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Tse J, Gongolli J, Prahlow JA. Hereditary thrombophilia as a possible risk factor for severe disease in COVID-19: a case series. Forensic Sci Med Pathol 2025; 21:260-266. [PMID: 39331315 DOI: 10.1007/s12024-024-00879-4] [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] [Accepted: 08/14/2024] [Indexed: 09/28/2024]
Abstract
PURPOSE The risk factors that modulate one's susceptibility for severe COVID-19 have been well documented. Despite this, hypercoagulability remains an often overlooked risk factor for severe disease for COVID-19. Because COVID-19 infection is a risk factor for hypercoagulability, a reasonable presumption/hypothesis is that patients with hereditary thrombophilia would be at a higher risk of thrombotic complications associated with COVID-19 infection. METHODS This case report details two cases where previously unknown hereditary thrombophilias likely contributed to the mortality of COVID-19 patients. RESULTS The first COVID-19 patient's cause of death was pulmonary thromboemboli from deep vein thrombosis due to heterozygous MTHFR C667T and heterozygous PAI-1 4G/5G mutations. The second COVID-19 patient's cause of death was an acute myocardial infarct due to a coronary artery thrombosis in the setting of heterozygous MTHFR A1298C and homozygous PAI-1 4G/5G mutations. In each case, COVID-19 infection was also considered contributory to death. CONCLUSION The occurrence of these fatal thrombotic events in COVID-19 patients with hereditary thrombophilias raises questions as to whether this combination of thrombotic risk factors for hypercoagulability may have placed patients at a significant enough risk to experience these fatal thrombotic complications. Thus, while not sufficient alone to prove that SARS-CoV-2 patients with hereditary thrombophilias are at increased risk for thrombotic complications, these two cases indicate that further investigation is warranted into elucidating the relationship between thrombotic risk factors as it may identify an additional high-risk medical condition for COVID-19 and have important diagnostic and therapeutic ramifications.
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Affiliation(s)
- Jonathan Tse
- Western Michigan University Homer Stryker MD School of Medicine, 300 Portage St. Kalamazoo, Kalamazoo, MI, 49007, USA.
| | - Julita Gongolli
- Western Michigan University Homer Stryker MD School of Medicine, 300 Portage St. Kalamazoo, Kalamazoo, MI, 49007, USA
| | - Joseph A Prahlow
- Department of Pathology, St. Louis University School of Medicine, City of St. Louis, MO, USA
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Trempelis KP, Kosmeri C, Kalavas P, Ladomenou F, Siomou E, Makis A. SARS-CoV-2 Variants and Their Impact on Pediatric COVID-19: Clinical Manifestations and Hematological Profiles. Diseases 2025; 13:48. [PMID: 39997055 PMCID: PMC11854181 DOI: 10.3390/diseases13020048] [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: 01/06/2025] [Revised: 02/04/2025] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND The aim of this study was to analyze data on pediatric cases of COVID-19 admitted to a tertiary referral hospital in northwest Greece. METHODS A retrospective analysis was conducted on the most common clinical manifestations and laboratory findings, stratified by age group and SARS-CoV-2 strain. RESULTS A total of 254 children were hospitalized, with a mean age of 4.5 years. Underlying conditions were present in 10.2% of cases; two children required pediatric intensive care unit (PICU) admission, and one child died. The most common hematological manifestations, in general, were neutropenia (30%) and lymphopenia (23%), whereas the findings varied when the children were stratified by age group. Eight children developed multisystem inflammatory syndrome (MIS-C), with the most common findings being anemia (75%), lymphopenia (50%), and thrombocytopenia (25%). Analysis of the SARS-CoV-2 strains revealed the proportions of the dominant strain over time. Fever was the predominant symptom across all strains, particularly in the Omicron group, which also had a high incidence of gastrointestinal symptoms. The longest hospital admission occurred in children with the Omicron strain, followed by the Wuhan, Alpha, and Delta strains. CONCLUSIONS Fever was the most consistent symptom across all age groups and virus strains. The most common hematological manifestations were neutropenia (30%) and lymphopenia (23%). The Omicron strain was associated with the longest hospital stay.
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Affiliation(s)
- Konstantinos Paris Trempelis
- Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (K.P.T.); (F.L.); (E.S.)
| | - Chrysoula Kosmeri
- Department of Pediatrics, University Hospital of Ioannina, 45500 Ioannina, Greece
| | - Panagiotis Kalavas
- Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (K.P.T.); (F.L.); (E.S.)
| | - Fani Ladomenou
- Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (K.P.T.); (F.L.); (E.S.)
- Department of Pediatrics, University Hospital of Ioannina, 45500 Ioannina, Greece
| | - Ekaterini Siomou
- Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (K.P.T.); (F.L.); (E.S.)
- Department of Pediatrics, University Hospital of Ioannina, 45500 Ioannina, Greece
| | - Alexandros Makis
- Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece; (K.P.T.); (F.L.); (E.S.)
- Department of Pediatrics, University Hospital of Ioannina, 45500 Ioannina, Greece
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Zaki DP, Zeng E, Duet ML, Stone CE, Giglio RS, Tapp MW, Llull R, Calder BW, Robinson JM. Impact of COVID-19 on Thrombotic Complications in Microsurgery: Deep Inferior Epigastric Perforator Flap Outcomes Amid Pandemic. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2025; 13:e6544. [PMID: 39958714 PMCID: PMC11828035 DOI: 10.1097/gox.0000000000006544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 12/13/2024] [Indexed: 02/18/2025]
Abstract
Background Emerging research underscores the heightened risk of vasculitis and microvascular thrombosis in COVID-19 patients, alongside concerns about prothrombotic events post-severe acute respiratory syndrome coronavirus 2 vaccination. Following the pandemic's end, we sought a comprehensive analysis to elucidate its impact on microsurgical thrombosis rates, informed by empirical and anecdotal evidence. Methods An institutional review board-approved retrospective review analyzed autologous breast reconstruction cases in women from January 2019 to March 2022. Data on patient history, COVID-19 infection, vaccination status, and postoperative complications were collected. Patients were categorized as prepandemic and pandemic, and based on COVID-19 influence (infection or vaccination) for statistical evaluation. Results Among 527 patients, 216 underwent surgery prepandemic and 311 during the pandemic, revealing thrombotic event rates of 3.2% and 5.4%, respectively. Further comparative analysis showed no significant difference in thrombotic events among patients affected by COVID-19 through infection or vaccination during the pandemic. Conclusions Contrary to concerns, COVID-19 infection or vaccination status does not significantly increase thrombotic event rates in deep inferior epigastric perforator flap breast reconstructions. This study offers vital insights, affirming the safety and efficacy of microsurgical procedures amid the pandemic, thereby guiding microsurgeons in optimizing patient care in the post-COVID-19 era.
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Affiliation(s)
- Daniel P. Zaki
- From the Department of Plastic and Reconstructive Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, NC
| | - Eric Zeng
- Wake Forest University School of Medicine, Winston-Salem, NC
| | - Mary L. Duet
- From the Department of Plastic and Reconstructive Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, NC
| | - Courtney E. Stone
- From the Department of Plastic and Reconstructive Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, NC
| | | | - Marion W. Tapp
- From the Department of Plastic and Reconstructive Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, NC
| | - Ramon Llull
- From the Department of Plastic and Reconstructive Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, NC
| | - Bennett W. Calder
- From the Department of Plastic and Reconstructive Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, NC
| | - John M. Robinson
- From the Department of Plastic and Reconstructive Surgery, Atrium Health Wake Forest Baptist, Winston-Salem, NC
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Amodio E, Di Maria G, Lodico M, Genovese D, Muggeo VMR, Maniscalco L, Conti M, Sergio M, Cascio A, Tuttolomondo A, Matranga D, Vitale F, Enea M. Evolution of Hospitalisation Due to Stroke in Italy Before and After the Outbreak of the COVID-19 Epidemic: A Population-Based Study Using Administrative Data. J Clin Med 2025; 14:353. [PMID: 39860359 PMCID: PMC11765534 DOI: 10.3390/jcm14020353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/31/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Stroke is a leading cause of mortality and disability worldwide, ranking as the second most common cause of death and the third in disability-adjusted life-years lost. Ischaemic stroke, which constitutes the majority of cases, poses significant public health and economic challenges. This study evaluates trends in ischaemic stroke hospitalisations in Italy from 2008 to 2022, focusing on differences before and after the COVID-19 pandemic. Methods: We analysed ischaemic stroke hospitalisations among individuals admitted through emergency services using Italian hospital discharge records from 2008 to 2022. Poisson Inverse Gaussian regression was employed to assess hospitalisation trends, accounting for age, sex, and geographic variations. Results: Among 1,689,844 ischaemic stroke hospitalisations, there was a marked age-related increase, particularly among individuals aged 74 and older, with males consistently showing higher rates. Hospitalisation trends demonstrated a 20% reduction over 15 years, suggesting improvements in stroke prevention and treatment. However, there was a slight increase in rates during the COVID-19 period, despite the overall declining trend, highlighting the potential healthcare challenges experienced during the pandemic. Multivariable analysis confirmed age and male sex as significant risk factors. Conclusions: This study underscores the age-related increase in stroke hospitalisation rates, emphasising the need for targeted prevention strategies for elderly populations. The overall reduction in stroke hospitalisation rates reflects advancements made in healthcare, although the impact of COVID-19 on access to stroke care is evident. Future policies must address the pandemic's effects on stroke care continuity and prioritise interventions tailored to age and sex.
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Affiliation(s)
- Emanuele Amodio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Gabriele Di Maria
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Manuela Lodico
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Dario Genovese
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Vito M. R. Muggeo
- Department of Economics, Business and Statistics, University of Palermo, 90128 Palermo, Italy;
| | - Laura Maniscalco
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Michela Conti
- Azienda Ospedaliera Ospedali Riuniti (AOOR) Villa Sofia Cervello, 90146 Palermo, Italy;
| | - Maria Sergio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Antonio Cascio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Antonino Tuttolomondo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Domenica Matranga
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Francesco Vitale
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
| | - Marco Enea
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; (E.A.); (G.D.M.); (M.L.); (D.G.); (L.M.); (M.S.); (A.C.); (A.T.); (D.M.); (F.V.)
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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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El-Menyar A, Ramzee AF, Asim M, Shahid F, Ata YM, El Baba H, Fino A, Nair AP, Peralta R, Almaslamani MA, Al Suwaidi J, Al-Thani H, Rizoli S. COVID-19 Increases the Risk of New Myocardial Infarction in Patients with Old Myocardial Infarction: A Retrospective Observational Study. CLINICAL MEDICINE INSIGHTS-CARDIOLOGY 2024; 18:11795468241301133. [PMID: 39697349 PMCID: PMC11653445 DOI: 10.1177/11795468241301133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 10/07/2024] [Indexed: 12/20/2024]
Abstract
Background We aimed to investigate the incidence of new acute myocardial infarction (AMI), in patients with Coronavirus disease (COVID-19) who had old MI. We hypothesized that COVID-19 increases the rate of repeated AMI in this population regardless of age and gender. Methods A retrospective analysis was conducted for adult patients admitted with COVID-19 and developed thromboembolic event (TEE) in 2020. Patients were categorized based on the history of old MI, new MI, age, and gender. Results Among 16,903 patients with COVID-19 who were admitted, 210 (1.2%) developed TEE (89% were males, 55% were <55 years old, and 80.5% had an old MI). COVID-19 was severe in 32% of cases. AMI occurred in 160 patients (42.5% STEMI and 57.5% NSTEMI). In patients with prior MI, 92.5% developed another AMI. NSTEMI was higher in patients with severe COVID-19 than STEMI (33% vs 21%). Patients with severe COVID-19 had higher mortality (39.4% vs 5.6%), fewer rates of prior MI (74% vs 83%), hypertension (40% vs 60%), and STEMI (31.8% vs 46.5%) than mild COVID-19 patients. On multivariable analysis, COVID-19 severity was an independent predictor of mortality (OR10; 95%CI 1.62-67.19) after adjustment for age, gender, diabetes mellitus, C-reactive protein, serum Ferritin, Procalcitonin, and Fibrinogen values, and prior or new MI. Conclusions Patients with old MI could develop a new AMI in 80% of COVID-19. However, the mortality was higher in patients without a history of MI due to the severity of COVID-19. Attention should be given to patients who possess thrombotic risk factors in pandemics.
