, NY 10467 USA
| | - Mohamed Gabr
- Albert Einstein College of Medicine, Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Medicine, Division of Cardiology, Montefiore Medical Center, 111 E 210th Street, Bronx, NY 10467 USA
| | - Jose Wiley
- Albert Einstein College of Medicine, Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Medicine, Division of Cardiology, Montefiore Medical Center, 111 E 210th Street, Bronx, NY 10467 USA
| | - Anna E Bortnick
- Albert Einstein College of Medicine, Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY 10461, USA; Department of Medicine, Division of Cardiology, Montefiore Medical Center, 111 E 210th Street, Bronx, NY 10467 USA; Division of Geriatrics, Montefiore Medical Center, 111 E 210th Street, Bronx, NY 10467 USA.
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Brechko A, Jiroutek MR, Jones K, Brenseke B, Maharty DC, Cappola J, Holly SP. Retrospective Study of Thrombosis in Hospitalized Patients with COVID-19 in Rural North Carolina. N C Med J 2023; 84:127-133. [PMID: 39302334 DOI: 10.18043/001c.73024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
Background Some patients with COVID-19 develop life-threatening thrombotic complications including myocardial infarction, deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, and ischemic stroke. These inflammatory and hypercoagulable states have been well documented in patient cohorts from metropolitan areas, but not in more rural populations, nor has a data-driven treatment plan been developed for thrombotic COVID-19 patients. Methods We undertook a retrospective case-control study of COVID-19-positive patients to analyze the impact of thrombosis on various clinical endpoints including terminal diagnosis and disease severity. Prevalence and impact of thrombosis were determined using medical records from 2237 COVID-19-positive patients hospitalized in Cumberland County, North Carolina. Odds ratios for terminal diagnosis, death, ICU admission, and ventilation were calculated based on thrombosis status, D-dimer level, or type of antithrombotic treatment. Results Terminal diagnosis [OR 1.81; 95% CI (1.10, 2.98)], ICU admission [2.25; (1.33, 3.81)], and ventilation [2.46; (1.45, 4.18)] were all more likely in thrombotic patients (N = 97) compared to nonthrombotic patients (N = 2140) after adjusting for age. D-dimer levels were associated with death overall, but not among thrombotic patients. Treatments that combined antiplatelet and anticoagulant drugs appeared to be more efficacious than anticoagulants alone in preventing death and severe disease. Limitations Patient medical history prior to hospitalization was not evaluated. Conclusion In this cohort, those with thrombosis are at increased risk for adverse outcomes including death and severe disease. Antithrombotic therapy that includes antiplatelet drugs provides improved outcomes. Higher-powered prospective trials will be necessary to confirm any potential merits of antiplatelet therapy.
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Affiliation(s)
| | | | - Kyla Jones
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
| | - Bonnie Brenseke
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
| | - Donald C Maharty
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
- Cape Fear Valley Medical Center
| | - James Cappola
- Jerry M. Wallace School of Osteopathic Medicine, Campbell University
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Zaid Y, Lahlimi Q, Khalki L, Zaid N, Oudghiri M, Cheikh A, Naya A, Merhi Y, Guessous F. Aspirin use Reduces Platelet Hyperreactivity and Degranulation in COVID-19 Patients. Semin Thromb Hemost 2023; 49:92-96. [PMID: 35255504 DOI: 10.1055/s-0042-1744281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Younes Zaid
- Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco.,Research Center of Abulcasis University of Health Sciences, Rabat, Morocco.,Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences, Hassan II University, Casablanca, Morocco
| | - Qamar Lahlimi
- Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco
| | - Loubna Khalki
- Laboratory of Thrombosis and Hemostasis, Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada
| | - Nabil Zaid
- Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco
| | - Mounia Oudghiri
- Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences, Hassan II University, Casablanca, Morocco
| | - Amine Cheikh
- Research Center of Abulcasis University of Health Sciences, Rabat, Morocco
| | - Abdallah Naya
- Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences, Hassan II University, Casablanca, Morocco
| | - Yahye Merhi
- Laboratory of Thrombosis and Hemostasis, Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada
| | - Fadila Guessous
- Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, Morocco
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Abstract
Although thrombosis frequently occurs in infectious diseases, the coagulopathy associated with COVID-19 has unique characteristics. Compared with bacterial sepsis, COVID-19-associated coagulopathy presents with minimal changes in platelet counts, normal prothrombin times, and increased D-dimer and fibrinogen levels. These differences can be explained by the distinct pathophysiology of the thromboinflammatory responses. In sepsis-induced coagulopathy, leukocytes are primarily responsible for the coagulopathy by expressing tissue factor, releasing neutrophil extracellular traps, multiple procoagulant substances, and systemic endothelial injury that is often associated with vasoplegia and shock. In COVID-19-associated coagulopathy, platelet activation is a major driver of inflammation/thrombogenesis and von Willebrand factor and platelet factor 4 are deeply involved in the pathogenesis. Although the initial responses are localized to the lung, they can spread systemically if the disease is severe. Since the platelets play major roles, arterial thrombosis is not uncommon in COVID-19. Despite platelet activation, platelet count is usually normal at presentation, but sensitive biomarkers including von Willebrand factor activity, soluble P-selectin, and soluble C-type lectin-like receptor-2 are elevated, and they increase as the disease progresses. Although the role of antiplatelet therapy is still unproven, current studies are ongoing to determine its potential effects.
