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Serapide F, Talarico M, Rotundo S, Pascale V, Serraino R, Trecarichi EM, Russo A. Lights and Shadows of Long COVID: Are Latent Infections the Real Hidden Enemy? J Clin Med 2024; 13:7124. [PMID: 39685583 DOI: 10.3390/jcm13237124] [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: 10/27/2024] [Revised: 11/20/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Long COVID-19 (LC) is a poorly understood, multifactorial condition that persists for at least three months following SARS-CoV-2 infection. The underlying pathophysiological mechanisms responsible for the wide range of associated symptoms-including fatigue, brain fog, and respiratory issues-remain unclear. However, emerging evidence suggests that the reactivation of latent viral infections, such as Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus, may significantly contribute to the complexity of LC. These latent viruses can be reactivated by SARS-CoV-2, contributing to a chronic inflammatory state that prolongs symptomatology. This review confirms the potential involvement of latent viral infections in LC and examines whether these infections play an independent role or act synergistically with other factors. In addition, recent studies have highlighted viral persistence and immune dysregulation as key elements in LC. Our findings suggest that preventative strategies, including vaccination and antiviral treatments during the acute phase of COVID-19, show potential in reducing LC risk by preventing viral reactivation. However, tailored diagnostic and therapeutic strategies targeting these latent infections are urgently needed. Identifying biomarkers of viral reactivation, particularly for high-risk populations, could be considered another effective strategy to mitigate LC severity. Further research is crucial to better understand the interactions between SARS-CoV-2 and latent infections, and to improve the prevention and treatment of LC.
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Affiliation(s)
- Francesca Serapide
- Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", 88100 Catanzaro, Italy
| | - Marisa Talarico
- Unità Operativa di Cardiologia, Azienda Ospedaliero Universitaria Renato Dulbecco, 88100 Catanzaro, Italy
| | - Salvatore Rotundo
- Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", 88100 Catanzaro, Italy
| | - Vittorio Pascale
- Unità Operativa di Cardiologia, Azienda Ospedaliero Universitaria Renato Dulbecco, 88100 Catanzaro, Italy
| | - Riccardo Serraino
- Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", 88100 Catanzaro, Italy
| | - Enrico Maria Trecarichi
- Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", 88100 Catanzaro, Italy
- Unità Operativa Complessa di Malattie Infettive e Tropicali, Azienda Ospedaliera Universitaria Renato Dulbecco, 88100 Catanzaro, Italy
| | - Alessandro Russo
- Dipartimento di Scienze Mediche e Chirurgiche, Università "Magna Graecia", 88100 Catanzaro, Italy
- Unità Operativa Complessa di Malattie Infettive e Tropicali, Azienda Ospedaliera Universitaria Renato Dulbecco, 88100 Catanzaro, Italy
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Iqbal K, Banga A, Arif TB, Rathore SS, Bhurwal A, Naqvi SKB, Mehdi M, Kumar P, Salklan MM, Iqbal A, Ahmed J, Sharma N, Lal A, Kashyap R, Bansal V, Domecq JP. Anticoagulant use before COVID-19 diagnosis prevent COVID-19 associated acute venous thromboembolism or not: A systematic review and meta-analysis. World J Methodol 2024; 14:92983. [PMID: 39310244 PMCID: PMC11230074 DOI: 10.5662/wjm.v14.i3.92983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 04/24/2024] [Accepted: 05/11/2024] [Indexed: 06/25/2024] Open
Abstract
BACKGROUND Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease. AIM To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients. METHODS A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs). RESULTS Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76]. CONCLUSION Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.