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Affiliation(s)
- Ayman El-Menyar
- Clinical Research, Trauma and Vascular Surgery, Hamad Medical Corporation, Doha, Qatar
- Clinical Medicine, Weill Cornell Medical College, Doha, Qatar
| | | | - Mohammad Asim
- Clinical Research, Trauma and Vascular Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Fakhar Shahid
- Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Yaser M Ata
- Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Hamzah El Baba
- Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Areen Fino
- Department of Family Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Arun P Nair
- Communicable Disease Center (CDC), Hamad Medical Corporation, Doha, Qatar
| | - Ruben Peralta
- Trauma Surgery Section, Hamad Medical Corporation, Doha, Qatar
- Department of Surgery, Universidad Nacional Pedro Henriquez Urena, Santo Domingo, Dominican Republic
| | - Muna A Almaslamani
- Communicable Disease Center (CDC), Hamad Medical Corporation, Doha, Qatar
| | - Jassim Al Suwaidi
- Department of Cardiology, Heart Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Hassan Al-Thani
- Trauma Surgery Section, Hamad Medical Corporation, Doha, Qatar
| | - Sandro Rizoli
- Trauma Surgery Section, Hamad Medical Corporation, Doha, Qatar
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Cao J, Huang Z, Zeng J, Liu J, Zuo W, Su Z, Chen Y, Yu W, Ye H. Maternal and neonatal outcomes and clinical laboratory testing of pregnant women with COVID-19 during the BA.5.2/BF.7 surge. Virulence 2024; 15:2360130. [PMID: 38803076 PMCID: PMC11152110 DOI: 10.1080/21505594.2024.2360130] [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: 02/27/2024] [Accepted: 05/22/2024] [Indexed: 05/29/2024] Open
Abstract
The impact of COVID-19 on pregnant women and newborns continues to be a critical societal concern. However, the majority of research focuses on the disease resulting from the early pandemic variants, without sufficient study on the more recent BA.5.2/BF.7. We retrospectively recruited pregnant women giving birth during the surge of the BA.5.2/BF.7 and analysed the risk impact of COVID-19 on maternal and neonatal outcomes. Furthermore, subjects matched through propensity scores were used for the analysis of clinical laboratory tests. A total of 818 pregnant women were enrolled, among 276 (33.7%) were diagnosed with SARS-CoV-2 during childbirth. COVID-19 significantly increased the risk of a hospital length of stay equal to or greater than seven days and neonatal admission to the neonatal intensive care unit, with an aHR of 2.03 (95% CI, 1.22-3.38) and 1.51 (95% CI, 1.12-2.03), respectively. In the analysis of 462 matched subjects, it was found that subjects infected with SARS-CoV-2 tended slight leucopenia and coagulation abnormalities. We found that during the surge of the BA.5.2/BF.7, COVID-19 increased the risk of maternal and neonatal outcomes among Chinese pregnant women. This finding offers significant insights to guide clinical practices involving pregnant women infected with the recently emerged Omicron subvariants.
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Affiliation(s)
- Jiali Cao
- Department of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Zehong Huang
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, China
| | - Jing Zeng
- School of Pharmacy, Xiamen University, Xiamen, China
| | - Jumei Liu
- Department of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Weilun Zuo
- Department of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Zhiying Su
- Department of Obstetrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Yujuan Chen
- Department of Obstetrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Weiwei Yu
- Department of Obstetrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Huiming Ye
- Department of Laboratory Medicine, Fujian Key Clinical Specialty of Laboratory Medicine, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
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8
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Webster TK, Lowe LS, Kim DK, Rohde CH. COVID-19 and postoperative complications after plastic surgery procedures: More than just hypercoagulability. J Plast Reconstr Aesthet Surg 2024; 98:287-297. [PMID: 39321531 DOI: 10.1016/j.bjps.2024.09.024] [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: 05/30/2024] [Revised: 08/04/2024] [Accepted: 09/01/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND Although plastic surgery procedures generally demonstrate less than 2% incidence of venous thromboembolism (VTE) outcomes, the post-COVID era data remain elusive. This study sought to elucidate the relationship between COVID-19 infection and the risk of VTE outcomes across plastic surgery procedures. METHODS Plastic surgery procedures were identified in the 2012-2022 National Surgical Quality Improvement Program databases. The outcomes of interest were the postoperative occurrence of VTE, defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), and postoperative complication. Propensity score matching was used to 1) compare overall rates of VTE between the pre-pandemic era and pandemic era cohorts and 2) compare rates of VTE and overall postoperative complications in cases with and without COVID-19 diagnosis in the years 2021-2022 (p < 0.05). RESULTS Overall, 269,006 plastic surgery cases were identified, comprising general breast (76%) and trunk (9.4%) procedures. Non-breast free tissue transfer cases were associated with the highest rates of DVT (1.3%) and trunk procedures with the highest rates of PE (0.7%). After propensity score matching, the overall rate of VTE after the onset of the COVID-19 pandemic was not significantly different from the pre-pandemic era (p = 0.40). In a separately matched cohort, COVID-19 diagnosis did not significantly predict the risk for VTE (p = 0.48) but did significantly predict the risk for overall postoperative complications (p < 0.001). CONCLUSIONS Although COVID-19 diagnosis itself did not predict the risk of VTE in matched analysis, it significantly predicted the overall postoperative complications. Future studies may further investigate the effects of COVID-19 infection over longer periods of follow-up.
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Affiliation(s)
- Theresa K Webster
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Lauren S Lowe
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Dylan K Kim
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Christine H Rohde
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA.
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Aguilera F, Wagner G, Bald M, Richman J, de la Torre JI. Incidence of Postoperative Complications among Patients with Active or Resolved COVID-19 Undergoing Elective Abdominal Wall Reconstruction. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2024; 12:e6301. [PMID: 39559265 PMCID: PMC11573325 DOI: 10.1097/gox.0000000000006301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 09/23/2024] [Indexed: 11/20/2024]
Abstract
Background The incidence of postoperative complications among patients with coronavirus disease 2019 (COVID-19) positivity undergoing elective surgical operations is poorly understood. This study aimed to identify differences in postoperative complications after elective abdominal wall reconstruction (AWR) in patients diagnosed with COVID-19 compared with patients presenting prepandemic. Methods A single-institution, retrospective chart review was performed of patients undergoing AWR between January 2017 and September 2022. Patients were stratified by date: pre-COVID-19 (January 2017 to December 2019) and post-COVID-19 (January 2020 to September 2022). Patients confirmed as COVID-19-positive were also identified. Data collected included demographics, clinical characteristics, and complications. Univariate and multivariate analyses were performed. Results We included 168 patients. The mean age was 54 years, and the mean body mass index was 33 kg/m2. Seventy-five patients underwent surgery pre-COVID-19 and 93 patients after. Of 93 patients, 16 (17%) had a positive COVID-19 test before surgery or during the perioperative period. These 2 groups were risk-matched. Patients with COVID-19 had no significant increase in postoperative complications. Major complications occurred at 13.3% in the pre-COVID-19 group and 7.5% in the post-COVID-19 group. Patients with COVID-19 were more likely to be younger (48 versus 57; P = 0.049) and more likely to have a shorter length of stay in the hospital (3 versus 5.8; P = 0.038). Conclusions In our case series, there was an associated increase in the incidence of overall pulmonary-related complications in the postpandemic group. This study is limited by its small sample size. Further investigation should be carried out on this topic.
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Affiliation(s)
- Fabiola Aguilera
- From the Division of Plastic Surgery, Department of Surgery, The University of Alabama at Birmingham, Birmingham, Ala
| | - Grant Wagner
- Department of Surgery, The University of Alabama at Birmingham, Birmingham, Ala
| | - Madeline Bald
- School of Medicine, The University of Alabama at Birmingham, Birmingham, Ala
| | - Joshua Richman
- Department of Surgery, The University of Alabama at Birmingham, Birmingham, Ala
| | - Jorge I. de la Torre
- From the Division of Plastic Surgery, Department of Surgery, The University of Alabama at Birmingham, Birmingham, Ala
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Pardo K, Harnof O, Barnea R, Naftali J, Kenan G, Auriel E, Peretz S. Arterial floating mural thrombi are a characteristic imaging pattern in SARS-CoV-2-related ischemic stroke. PLoS One 2024; 19:e0311622. [PMID: 39453913 PMCID: PMC11508162 DOI: 10.1371/journal.pone.0311622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 09/17/2024] [Indexed: 10/27/2024] Open
Abstract
BACKGROUND Acute ischemic stroke (AIS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to explore neurovascular imaging patterns in patients with SARS-CoV-2-related AIS. METHODS We retrospectively analyzed clinical and radiological data of patients hospitalized with AIS and a positive PCR test for SARS-CoV-2 prior to AIS onset. The control group comprised of AIS patients from a pre-COVID-19 pandemic period matched for gender and age. RESULTS Thirty-five SARS-CoV-2-related stroke patients, and 35 controls were included. Fifty-seven percent of SARS-CoV-2 patients had either mild or asymptomatic disease. A distinctive imaging pattern of floating arterial mural thrombus was detected in 5 patients of the SARS-CoV-2 group. In 4 patients thrombus was attached to a stenotic atherosclerotic plaque in the proximal internal carotid artery. In the 5th patient a cardiac CTA showed multiple floating thrombi in the descending aorta. In the control group, floating thrombus was only detected in one patient. Treatment with dual antiplatelet therapy was associated with thrombus dissolution and good clinical outcome. Patients with floating thrombi had a longer time from SARS-CoV-2 diagnosis to stroke onset (mean 7.4 versus 3.4 days). CONCLUSIONS Floating arterial mural thrombi attached to atherosclerotic plaques are unique characteristic source of AIS in SARS-CoV-2 patients. They may lead to ischemic stroke in patients with mild or asymptomatic infection up to 1-2 weeks from SARS-CoV-2 diagnosis. Patients with embolic AIS and SARS-CoV-2 diagnosis should perform high resolution cranio-cervical vascular imaging to evaluate floating thrombi as a potential embolic source.
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Affiliation(s)
- Keshet Pardo
- Department of Neurology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Omer Harnof
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rani Barnea
- Department of Neurology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Jonathan Naftali
- Department of Neurology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Gilad Kenan
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Neurology, Shamir Medical Center, Be’er Ya’akov, Israel
| | - Eithan Auriel
- Department of Neurology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Shlomi Peretz
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Neurology, Shamir Medical Center, Be’er Ya’akov, Israel
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11
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Singh K, Rocco JM, Nussenblatt V. The winding road: Infectious disease considerations for CAR-T and other novel adoptive cellular therapies in the era of COVID-19. Semin Hematol 2024; 61:321-332. [PMID: 39379249 PMCID: PMC11626729 DOI: 10.1053/j.seminhematol.2024.08.002] [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: 05/30/2024] [Revised: 08/09/2024] [Accepted: 08/19/2024] [Indexed: 10/10/2024]
Abstract
Adoptive cellular therapies (ACT) are novel, promising treatments for life-threatening malignancies. In addition to the better known chimeric antigen receptor (CAR) T cells, ACTs include tumor infiltrating lymphocytes (TIL), cancer antigen-specific T cell receptors (TCRs), and CAR-NK (natural killer) cells. In key historic milestones, several adoptive therapies recently received FDA approvals, including 6 CAR-T products for the treatment of hematologic malignancies and the first TIL therapy for the treatment for metastatic melanoma. The rapid pace of clinical trials in the field and the discoveries they provide are ushering in a new era of cancer immunotherapy. However, the potential complications of these therapies are still not fully understood. In particular, patients receiving ACT may be at increased risk for severe infections due to immunocompromise resulting from their underlying malignancies, which are further compounded by the immune derangements that develop in the setting of cellular immunotherapy and/or the preconditioning treatment needed to enhance ACT efficacy. Moreover, these treatments are being readily implemented at a time following the height of the COVID-19 pandemic, and it remains unclear what additional risks these patients may face from SARS-CoV-2 and similar infections. Here, we examine the evidence for infectious complications with emerging adoptive therapies, and provide a focused review of the epidemiology, complications, and clinical management for COVID-19 in CAR-T recipients to understand the risk this disease may pose to recipients of other forms of ACT.
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Affiliation(s)
- Kanal Singh
- Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
| | - Joseph M Rocco
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
| | - Veronique Nussenblatt
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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12
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Gracia Aznar A, Moreno Egea F, Gracia Banzo R, Gutierrez R, Rizo JM, Rodriguez-Ledo P, Nerin I, Regidor PA. Pro-Resolving Inflammatory Effects of a Marine Oil Enriched in Specialized Pro-Resolving Mediators (SPMs) Supplement and Its Implication in Patients with Post-COVID Syndrome (PCS). Biomedicines 2024; 12:2221. [PMID: 39457534 PMCID: PMC11505212 DOI: 10.3390/biomedicines12102221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 09/11/2024] [Accepted: 09/19/2024] [Indexed: 10/28/2024] Open
Abstract
OBJECTIVES This study aimed to evaluate the eicosanoid and pro-resolutive parameters in patients with Post-COVID Syndrome (PCS) during a 12-week supplementation with a marine oil enriched in specialized pro-resolving mediators (SPMs). PATIENT AND METHODS This study was conducted on 53 adult patients with PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: polyunsaturated fatty acids EPA, DHA, ARA, and DPA; specialized pro-resolving mediators (SPMs), 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different intake amounts were evaluated (daily use of 500 mg, 1500 mg, and 3000 mg) and compared to a control group not using the product. RESULTS In the serum from patients with PCS, an increase in 17-HDHA, 18-HEPE, and 14-HDHA could be observed, and a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected; both differences were significant (p < 0.05). There were no differences found between the three treatment groups. Fatigue and dyspnea showed a trend of improvement after supplementation in all groups. CONCLUSIONS A clear enrichment in the serum of the three monohydroxylated SPMs could be observed at a dosage of 500 mg per day. Similarly, a clear improvement in fatigue and dyspnea was observed with this dosage.