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Affiliation(s)
- Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hideo Wada
- Department of General Medicine, Mie Prefectural General Medical Center, Mie, Japan
| | - Jerrold H Levy
- Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, North Carolina
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Perico N, Cortinovis M, Suter F, Remuzzi G. Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents. THE LANCET. INFECTIOUS DISEASES 2023; 23:e22-e33. [PMID: 36030796 PMCID: PMC9411261 DOI: 10.1016/s1473-3099(22)00433-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/20/2022] [Accepted: 06/20/2022] [Indexed: 02/09/2023]
Abstract
COVID-19, caused by SARS-CoV-2, is characterised by a broad spectrum of symptom severity that requires varying amounts of care according to the different stages of the disease. Intervening at the onset of mild to moderate COVID-19 symptoms in the outpatient setting would provide the opportunity to prevent progression to a more severe illness and long-term complications. As early disease symptoms variably reflect an underlying excessive inflammatory response to the viral infection, the use of anti-inflammatory drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), in the initial outpatient stage of COVID-19 seems to be a valuable therapeutic strategy. A few observational studies have tested NSAIDs (especially relatively selective COX-2 inhibitors), often as part of multipharmacological protocols, for early outpatient treatment of COVID-19. The findings from these studies are promising and point to a crucial role of NSAIDs for the at-home management of people with initial COVID-19 symptoms.
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Affiliation(s)
- Norberto Perico
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy
| | - Monica Cortinovis
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy
| | - Fredy Suter
- Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy; Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy.
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Ali RM, Tharwat AI, Labib HA. Effect of Aspirin Use on clinical Outcome among Critically Ill Patients with COVID- 19. EGYPTIAN JOURNAL OF ANAESTHESIA 2022. [DOI: 10.1080/11101849.2022.2139104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Rania M. Ali
- Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ayman I. Tharwat
- Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Heba A. Labib
- Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Toppen W, Yan P, Markovic D, Shover CM, Buhr RG, Fulcher JA, Tashkin DP, Barjaktarevic I. Chronic Obstructive Pulmonary Disease is Not Associated with In-Hospital Mortality in COVID-19: An Observational Cohort Analysis. Int J Chron Obstruct Pulmon Dis 2022; 17:3111-3121. [PMID: 36570857 PMCID: PMC9788836 DOI: 10.2147/copd.s386463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 11/24/2022] [Indexed: 12/23/2022] Open
Abstract
Background Chronic obstructive pulmonary disease (COPD) is associated with worsened outcomes in COVID-19 (coronavirus disease 2019). However, data remain fraught with heterogeneity and bias from comorbid conditions. Additionally, data on the impact of COPD-specific factors, such as pre-hospital medications and pulmonologist involvement, remain sparse. Objective We report a single-center analysis of COPD patients hospitalized with COVID-19 compared to those without COPD. Primary outcomes include ICU admission, mechanical ventilation, and in-hospital mortality. Methods We evaluated all patients ≥40 years admitted with PCR-confirmed COVID-19 between February 2020 and February 2021. COPD was defined by documented ICD-10 diagnosis of COPD, confirmed smoking history, and active bronchodilator use. We compared outcomes between COPD patients and the remainder of the COVID-19 cohort. Multivariable analyses were adjusted for age, sex, smoking status, and comorbid conditions. Results Of 1537 hospitalized COVID-19 patients, 122 (7.9%) carried a diagnosis of COPD. The COPD cohort was older (74 ± 13 vs 66 ± 15 years, P < 0.001) and more often former smokers (P < 0.001). Comorbid conditions including diabetes, cardiovascular disease, and kidney disease were more prevalent in the COPD group (P < 0.001). After adjusting for comorbid conditions, the COPD cohort had higher severity scores and trended towards fewer hospital-free days. Among patients with COPD, pre-hospital use of aspirin was associated with decreased ICU admissions (aHR 0.56, P = 0.049) and mechanical ventilation (aHR 0.25, P = 0.008), while LAMAs (long-acting muscarinic antagonists) were associated with decreased in-hospital mortality (aHR 0.34, P = 0.047). Involvement of pulmonology in pre-hospital management of COPD was not found to significantly affect outcomes. Conclusion When corrected for comorbid illnesses, COPD was associated with more severe disease but not with increased ICU admission, mechanical ventilation, or in-hospital mortality rates. Among COPD patients, prehospital treatment with aspirin and COPD-directed therapies were associated with improved outcomes.
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Affiliation(s)
- William Toppen
- Section of Hospital Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Peter Yan
- David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Daniela Markovic
- Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Carolyn M Shover
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Offsite Care, Santa Rosa, CA, USA
| | - Russell G Buhr
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Department of Medicine, Greater Los Angeles Veterans Affairs Health Care System, Los Angeles, CA, USA
| | - Jennifer A Fulcher
- Department of Medicine, Greater Los Angeles Veterans Affairs Health Care System, Los Angeles, CA, USA
- Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Donald P Tashkin
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Igor Barjaktarevic
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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Knowledge, practice and attitude associated with SARS-CoV-2 Delta Variant among adults in Jordan. PLoS One 2022; 17:e0278243. [PMID: 36477269 PMCID: PMC9728918 DOI: 10.1371/journal.pone.0278243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 11/14/2022] [Indexed: 12/12/2022] Open
Abstract
COVID-19 infection is a global pandemic health emergency. This contagious disease was caused by the Severe Acute Respiratory Syndrome Coronavirus‑2 (SARS‑CoV-2) which is mutating over time. In 2021, the Delta variant became the most dominant transmissible form. During the crisis, human practice and knowledge were critical in the overall efforts to encompass the outbreak. A cross-sectional, web-based approach was conducted among adults in Jordan to quantify knowledge, attitude, and practices towards SARS-CoV-2 (Delta variant). This research was carried out between 15th April and 15th of May 2021. The study questionnaire consisted of four sections including the participant's demographics, knowledge, practices and attitude. Comparative evaluation of responses was accomplished using a scoring system. Respondents who scored above the mean score (60%) on the item measured were categorized as knowledgeable, having a positive attitude, and good practices. Participants were allocated to one of the three groups; medical, non-medical and others (unemployed and housewives). Data collected was analyzed using Statistical Package for Social Sciences (SPSS) version 23.0 software. A variance test to assess the statistical difference between groups was used. Pearson's chi-squared test was applied to compare the variables and identify significant predictors. Of the participants, 308 (66%) were in the age group of 18-25yrs, 392 (84.1%) females, 120 (25.8%) employed and 346 (74.2%) unemployed. The principle source of knowledge was social media (291, 62.4%). Interestingly, participants had adequate overall knowledge. The mean knowledge score was 22.6 (± 0.19), 20.6 (± 0.19), and 21.3 (± 0.18) for the medical, the non-medical and the others group, respectively. Also, participants showed a positive attitude and good practices towards SARS-CoV-2 (Delta variant). The mean practice score for medical, the non-medical and the others groups was 7.35 (± 0.25), 7.38 (± 0.24), 7.35 (± 0.24) and the mean attitude score was 10.8 (± 0.16), 9.4 (± 0.21), 9.5 (± 0.22), respectively. The studied groups generally had good knowledge, positive attitudes and good practices about SARS-CoV-2 (Delta variant). This was expected due to the authorities' successful management of the pandemic and the high educational level of the Jordanian society, bearing in mind the economic and social impact of COVID-19 disease.