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Affiliation(s)
- Kinza Iqbal
- Department of Internal Medicine, Dow Medical College, Karachi 74200, Pakistan
| | - Akshat Banga
- Department of Internal Medicine, Sawai Man Singh Medical College, Jaipur 302004, India
| | - Taha Bin Arif
- Department of Internal Medicine, Dow Medical College, Karachi 74200, Pakistan
| | - Sawai Singh Rathore
- Department of Internal Medicine, Dr. Sampurnanand Medical College, Jodhpur 342003, Rajasthan, India
| | - Abhishek Bhurwal
- Department of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson School of Medicine, New Brunswick, NJ 08901, United States
| | | | - Muhammad Mehdi
- Department of Internal Medicine, Dow Medical College, Karachi 74200, Pakistan
| | - Pankaj Kumar
- Department of Internal Medicine, Dow Medical College, Karachi 74200, Pakistan
| | - Mitali Madhu Salklan
- Department of Internal Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
| | - Ayman Iqbal
- Department of Internal Medicine, Dow Medical College, Karachi 74200, Pakistan
| | - Jawad Ahmed
- Department of Internal Medicine, Dow Medical College, Karachi 74200, Pakistan
| | - Nikhil Sharma
- Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, United States
| | - Amos Lal
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Rahul Kashyap
- Department of Research, Wellspan Health, York, PA 17403, United States
| | - Vikas Bansal
- Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, United States
| | - Juan Pablo Domecq
- Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, United States
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Boutkourt F, van Haaps T, Brüggemann R, Bhoelan S, ten Cate H, Kruip MJHA, Spaetgens B, van Es N, Roest T, Joling KJ, Meijer K, Hugtenburg J. The effect of current antithrombotic therapy on mortality in nursing home residents with COVID-19: a multicentre retrospective cohort study. Age Ageing 2024; 53:afae094. [PMID: 38748450 PMCID: PMC11095411 DOI: 10.1093/ageing/afae094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 01/31/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND The first wave of COVID led to an alarmingly high mortality rate among nursing home residents (NHRs). In hospitalised patients, the use of anticoagulants may be associated with a favourable prognosis. However, it is unknown whether the use of antithrombotic medication also protected NHRs from COVID-19-related mortality. OBJECTIVES To investigate the effect of current antithrombotic therapy in NHRs with COVID-19 on 30-day all-cause mortality during the first COVID-19 wave. METHODS We performed a retrospective cohort study linking electronic health records and pharmacy data in NHRs with COVID-19. A propensity score was used to match NHRs with current use of therapeutic dose anticoagulants to NHRs not using anticoagulant medication. The primary outcome was 30-day all-cause mortality, which was evaluated using a logistic regression model. In a secondary analysis, multivariable logistic regression was performed in the complete study group to compare NHRs with current use of therapeutic dose anticoagulants and those with current use of antiplatelet therapy to those without such medication. RESULTS We included 3521 NHRs with COVID-19 based on a positive RT-PCR for SARS-CoV-2 or with a well-defined clinical suspicion of COVID-19. In the matched propensity score analysis, NHRs with current use of therapeutic dose anticoagulants had a significantly lower all-cause mortality (OR = 0.73; 95% CI: 0.58-0.92) compared to NHRs who did not use therapeutic anticoagulants. In the secondary analysis, current use of therapeutic dose anticoagulants (OR: 0.62; 95% CI: 0.48-0.82) and current use of antiplatelet therapy (OR 0.80; 95% CI: 0.64-0.99) were both associated with decreased mortality. CONCLUSIONS During the first COVID-19 wave, therapeutic anticoagulation and antiplatelet use were associated with a reduced risk of all-cause mortality in NHRs. Whether these potentially protective effects are maintained in vaccinated patients or patients with other COVID-19 variants, remains unknown.