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Affiliation(s)
- Asun Gracia Aznar
- Sociedad Española de Médicos Generales y de Familia (SEMG), 28005 Madrid, Spain; (A.G.A.); (P.R.-L.)
| | | | - Rafael Gracia Banzo
- Solutex GC SL, Parque Empresarial Utebo, Avda. Miguel Servet nº 81, 50180 Utebo, Spain;
| | - Rocio Gutierrez
- OTC Chemo, Manuel Pombo Angulo 28-4th Floor, 28050 Madrid, Spain; (R.G.); (J.M.R.)
| | - Jose Miguel Rizo
- OTC Chemo, Manuel Pombo Angulo 28-4th Floor, 28050 Madrid, Spain; (R.G.); (J.M.R.)
| | - Pilar Rodriguez-Ledo
- Sociedad Española de Médicos Generales y de Familia (SEMG), 28005 Madrid, Spain; (A.G.A.); (P.R.-L.)
| | - Isabel Nerin
- Directora de la Cátedra SEMG-Estilos de Vida Unidad de Tabaquismo FMZ Profª Dpto. Medicina, Psiquiatría y Dermatología Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain;
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13
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Zhou B, Zong NC, Zhang Y, Huang Y, Youn JY, Cai H. Clinical characteristics of a COVID-19 cohort treated at UCLA Ronald Reagan Medical Center during the breaking phase of the pandemic: A retrospective study. Redox Biol 2024; 75:103178. [PMID: 38986245 PMCID: PMC11280086 DOI: 10.1016/j.redox.2024.103178] [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: 02/26/2024] [Revised: 04/08/2024] [Accepted: 04/29/2024] [Indexed: 07/12/2024] Open
Abstract
To this date, COVID-19 remains an unresolved pandemic, and the impairment of redox homeostasis dictates the severity of clinical outcomes. Here we examined initial UCLA cohort of 440 COVID-19 patients hospitalized between March 1st and April 1st, 2020, representing the first wave of the pandemic. The mean age was 58.88 ± 21.12, among which males were significantly more than females (55.5 % vs. 44.5 %), most distinctively in age group of 50-69. The age groups of 50-69 (33.6 %) and ≥70 (34.8 %) dominated. The racial composition was in general agreement with Census data with slight under-representation of Hispanics and Asians, and over-representation of Caucasians. Smoking was a significant factor (28.8 % vs. 11.0 % in LA population), likewise for obesity (BMI ≥30) (37.4 % vs. 27.7 % in LA population). Patients suffering from obesity or BMI<18.5 checked into ICU at a significantly higher rate. A 74.5 % of the patients had comorbidities including diabetes, chronic kidney disease, chronic pulmonary disease, congestive heart failure and peripheral vascular disease. The levels of d-dimer were drastically upregulated (1159.5 ng/mL), indicating hypercoagulative state. Upregulated LDH (328 IU/L) indicated significant tissue damages. A distorted redox hemeostasis is a common trait associated with these risk factors and clinical markers. A quarter of the patients received antivirals, among which Remdesivir most prescribed (23.6 %). Majority received antithrombotics (75 %), and antibiotics. Upon admission, 67 patients were intubated or received CPR; 177 patients eventually received intensive care (40.2 %). While 290 were discharged alive, 10 remained hospitalized, 73 were transferred, and 36 died with 3 palliatively discharged. In summary, our data fully characterized a Californian cohort of COVID-19 at the breaking phase of the pandemic, indicating that population demographics, biophysical characters, comorbidities and molecular pathological parameters have significant impacts on the evolvement of a pandemic. These provide critical insights into effective management of COVID-19, and future break from another pathogen.
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Affiliation(s)
- Bo Zhou
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Nobel Chenggong Zong
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Yuhan Zhang
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Yuanli Huang
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Ji-Youn Youn
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA
| | - Hua Cai
- Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, California, 90095, USA.
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14
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El-Assaad AM, Hamieh T. SARS-CoV-2: Prediction of critical ionic amino acid mutations. Comput Biol Med 2024; 178:108688. [PMID: 38870723 DOI: 10.1016/j.compbiomed.2024.108688] [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: 10/31/2023] [Revised: 05/26/2024] [Accepted: 06/01/2024] [Indexed: 06/15/2024]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that caused coronavirus disease 2019 (COVID-19), has been studied thoroughly, and several variants are revealed across the world with their corresponding mutations. Studies and vaccines development focus on the genetic mutations of the S protein due to its vital role in allowing the virus attach and fuse with the membrane of a host cell. In this perspective, we study the effects of all ionic amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 within the SARS-CoV-2:CC12.1 complex model. Binding free energy calculations between SARS-CoV-2 and antibody CC12.1 are based on the Analysis of Electrostatic Similarities of Proteins (AESOP) framework, where the electrostatic potentials are calculated using Adaptive Poisson-Boltzmann Solver (APBS). The atomic radii and charges that feed into the APBS calculations are calculated using the PDB2PQR software. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants worldwide. We find each of the following mutations: K378A, R408A, K424A, R454A, R457A, K458A, and K462A, to play significant roles in the binding to Antibody CC12.1, since they are turned into strong inhibitors on both chains of the S1 protein, whereas the mutations D405A, D420A, and D427A, show to play important roles in this binding, as they are turned into mild inhibitors on both chains of the S1 protein.
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Affiliation(s)
- Atlal M El-Assaad
- Department of Electrical Engineering & Computer Science, University of Toledo (UT), Toledo OH 43606, USA; Department of Computer Science, Lebanese International University (LIU), Bekaa, Lebanon.
| | - Tayssir Hamieh
- Faculty of Science and Engineering, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands; Laboratory of Materials, Catalysis, Environment and Analytical Methods (MCEMA), Faculty of Sciences, Lebanese University, Hadath, Lebanon.
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15
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Ekim M, Ekim H, Akarsu GD. Diabetic peripheral arterial disease in COVID-19 pandemic. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2024; 29:35. [PMID: 39239073 PMCID: PMC11376723 DOI: 10.4103/jrms.jrms_509_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 01/05/2024] [Accepted: 01/31/2024] [Indexed: 09/07/2024]
Abstract
Both diabetes and peripheral arterial disease (PAD) have complex interactions with COVID-19. PAD is one of the most important underlying factors in the development of diabetic foot. The COVID-19 pandemic has also caused an increase in cardiovascular complications in those with chronic diseases, including diabetics, due to both the thrombophilic course of the viral disease and the lockdown measures applied for prevention. Since both COVID-19 and diabetes mellitus predispose to thrombosis, PAD is likely to have a more severe course in diabetic patients with COVID-19. The aim of our study is to discuss the complications, prophylaxis, and treatment of PAD, which is a serious complication of diabetes, during the pandemic period.
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Affiliation(s)
- Meral Ekim
- Department of Nutrition and Dietetics, Yozgat Bozok University Faculty of Health Sciences, Yozgat, Turkey
| | - Hasan Ekim
- Department of Cardiovascular Surgery, Yozgat Bozok University Faculty of Medicine, Yozgat, Turkey
| | - Gökhan Doğukan Akarsu
- Division of Molecular Medicine, Laboratory for Advanced Genomics, Ruder Boskovic Institute, Zagreb, Croatia
- Department of Pharmacy Services, Yozgat Bozok University School of Health Services, Yozgat, Turkey
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16
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Jin T, Ji J, Xu X, Li X, Gong B. Identification and validation of a novel 17 coagulation-related genes signature for predicting prognostic risk in colorectal cancer. Heliyon 2024; 10:e32687. [PMID: 38988584 PMCID: PMC11233961 DOI: 10.1016/j.heliyon.2024.e32687] [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: 04/13/2023] [Revised: 05/31/2024] [Accepted: 06/06/2024] [Indexed: 07/12/2024] Open
Abstract
Background Patients with colorectal cancer commonly experience disturbances in coagulation homeostasis. Activation of the coagulation system contributes to cancer-associated thrombosis as the second risk factor for death in cancer patients. This study intended to discover coagulation-related genes and construct a risk model for colorectal cancer patients' prognosis. Methods Coagulation-related genes were identified by searching coagulation-related pathways in the Molecular Signatures Database. Transcriptomic data and clinical data were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Univariate Cox and backward stepwise regression were utilized to identify prognosis-related genes and construct a predictive risk model for the training cohort. Next, survival analysis determines the risk model's predictive power, correlation with clinicopathological characteristics, and nomogram. Additionally, we characterized the variances in immune cell infiltration, somatic mutations, immune checkpoint molecules, biological functions, and drug sensitivity between the high- and low-score patients. Result Eight hundred forty-five genes were obtained by searching the theme term "coagulation" after de-duplication. After univariate regression analysis, 69 genes correlated with prognosis were obtained from the Cancer Genome Atlas dataset. A signature consisting of 17 coagulation-related genes was established through backward stepwise regression. The Kaplan-Meier curve indicated a worse prognosis for high-score patients. Time-dependent receiver operating characteristic curve analysis demonstrated high accuracy in predicting overall survival. Further, the results were validated by two independent datasets (GSE39582 and GSE17536). Combined with clinicopathological characteristics, the risk model was proven to be an independent prognostic factor to predict poor pathological status and worse prognosis. Furthermore, high-score patients had significantly higher stromal cell infiltration. Low-score patients were associated with high infiltration of resting memory CD4+ T cells, activated CD4+ T cells, and T follicular helper cells. The low-score patients exhibited increased expression of immune checkpoint genes, and this might be relevant to their better prognosis. High-score patients exhibited lower IC50 values of Paclitaxel, Rapamycin, Temozolomide, Cyclophosphamide, etc. The differential signaling pathways mainly involve the calcium signaling pathway and the neuroactive ligand-receptor interaction. Lastly, a nomogram was constructed and showed a good prediction. Conclusion The prognostic signature of 17 coagulation-related genes had significant prognostic value for colorectal cancer patients. We expect to improve treatment modalities and benefit more patients through research on molecular features.
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Affiliation(s)
- Taojun Jin
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jianmei Ji
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xiaowen Xu
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xinxing Li
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China
| | - Biao Gong
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
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17
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Letelier P, Delgado H, Garrido F, Quiñones F, San MA, Hernández L, Garcés P, Guzmán-Oyarzo D, Boguen R, Hernandez A, Medina G, Schwerter P, Guzmán N. Dynamic changes of hematological and hemostatic parameters in COVID-19 hospitalized patients: Potential role as severity biomarkers for the Chilean population. J Med Biochem 2024; 43:556-564. [PMID: 39139154 PMCID: PMC11318854 DOI: 10.5937/jomb0-47588] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 12/29/2023] [Indexed: 08/15/2024] Open
Abstract
Background COVID-19 is still a global health issue, there is limited evidence in South America regarding laboratory biomarkers associated with severe disease. The objective of our study was to identify hematological and hemostatic changes associated with severe COVID-19. Methods A total of 170 hospitalized patients with COVID19 were included in the study, defining their severity according to established criteria. Demographic, clinical, and laboratory (days 1, 3, 7, 15) data were obtained. We performed a statistical analysis, assuming significance with a value of p < 0.05. We analyzed the correlation between severity and biomarkers and established cut-off values for severe patients through ROC curves, estimating Odds Ratio associated with severe disease. Results Day 1 was observed significant differences between moderate vs severe patients for leukocytes (WBC), Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and D-dimer, establishing cut-off points for each of them. The markers we found associated to risk of severe disease were WBC (OR=3.2396; p = 0.0003), NLR (OR=5.7084; p < 0.0001), PLR (OR=4.4094; p < 0.0001), Neutrophil (OR=4.1193; p < 0.0001), D-dimer (OR=2.7827; p = 0.0124). Conclusions The results allow to establish basic laboratory biomarkers associated to severe disease, which could be used as prognostic markers.
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Affiliation(s)
- Pablo Letelier
- Universidad Católica de Temuco, Facultad de Ciencias de la Salud, Departamento de Procesos Diagnósticos y Evaluación, Precision Health Research Laboratory, Temuco, Chile
| | - Hugo Delgado
- Dr. Hernán Henríquez Aravena Hospital, Clinical Laboratory, Temuco, Chile
| | - Felipe Garrido
- Dr. Hernán Henríquez Aravena Hospital, Clinical Laboratory, Temuco, Chile
| | - Francisco Quiñones
- Dr. Hernán Henríquez Aravena Hospital, Clinical Laboratory, Temuco, Chile
| | - Martín Andrés San
- Dr. Hernán Henríquez Aravena Hospital, Clinical Laboratory, Temuco, Chile
| | - Loreto Hernández
- Complejo Asistencial Padre Las Casas, Padre Las Casas, Araucanía, Chile
| | | | - Dina Guzmán-Oyarzo
- Universidad San Sebastián, Facultad de Medicina y Ciencias, School of Medical Technology, Campus Concepción, Concepción, Chile
| | - Rodrigo Boguen
- Universidad Católica de Temuco, Facultad de Ciencias de la Salud, Departamento de Procesos Diagnósticos y Evaluación, Precision Health Research Laboratory, Temuco, Chile
| | - Alfonso Hernandez
- Universidad Católica de Temuco, Facultad de Ciencias de la Salud, Departamento de Procesos Diagnósticos y Evaluación, Precision Health Research Laboratory, Temuco, Chile
| | - Gustavo Medina
- Universidad Católica de Temuco, Facultad de Ciencias de la Salud, Departamento de Procesos Diagnósticos y Evaluación, Precision Health Research Laboratory, Temuco, Chile
| | - Patricia Schwerter
- Universidad Católica de Temuco, Facultad de Ingeniería, Department of Mathematical and Physics Sciences, Temuco, Chile
| | - Neftalí Guzmán
- Universidad Católica de Temuco, Facultad de Ciencias de la Salud, Departamento de Procesos Diagnósticos y Evaluación, Precision Health Research Laboratory, Temuco, Chile
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Ebrahimi R, Nasri F, Kalantari T. Coagulation and Inflammation in COVID-19: Reciprocal Relationship between Inflammatory and Coagulation Markers. Ann Hematol 2024; 103:1819-1831. [PMID: 38349409 DOI: 10.1007/s00277-024-05630-1] [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: 09/17/2023] [Accepted: 01/16/2024] [Indexed: 05/14/2024]
Abstract
The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV. Numerous cellular and biochemical issues arise after COVID-19 infection. The severe inflammation that is caused by a number of cytokines appears to be one of the key hallmarks of COVID-19. Additionally, people with severe COVID-19 have coagulopathy and fulminant thrombotic events. We briefly reviewed the COVID-19 disease at the beginning of this paper. The inflammation and coagulation markers and their alterations in COVID-19 illness are briefly discussed in the parts that follow. Next, we talked about NETosis, which is a crucial relationship between coagulation and inflammation. In the end, we mentioned the two-way relationship between inflammation and coagulation, as well as the factors involved in it. We suggest that inflammation and coagulation are integrated systems in COVID-19 that act on each other in such a way that not only inflammation can activate coagulation but also coagulation can activate inflammation.