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Zhao H, Huang S, Huang S, Liu F, Shao W, Mei K, Ma J, Jiang Y, Wan J, Zhu W, Yu P, Liu X. Prevalence of NSAID use among people with COVID-19 and the association with COVID-19-related outcomes: Systematic review and meta-analysis. Br J Clin Pharmacol 2022; 88:5113-5127. [PMID: 36029185 PMCID: PMC9538204 DOI: 10.1111/bcp.15512] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 03/23/2022] [Accepted: 04/25/2022] [Indexed: 11/29/2022] Open
Abstract
AIM Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating patients with coronavirus disease 2019 (COVID-19) have raised great concern. METHODS We searched the PubMed, EMBASE, Cochrane Library and MedRxiv databases to examine the prevalence of NSAID use and associated COVID-19 risk, outcomes and safety. RESULTS Twenty-five studies with a total of 101 215 COVID-19 patients were included. Prevalence of NSAID use among COVID-19 patients was 19% (95% confidence interval [CI] 14-23%, no. of studies [n] = 22) and NSAID use prior to admission or diagnosis of COVID-19 was not associated with an increased risk of COVID-19 (adjusted odds ratio [aOR] = 0.93, 95% CI 0.82-1.06, I2 = 34%, n = 3), hospitalization (aOR = 1.06, 95% CI 0.76-1.48, I2 = 81%, n = 5), mechanical ventilation (aOR = 0.71, 95% CI 0.47-1.06, I2 = 38%, n = 4) or length of hospital stay. Moreover, prior use of NSAIDs was associated with a decreased risk of severe COVID-19 (aOR = 0.79, 95% CI 0.71-0.89, I2 = 0%, n = 7) and death (aOR = 0.68, 95% CI 0.52-0.89, I2 = 85%, n = 10). Prior NSAID administration might also be associated with an increased risk of stroke (aOR = 2.32, 95% CI 1.04-5.2, I2 = 0%, n = 2), but not myocardial infarction (aOR = 1.49, 95% CI 0.25-8.92, I2 = 0, n = 2) and composite thrombotic events (aOR = 1.56, 95% CI 0.66-3.69, I2 = 52%, n = 2). CONCLUSION Based on current evidence, NSAID use prior to admission or diagnosis of COVID-19 was not linked with increased odds or exacerbation of COVID-19. NSAIDs might provide a survival benefit, although they might potentially increase the risk of stroke. Controlled trials are still required to further assess the clinical benefit and safety (e.g., stroke and acute renal failure) of NSAIDs in treating patients with COVID-19.
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Affiliation(s)
- Huilei Zhao
- Department of AnesthesiologyThird Hospital of NanchangJiangxiChina
| | - Shanshan Huang
- Department of EndocrineSecond Affiliated Hospital of Nanchang UniversityJiangxiChina
| | - Shan Huang
- Department of PsychiatryThird People's Hospital of Gan ZhouJiangxiChina
| | - Fuwei Liu
- Department of CardiologyAffiliated Ganzhou Hospital of Nanchang UniversityJiangxiChina
| | - Wen Shao
- Department of EndocrineSecond Affiliated Hospital of Nanchang UniversityJiangxiChina
| | - Kaibo Mei
- Department of AnesthesiologyShangrao People's HospitalJiangxiChina
| | - Jianyong Ma
- Department of Pharmacology and Systems PhysiologyUniversity of Cincinnati College of MedicineCincinnatiOHUSA
| | - Yuan Jiang
- Department of PharmacyHarbin Medical UniversityHarbinChina
| | - Jingfeng Wan
- Institute for the Study of Endocrinology and Metabolism in Jiangxi ProvinceNanchangChina
| | - Wengen Zhu
- Department of CardiologyFirst Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Peng Yu
- Department of EndocrineSecond Affiliated Hospital of Nanchang UniversityJiangxiChina
| | - Xiao Liu
- Institute for the Study of Endocrinology and Metabolism in Jiangxi ProvinceNanchangChina
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Amponsah SK, Tagoe B, Adams I, Bugyei KA. Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review. Front Pharmacol 2022; 13:1063246. [PMID: 36532785 PMCID: PMC9751434 DOI: 10.3389/fphar.2022.1063246] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 11/17/2022] [Indexed: 12/19/2024] Open
Abstract
Due to the fact that coronavirus disease 2019 (COVID-19) is still prevalent, and current reports show that some parts of the world have seen increase in incidence, it is relevant that health professionals and scientists know about recent or novel trends, especially drug treatments. Additionally, the safety profiles of these drug treatments need to be documented and shared with the public. Some studies have demonstrated the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in COVID-19 treatment. On the contrary, others have also reported that NSAIDs and corticosteroids may worsen symptoms associated with COVID-19. While some researchers have suggested that corticosteroids may be helpful if used in the early stages of COVID-19, there are still some conflicting findings regarding the use of corticosteroids in certain viral infections. Our review suggests that methylprednisolone, dexamethasone, and ibuprofen have therapeutic potential in reducing mortality due to COVID-19 among hospitalized patients. This review also highlights the fact that the use of NSAIDs is not associated with adverse outcomes of COVID-19. In reality, evidence suggests that NSAIDs do not increase the risk of COVID-19 infections. Also, the literature reviewed suggests that corticosteroid treatment in COVID-19 was linked with a decrease in all-cause mortality and disease progression, without increase in adverse events when compared to no corticosteroid treatment.