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Affiliation(s)
- Firdaouss Boutkourt
- Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, location VUmc, De Boelelaan 1117, Amsterdam, The Netherlands
- Farmadam Pharmacy Group, Contactweg 127, Amsterdam, The Netherlands
| | - Thijs van Haaps
- Department of Vascular Medicine, Amsterdam UMC, location AMC Meibergdreef 9, Amsterdam, The Netherlands
- Pulmonary Hypertension & Thrombosis, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
| | - Reneé Brüggemann
- Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Soerajja Bhoelan
- Department of Hematology, UMC Groningen, University of Groningen, The Netherlands
| | - Hugo ten Cate
- Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Marieke J H A Kruip
- Department of Hematology, Erasmus MC Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bart Spaetgens
- Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Nick van Es
- Department of Vascular Medicine, Amsterdam UMC, location AMC Meibergdreef 9, Amsterdam, The Netherlands
- Pulmonary Hypertension & Thrombosis, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
| | - Tineke Roest
- Farmadam Pharmacy Group, Contactweg 127, Amsterdam, The Netherlands
| | - Karlijn J Joling
- Amsterdam Public Health Research Institute, Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands, Department of Medicine for Older People, Amsterdam UMC, Location VUmc, De Boelelaan 1117, Amsterdam, The Netherlands
| | - Karina Meijer
- Department of Hematology, UMC Groningen, University of Groningen, The Netherlands
| | - Jacqueline Hugtenburg
- Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, location VUmc, De Boelelaan 1117, Amsterdam, The Netherlands
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Kananen L, Molnár C, Ansker F, Kozlowska DJ, Hägg S, Jylhävä J, Religa D, Raaschou P. Anticoagulant treatment and COVID-19 mortality among older adults living in nursing homes in Sweden. Health Sci Rep 2023; 6:e1692. [PMID: 38028709 PMCID: PMC10644256 DOI: 10.1002/hsr2.1692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2023] Open
Abstract
Background Anticoagulants (AC) were introduced in March 2020 as standard of care in nursing home (NH) residents affected with COVID-19 in the Stockholm region, Sweden. ACs are proven to reduce the risk of complications and mortality from COVID-19 among patients of other ages and settings, but there is limited scientific evidence underpinning this practice in the NH setting. Methods This matched cohort study included 182 NH residents in the Stockholm Region diagnosed with COVID-19 in March-May 2020. The main exposure was any AC treatment. Exposed (n = 91), 49% prevalent (pre-COVID-19 diagnosis) AC and 51% incident AC were compared with unexposed controls (n = 91). The outcome was 28-days all-cause mortality after COVID-19 infection. The mortality odds ratios (OR) were assessed using logistic regression, adjusted for age, sex, multimorbidity, and mobility, also stratified by incident or prevalent AC-type, age group, and sex. Results Of the 182 individuals diagnosed with COVID-19 (median age 88 years, 68% women), 39% died within 28 days after diagnosis. Use of either incident or prevalent AC was associated with a reduced, adjusted 28-day mortality (OR[95% CI]: 0.31[0.16-0.62]). In stratified analyses, the association was significant in both age groups: 70-89 (OR: 0.37 [0.15-0.89]) and 90-99 years of age (OR: 0.22 [0.07-0.65]. In sex-stratified analysis, the AC-lowering effect was significant in women only (OR: 0.28[0.11-0.67]). In the analyses stratified by AC type, the mortality-lowering effect was observed for both prevalent AC (OR: 0.35[0.12-0.99]) and incident AC (OR: 0.29[0.11-0.76]). Conclusions Both prevalent and incident use of ACs in prophylactic dosing was associated with reduced 28-day mortality among older individuals with COVID-19 in a NH setting. The effect was seen across age-strata and in women. The findings present new insight in best practice for individuals diagnosed with COVID-19 in the NH setting.
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Affiliation(s)
- Laura Kananen
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaStockholmSweden
- Faculty of Social Sciences (Health Sciences), and Gerontology Research CenterTampere UniversityTampereFinland
- Faculty of Medicine and Health Technology, and Gerontology Research CenterTampere UniversityTampereFinland
| | - Christian Molnár
- Department of Neurobiology, Care Sciences and Society (NVS)Karolinska InstitutetStockholmSweden
- Familjeläkarna SÄBOFamiljeläkarna i SaltsjöbadenStockholmSweden
| | - Fredrik Ansker
- Familjeläkarna SÄBOFamiljeläkarna i SaltsjöbadenStockholmSweden
| | | | - Sara Hägg
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaStockholmSweden
| | - Juulia Jylhävä
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaStockholmSweden
- Faculty of Social Sciences (Health Sciences), and Gerontology Research CenterTampere UniversityTampereFinland
| | - Dorota Religa
- Department of Neurobiology, Care Sciences and Society (NVS)Karolinska InstitutetStockholmSweden