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Affiliation(s)
- Rasoul Ebrahimi
- Division of Laboratory Hematology and Blood Banking, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Nasri
- Division of Laboratory Hematology and Blood Banking, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Tahereh Kalantari
- Division of Laboratory Hematology and Blood Banking, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
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Jan MI, Anwar Khan R, Khan N, Iftikhar SM, Ali S, Khan MI, Gul S, Nishan U, Ali T, Ullah R, Bari A. Modulation in serum and hematological parameters as a prognostic indicator of COVID-19 infection in hypertension, diabetes mellitus, and different cardiovascular diseases. Front Chem 2024; 12:1361082. [PMID: 38741671 PMCID: PMC11089109 DOI: 10.3389/fchem.2024.1361082] [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: 12/24/2023] [Accepted: 04/10/2024] [Indexed: 05/16/2024] Open
Abstract
SARS-CoV-2 infection affects and modulates serum as well as hematological parameters. However, whether it modifies these parameters in the existing disease conditions, which help in the erection of specific treatments for the disease, is under investigation. Here, we aimed to determine whether serum and hematological parameters alteration in various diseases, diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD) and myocardial infarction (MI) conditions correlate and signal SARS-CoV-2 infection, which could be used as a rapid diagnosis tool for SARS-CoV-2 infection in disease conditions. To assess the projected goals, we collected blood samples of 1,113 male and female patients with solo and multiple disease conditions of DM/HTN/IHD/MI with severe COVID-19, followed by biochemical analysis, including COVID-19 virus detection by RT-qPCR. Furthermore, blood was collected from age-matched disease and healthy individuals 502 and 660 and considered as negative control. In our results, we examined higher levels of serum parameters, including D-dimer, ferritin, hs-CRP, and LDH, as well as hematological parameters, including TLC in sole and multiple diseases (DM/HTN/IHD/MI) conditions compared to the control subjects. Besides, the hematological parameters, including Hb, RBC, and platelet levels, decreased in the patients. In addition, we found declined levels of leukocyte count (%), lymphocyte (%), monocyte (%), and eosinophil (%), and elevated level of neutrophil levels (%) in all the disease patients infected with SARS-CoV-2. Besides, NLR and NMR ratios were also statistically significantly (p < 0.05) high in the patients with solo and multiple disease conditions of DM/HTN/IHD/MI infected with the SARS-CoV-2 virus. In conclusion, rapid alteration of sera and hematological parameters are associated with SARS-CoV-2 infections, which could help signal COVID-19 in respective disease patients. Moreover, our results may help to improve the clinical management for the rapid diagnosis of COVID-19 concurrent with respective diseases.
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Affiliation(s)
- Muhammad Ishtiaq Jan
- Department of Chemistry, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan
| | - Riaz Anwar Khan
- Qazi Hussain Ahmad Teaching Hospital, Nowshehra, Khyber Pakhtunkhwa, Pakistan
| | - Naeem Khan
- Department of Chemistry, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan
| | - Syed Muhammad Iftikhar
- Department of Chemistry, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan
| | - Sajid Ali
- Department of Chemistry, Bacha Khan University, Charsadda, Khyber Pakhtunkhwa, Pakistan
| | - M. I. Khan
- Department of Chemistry, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan
| | - Saima Gul
- Department of Chemistry, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan
| | - Umar Nishan
- Department of Chemistry, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan
| | - Tahir Ali
- State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, China
| | - Riaz Ullah
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Ahmed Bari
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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20
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Senevirathne TH, Wekking D, Swain JWR, Solinas C, De Silva P. COVID-19: From emerging variants to vaccination. Cytokine Growth Factor Rev 2024; 76:127-141. [PMID: 38135574 DOI: 10.1016/j.cytogfr.2023.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 11/28/2023] [Indexed: 12/24/2023]
Abstract
The vigorous spread of SARS-CoV-2 resulted in the rapid infection of millions of people worldwide and devastation of not only public healthcare, but also social, educational, and economic infrastructures. The evolution of SARS-CoV-2 over time is due to the mutations that occurred in the genome during each replication. These mutated forms of SARS-CoV-2, otherwise known as variants, were categorized as variants of interest (VOI) or variants of concern (VOC) based on the increased risk of transmissibility, disease severity, immune escape, decreased effectiveness of current social measures, and available vaccines and therapeutics. The swift development of COVID-19 vaccines has been a great success for biomedical research, and billions of vaccine doses, including boosters, have been administered worldwide. BNT162b2 vaccine (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 nCoV-19 (AstraZeneca), and Janssen (Johnson & Johnson) are the four major COVID-19 vaccines that received early regulatory authorization based on their efficacy. However, some SARS-CoV-2 variants resulted in higher resistance to available vaccines or treatments. It has been four years since the first reported infection of SARS-CoV-2, yet the Omicron variant and its subvariants are still infecting people worldwide. Despite this, COVID-19 vaccines are still expected to be effective at preventing severe disease, hospitalization, and death from COVID. In this review, we provide a comprehensive overview of the COVID-19 pandemic focused on evolution of VOC and vaccination strategies against them.
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Affiliation(s)
- Thilini H Senevirathne
- Faculty of Science, Katholieke Universiteit Leuven, Kasteelpark Arenberg, Leuven, Belgium
| | - Demi Wekking
- Amsterdam UMC, Location Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | | | - Cinzia Solinas
- Medical Oncology, AOU Cagliari, P.O. Duilio Casula, Monserrato (CA), Italy.
| | - Pushpamali De Silva
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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21
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Muneer A, Xie L, Xie X, Zhang F, Wrobel JA, Xiong Y, Yu X, Wang C, Gheorghe C, Wu P, Song J, Ming GL, Jin J, Song H, Shi PY, Chen X. Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.04.583415. [PMID: 38496599 PMCID: PMC10942352 DOI: 10.1101/2024.03.04.583415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
By largely unknown mechanism(s), SARS-CoV-2 hijacks the host translation apparatus to promote COVID-19 pathogenesis. We report that the histone methyltransferase G9a noncanonically regulates viral hijacking of the translation machinery to bring about COVID-19 symptoms of hyperinflammation, lymphopenia, and blood coagulation. Chemoproteomic analysis of COVID-19 patient peripheral mononuclear blood cells (PBMC) identified enhanced interactions between SARS-CoV-2-upregulated G9a and distinct translation regulators, particularly the N 6 -methyladenosine (m 6 A) RNA methylase METTL3. These interactions with translation regulators implicated G9a in translational regulation of COVID-19. Inhibition of G9a activity suppressed SARS-CoV-2 replication in human alveolar epithelial cells. Accordingly, multi-omics analysis of the same alveolar cells identified SARS-CoV-2-induced changes at the transcriptional, m 6 A-epitranscriptional, translational, and post-translational (phosphorylation or secretion) levels that were reversed by inhibitor treatment. As suggested by the aforesaid chemoproteomic analysis, these multi-omics-correlated changes revealed a G9a-regulated translational mechanism of COVID-19 pathogenesis in which G9a directs translation of viral and host proteins associated with SARS-CoV-2 replication and with dysregulation of host response. Comparison of proteomic analyses of G9a inhibitor-treated, SARS-CoV-2 infected cells, or ex vivo culture of patient PBMCs, with COVID-19 patient data revealed that G9a inhibition reversed the patient proteomic landscape that correlated with COVID-19 pathology/symptoms. These data also indicated that the G9a-regulated, inhibitor-reversed, translational mechanism outperformed G9a-transcriptional suppression to ultimately determine COVID-19 pathogenesis and to define the inhibitor action, from which biomarkers of serve symptom vulnerability were mechanistically derived. This cell line-to-patient conservation of G9a-translated, COVID-19 proteome suggests that G9a inhibitors can be used to treat patients with COVID-19, particularly patients with long-lasting COVID-19 sequelae.
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22
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Gu J, Wang Y, Zhang JF, Wang CQ. The impacts of prophylactic anticoagulation therapy during hospitalization on long-term cardiovascular outcomes in high-risk COVID-19 patients amid the omicron wave of the pandemic. IJC HEART & VASCULATURE 2024; 50:101353. [PMID: 38347941 PMCID: PMC10859301 DOI: 10.1016/j.ijcha.2024.101353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 01/30/2024] [Indexed: 02/15/2024]
Abstract
Background Although prophylactic anticoagulation therapy is suggested to be adopted in severe COVID-19 patients, its effects on the long-term cardiovascular (CV) outcomes, namely the risk of major adverse CV events(MACEs) in high-risk CV patients amid the omicron wave of the pandemic, remain unknown. Methods We conducted this prospective cohort study of consecutive adults hospitalized COVID-19 between 19 April and 12 June 2022, COVID-19 patients with at least two CV risk factors or pre-existing CV diseases were enrolled. A propensity score matching(PSM) method was used to evaluated the effects of prophylactic anticoagulation therapy in hospital on long-term MACEs, including CV death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina pectoris, coronary revascularization and arterial or venous thrombosis. Results Two cohorts (with or without anticoagulants during hospitalization) of each 230 patients with balanced baseline characteristics were formed using PSM. During the 15-month follow-up period, 13 patients with anticoagulants and 29 patients without anticoagulants developed MACEs. Overall, the anticoagulation group had a significantly lower risk of MACEs than the control group (hazard ratio [HR] 0.431; 95 % confidence interval [CI]: 0.224-0.830, P = 0.010). Regarding specific constituents of MACEs, the differences were mainly reflected in arterial or venous thrombosis. The significantly lower HRs of overall MACEs were significantly observed in subgroup of age > 75 years, women, higher D dimer level, unvaccinated and non-nirmatrelvir-ritonavir prescribed patients. Conclusions Prophylactic anticoagulation therapy during hospitalization was effective in reducing long-term MACEs among COVID-19 patients with CV risk factors or pre-existing CV diseases amid the omicron wave of the pandemic.
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Affiliation(s)
- Jun Gu
- Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
| | - Yue Wang
- Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
| | - Jun-feng Zhang
- Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
| | - Chang-qian Wang
- Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
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23
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Spiezia L, Campello E, Simioni P, Lumbreras-Marquez MI. Whole blood viscoelastic testing profile and mortality in patients hospitalized with acute COVID-19 pneumonia: A systematic review and meta-analysis. Thromb Res 2024; 234:21-31. [PMID: 38142487 DOI: 10.1016/j.thromres.2023.12.009] [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: 10/24/2023] [Revised: 12/16/2023] [Accepted: 12/18/2023] [Indexed: 12/26/2023]
Abstract
BACKGROUND Several studies have evaluated the possible association between whole blood viscoelastic testing (VET) parameters in patients hospitalized for acute Coronavirus disease 2019 (COVID-19) pneumonia and mortality. A few studies found no significant differences between survivors and non-survivors, though other studies identified potential predictors of COVID-19-related mortality. We conducted a systematic review and meta-analysis of the literature to evaluate the possible association between standard thromboelastometry/graphy parameters and mortality in patients hospitalized for acute COVID-19 pneumonia. METHODS Relevant studies were searched through MEDLINE, EMBASE, and Google Scholar from their inception until 15th June 2023. We aimed to identify any study including: i) adults admitted to intensive care units (ICU) or medicine wards (MW) for acute COVID-19 pneumonia; ii) viscoelastic testing; iii) mortality. RESULTS We included 13 studies: nine prospective and four retrospective, 231 (30.4 %) non-survivors and 528 (69.6 %) survivors. Mortality rates ranged from 12.8 % to 67.5 %. The studies using the TEG apparatus found a significant difference in K time in the Kaolin test among survivors vs. non-survivors (mean difference [MD] 0.20, 95 % confidence interval [CI] 0.12, 0.28, I2 0%). The studies using the rotational thromboelastometry apparatus found a significant difference in CT-INTEM (MD -17.14, 95 % CI -29.23, -5.06, I2 0%) and LI60-EXTEM (MD -1.00, 95 % CI -1.00, -1.00, I2 0%) assays among survivors vs. non-survivors. CONCLUSION We identified no specific hypercoagulable or hypocoagulable profile associated with mortality in patients with COVID-19-related pneumonia. Large prospective studies are needed to explore the possible prognostic role of VET in this subset of patients.