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Affiliation(s)
- Seth Kwabena Amponsah
- Department of Medical Pharmacology, University of Ghana Medical School, Accra, Ghana
| | - Benjamin Tagoe
- Fulfillment Operations and Academy, Zipline Ghana, Accra, Ghana
| | - Ismaila Adams
- Department of Medical Pharmacology, University of Ghana Medical School, Accra, Ghana
| | - Kwasi Agyei Bugyei
- Department of Medical Pharmacology, University of Ghana Medical School, Accra, Ghana
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Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans. J Gen Intern Med 2022; 37:4144-4152. [PMID: 35768681 PMCID: PMC9243908 DOI: 10.1007/s11606-022-07701-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 06/15/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Many severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive patients take commonly prescribed medications with properties which may affect mortality. OBJECTIVE Assess if common medications postulated to affect clinical outcomes are associated with mortality in SARS-CoV-2 positive patients in the Veterans Health Administration (VHA). DESIGN Observational national cohort analysis. PARTICIPANTS Consecutive 26,508 SARS-CoV-2 positive Veterans (7% of 399,290 tested from March 1 to September 10, 2020) constitute the study cohort. MAIN MEASURES The primary outcome was 30-day mortality from the first positive SARS-CoV-2 test date. In patients receiving medications or drug pairs within 2 weeks post-SARS-CoV-2 positive test, 30-day mortality was estimated as relative risk (RR) on the log-binomial scale or using multinomial models with and without adjusting for covariates. KEY RESULTS The 26,508 SARS-CoV-2 positive patients were predominantly male (89%) and White (59%), and 82% were overweight/obese. Medications associated with decreased 30-day mortality risk included the following: metformin (aRR, 0.33; 95% CI, 0.25-0.43), colchicine, angiotensin-converting-enzyme inhibitors (ACEi), angiotensin II receptor blockers, statins, vitamin D, antihistamines, alpha-blockers, anti-androgens, and nonsteroidal anti-inflammatory drugs (aRR, 0.69; 95% CI, 0.61-0.78). The effect of co-prescribed medications on 30-day mortality risk revealed the lowest risk for combined statins and metformin (aRR, 0.21; 95% CI, 0.15-0.31), followed by ACEi and statins (aRR, 0.25; 95% CI, 0.18-0.35), ACEi and metformin (aRR, 0.26; 95% CI, 0.17-0.40), antihistamines and NSAIDs (aRR, 0.41; 95% CI, 0.32-0.52), and in men, combined alpha-blockers and anti-androgens (aRR, 0.51; 95% CI, 0.42-0.64). CONCLUSIONS In this large national cohort, treatment of SARS-CoV-2 positive patients with individual or co-prescribed metformin and statins, ACEi and statins (or metformin) and other medications was associated with a markedly decreased 30-day mortality and can likely be continued safely. Clinical trials may assess their therapeutic benefit.
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Fijałkowski Ł, Skubiszewska M, Grześk G, Koech FK, Nowaczyk A. Acetylsalicylic Acid-Primus Inter Pares in Pharmacology. Molecules 2022; 27:8412. [PMID: 36500502 PMCID: PMC9738180 DOI: 10.3390/molecules27238412] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 11/24/2022] [Accepted: 11/27/2022] [Indexed: 12/05/2022] Open
Abstract
Acetylsalicylic acid (ASA) is one of the first drugs to be obtained by synthesis while being the most used. It has experienced the longest lasting commercial success and is considered the most popular drug of the modern era. ASA, originally used as an anti-inflammatory medication, nowadays is predominantly used as an antiplatelet agent for prophylaxis in cardiac patients. Many studies show that the benefits of using ASA far outweigh the potential risk of side effects. With particular emphasis on the possibility of ASA repositioning for new therapies, extending the indications for use beyond the diseases from the spectrum of atherosclerotic diseases, such as cancer, requires shifting the benefit-risk ratio, although very good, even more towards safety. Interesting activities consisting not only of changing the formulation but also modifying the drug molecule seem to be an important goal of the 21st century. ASA has become a milestone in two important fields: pharmacy and medicine. For a pharmacist, ASA is a long-used drug for which individual indications are practically maintained. For a doctor, acetylsalicylic acid is primarily an antiplatelet drug that saves millions of lives of patients with coronary heart disease or after a stroke. These facts do not exempt us from improving therapeutic methods based on ASA, the main goal of which is to reduce the risk of side effects, as well as to extend effectiveness. Modified acetylsalicylic acid molecules already seem to be a promising therapeutic option.