| | - Pauline Raaschou
- Department of Medicine Solna, Clinical Epidemiology Section & Clinical Pharmacology UnitKarolinska InstitutetSolnaStockholmSweden
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Taha A, Badu I, Sandhyavenu H, Victor V, Duhan S, Atti L, Qureshi HM, Goni TS, Keisham B, Sandhya Venu V, Thyagaturu H, Gonuguntla K, Ullah W, Deshwal H, Balla S. Contemporary outcomes of long-term anticoagulation in COVID-19 patients: a regression matched sensitivity analysis of the national inpatient sample. Expert Rev Cardiovasc Ther 2023; 21:601-608. [PMID: 37409406 DOI: 10.1080/14779072.2023.2234282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 07/05/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND The role of oral anticoagulation during the COVID-19 pandemic has been debated widely. We studied the clinical outcomes of COVID-19 hospitalizations in patients who were on long-term anticoagulation. RESEARCH DESIGN AND METHODS The Nationwide Inpatient Sample (NIS) database from 2020 was queried to identify COVID-19 patients with and without long-term anticoagulation. Multivariate regression analysis was used to calculate the adjusted odds ratio (aOR) of in-hospital outcomes. RESULTS Of 1,060,925 primary COVID-19 hospitalizations, 102,560 (9.6%) were on long-term anticoagulation. On adjusted analysis, COVID-19 patients on anticoagulation had significantly lower odds of in-hospital mortality (aOR 0.61, 95% CI 0.58-0.64, P < 0.001), acute myocardial infarction (aOR 0.72, 95% CI 0.63-0.83, P < 0.001), stroke (aOR 0.79, 95% CI 0.66-0.95, P < 0.013), ICU admissions, (aOR 0.53, 95% CI 0.49-0.57, P < 0.001) and higher odds of acute pulmonary embolism (aOR 1.47, 95% CI 1.34-1.61, P < 0.001), acute deep vein thrombosis (aOR 1.17, 95% CI 1.05-1.31, P = 0.005) compared to COVID-19 patients who were not on anticoagulation. CONCLUSIONS Compared to COVID-19 patients not on long-term anticoagulation, we observed lower in-hospital mortality, stroke and acute myocardial infarction in COVID-19 patients on long-term anticoagulation. Prospective studies are needed for optimal anticoagulation strategies in hospitalized patients.
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Affiliation(s)
- Amro Taha
- Department of Internal Medicine, Weiss Memorial Hospital, Chicago, IL, USA
| | - Irisha Badu
- Department of Internal Medicine, Onslow Memorial Hospital, Jacksonville, NC, USA
| | | | - Varun Victor
- Department of Internal Medicine, Canton Medical Education Foundation, Canton, Ohio, USA
| | - Sanchit Duhan
- Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Lalitsiri Atti
- Department of Internal Medicine, Sparrow Hospital- Michigan State University, Lansing, MI, USA
| | | | | | - Bijeta Keisham
- Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, USA
| | - Vasantha Sandhya Venu
- Department of Computer Science and Engineering, Vardhaman College of Engineering, Hyderabad, India
| | | | | | - Waqas Ullah
- Department of Cardiology, Thomas Jefferson University Hospital, Philadelphia, USA
| | - Himanshu Deshwal
- Department of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, West Virginia University School of Medicine, Morgantown, WV, USA
| | - Sudarshan Balla
- Department of Cardiology, West Virginia University, Morgantown, WV, USA
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Peng Y, Chen SY, Wang ZN, Zhou ZQ, Sun J, Zhang GA, Li J, Wang L, Zhao JC, Tang XX, Wang DY, Zhong NS. Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium. Signal Transduct Target Ther 2023; 8:242. [PMID: 37301869 PMCID: PMC10256976 DOI: 10.1038/s41392-023-01511-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/08/2023] [Accepted: 05/17/2023] [Indexed: 06/12/2023] Open
Abstract
Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron variants (including BA.1, BQ.1 and XBB.1). Time-of-addition and drug withdrawal assays revealed that early treatment (continuously incubated after viral absorption) of DCM could markedly inhibit Omicron replication in AECs, but DCM did not affect the absorption, exocytosis and spread of viruses or directly eliminate viruses. Mechanistically, we performed single-cell sequencing analysis (a database of 77,969 cells from different airway locations from 10 healthy volunteers) and immunofluorescence staining, and showed that the expression of NAD(P)H quinone oxidoreductase 1 (NQO1), one of the known DCM targets, was predominantly localised in ciliated AECs. We further found that the NQO1 expression level was positively correlated with both the disease severity of COVID-19 patients and virus copy levels in cultured AECs. In addition, DCM treatment downregulated NQO1 expression and disrupted signalling pathways associated with SARS-CoV-2 disease outcomes (e.g., Endocytosis and COVID-19 signalling pathways) in cultured AECs. Collectively, we demonstrated that DCM is an effective post-exposure prophylactic for SARS-CoV-2 infection in the human AECs, and these findings could help physicians formulate novel treatment strategies for COVID-19.