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Affiliation(s)
- Luca Spiezia
- General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University School of Medicine, Padova, Italy.
| | - Elena Campello
- General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University School of Medicine, Padova, Italy
| | - Paolo Simioni
- General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University School of Medicine, Padova, Italy
| | - Mario I Lumbreras-Marquez
- Universidad Panamericana School of Medicine, Mexico City, Mexico; Maternal-Fetal Medicine Division, Instituto Nacional de Perinatologia, Mexico City, Mexico
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24
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Fujii T, Rennert RC, Hurth KM, Ward PM, Campan M, Mathew AJ, Dubeau L, Wallace WD, Liu CY, Russin JJ. Neurotropism of SARS-CoV-2: A Pathological Examination of Neurosurgical Specimens. Neurosurgery 2024; 94:379-388. [PMID: 37728367 DOI: 10.1227/neu.0000000000002684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/23/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Neurological manifestations may occur in more than 80% of patients hospitalized with COVID-19 infection, including severe disruptions of the central nervous system (CNS), such as strokes, encephalitis, or seizures. Although the primary pathophysiological mechanism for the effects of COVID-19 in CNS remains unknown, evidence exists for both direct injury from neuroinvasion and indirect effects from disruptions in systemic inflammatory and coagulation pathways. In this study, we analyzed CNS tissue from living patients to better understand these processes. METHODS With institutional review board approval and patient consent, samples that would be otherwise discarded from patients with active or recent (within 6 days of surgery) COVID-19 infection undergoing neurosurgical intervention were collected and tested for the presence of SARS-CoV-2 using immunohistochemistry, in situ hybridization, electron microscopy, and reverse transcription polymerase chain reaction. RESULTS Five patients with perioperative mild-to-moderate COVID-19 infection met inclusion criteria (2 male, 3 female; mean age 38.8 ± 13.5 years). Neurosurgical diagnoses included a glioblastoma, a ruptured arteriovenous malformation, a ruptured posterior inferior cerebellar artery aneurysm, a middle cerebral artery occlusion, and a hemorrhagic pontine cavernous malformation. Samples analyzed included the frontal lobe cortex, olfactory nerve, arteriovenous malformation/temporal lobe parenchyma, middle cerebral artery, cerebellum, and cavernous malformation/brainstem parenchyma. Testing for the presence of SARS-CoV-2 was negative in all samples. CONCLUSION The CNS is likely not a significant viral reservoir during mild-to-moderate COVID-19 infection, although direct neuroinvasion is not definitively excluded. Additional testing to help elucidate the relative contributions of direct and indirect pathways for CNS injury from COVID is warranted.
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Affiliation(s)
- Tatsuhiro Fujii
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Robert C Rennert
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Kyle M Hurth
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Pamela M Ward
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Mihaela Campan
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Anna J Mathew
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Louis Dubeau
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - William D Wallace
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Charles Y Liu
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
| | - Jonathan J Russin
- Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles , California , USA
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25
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Kiliç A, Aslan M, Levent A. Investigation of the electrochemical properties of edoxaban using glassy carbon and boron-doped diamond electrodes and development of an eco-friendly and cost effective voltammetric method for its determination. Anal Biochem 2024; 685:115386. [PMID: 37977214 DOI: 10.1016/j.ab.2023.115386] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/28/2023] [Accepted: 11/04/2023] [Indexed: 11/19/2023]
Abstract
In this study, the highly risky drug Edoxaban (EDX), which can threaten life and cause bleeding, was electro analytically evaluated. The electrochemical behavior of EDX was investigated using glassy carbon electrode (GCE) and boron-doped diamond electrode (BDDE). In this study, for the first time, a simple, rapid, sensitive, and selective voltammetric technique was developed by using different electrodes for the electrochemical characterization and detection of EDX. The optimized voltammetric technique showed anodic signals of EDX at +1.09 V and +1.08 V on GCE and BDDE, respectively, in BR (pH 5.0) solution. The developed voltammetric method provided a very good analytical working range for EDX in BR (pH 5.0) solution on GCE and BDDE, covering concentration ranges from 1.84 μM to 12.88 μM and from 3.68 μM to 14.72 μM, respectively. The limits of detection for EDX on GCE and BDDE under these experimental conditions were calculated as 0.24 μM and 0.57 μM, respectively. The developed voltammetric methods on both electrodes were successfully applied to urine and tablet samples. Additionally, the obtained voltammetric results were compared with UV-Vis spectroscopy results.
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Affiliation(s)
- Abdulkadir Kiliç
- Batman University, Faculty of Arts and Sciences, Department of Analytical Chemistry, 72100, Batman, Turkey
| | - Mehmet Aslan
- Dicle University, Faculty of Sciences, Department of Analytical Chemistry, 2100, Diyarbakır, Turkey
| | - Abdulkadir Levent
- Batman University, Faculty of Arts and Sciences, Department of Analytical Chemistry, 72100, Batman, Turkey.
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26
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Zhang M, Cheng Q, Zhao F, Xu A, Li Q, Hu Y, Sun C. Development of a nomogram prognostic model for early Grade ≥ 3 infection in newly diagnosed multiple myeloma based on immunoparesis. Int Immunopharmacol 2024; 126:111277. [PMID: 38061120 DOI: 10.1016/j.intimp.2023.111277] [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: 09/03/2023] [Revised: 11/08/2023] [Accepted: 11/20/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND Infection, a significant cause of death in multiple myeloma (MM) patients, is a common complication and is closely associated with immunoparesis. There exists no clear definition of early infection, so early infection is defined in this paper as the occurrence within 3 months after diagnosis, considering the high incidence of infections within 3 months after diagnosis. This study established a new nomogram model based on immunoparesis to identify MM patients with high-risk early infection. METHODS A retrospective collection of 430 NDMM patients from June 2013 to June 2022 was conducted, and the patients were further divided into a training cohort and a validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) was used to select the best variables that can be used to establish a new nomogram prediction model. Validation was performed in the validation and entire cohorts. RESULTS After diagnosis, 67.7 % of the patients suffered from severe infection within 1 year, and 59.5 % experienced the first severe infection within 3 months. Variables associated with an increased risk of severe infection in the first 3 months included: BMPC, D-dimer, serum β2 microglobulin, immunoparesis, albumin, and eGFR. The nomogram based on the above six factors achieved a good C-index of 0.754, 0.73, and 0.731 in predicting early infection in the training cohort, validation cohort, and entire cohort, respectively. Finally, the time-dependent receiver operating characteristic (ROC) curve and decision curve analysis (DCA) of the nomogram showed that the model provided superior diagnostic capacity and clinical net benefit. CONCLUSION In this study, we established a nomogram model to predict early grade ≥ 3 infection in NDMM patients. This model can assist clinicians in identifying NDMM patients with high-risk infections and improve their prognosis through early intervention.
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Affiliation(s)
- Min Zhang
- Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Qianwen Cheng
- Emergency Department, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Fei Zhao
- Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Aoshuang Xu
- Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Qun Li
- Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Yu Hu
- Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan 430000, China.
| | - Chunyan Sun
- Institute of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan 430000, China.
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27
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Kiliç A, Aslan M, Levent A. Investigation of the electrochemical properties of edoxaban using glassy carbon and boron-doped diamond electrodes and development of an eco-friendly and cost effective voltammetric method for its determination. Anal Biochem 2024; 685:115386. [DOI: https:/doi.org/10.1016/j.ab.2023.115386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
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28
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Kato CD, Nsubuga J, Niyonzima N, Kitibwa A, Matovu E, Othieno E, Ssebugere P, Tumwine AA, Namayanja M. Immunological and biochemical biomarker alterations among SARS-COV-2 patients with varying disease phenotypes in Uganda. BMC Infect Dis 2023; 23:857. [PMID: 38057707 DOI: 10.1186/s12879-023-08854-0] [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: 05/11/2023] [Accepted: 11/29/2023] [Indexed: 12/08/2023] Open
Abstract
Every novel infection requires an assessment of the host response coupled with identification of unique biomarkers for predicting disease pathogenesis, treatment targets and diagnostic utility. Studies have exposed dysregulated inflammatory response induced by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as significant predictor or cause of disease severity/prognosis and death. This study evaluated inflammatory biomarkers induced by SARS-CoV-2 in plasma of patients with varying disease phenotypes and healthy controls with prognostic or therapeutic potential. We stratified SARS-CoV-2 plasma samples based on disease status (asymptomatic, mild, severe, and healthy controls), as diagnosed by RT-PCR SARS-CoV-2. We used a solid phase sandwich and competitive Enzyme-Linked Immunosorbent Assay (ELISA) to measure levels of panels of immunological (IFN-γ, TNF-α, IL-6, and IL-10) and biochemical markers (Ferritin, Procalcitonin, C-Reactive Protein, Angiotensin II, Homocysteine, and D-dimer). Biomarker levels were compared across SARS-CoV-2 disease stratification. Plasma IFN-γ, TNF-α, IL-6, and IL-10 levels were significantly (P < 0.05) elevated in the severe SARS-CoV-2 patients as compared to mild, asymptomatic, and healthy controls. Ferritin, Homocysteine, and D-dimer plasma levels were significantly elevated in severe cases over asymptomatic and healthy controls. Plasma C-reactive protein and Angiotensin II levels were significantly (P < 0.05) higher in mild than severe cases and healthy controls. Plasma Procalcitonin levels were significantly higher in asymptomatic than in mild, severe cases and healthy controls. Our study demonstrates the role of host inflammatory biomarkers in modulating the pathogenesis of COVID-19. The study proposes a number of potential biomarkers that could be explored as SARS-CoV-2 treatment targets and possible prognostic predictors for a severe outcome. The comprehensive analysis of prognostic biomarkers may contribute to the evidence-based management of COVID-19 patients.
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Affiliation(s)
- Charles Drago Kato
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda.
| | - Julius Nsubuga
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda.
| | | | - Annah Kitibwa
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda
| | - Enock Matovu
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda
| | - Emmanuel Othieno
- Department of Pathology, Soroti University, P.O. Box 211, Soroti, Uganda
| | - Patrick Ssebugere
- Department of Chemistry, College of Natural Sciences, Makerere University, P.O Box 7062, Kampala, Uganda
| | - Amanda Agnes Tumwine
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda
| | - Monica Namayanja
- School of Bio-security, Biotechnical & Laboratory Sciences, College of Veterinary Medicine, Animal Resources & Bio-security, Makerere University, P.O Box 7062, Kampala, Uganda
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Ludhiadch A, Paul SR, Khan R, Munshi A. COVID-19 induced ischemic stroke and mechanisms of viral entry in brain and clot formation: a systematic review and current update. Int J Neurosci 2023; 133:1153-1166. [PMID: 35412938 DOI: 10.1080/00207454.2022.2056460] [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: 11/29/2021] [Accepted: 03/16/2022] [Indexed: 10/18/2022]
Abstract
Background: Coronavirus disease 2019, caused by SARS-CoV-2 (SCV-2) was stated as a pandemic on March 11 2020 by World Health Organization (WHO), and since then, it has become a major health issue worldwide. It mainly attacks the respiratory system with various accompanying complications, including cardiac injury, renal failure, encephalitis and Stroke.Materials and Methods: The current systematic review has been compiled to summarize the available literature on SCV-2 induced ischemic Stroke and its subtypes. Further, the mechanisms by which the virus crosses the blood-brain barrier (BBB) to enter the brain have also been explored. The role of CRP and D-dimer as potent prognostic markers was also explored. The literature search was carried out comprehensively on Google scholar, PubMed, SCOP US, Embase and Cochrane databases by following guidelines.Results: All the studies were reviewed thoroughly by authors and disagreements were resolved by consensus and help of the senior authors. The most common subtype of the IS was found to be large artery atherosclerosis in SCV-2 induced IS. Hypertension emerged as the most significant risk factor. The mechanism resulting in elevated levels of CRP and D-dimer have also been discussed. However, there is a scarcity of definitive evidence on how SCV-2 enters the human brain. The available literature based on various studies demonstrated that SCV-2 enters through the nasopharyngeal tract via olfactory cells to olfactory neurons, astrocytes and via choroid plexus through endothelial cells. Further, disruption of gut-brain axis has been also discussed.Conclusion: Data available in the literature is not adequate to come to a conclusion. Therefore, there is a need to carry out further studies to delineate the possible association between SCV-2 induced IS.
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Affiliation(s)
- Abhilash Ludhiadch
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
| | - Swaraj Ranjan Paul
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
| | - Rahul Khan
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
| | - Anjana Munshi
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
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Siddique YA, Chaudhry R, Ahmad M, Sebai A, Sharma L, Hassouba M, Virk GS. The Trend of Arrhythmias in Patients With COVID-19: A Complication or Late Manifestation? Cureus 2023; 15:e50746. [PMID: 38239526 PMCID: PMC10794791 DOI: 10.7759/cureus.50746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2023] [Indexed: 01/22/2024] Open
Abstract
Patients diagnosed with coronavirus disease (CVD) who experience cardiovascular complications or have pre-existing cardiovascular disease are at an increased risk of death. The primary heart-related consequences associated with COVID-19 encompass venous thromboembolism, shock, heart failure, arrhythmias, myocarditis, acute myocardial infarction, and acute cardiac damage. The coronavirus has the potential to induce cardiovascular complications or exacerbate pre-existing CVD through various mechanisms. These mechanisms include dysregulation of the renin-angiotensin-aldosterone system; direct viral toxicity; damage to endothelial cells; formation of blood clots and subsequent inflammation, a phenomenon known as thromboinflammation; an excessive immune response known as cytokine storm; and an imbalance between the demand and supply of oxygen in the body. In this study, we comprehensively analyze the cardiovascular symptoms, histology, and underlying mechanisms associated with COVID-19. Our aim is to contribute to the identification of future research objectives and aid in the advancement of therapeutic management approaches.