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Affiliation(s)
- Łukasz Fijałkowski
- Department of Pharmacometrics and Molecular Modeling, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland
| | - Magdalena Skubiszewska
- Department of Pharmacometrics and Molecular Modeling, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland
| | - Grzegorz Grześk
- Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 75 Ujejskiego St., 85-168 Bydgoszcz, Poland
| | | | - Alicja Nowaczyk
- Department of Pharmacometrics and Molecular Modeling, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland
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40
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Völkel L, Seibel J, Rychlik RPT. Einsatz von OTC-Arzneimitteln bei
SARS-CoV-2-Infektionen. GESUNDHEITSÖKONOMIE & QUALITÄTSMANAGEMENT 2022. [DOI: 10.1055/a-1965-1598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
ZusammenfassungPublizierte Studien aus dem Jahr 2021 zeigen, dass Acetylsalicylsäure
(ASS) bei hospitalisierten Covid-19-Patienten zu einer Verbesserung des
Krankheitsverlaufs führen kann. Darauf aufbauend wurde mittels eines
Surveys eine retrospektive Datenerhebung von 866 Covid-19-Patienten, die eine
Behandlung mit OTC-Arzneimitteln erhielten, sowie deren Krankheitsverlauf
erhoben (2021/2022).Die Patientengruppe, die eine Behandlung mit ASS erhielt, war deutlich
älter und schwerer grunderkrankt als die Vergleichsgruppen an Patienten,
die entweder mit Ibuprofen, Paracetamol oder ohne OTC-Arzneimittel behandelt
wurden. Obwohl die SARS-CoV-2-Patienten mit ASS älter und schwerer
vorerkrankt sind, stellt sich der Behandlungsverlauf vergleichbar zu
jüngeren und leichter vorerkrankten Patienten dar. Symptome wie
Gliederschmerzen und Schüttelfrost wurden beispielsweise in der
Subgruppe (Behandlung mit Ibuprofen bzw. Paracetamol) häufiger
dokumentiert. Ebenso waren rein von den relativen Werten Patienten mit einer
ASS-Behandlung häufiger besser eingestellt, wenn es um ambulante
Behandlungen, Notfallbehandlungen, Krankenhauseinweisungen und
Facharztüberweisungen ging.Ein signifikanter Unterschied konnte bezüglich der ambulanten
Behandlungen und Notfallbehandlungen von Patienten mit einer ASS Behandlung im
Vergleich zu Patienten, die mit Paracetamol behandelt wurden, aufgezeigt werden.
Die Ergebnisse sind Indizien dafür, dass ASS bei älteren
Patienten mit SARS-CoV-2-Infektion, einen milderen Krankheitsverlauf
begünstigen kann.
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Affiliation(s)
- Lukas Völkel
- Institut für Empirische Gesundheitsökonomie,
Burscheid
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41
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Huang L, Lin J, Liu R, Zheng Z, Meng L, Chen X, Li X, Wong KC. CoaDTI: multi-modal co-attention based framework for drug-target interaction annotation. Brief Bioinform 2022; 23:6770087. [PMID: 36274236 DOI: 10.1093/bib/bbac446] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/26/2022] [Accepted: 09/18/2022] [Indexed: 12/14/2022] Open
Abstract
MOTIVATION The identification of drug-target interactions (DTIs) plays a vital role for in silico drug discovery, in which the drug is the chemical molecule, and the target is the protein residues in the binding pocket. Manual DTI annotation approaches remain reliable; however, it is notoriously laborious and time-consuming to test each drug-target pair exhaustively. Recently, the rapid growth of labelled DTI data has catalysed interests in high-throughput DTI prediction. Unfortunately, those methods highly rely on the manual features denoted by human, leading to errors. RESULTS Here, we developed an end-to-end deep learning framework called CoaDTI to significantly improve the efficiency and interpretability of drug target annotation. CoaDTI incorporates the Co-attention mechanism to model the interaction information from the drug modality and protein modality. In particular, CoaDTI incorporates transformer to learn the protein representations from raw amino acid sequences, and GraphSage to extract the molecule graph features from SMILES. Furthermore, we proposed to employ the transfer learning strategy to encode protein features by pre-trained transformer to address the issue of scarce labelled data. The experimental results demonstrate that CoaDTI achieves competitive performance on three public datasets compared with state-of-the-art models. In addition, the transfer learning strategy further boosts the performance to an unprecedented level. The extended study reveals that CoaDTI can identify novel DTIs such as reactions between candidate drugs and severe acute respiratory syndrome coronavirus 2-associated proteins. The visualization of co-attention scores can illustrate the interpretability of our model for mechanistic insights. AVAILABILITY Source code are publicly available at https://github.com/Layne-Huang/CoaDTI.
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Affiliation(s)
- Lei Huang
- Department of Computer Science, City University of Hong Kong, Hong Kong SAR
| | - Jiecong Lin
- Department of Pathology, Harvard Medical School, Boston, USA.,Department of Computer Science, The University of Hong Kong, Hong Kong SAR
| | - Rui Liu
- Department of Computer Science, City University of Hong Kong, Hong Kong SAR
| | - Zetian Zheng
- Department of Computer Science, City University of Hong Kong, Hong Kong SAR
| | - Lingkuan Meng
- Department of Computer Science, City University of Hong Kong, Hong Kong SAR
| | - Xingjian Chen
- Department of Computer Science, City University of Hong Kong, Hong Kong SAR
| | - Xiangtao Li
- School of Artificial Intelligence, Jilin University, China
| | - Ka-Chun Wong
- Department of Computer Science, City University of Hong Kong, Hong Kong SAR.,Hong Kong Institute for Data Science, City University of Hong Kong, Hong Kong SAR
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42
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Batiha GES, Al-Gareeb AI, Rotimi D, Adeyemi OS, Al-kuraishy HM. Common NLRP3 inflammasome inhibitors and Covid-19: Divide and conquer. SCIENTIFIC AFRICAN 2022; 18:e01407. [PMID: 36310607 PMCID: PMC9595499 DOI: 10.1016/j.sciaf.2022.e01407] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 10/19/2022] [Indexed: 11/07/2022] Open
Abstract
Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm, and hypercytokinemia due to activation of the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the stimulation and synthesis of natural killer cells (NKs), NFκB, and interferon-gamma (INF-γ), while inhibiting IL-33 expression. Various efforts have identified selective inhibitors of NLRP3 inflammasome. To achieve this, studies are exploring the screening of natural compounds and/or repurposing of clinical drugs to identify potential NLRP3 inhibitors. NLRP3 inflammasome inhibitors are expected to suppress exaggerated immune reaction and cytokine storm-induced-organ damage in SARS-CoV-2 infection. Therefore, NLRP3 inflammasome inhibitors could mitigate the immune-overreaction and hypercytokinemia in Covid-19 infection.