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Affiliation(s)
- Yang Peng
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
- Department of Otolaryngology, Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Shi-Ying Chen
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhao-Ni Wang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zi-Qing Zhou
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jing Sun
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Gui-An Zhang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jia Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Laboratory, Guangzhou, China
| | - Lei Wang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
- Guangzhou Laboratory, Guangzhou, China
| | - Jin-Cun Zhao
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiao Xiao Tang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
- Guangzhou Laboratory, Guangzhou, China.
| | - De-Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
| | - Nan-Shan Zhong
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
- Guangzhou Laboratory, Guangzhou, China.
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7
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Yousefi P, Soltani S, Siri G, Rezayat SA, Gholami A, Zafarani A, Razizadeh MH, Alborzi E, Mokhtary‐Irani G, Abedi B, Karampoor S, Tabibzadeh A, Farahani A. Coagulopathy and thromboembolic events a pathogenic mechanism of COVID-19 associated with mortality: An updated review. J Clin Lab Anal 2023; 37:e24941. [PMID: 37431777 PMCID: PMC10431412 DOI: 10.1002/jcla.24941] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 05/24/2023] [Accepted: 06/26/2023] [Indexed: 07/12/2023] Open
Abstract
During 2019, the SARS-CoV-2 emerged from China, and during months, COVID-19 spread in many countries around the world. The expanding data about pathogenesis of this virus could elucidate the exact mechanism by which COVID-19 caused death in humans. One of the pathogenic mechanisms of this disease is coagulation. Coagulation disorders that affect both venous and arterial systems occur in patients with COVID-19. The possible mechanism involved in the coagulation could be excessive inflammation induced by SARS-CoV-2. However, it is not yet clear well how SARS-CoV-2 promotes coagulopathy. However, some factors, such as pulmonary endothelial cell damage and some anticoagulant system disorders, are assumed to have an important role. In this study, we assessed conducted studies about COVID-19-induced coagulopathy to obtain clearer vision of the wide range of manifestations and possible pathogenesis mechanisms.
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Affiliation(s)
- Parastoo Yousefi
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
| | - Saber Soltani
- Department of Virology, School of Public HealthTehran University of Medical SciencesTehranIran
| | - Goli Siri
- Department of Internal Medicine, Amir Alam HospitalTehran University of Medical SciencesTehranIran
| | - Sara Akhavan Rezayat
- Department of Health Care Management and Economics, School of Public HealthTehran University of Medical SciencesTehranIran
| | - Ali Gholami
- School of MedicineArak University of Medical SciencesArakIran
| | - Alireza Zafarani
- Department of Hematology and Blood Banking, Faculty of Allied MedicineIran University of Medical SciencesTehranIran
| | | | - Ehsan Alborzi
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
| | - Golnaz Mokhtary‐Irani
- Department of Virology, Faculty of MedicineAhvaz Jondishapur University of Medical SciencesAhvazIran
| | - Behnam Abedi
- Department of Medical Laboratory SciencesKhomein University of Medical SciencesKhomeinIran
| | - Sajad Karampoor
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
- Gastrointestinal and Liver Diseases Research CenterIran University of Medical SciencesTehranIran
| | - Alireza Tabibzadeh
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
| | - Abbas Farahani
- Department of Medical Laboratory SciencesKhomein University of Medical SciencesKhomeinIran
- Molecular and Medicine Research CenterKhomein University of Medical SciencesKhomeinIran
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8
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Hayashi M, Morikawa S, Goto Y, Yoshida T, Kimura Y, Kawabe T, Tsuzuki S, Imaizumi K. Clinical characteristics and courses of 200 patients hospitalized for COVID-19 during the second and third waves at Fujita Health University Okazaki Medical Center in Japan. FUJITA MEDICAL JOURNAL 2023; 9:17-21. [PMID: 36789122 PMCID: PMC9923452 DOI: 10.20407/fmj.2021-018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 11/21/2021] [Indexed: 02/16/2023]
Abstract