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Affiliation(s)
- Yusuf A Siddique
- Basic Sciences, St. George's University School of Medicine, True Blue, GRD
| | | | | | - Ahmad Sebai
- School of Medicine, California University of Science and Medicine, Colton, USA
| | - Lubhani Sharma
- Family Medicine, Dayanand Medical College and Hospital, Ludhiana, IND
| | - Mohamed Hassouba
- Pediatrics, SUNY Downstate Health Sciences University, Brooklyn, USA
| | - Ghazala S Virk
- Internal Medicine, Avalon University School of Medicine, Ohio, USA
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Zhu J, Li X, Lv F, Zhou W. Bioinformatics Approach to Identify the Influences of COVID-19 on Ischemic Stroke. Biochem Genet 2023; 61:2222-2241. [PMID: 37184686 PMCID: PMC10184096 DOI: 10.1007/s10528-023-10366-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 03/09/2023] [Indexed: 05/16/2023]
Abstract
As severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is becoming more infectious and less virulent, symptoms beyond the lungs of the Coronavirus Disease 2019 (COVID-19) patients are a growing concern. Studies have found that the severity of COVID-19 patients is associated with an increased risk of ischemic stroke (IS); however, the underlying pathogenic mechanisms remain unknown. In this study, bioinformatics approaches were utilized to explore potential pathogenic mechanisms and predict potential drugs that may be useful in the treatment of COVID-19 and IS. The GSE152418 and GSE122709 datasets were downloaded from the GEO website to obtain the common differentially expressed genes (DEGs) of the two datasets for further functional enrichment, pathway analysis, and drug candidate prediction. A total of 80 common DEGs were identified in COVID-19 and IS datasets for GO and KEGG analysis. Next, the protein-protein interaction (PPI) network was constructed and hub genes were identified. Further, transcription factor-gene interactions and DEGs-miRNAs coregulatory network were investigated to explore their regulatory roles in disease. Finally, protein-drug interactions with common DEGs were analyzed to predict potential drugs. We successfully identified the top 10 hub genes that could serve as novel targeted therapies for COVID-19 and screened out some potential drugs for the treatment of COVID-19 and IS.
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Affiliation(s)
- Jiabao Zhu
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China
| | - Xiangui Li
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China
| | - Fanzhen Lv
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China
| | - Weimin Zhou
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China.
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32
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Kiliç A, Aslan M, Önal G, Levent A. Firstly electrochemical investigetions and determination of anticoagulant drug edoxaban at single-use pencil graphite electrode: an eco-friendly and cost effective voltammetric method. Daru 2023; 31:233-241. [PMID: 37695455 PMCID: PMC10624777 DOI: 10.1007/s40199-023-00478-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 08/11/2023] [Indexed: 09/12/2023] Open
Abstract
OBJECTIVES The anticoagulant drug edoxaban has a blood thinning mechanism of action. In this study, a pencil graphite electrode was electrochemically activated at + 1.4 V for 60 s. in a Britton-Robinson (pH 9.0) supporting electrolyte solution. EVIDENCE ACQUISITION A simple, fast, and sensitive electrochemical procedure was developed using cyclic voltammetry and square wave voltammetry techniques. It was observed that edoxaban gave a good oxidation signal with cyclic voltammetry technique at a potential of + 0.98 V (vs. Ag/AgCl). RESULTS This procedure showed a linear response in a Britton-Robinson (pH 9.0) media within the concentration range of 0.2-1.8 µM and limit of detection (LOD) and the limit of quantification (LOQ) values were determined to be 0.073 μM (0.133 μg mL-1) and 0.243 μM (0.443 μg mL-1), respectively. CONCLUSION The method developed in this study was successfully applied to drug and urine samples. The developed voltammetric method was highly selective and gave satisfactory recovery results in urine and pharmaceutical samples. The results of the voltammetric method were compared with the spectroscopic method and it was determined that the results were compatible.
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Affiliation(s)
- Abdulkadir Kiliç
- Department of Chemistry, Faculty of Sciences, Batman University, Batman, Turkey
| | - Mehmet Aslan
- Graduate School of Education, Chemistry Department, Dicle University, Diyarbakır, Turkey
| | - Günay Önal
- Department of Medical Services and Techniques, Health Services Vocational School, Batman University, Batman, Turkey
| | - Abdulkadir Levent
- Department of Chemistry, Faculty of Sciences, Batman University, Batman, Turkey.
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Berlot AA, Moskowitz HS, Lin J, Liu J, Sehanobish E, Jerschow E, Ow TJ, Sussman ES. Acute and Longer-Term Effects of COVID-19 on Auditory and Vestibular Symptoms. Otol Neurotol 2023; 44:1100-1105. [PMID: 37758317 DOI: 10.1097/mao.0000000000004027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
OBJECTIVE To evaluate long-term effects of COVID-19 on auditory and vestibular symptoms in a diverse cohort impacted by the initial 2020 COVID-19 infection in the pandemic's epicenter, before vaccine availability. STUDY DESIGN Cohort study of individuals with confirmed COVID-19 infection, diagnosed in the March-May 2020 infection wave. A randomized, retrospective chart review of 1,352 individuals was performed to identify those with documented new or worsening auditory (aural fullness, tinnitus, hyperacusis, hearing loss) or vestibular (dizziness, vertigo) symptoms. Those with documented symptoms (613 of the 1,352 initial cohort) were contacted for a follow-up telephone survey in 2021-2022 to obtain self-report of aforementioned symptoms. SETTING Academic tertiary hospital system in Bronx, NY. PATIENTS Adults 18 to 99 years old with confirmed COVID-19 infection, alive at time of review. One hundred forty-eight charts were excluded for restricted access, incomplete data, no COVID-19 swab, or deceased at time of review. INTERVENTION Confirmed COVID-19 infection, March to May 2020. MAIN OUTCOMES MEASURES Auditory and vestibular symptoms documented in 2020 medical records and by self-report on 2021 to 2022 survey. RESULTS Among the 74 individuals with documented symptoms during the first 2020 COVID-19 wave who participated in the 2021 to 2022 follow-up survey, 58% had documented vestibular symptoms initially in 2020, whereas 43% reported vestibular symptoms on the 2021 to 2022 survey ( p = 0.10). In contrast, 9% had documented auditory symptoms initially in 2020 and 55% reported auditory symptoms on the 2021 to 2022 survey ( p < 0.01). CONCLUSIONS COVID-19 may impact vestibular symptoms early and persistently, whereas auditory effects may have more pronounced long-term impact, suggesting the importance of continually assessing COVID-19 patients.
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Affiliation(s)
| | | | - Juan Lin
- Albert Einstein College of Medicine, the Bronx, New York
| | - Jianyou Liu
- Albert Einstein College of Medicine, the Bronx, New York
| | | | - Elina Jerschow
- Allergy Division Chair, Mayo Clinic, Rochester, Minnesota
| | - Thomas J Ow
- Albert Einstein College of Medicine, the Bronx, New York
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Yang L, Wu Y, Jin W, Mo N, Ye G, Su Z, Tang L, Wang Y, Li Y, Du J. The potential role of ferroptosis in COVID-19-related cardiovascular injury. Biomed Pharmacother 2023; 168:115637. [PMID: 37844358 DOI: 10.1016/j.biopha.2023.115637] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 09/26/2023] [Accepted: 10/03/2023] [Indexed: 10/18/2023] Open
Abstract
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms of SARS-CoV-2 infection persist after recovery. Evidence indicates that people who recovered from COVID-19, even those under the age of 65 years without cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, had a significantly increased risk of cardiovascular disease for up to one year after diagnosis. Therefore, it is important to closely monitor individuals who have recovered from COVID-19 for potential cardiovascular damage that may manifest at a later stage. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the production of reactive oxygen species (ROS) and increased lipid peroxide levels. Several studies have demonstrated that ferroptosis plays an important role in cancer, ischemia/reperfusion injury (I/RI), and other cardiovascular diseases. Altered iron metabolism, upregulation of reactive oxygen species, and glutathione peroxidase 4 inactivation are striking features of COVID-19-related cardiovascular injury. SARS-CoV-2 can cause cardiovascular ferroptosis, leading to cardiovascular damage. Understanding the mechanism of ferroptosis in COVID-19-related cardiovascular injuries will contribute to the development of treatment regimens for preventing or reducing COVID-19-related cardiovascular complications. In this article, we go over the pathophysiological underpinnings of SARS-CoV-2-induced acute and chronic cardiovascular injury, the function of ferroptosis, and prospective treatment approaches.
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Affiliation(s)
- Lei Yang
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China; Department of Central Laboratory, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yunyi Wu
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Weidong Jin
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Nan Mo
- Department of Central Laboratory, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Gaoqi Ye
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zixin Su
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Lusheng Tang
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Ying Wang
- Department of Central Laboratory, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
| | - Yanchun Li
- Department of Central Laboratory, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
| | - Jing Du
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Cappelletti P, Gallo G, Marino R, Palaniappan S, Corbo M, Savoia C, Feligioni M. From cardiovascular system to brain, the potential protective role of Mas Receptors in COVID-19 infection. Eur J Pharmacol 2023; 959:176061. [PMID: 37775018 DOI: 10.1016/j.ejphar.2023.176061] [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: 07/13/2023] [Revised: 09/15/2023] [Accepted: 09/18/2023] [Indexed: 10/01/2023]
Abstract
Coronavirus disease 2019 (COVID-19) has been declared a new pandemic in March 2020. Although most patients are asymptomatic, those with underlying cardiovascular comorbidities may develop a more severe systemic infection which is often associated with fatal pneumonia. Nonetheless, neurological and cardiovascular manifestations could be present even without respiratory symptoms. To date, no COVID-19-specific drugs are able for preventing or treating the infection and generally, the symptoms are relieved with general anti-inflammatory drugs. Angiotensin-converting-enzyme 2 (ACE2) may function as the receptor for virus entry within the cells favoring the progression of infection in the organism. On the other hand, ACE2 is a relevant enzyme in renin angiotensin system (RAS) cascade fostering Ang1-7/Mas receptor activation which promotes protective effects in neurological and cardiovascular systems. It is known that RAS is composed by two functional countervailing axes the ACE/AngII/AT1 receptor and the ACE/AngII/AT2 receptor which counteracts the actions mediated by AngII/AT1 receptor by inducing anti-inflammatory, antioxidant and anti-growth functions. Subsequently an "alternative" ACE2/Ang1-7/Mas receptor axis has been described with functions similar to the latter protective arm. Here, we discuss the neurological and cardiovascular effects of COVID-19 highlighting the role of the stimulation of the RAS "alternative" protective arm in attenuating pulmonary, cerebral and cardiovascular damages. In conclusion, only two clinical trials are running for Mas receptor agonists but few other molecules are in preclinical phase and if successful these drugs might represent a successful strategy for the treatment of the acute phase of COVID-19 infection.
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Affiliation(s)
- Pamela Cappelletti
- Department of Neuro-Rehabilitation Sciences, Casa di Cura Igea, Milan, Italy.
| | - Giovanna Gallo
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Rachele Marino
- European Brain Research Institute (EBRI) Rita Levi Montalcini Foundation, Rome, Italy
| | | | - Massimo Corbo
- Department of Neuro-Rehabilitation Sciences, Casa di Cura Igea, Milan, Italy
| | - Carmine Savoia
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Marco Feligioni
- Department of Neuro-Rehabilitation Sciences, Casa di Cura Igea, Milan, Italy; European Brain Research Institute (EBRI) Rita Levi Montalcini Foundation, Rome, Italy.
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Lopes TRR, Silva Júnior JVJ, Carmo RF, Weiblen R, Flores EF. Epidemiological analysis over two years of SARS-CoV-2 circulation in southern Brazil: old and novel predictors of COVID-19 outcome. Acta Trop 2023; 247:107007. [PMID: 37659686 DOI: 10.1016/j.actatropica.2023.107007] [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: 05/26/2023] [Revised: 08/17/2023] [Accepted: 08/25/2023] [Indexed: 09/04/2023]
Abstract
The overwhelming majority of SARS-CoV-2 epidemiological studies cover a narrow time period, making general knowledge about the COVID-19 pandemic difficult. To assess COVID-19-related host aspects in the overall pandemic, we analyzed COVID-19 cases during the first two years of SARS-CoV-2 circulation in southern Brazil. Herein, 390 patients admitted in 2020-2022 to a Brazilian public referral hospital were allocated into two groups according to the COVID-19 outcome: hospital discharge (n=237) or death (n=153). In the univariate analysis, several variables, including sociodemographic, clinical and laboratory aspects (primary data), were significantly different between the analyzed groups. In multivariate logistic regression, eight of these factors remained associated with the COVID-19 outcome. In particular, we report oxygen supplementation and the need for hemodialysis as predictors of hospital discharge and death from COVID-19, respectively. To the best of our knowledge, none of these findings have been previously reported in the Brazilian or world population. In conclusion, our results contribute to current knowledge by demonstrating that factors described at different times may remain associated with COVID-19 over the pandemic and by identifying novel predictors of COVID-19 outcome.
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Affiliation(s)
- T R R Lopes
- Programa de Pós-graduação em Medicina Veterinária, Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil; Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil
| | - J V J Silva Júnior
- Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil; Setor de Virologia, Instituto Keizo Asami, Universidade Federal de Pernambuco, Pernambuco, Brazil; Departamento de Análises Clínicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil.
| | - R F Carmo
- Colegiado de Ciências Farmacêuticas, Universidade Federal do Vale do São Francisco, Pernambuco, Brazil
| | - R Weiblen
- Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil
| | - E F Flores
- Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria, Rio Grande do Sul, Brazil.