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Affiliation(s)
- Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, AlBeheira, Damanhour 22511, Egypt,Corresponding authors
| | - Ali I. Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Damilare Rotimi
- Department of Biochemistry, Landmark University, KM 4 Ipetu Road, Omu-Aran, Kwara 251101, Nigeria
| | - Oluyomi Stephen Adeyemi
- Department of Biochemistry, Landmark University, KM 4 Ipetu Road, Omu-Aran, Kwara 251101, Nigeria,Corresponding authors
| | - Hayder M. Al-kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
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43
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Tung A, Dalton A, Hastie J, Jabaley CS, Mittel AM, Nunnally ME, Siddiqui S. The Next Next Wave: How Critical Care Might Learn From COVID in Responding to the Next Pandemic. Anesth Analg 2022; 135:903-910. [PMID: 36269981 DOI: 10.1213/ane.0000000000006204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Avery Tung
- From the Departments of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois
| | - Allison Dalton
- From the Departments of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois
| | - Jonathan Hastie
- Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
| | - Craig S Jabaley
- Department of Anesthesiology, Emory University Atlanta, Georgia
| | - Aaron M Mittel
- Department of Anesthesiology, Columbia University Irving Medical Center, New York, New York
| | - Mark E Nunnally
- Department of Anesthesiology, Perioperative Care & Pain Medicine, NYU Langone Health, New York, New York
| | - Shahla Siddiqui
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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44
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Lal A, Garces JPD, Bansal V, Tekin A, Zec S, Khanna AK, Warner MA, Christie AB, Cartin-Ceba R, Banner-Goodspeed VM, Armaignac DL, Cheruku SR, Raju U, Tarabichi Y, Denson JL, Kumar V, Walkey A, Boman K, Deo N, Kashyap R, Gajic O. Pre-hospital Aspirin Use and Patient Outcomes in COVID-19: Results from the International Viral Infection and Respiratory Illness Universal Study (VIRUS). Arch Bronconeumol 2022; 58:746-753. [PMID: 36153214 PMCID: PMC9451929 DOI: 10.1016/j.arbres.2022.07.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The goal of this investigation is to assess the association between prehospital use of aspirin (ASA) and patient-centered outcomes in a large global cohort of hospitalized COVID-19 patients. METHODS This study utilizes data from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. Adult patients hospitalized from February 15th, 2020, to September 30th, 2021, were included. Multivariable regression analyses were utilized to assess the association between pre-hospital use of ASA and the primary outcome of overall hospital mortality. RESULTS 21,579 patients were included from 185 hospitals (predominantly US-based, 71.3%), with 4691 (21.7%) receiving pre-hospital ASA. Patients receiving ASA, compared to those without pre-admission ASA use, were generally older (median 70 vs. 59 years), more likely to be male (58.7 vs. 56.0%), caucasian (57.4 vs. 51.6%), and more commonly had higher rates of medical comorbidities. In multivariable analyses, patients receiving pre-hospital ASA had lower mortality (HR: 0.89, 95% CI 0.82-0.97, p=0.01) and reduced hazard for progression to severe disease or death (HR: 0.91, 95% CI 0.84-0.99, p=0.02) and more hospital free days (1.00 days, 95% CI 0.66-1.35, p=0.01) compared to those without pre-hospital ASA use. The overall direction and significance of the results remained the same in sensitivity analysis, after adjusting the multivariable model for time since pandemic. CONCLUSIONS In this large international cohort, pre-hospital use of ASA was associated with a lower hazard for death in hospitalized patients with COVID-19. Randomized controlled trials may be warranted to assess the utility of pre-hospital use of ASA.
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Affiliation(s)
- Amos Lal
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
| | - Juan Pablo Domecq Garces
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; Division of Critical Care Medicine, Department of Internal Medicine, Mayo Clinic Health System, Mankato, MN, USA
| | - Vikas Bansal
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Aysun Tekin
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Simon Zec
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ashish K Khanna
- Section on Critical Care Medicine, Department of Anesthesiology, Wake Forest University School of Medicine, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, USA; Outcomes Research Consortium, Cleveland, OH, USA
| | - Matthew A Warner
- Division of Critical Care Medicine, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | | | | | | | | | - Sreekanth R Cheruku
- Department of Anesthesiology and Pain Management, UT Southwestern Medical Center, USA
| | | | | | - Joshua L Denson
- Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane School of Medicine, New Orleans, USA
| | - Vishakha Kumar
- Society of Critical Care Medicine, Mount Prospect, IL, USA
| | - Allan Walkey
- Pulmonary Center, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Evans Center of Implementation and Improvement Sciences, Boston University School of Medicine, Boston, MA, USA
| | - Karen Boman
- Society of Critical Care Medicine, Mount Prospect, IL, USA
| | - Neha Deo
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Rahul Kashyap
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ognjen Gajic
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
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45
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Zhang J, Sheng H, Tang X, Xia P, Li Z, Xu M, Ma J, Shen Y, Yu P, Liu X. Non-steroidal anti-inflammatory drugs and clinical outcomes in patients with COVID-19. Front Cell Infect Microbiol 2022; 12:935280. [PMID: 36325468 PMCID: PMC9618688 DOI: 10.3389/fcimb.2022.935280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022] Open
Abstract
The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with coronavirus disease 2019 (COVID-19) has raised great concerns. The effect of NSAIDs on the clinical status of COVID-19 remains in question. Therefore, we performed a post-hoc analysis from the ORCHID trial. Patients with COVID-19 from the ORCHID trial were categorized into two groups according to NSAID use. The 28-day mortality, hospitalized discharge, and safety outcomes with NSAIDs for patients with COVID-19 were analyzed. A total of 476 hospitalized patients with COVID-19 were included; 412 patients (86.5%) did not receive NSAIDs, while 64 patients (13.5%) took NSAIDs as regular home medication. Patients who took NSAIDs did not have a significant increase in the risk of 28-day mortality (fully adjusted: hazard ratio [HR]: 1.12, 95% CI: 0.52–2.42) in the Cox multivariate analysis. Moreover, NSAIDs did not decrease hospital discharge through 28 days (fully adjusted: HR: 1.02, 95% CI: 0.75–1.37). The results of a meta-analysis including 14 studies involving 48,788 patients with COVID-19 showed that the use of NSAIDs had a survival benefit (summary risk ratio [RR]: 0.70, 95% CI: 0.54–0.91) and decreased the risk of severe COVID-19 (summary: RR: 0.79, 95% CI: 0.71–0.88). In conclusion, the use of NSAIDs is not associated with worse clinical outcomes, including 28-day mortality or hospital discharge in American adult hospitalized patients with COVID-19. Based on current evidence, the use of NSAIDs is safe and should not be cautioned against during the COVID-19 pandemic. Ongoing trials should further assess in-hospital treatment with NSAIDs for patients with COVID-19.