Objectives There are few reports about patients hospitalized for COVID-19 in Japan. We investigated 200 patients hospitalized for COVID-19 over a 6-month period with the aim of elucidating their clinical characteristics and clinical courses. Methods The study cohort comprised 200 patients hospitalized for COVID-19 during a 6-month period. We examined baseline characteristics, source of transmission, preadmission course, initial symptoms, concomitant symptoms, comorbidities, treatments, and prognosis. Results The number of inpatients from outside our region increased from 9 in the second wave to 53 in the third wave. The initial manifestations were cold-like and gastroenteritis-like symptoms, gustatory and olfactory dysfunction being frequently occurring concomitant symptoms. On admission 32 patients had mild disease, 108 moderate I, 54 moderate II, and 6 severe. We divided the 200 patients into second and third wave groups and compared their baseline characteristics. The third wave group was older and had more severe disease. The main treatments implemented were dexamethasone and remdesivir. Three patients (1.5%) required ventilation and 12 (6.0%) died in hospital. Conclusions We investigated 200 patients hospitalized for COVID-19 over a period of 6 months. The patients in the second wave were relatively young and most had mild disease. In contrast, the patients in the third wave were older and had more severe disease and higher in-hospital mortality.
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Affiliation(s)
- Masamichi Hayashi
- Department of Internal Medicine, Division of Respiratory Medicine, Fujita Health University, School of Medicine, Okazaki, Aichi, Japan,Department of Respiratory Medicine I, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Sayako Morikawa
- Department of Internal Medicine, Division of Respiratory Medicine, Fujita Health University, School of Medicine, Okazaki, Aichi, Japan,Department of Respiratory Medicine I, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Yusuke Goto
- Department of Internal Medicine, Division of Respiratory Medicine, Fujita Health University, School of Medicine, Okazaki, Aichi, Japan,Department of Respiratory Medicine I, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Takazumi Yoshida
- Department of Internal Medicine, Division of Respiratory Medicine, Fujita Health University, School of Medicine, Okazaki, Aichi, Japan,Department of Respiratory Medicine II, Fujita Health University, School of Medicine, Nagoya, Aichi, Japan
| | - Yutaro Kimura
- Department of Internal Medicine, Division of Respiratory Medicine, Fujita Health University, School of Medicine, Okazaki, Aichi, Japan,Department of Respiratory Medicine I, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
| | - Taku Kawabe
- Department of General Practice, Fujita Health University, School of Medicine, Okazaki, Aichi, Japan
| | - Seiichiro Tsuzuki
- Department of General Internal Medicine and Emergency, Fujita Health University, School of Medicine, Okazaki, Aichi, Japan
| | - Kazuyoshi Imaizumi
- Department of Respiratory Medicine I, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan
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9
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Vio R, Giordani AS, Stefil M, Alturki A, Russo V, China P, Gasperetti A, Schiavone M, Čulić V, Biondi-Zoccai G, Themistoclakis S, Lip GY, Proietti R. Therapeutic vs. prophylactic anticoagulation in COVID-19 patients: a systematic review and meta-analysis of real-world studies. Minerva Cardiol Angiol 2022; 70:652-662. [PMID: 36305780 DOI: 10.23736/s2724-5683.22.06230-5] [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: 11/06/2022]
Abstract
INTRODUCTION Coagulopathy, in the form of either venous or arterial thromboembolism, is one of the most severe sequelae of coronavirus disease (COVID-19) and has been associated with poorer outcomes. However, the role of therapeutic anticoagulation (tAC) or prophylactic anticoagulation (pAC) in COVID-19 patients has not been definitely established. Therefore, the aim of this systematic review and meta-analysis was to gather all the available real-world data in the field and to provide a reliable effect size of the effect on mortality of tAC compared to pAC in COVID-19 patients. EVIDENCE ACQUISITION Real-world studies (RWS) were identified by searching electronic databases from inception to 31st October, 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively. EVIDENCE SYNTHESIS 10 RWS and 5541 patients were included in the analysis. Overall, tAC was associated with lower mortality (HR=0.62, 95% CI: 0.54-0.71). There was asymmetry at the funnel plot suggesting publication bias, that was not confirmed at the Egger test (P=0.07). For the secondary endpoint, there was a non-statistically significant tendency for more bleedings in patients treated with tAC compared to pAC (RR=1.75, 95% CI: 0.81-3.81). CONCLUSIONS Our meta-analysis, based on RWS and adjusted estimates of risk, suggests a survival benefit of tAC over pAC in COVID-19 patients in the real world.