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Duvall LR, Lyvers JT, Hang D, Pagel PS. An Unexpected Finding in a Patient With Near-Syncope, Upper Extremity Paresthesias, and COVID-19. J Cardiothorac Vasc Anesth 2023; 37:2387-2390. [PMID: 37612201 DOI: 10.1053/j.jvca.2023.07.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 07/29/2023] [Indexed: 08/25/2023]
Affiliation(s)
- Lydia R Duvall
- Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI
| | - Jeffrey T Lyvers
- Department of Anesthesiology, Aurora St. Luke's Medical Center, Milwaukee, WI
| | - Dustin Hang
- Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI
| | - Paul S Pagel
- Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI.
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38
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Ang CH, Ho D. Delayed acute upper limb ischaemia manifesting months after COVID-19 infection. Singapore Med J 2023; 64:620-623. [PMID: 34717296 PMCID: PMC10645008 DOI: 10.11622/smedj.2021194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 06/02/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Chuan Han Ang
- Department of General Surgery, Changi General Hospital, Singapore
| | - Derek Ho
- Department of General Surgery, Changi General Hospital, Singapore
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39
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Burrows KR, Remington DL, Cappola JJ. Implications of COVID-19 in Acute Mesenteric Ischemia and Bowel Necrosis: A Case Report. Cureus 2023; 15:e47867. [PMID: 38021891 PMCID: PMC10680998 DOI: 10.7759/cureus.47867] [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: 10/28/2023] [Indexed: 12/01/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to provoke a state of hypercoagulability that may lead to devastating consequences. This has been well established since the onset of the coronavirus pandemic in 2019; however, the specific relationship between COVID-19 and thrombus formation remains poorly understood. There has been increasing documentation of gastrointestinal (GI) complications in patients infected with the virus, including potentially lethal acute mesenteric ischemia (AMI), regardless of prior history of GI disease or risk factors for hypercoagulable states. Not only is mesenteric ischemia difficult to diagnose but it is also associated with high rates of morbidity and mortality, warranting prompt identification and treatment to improve clinical outcomes. We herein present a case of diffuse intestinal necrosis secondary to mesenteric thrombus formation in a previously healthy female five days after the resolution of her COVID-19 symptoms. The high rates of morbidity and mortality linked to AMI underpin the need for clinicians to maintain a high index of suspicion for thrombotic complications of COVID, even in healthy patients. This case emphasizes the importance of a thorough history-taking, physical examination, and laboratory workup even in patients without a current COVID-19 infection or predisposing thrombotic risk factors. Additionally, it suggests that the hypercoagulable state associated with a COVID-19 infection may persist after the primary COVID-19 symptoms have resolved.
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Affiliation(s)
- Kelsey R Burrows
- General Surgery, Campbell University School of Osteopathic Medicine, Lillington, USA
| | - David L Remington
- General Surgery, University of North Carolina (UNC) Wayne, Goldsboro, USA
| | - James J Cappola
- Internal Medicine, Campbell University School of Osteopathic Medicine, Lillington, USA
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40
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Kiliç A, Aslan M, Önal G, Levent A. Firstly electrochemical investigetions and determination of anticoagulant drug edoxaban at single-use pencil graphite electrode: an eco-friendly and cost effective voltammetric method. Daru 2023; 31:233-241. [DOI: https:/doi.org/10.1007/s40199-023-00478-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 08/11/2023] [Indexed: 07/01/2024] Open
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41
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Zhao J, Xie Y, Meng Z, Liu C, Wu Y, Zhao F, Ma X, Christopher TA, Lopez BJ, Wang Y. COVID-19 and cardiovascular complications: updates of emergency medicine. EMERGENCY AND CRITICAL CARE MEDICINE 2023; 3:104-114. [PMID: 38314258 PMCID: PMC10836842 DOI: 10.1097/ec9.0000000000000095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2024]
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 variants, has become a global pandemic resulting in significant morbidity and mortality. Severe cases of COVID-19 are characterized by hypoxemia, hyper-inflammation, cytokine storm in lung. Clinical studies have reported an association between COVID-19 and cardiovascular disease (CVD). Patients with CVD tend to develop severe symptoms and mortality if contracted COVID-19 with further elevations of cardiac injury biomarkers. Furthermore, COVID-19 itself can induce and promoted CVD development, including myocarditis, arrhythmia, acute coronary syndrome, cardiogenic shock, and venous thromboembolism. Although the direct etiology of SARS-CoV-2 induced cardiac injury remains unknown and under-investigated, it is suspected that it is related to myocarditis, cytokine-mediated injury, microvascular injury, and stress-related cardiomyopathy. Despite vaccinations having provided the most effective approach to reducing mortality overall, an adapted treatment paradigm and regular monitoring of cardiac injury biomarkers is critical for improving outcomes in vulnerable populations at risk for severe COVID-19. In this review, we focus on the latest progress in clinic and research on the cardiovascular complications of COVID-19 and provide a perspective of treating cardiac complications deriving from COVID-19 in Emergency Medicine.
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Affiliation(s)
- Jianli Zhao
- Emergency Medicine Department, Thomas Jefferson University, Philadelphia, PA, USA
- Department of Biomedical Engineering, University of Alabama at Birmingham, AL, USA
| | - Yaoli Xie
- Emergency Medicine Department, Thomas Jefferson University, Philadelphia, PA, USA
| | - Zhijun Meng
- Emergency Medicine Department, Thomas Jefferson University, Philadelphia, PA, USA
| | - Caihong Liu
- Emergency Medicine Department, Thomas Jefferson University, Philadelphia, PA, USA
| | - Yalin Wu
- Department of Biomedical Engineering, University of Alabama at Birmingham, AL, USA
| | - Fujie Zhao
- Department of Biomedical Engineering, University of Alabama at Birmingham, AL, USA
| | - Xinliang Ma
- Emergency Medicine Department, Thomas Jefferson University, Philadelphia, PA, USA
| | | | - Bernard J. Lopez
- Emergency Medicine Department, Thomas Jefferson University, Philadelphia, PA, USA
| | - Yajing Wang
- Emergency Medicine Department, Thomas Jefferson University, Philadelphia, PA, USA
- Department of Biomedical Engineering, University of Alabama at Birmingham, AL, USA
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42
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Shama, Mahmood A, Mehmood S, Zhang W. Pathological Effects of SARS-CoV-2 Associated with Hematological Abnormalities. Curr Issues Mol Biol 2023; 45:7161-7182. [PMID: 37754237 PMCID: PMC10528388 DOI: 10.3390/cimb45090453] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 08/09/2023] [Accepted: 08/22/2023] [Indexed: 09/28/2023] Open
Abstract
The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has claimed the lives of 6.9 million people and infected over 765 million. It has become a major worldwide health problem and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower respiratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse outcomes. Prophylactic anticoagulation is essential to prevent complications and death rates associated with the virus's effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation (DIC) exhibits some similarities to DIC induced by sepsis. Lactate dehydrogenase (LDH), D-dimer, ferritin, and C-reactive protein (CRP) biomarkers often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.
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Affiliation(s)
- Shama
- Department of Microbiology, School of Medicine, Jiangsu University, Zhenjiang 212013, China (A.M.)
| | - Asif Mahmood
- Department of Microbiology, School of Medicine, Jiangsu University, Zhenjiang 212013, China (A.M.)
- School of Material Science and Engineering, Jiangsu University, Zhenjiang 212013, China
| | - Shahid Mehmood
- Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China;
| | - Wen Zhang
- Department of Microbiology, School of Medicine, Jiangsu University, Zhenjiang 212013, China (A.M.)
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Yao M, Ma J, Wu D, Fang C, Wang Z, Guo T, Mo J. Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy. Front Immunol 2023; 14:1198952. [PMID: 37680629 PMCID: PMC10482110 DOI: 10.3389/fimmu.2023.1198952] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 08/10/2023] [Indexed: 09/09/2023] Open
Abstract
Deep venous thrombosis (DVT) is a part of venous thromboembolism (VTE) that clinically manifests as swelling and pain in the lower limbs. The most serious clinical complication of DVT is pulmonary embolism (PE), which has a high mortality rate. To date, its underlying mechanisms are not fully understood, and patients usually present with clinical symptoms only after the formation of the thrombus. Thus, it is essential to understand the underlying mechanisms of deep vein thrombosis for an early diagnosis and treatment of DVT. In recent years, many studies have concluded that Neutrophil Extracellular Traps (NETs) are closely associated with DVT. These are released by neutrophils and, in addition to trapping pathogens, can mediate the formation of deep vein thrombi, thereby blocking blood vessels and leading to the development of disease. Therefore, this paper describes the occurrence and development of NETs and discusses the mechanism of action of NETs on deep vein thrombosis. It aims to provide a direction for improved diagnosis and treatment of deep vein thrombosis in the near future.
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Affiliation(s)
- Mengting Yao
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Jiacheng Ma
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Dongwen Wu
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Chucun Fang
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Zilong Wang
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
- Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Tianting Guo
- Department of Orthopedics, Guangdong Provincial People’s Hospital Ganzhou Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China
| | - Jianwen Mo
- Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
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Zhang Z, Dai W, Zhu W, Rodriguez M, Lund H, Xia Y, Chen Y, Rau M, Schneider EA, Graham MB, Jobe S, Wang D, Cui W, Wen R, Whiteheart SW, Wood JP, Silverstein R, Berger JS, Kreuziger LB, Barrett TJ, Zheng Z. Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19. Res Pract Thromb Haemost 2023; 7:102164. [PMID: 37680312 PMCID: PMC10480648 DOI: 10.1016/j.rpth.2023.102164] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 09/09/2023] Open
Abstract
Background Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown. Objectives To assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection. Methods Endogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed. Results In hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non-COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged. Conclusion High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.
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Affiliation(s)
- Ziyu Zhang
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
| | - Wen Dai
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
| | - Wen Zhu
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
- Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Maya Rodriguez
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
- Diversity Summer Health-Related Research Education Program (DSHREP), Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- College of Arts and Sciences, Marquette University, Milwaukee, Wisconsin, USA
| | - Hayley Lund
- Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Yuhe Xia
- Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA
| | - Yiliang Chen
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
- Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Mary Rau
- Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Ellen Anje Schneider
- Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Mary Beth Graham
- Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Shawn Jobe
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
- Center for Bleeding and Clotting Disorders, Michigan State University, Lansing, Michigan, USA
| | - Demin Wang
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
| | - Weiguo Cui
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
| | - Renren Wen
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
| | - Sidney W. Whiteheart
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA
- Divison of Cardiovascular Medicine, Gill Heart and Vascular Institute, University of Kentucky, Lexington, Lexington, Kentucky, USA
| | - Jeremy P. Wood
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA
- Divison of Cardiovascular Medicine, Gill Heart and Vascular Institute, University of Kentucky, Lexington, Lexington, Kentucky, USA
| | - Roy Silverstein
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
- Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Jeffery S. Berger
- Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA
- Department of Surgery, New York University Langone Health, New York, New York, USA
| | - Lisa Baumann Kreuziger
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
- Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Tessa J. Barrett
- Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA
| | - Ze Zheng
- Versiti Blood Research Institute, Milwaukee, Wisconsin, USA
- Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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Mavropoulou X, Psoma E, Papachristodoulou A, Pyrrou N, Spanou E, Alexandratou M, Sidiropoulou M, Theocharidou A, Rafailidis V, Chrysanthidis T, Prassopoulos P. Gastrointestinal Imaging Findings in the Era of COVID-19: A Pictorial Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1332. [PMID: 37512143 PMCID: PMC10385728 DOI: 10.3390/medicina59071332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/03/2023] [Accepted: 07/04/2023] [Indexed: 07/30/2023]
Abstract
The potentially fatal COVID-19 pandemic has been associated with a largespectrum of clinical presentations. Beyond the classical pulmonary manifestations, gastrointestinal tract-related symptoms suchas nausea, diarrhea, abdominal distention and pain have been observed in patients, as a consequence of the binding of SARS-CoV-19 to Angiotensin-converting Enzyme 2 (ACE2) receptors in the gastrointestinal (GI) tract. The early recognition ofspecific imaging features, including hepatobiliary involvement, pancreatic involvement, development of solid organ infarcts, ischemic bowel changes and vascular occlusion, plays a key role through the course of the disease. Also, suspicious symptoms, especially in critically ill patients with clinical and biochemical markers of hypovolemia, necessitate timely imaging for bleeding complications. The aim of this pictorial review is to illustrate the spectrum of the GIimaging findings in patients with COVID-19. Awareness of diagnostic imaging hallmarks is crucial to optimize the management of these patients.