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Affiliation(s)
- Jing Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hongguang Sheng
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaoyi Tang
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Panpan Xia
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, China
| | - Zhangwang Li
- The Second Clinical Medical College of Nanchang University, Nanchang, China
| | - Minxuan Xu
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, China
| | - Jianyong Ma
- Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Yunfeng Shen
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, China
| | - Peng Yu
- Department of Metabolism and Endocrinology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, China
- *Correspondence: Peng Yu, ; Xiao Liu,
| | - Xiao Liu
- Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, China
- *Correspondence: Peng Yu, ; Xiao Liu,
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46
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Morrison FJ, Su M, Turchin A. COVID-19 outcomes in patients taking cardioprotective medications. PLoS One 2022; 17:e0275787. [PMID: 36215288 PMCID: PMC9550077 DOI: 10.1371/journal.pone.0275787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 09/22/2022] [Indexed: 11/05/2022] Open
Abstract
Introduction The coronavirus disease 2019 (COVID-19) caused a worldwide pandemic and has led to over five million deaths. Many cardiovascular risk factors (e.g. obesity or diabetes) are associated with an increased risk of adverse outcomes in COVID-19. On the other hand, it has been suggested that medications used to treat cardiometabolic conditions may have protective effects for patients with COVID-19. Objectives To determine whether patients taking four classes of cardioprotective medications—aspirin, metformin, renin angiotensin aldosterone system inhibitors (RAASi) and statins–have a lower risk of adverse outcomes of COVID-19. Methods We conducted a retrospective cohort study of primary care patients at a large integrated healthcare delivery system who had a positive COVID-19 test between March 2020 and March 2021. We compared outcomes of patients who were taking one of the study medications at the time of the COVID-19 test to patients who took a medication from the same class in the past (to minimize bias by indication). The following outcomes were compared: a) hospitalization; b) ICU admission; c) intubation; and d) death. Multivariable analysis was used to adjust for patient demographics and comorbidities. Results Among 13,585 study patients, 1,970 (14.5%) were hospitalized; 763 (5.6%) were admitted to an ICU; 373 (2.8%) were intubated and 720 (5.3%) died. In bivariate analyses, patients taking metformin, RAASi and statins had lower risk of hospitalization, ICU admission and death. However, in multivariable analysis, only the lower risk of death remained statistically significant. Patients taking aspirin had a significantly higher risk of hospitalization in both bivariate and multivariable analyses. Conclusions Cardioprotective medications were not associated with a consistent benefit in COVID-19. As vaccination and effective treatments are not yet universally accessible worldwide, research should continue to determine whether affordable and widely available medications could be utilized to decrease the risks of this disease.
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Affiliation(s)
- Fritha J. Morrison
- Division of Endocrinology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America
| | - Maxwell Su
- Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America
- Phase V Technologies, Wellesley Hills, Massachusetts, United States of America
| | - Alexander Turchin
- Division of Endocrinology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America
- Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail:
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47
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Su W, Miao H, Guo Z, Chen Q, Huang T, Ding R. Associations between the use of aspirin or other antiplatelet drugs and all-cause mortality among patients with COVID-19: A meta-analysis. Front Pharmacol 2022; 13:989903. [PMID: 36278186 PMCID: PMC9581252 DOI: 10.3389/fphar.2022.989903] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 09/21/2022] [Indexed: 12/15/2022] Open
Abstract
Introduction: Whether aspirin or other antiplatelet drugs can reduce mortality among patients with coronavirus disease (COVID-19) remains controversial.Methods: We identified randomized controlled trials, prospective cohort studies, and retrospective studies on associations between aspirin or other antiplatelet drug use and all-cause mortality among patients with COVID-19 in the PubMed database between March 2019 and September 2021. Newcastle–Ottawa Scale and Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias. The I2 statistic was used to assess inconsistency among trial results. The summary risk ratio (RR) and odds ratio (OR) were obtained through the meta-analysis.Results: The 34 included studies comprised three randomized controlled trials, 27 retrospective studies, and 4 prospective cohort studies. The retrospective and prospective cohort studies showed low-to-moderate risks of bias per the Newcastle–Ottawa Scale score, while the randomized controlled trials showed low-to-high risks of bias per the Cochrane Risk of Bias Assessment Tool. The randomized controlled trials showed no significant effect of aspirin use on all-cause mortality in patients with COVID-19 {risk ratio (RR), 0.96 [95% confidence interval (CI) 0.90–1.03]}. In retrospective studies, aspirin reduced all-cause mortality in patients with COVID-19 by 20% [odds ratio (OR), 0.80 (95% CI 0.70–0.93)], while other antiplatelet drugs had no significant effects. In prospective cohort studies, aspirin decreased all-cause mortality in patients with COVID-19 by 15% [OR, 0.85 (95% CI 0.80–0.90)].Conclusion: The administration of aspirin may reduce all-cause mortality in patients with COVID-19.