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Affiliation(s)
- Xanthippi Mavropoulou
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Elisavet Psoma
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Angeliki Papachristodoulou
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Nikoletta Pyrrou
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Ekaterini Spanou
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Maria Alexandratou
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Maria Sidiropoulou
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Anastasia Theocharidou
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Vasileios Rafailidis
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Theofilos Chrysanthidis
- Infectious Diseases Division, First Internal Medicine Department, School of Medicine, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
| | - Panos Prassopoulos
- Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece
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Libruder C, Hershkovitz Y, Ben-Yaish S, Tanne D, Keinan-Boker L, Binyaminy B. An Increased Risk for Ischemic Stroke in the Short-Term Period following COVID-19 Infection: A Nationwide Population-Based Study. Neuroepidemiology 2023; 57:253-259. [PMID: 37399799 PMCID: PMC11251667 DOI: 10.1159/000531163] [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: 03/23/2023] [Accepted: 05/09/2023] [Indexed: 07/05/2023] Open
Abstract
INTRODUCTION The association disclosed between coronavirus disease 2019 (COVID-19) infection and ischemic stroke (IS) raises concern. The exact risk periods, which were not consistent between studies, require further investigation. METHODS We linked two national databases: the COVID-19 database and the Israeli National Stroke Registry. The self-controlled case series method was used to estimate the association between COVID-19 infection and a first IS. The study population included all Israeli residents who had both a first IS event and a first COVID-19 diagnosis during 2020. The date of the PCR test served to define the day of exposure, and the 28 days following it were categorized into three risk periods: days 1-7, 8-14, and 15-28. A relative incidence (RI) with a 95% confidence interval (95% CI) was calculated based on the incidence rate of events in a post-exposure period, compared to the incidence rate in a control period. RESULTS From January 1, 2020, to December 31, 2020, 308,015 Israelis aged 18+ were diagnosed with COVID-19 and 9,535 were diagnosed with a first IS. Linking the two databases, 555 persons had both diagnoses during 2020. The mean age of the study population was 71.5 ± 13.7, 55.1% were males, 77.8% had hypertension, 73.7% had hyperlipidemia, 51.9% had diabetes, and 28.5% had ischemic heart disease. Comparing the risk period and the control period, we found a very similar distribution of the cardiovascular risk factors. The risk for an acute IS was 3.3-fold higher in the first week following COVID-19 diagnosis, compared with a control period (RI = 3.3; 95% CI: 2.3-4.6). The RI among males (RI = 4.5; 95% CI: 2.9-6.8) was 2.2-fold higher compared to females. The increased risk did not last beyond the first week following exposure. CONCLUSION Physicians should be aware of the elevated risk for IS among patients experiencing COVID-19, particularly among men with high burden of cardiovascular risk factors.
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Affiliation(s)
- Carmit Libruder
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
| | - Yael Hershkovitz
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
| | - Shir Ben-Yaish
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
| | - David Tanne
- Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Lital Keinan-Boker
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
- School of Public Health, University of Haifa, Haifa, Israel
| | - Binyamin Binyaminy
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
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Rodrigues A, Dias Domingues T, Nobre Jesus G, Garção A, Rodrigues AR, Jacinto Correia C, Leal Pereira C, Correia D, Beleza Á, Ribeiro JM. COVID-19-associated Coagulopathy Characterization using Rotational Thromboelastometry in a Prospective, Observational Cohort Study: The HemoCoV Study. ACTA MEDICA PORT 2023; 36:496-505. [PMID: 37429589 DOI: 10.20344/amp.19475] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/31/2023] [Indexed: 07/12/2023]
Abstract
INTRODUCTION COVID-19-associated coagulopathy includes systemic and endothelial inflammation with coagulation dysregulation related to immunothrombosis. The aim of this study was to characterize this complication of SARS-CoV-2 infection in patients with moderate to severe COVID-19. METHODS An open-label, prospective observational study conducted in patients with COVID-19 moderate to severe acute respiratory failure admitted to an intensive care unit (ICU). Coagulation testing, including thromboelastometry, biochemical analysis and clinical variables, were collected at prespecified time points during the 30 days of ICU stay. RESULTS The study included 145 patients, 73.8% male, with a median age of 68 years (interquartile range - IQR 55 - 74). The most prevalent comorbidities were arterial hypertension (63.4%), obesity (44.1%) and diabetes (22.1%). Simplified acute physiology score II (SAPS II) was on average 43.5 (11 - 105) and sequential organ failure assessment (SOFA) at admission was 7.5 (0 - 14). During ICU stay, 66.9% of patients underwent invasive mechanical ventilation and 18.4% extracorporeal membrane oxygenation support; thrombotic and hemorrhagic events occurred in 22.1% and 15.1% of the patients respectively; anticoagulation with heparin was present in 99.2% of patients since early ICU stay. Death occurred in 35% of patients. Longitudinal studies revealed changes in almost all coagulation tests during the ICU stay. SOFA score, lymphocyte counts, some biochemical, inflammatory and coagulation parameters, including hypercoagulability and hypofibrinolysis seen in thromboelastometry, differed significantly (p < 0.05), between ICU admission and discharge. Hypercoagulability and hypofibrinolysis persisted throughout ICU hospitalization, showing higher incidence and severity in non-survivors. CONCLUSION COVID-19-associated coagulopathy is characterized by hypercoagulability and hypofibrinolysis from ICU admission, and persisted throughout the clinical course in severe COVID-19. These changes were more pronounced in patients with higher disease burden and in non-survivors.
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Affiliation(s)
- Anabela Rodrigues
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Tiago Dias Domingues
- Centro de Estatística e Aplicações - CEAUL. Faculdade de Ciências. Universidade de Lisboa. Lisbon. Portugal
| | - Gustavo Nobre Jesus
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon; Clínica Universitária de Medicina Intensiva. Faculdade de Medicina. Universidade de Lisboa. Lisbon. Portugal
| | - Ana Garção
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Ana Rita Rodrigues
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Catarina Jacinto Correia
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Carla Leal Pereira
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Dulce Correia
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Álvaro Beleza
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - João Miguel Ribeiro
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
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Yessenbayeva A, Apsalikov B, Massabayeva M, Kazymov M, Shakhanova A, Mussazhanova Z, Kadyrova I, Aukenov N, Shaimardanov N. Biomarkers of immunothrombosis and polymorphisms of IL2, IL6, and IL10 genes as predictors of the severity of COVID-19 in a Kazakh population. PLoS One 2023; 18:e0288139. [PMID: 37390087 PMCID: PMC10313014 DOI: 10.1371/journal.pone.0288139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 06/20/2023] [Indexed: 07/02/2023] Open
Abstract
OBJECTIVES To study the role of biological markers of immunothrombosis and polymorphisms of cytokine genes IL2, IL6, IL10 and their influence on the severity of COVID-19 in a Kazakh population. METHODS A total of 301 patients of Kazakh nationality with a confirmed diagnosis of COVID-19 participated in the retrospective study, including 142 patients with severe and 159 with a mild course. Single nucleotide polymorphisms IL2R rs1801274, IL6 rs2069840, and IL10 rs1800872 were genotyped by real-time PCR. Activated partial thromboplastin time, normalized ratio, prothrombin index, prothrombin time, fibrinogen prothrombin time, fibrinogen, D-dimer, and C-reactive protein analysis were also conducted. RESULTS The average age of patients with severe COVID-19 is higher than of patients with mild COVID-19 (p = 0.03). The findings showed that fibrinogen, D-dimer, and C-reactive protein were significantly greater in the group of patients with severe COVID-19 (p = 0.0001). A very strong correlation between the severity of COVID-19 with the D-dimer and C-reactive protein (p = 0.9) (p = 0.02) was found. CONCLUSION The results of our study confirm that D-dimer, fibrinogen, and CRP are biomarkers of inflammation and hypercoagulation that serve as predictors of immunothrombosis affecting the severity of COVID-19. D-dimer is also associated with IL10 rs1800872 gene polymorphism in the Kazakh population with severe COVID-19.
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Affiliation(s)
| | | | | | | | | | - Zhanna Mussazhanova
- Department of Tumor and Diagnostic Pathology, Nagasaki University, Nagasaki, Japan
- High Medical School, Faculty of Medicine and Health Care, Al Farabi Kazakh National University, Almaty, Republic of Kazakhstan
| | - Irina Kadyrova
- Shared Resource Laboratory of Karaganda Medical University, Karaganda, Republic of Kazakhstan
| | - Nurlan Aukenov
- Department of Health and Human Resources, Ministry of Health of the Republic of Kazakhstan, Astana, Republic of Kazakhstan
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Milić D, Lazarević M, Vuković N, Kamenov A, Perić V, Golubović M, Stošić M, Spasić D, Stojiljković V, Stokanović D. Monitoring the Coagulation Profile of COVID-19 Patients Using Standard and ClotPro ® Hemostasis Tests. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1202. [PMID: 37512014 PMCID: PMC10386453 DOI: 10.3390/medicina59071202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/20/2023] [Accepted: 06/23/2023] [Indexed: 07/30/2023]
Abstract
Background and Objectives: Coagulation disorders during COVID-19 infection are associated with a poorer prognosis and higher disease severity because thrombosis and inflammation are two processes that interfere with each other. A very important issue for clinicians is timely and adequate hemostasis and inflammation monitoring to prevent and treat potentially lethal consequences. The aim of this study was to identify specific hemostatic parameters that are associated with a higher risk of intrahospital mortality. Materials and Methods: This study was approved by the Ethics Committee of the Clinical Center Nis in Serbia. One hundred and forty-two patients presented with COVID-19 ARDS and were admitted to the ICU in the Clinic for Anesthesiology at the Clinical Center Nis from 14 April 2020 to 25 May 2020. Upon admission, blood was collected for biochemical and coagulation testing. The data obtained were analyzed using the Statistical Package for Social Sciences (SPSS v. 25, Chicago, IL, USA). Results: Among all the parameters assessed, older age; increased levels of fibrinogen, INR, D-dimer, and presepsin; and higher results in the platelet aggregation tests (aggregation induced by adenosine diphosphate based on the ADP test (AU/min), aggregation induced by arachidonic acid based on the ASPI test (AU/min), and aggregation induced by thrombin based on the TRAP test (AU/min)) and some assays of the viscoelastic test (clot amplitude after 5 min in the extrinsic coagulation pathway based on the A5 EX-test (mm), clot amplitude after 10 min in the extrinsic coagulation pathway based on the A10 EX-test (mm), clot amplitude after 5 min regarding functional fibrinogen based on the A5 FIB-test (mm), clot amplitude after 10 min regarding functional fibrinogen based on the A10 FIB-test (mm), and maximum clot firmness based on the MCF FIB-test (mm)); and lower values of viscoelastic clotting time in the extrinsic coagulation pathway based on the CT EX-test (s) were significantly correlated with mortality. In the multivariate analysis, D-dimer levels above 860 ng/mL, higher TRAP test value bins, and values above the normal reference range of the A10 FIB test were found to be independent predictors of mortality. Conclusions: Sophisticated hemostasis parameters can contribute to early risk assessment, which has initially been performed only on the basis of patients' clinical status. Hypercoagulability is the main coagulation disorder in COVID-19 infection.
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Affiliation(s)
- Dragan Milić
- Medical School of Nis, University of Nis, 18000 Nis, Serbia
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
| | - Milan Lazarević
- Medical School of Nis, University of Nis, 18000 Nis, Serbia
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
| | - Natalija Vuković
- Clinic for Anesthesiology and Intensive Therapy, University Clinical Center Nis, 18000 Nis, Serbia
| | - Aleksandar Kamenov
- Medical School of Nis, University of Nis, 18000 Nis, Serbia
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
| | - Velimir Perić
- Medical School of Nis, University of Nis, 18000 Nis, Serbia
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
| | - Mlađan Golubović
- Medical School of Nis, University of Nis, 18000 Nis, Serbia
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
| | - Marija Stošić
- Medical School of Nis, University of Nis, 18000 Nis, Serbia
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
| | - Dimitrije Spasić
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
| | - Vladimir Stojiljković
- Medical School of Nis, University of Nis, 18000 Nis, Serbia
- Clinic of Cardiovascular Surgery, University Clinical Center Nis, 18000 Nis, Serbia
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Wang Z, Mao H, Xu G. Fibrinogen, albumin-to-globulin ratio, and fibrinogen to albumin-to-globulin ratio may be potential diagnostic biomarkers for infected tibial nonunion. Int Immunopharmacol 2023; 121:110542. [PMID: 37356122 DOI: 10.1016/j.intimp.2023.110542] [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: 04/05/2023] [Revised: 06/02/2023] [Accepted: 06/17/2023] [Indexed: 06/27/2023]
Abstract
AIM The accurate preoperative diagnosis of infected tibial nonunion remains challenging. Hence, we evaluated the diagnostic potential of novel biomarkers for infected tibial nonunion. METHODS This single-center retrospective study was conducted in 252 patients divided into two groups: infected tibial nonunion (67 patients) and aseptic tibial nonunion (185 patients). The preoperative clinical biomarkers included D-dimer, fibrinogen, albumin, globulin, total protein, and C-reactive protein (CRP) levels; albumin-to-globulin ratio (AGR); erythrocyte sedimentation rate (ESR); and white blood cell (WBC) count. Receiver operating characteristic (ROC) curves, sensitivity, and specificity were utilized to compare the biomarkers' diagnostic potential. RESULTS The area under the curve (AUC) values for fibrinogen and AGR were 0.829 and 0.821, respectively, suggesting similarly good diagnostic potentials for infected tibial nonunion. Fibrinogen and AGR were better diagnostic biomarkers for infected tibial nonunion than the WBC count; ESR; D-dimer, albumin, globulin, CRP, and total protein levels, whose AUC values were 0.623, 0.684, 0.741, 0.797, 0.765, 0.715, and 0.554, respectively. The sensitivity and specificity of fibrinogen with a cut-off value of 3.35 g/L were 71.64% and 84.86%, respectively. The corresponding values for AGR with a cut-off value of 1.33 were 73.13% and 86.49%. Moreover, the fibrinogen-AGR (FAGR), i.e., the combination of fibrinogen and AGR, had the highest diagnostic accuracy for infected tibial nonunion (AUC = 0.906). The optimal FAGR cut-off was 2.69, with fair sensitivity (74.63%) but the highest specificity (94.59%). CONCLUSION Fibrinogen, AGR, and FAGR are promising biomarkers for the diagnosis of infected tibial nonunion.
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Affiliation(s)
- Zhen Wang
- Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Haijun Mao
- Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Guangyue Xu
- Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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