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Affiliation(s)
- Wanting Su
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - He Miao
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhaotian Guo
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Qianhui Chen
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Tao Huang
- Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China
- Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China
- Center for Intelligent Public Health, Institute for Artificial Intelligence, Peking University, Beijing, China
- *Correspondence: Tao Huang, ; Renyu Ding,
| | - Renyu Ding
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
- *Correspondence: Tao Huang, ; Renyu Ding,
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48
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Xiang M, Wu X, Jing H, Liu L, Wang C, Wang Y, Novakovic VA, Shi J. The impact of platelets on pulmonary microcirculation throughout COVID-19 and its persistent activating factors. Front Immunol 2022; 13:955654. [PMID: 36248790 PMCID: PMC9559186 DOI: 10.3389/fimmu.2022.955654] [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: 05/29/2022] [Accepted: 08/15/2022] [Indexed: 12/05/2022] Open
Abstract
Patients with COVID-19 often have hypoxemia, impaired lung function, and abnormal imaging manifestations in acute and convalescent stages. Alveolar inflammation, pulmonary vasculitis, and thromboembolism synergistically damage the blood-air barrier, resulting in increased pulmonary permeability and gas exchange disorders. The incidence of low platelet counts correlates with disease severity. Platelets are also involved in the impairment of pulmonary microcirculation leading to abnormal lung function at different phases of COVID-19. Activated platelets lose the ability to protect the integrity of blood vessel walls, increasing the permeability of pulmonary microvasculature. High levels of platelet activation markers are observed in both mild and severe cases, short and long term. Therefore, the risk of thrombotic events may always be present. Vascular endothelial injury, immune cells, inflammatory mediators, and hypoxia participate in the high reactivity and aggregation of platelets in various ways. Microvesicles, phosphatidylserine (PS), platelets, and coagulation factors are closely related. The release of various cell-derived microvesicles can be detected in COVID-19 patients. In addition to providing a phospholipid surface for the synthesis of intrinsic factor Xase complex and prothrombinase complex, exposed PS also promotes the decryption of tissue factor (TF) which then promotes coagulant activity by complexing with factor VIIa to activate factor X. The treatment of COVID-19 hypercoagulability and thrombosis still focuses on early intervention. Antiplatelet therapy plays a role in relieving the disease, inhibiting the formation of the hypercoagulable state, reducing thrombotic events and mortality, and improving sequelae. PS can be another potential target for the inhibition of hypercoagulable states.
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Affiliation(s)
- Mengqi Xiang
- Department of Hematology, the First Hospital, Harbin Medical University, Harbin, China
| | - Xiaoming Wu
- Department of Hematology, the First Hospital, Harbin Medical University, Harbin, China
| | - Haijiao Jing
- Department of Hematology, the First Hospital, Harbin Medical University, Harbin, China
| | - Langjiao Liu
- Department of Hematology, the First Hospital, Harbin Medical University, Harbin, China
| | - Chunxu Wang
- Department of Hematology, the First Hospital, Harbin Medical University, Harbin, China
| | - Yufeng Wang
- Department of Hematology, the First Hospital, Harbin Medical University, Harbin, China
| | - Valerie A. Novakovic
- Department of Research, Veterans Affairs (VA) Boston Healthcare System, Harvard Medical School, Boston, MA, United States
| | - Jialan Shi
- Department of Hematology, the First Hospital, Harbin Medical University, Harbin, China
- Department of Research, Veterans Affairs (VA) Boston Healthcare System, Harvard Medical School, Boston, MA, United States
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
- *Correspondence: Jialan Shi, ;
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Kushner P, McCarberg BH, Grange L, Kolosov A, Haveric AL, Zucal V, Petruschke R, Bissonnette S. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19. NPJ Prim Care Respir Med 2022; 32:35. [PMID: 36127354 PMCID: PMC9489480 DOI: 10.1038/s41533-022-00300-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 07/26/2022] [Indexed: 11/19/2022] Open
Abstract
Early in the COVID-19 pandemic, anecdotal reports emerged suggesting non-steroidal anti-inflammatory drugs (NSAIDs) may increase susceptibility to infection and adversely impact clinical outcomes. This narrative literature review (March 2020–July 2021) attempted to clarify the relationship between NSAID use and COVID-19 outcomes related to disease susceptibility or severity. Twenty-four relevant publications (covering 25 studies) reporting original research data were identified; all were observational cohort studies, and eight were described as retrospective. Overall, these studies are consistent in showing that NSAIDs neither increase the likelihood of SARS-CoV-2 infection nor worsen outcomes in patients with COVID-19. This is reflected in current recommendations from major public health authorities across the world, which support NSAID use for analgesic or antipyretic treatment during COVID-19. Thus, there is no basis on which to restrict or prohibit use of these drugs by consumers or patients to manage their health conditions and symptoms during the pandemic.
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Affiliation(s)
- Pamela Kushner
- Kushner Wellness Center, Los Angeles, CA, USA. .,Department of Family Medicine, University of California, Irvine, CA, USA.
| | - Bill H McCarberg
- Department of Family Medicine, University of California at San Diego School of Medicine, San Diego, CA, USA
| | - Laurent Grange
- Rheumatology Department, Grenoble-Alpes University Hospital, Echirolles, France.,President of the French League Against Rheumatism (AFLAR), Paris, France
| | - Anton Kolosov
- Medical Affairs, GSK Consumer Healthcare, Rochester Park, Singapore, Singapore
| | | | - Vincent Zucal
- Consumer Safety, GSK Consumer Healthcare, Warren, NJ, USA
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50
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Design of spherical agglomerates via crystallization with a non-toxic bridging liquid: From mechanism to application. POWDER TECHNOL 2022. [DOI: 10.1016/j.powtec.2022.117725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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