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Affiliation(s)
- Riccardo Vio
- Department of Cardiothoracic, Vascular Medicine and Intensive Care, Dell'Angelo Hospital, Mestre, Venice, Italy -
| | - Andrea S Giordani
- Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Maria Stefil
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK
| | - Ahmed Alturki
- Division of Cardiology, McGill University Health Center, Montreal, Canada
| | - Vincenzo Russo
- Department of Medical Translational Sciences, Monaldi Hospital, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Paolo China
- Department of Cardiothoracic, Vascular Medicine and Intensive Care, Dell'Angelo Hospital, Mestre, Venice, Italy
| | - Alessio Gasperetti
- Unit of Cardiology, ASST Fatebenefratelli Sacco-Luigi Sacco University Hospital, Milan, Italy
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Marco Schiavone
- Unit of Cardiology, ASST Fatebenefratelli Sacco-Luigi Sacco University Hospital, Milan, Italy
| | - Viktor Čulić
- School of Medicine, University of Split, Split, Croatia
- Department of Cardiology and Angiology, University Hospital Centre Split, Split, Croatia
| | - Giuseppe Biondi-Zoccai
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy
- Mediterranea Cardiocentro, Naples, Italy
| | - Sakis Themistoclakis
- Department of Cardiothoracic, Vascular Medicine and Intensive Care, Dell'Angelo Hospital, Mestre, Venice, Italy
| | - Gregory Y Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK
| | - Riccardo Proietti
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK
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10
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Giner-Soriano M, Gomez-Lumbreras A, Vedia C, Ouchi D, Morros R. Risk of thrombotic events and other complications in anticoagulant users infected with SARS-CoV-2: an observational cohort study in primary health care in SIDIAP (Catalonia, Spain). BMC PRIMARY CARE 2022; 23:147. [PMID: 35676639 PMCID: PMC9174624 DOI: 10.1186/s12875-022-01752-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 05/26/2022] [Indexed: 09/02/2023]
Abstract
Abstract
Background
The risk of thromboembolic events and COVID-19 complications in anticoagulated patients once hospitalized has been widely analyzed. We aim to assess these outcomes in primary health care (PHC) patients chronically treated with oral anticoagulants (OAC) in comparison with non-treated.
Methods
Cohort study including adults with COVID-19 diagnosis in the PHC records in Catalonia, Spain; from March to June 2020. Patients were matched between exposed and non-exposed to OAC based on age and gender in a 1:2 design. Data source is the Information System for Research in Primary Care (SIDIAP).
Results
We included 311,542 individuals with COVID-19. After propensity score matching, we obtained a cohort of 20,360 people, 10,180 exposed and 10,180 non-exposed to OAC. Their mean age was 79.9 and 52.1% were women. Patients exposed to OAC had a higher frequency of comorbidities than non-exposed. Anticoagulated patients had a higher risk of hospital admission (IRR 1.16, 95% CI 1.03–1.29), and of stroke and pulmonary embolism than non-anticoagulated (IRR 1,80, 95% CI 1.06–3.06). The risk of pneumonia was not different between groups (IRR 1.04, 95% CI 0.84–1.30). We found a lower risk of death in patients exposed to OAC (IRR 0.60, 95% CI 0.55–0.65).
Conclusions
OAC users in our study had more comorbidities and were older than non-users, well known risks for hospitalization being confirmed with our results. We also found in our study that OAC exposure was not associated to an increased risk in the mortality rate, and it was associated with higher risks of hospital admission and thromboembolic events, although we cannot assess the effect of the interventions applied during hospital admission on the outcomes studied, as our database is a PHC database.
Trial registration
EUPAS register: EUPAS37205.
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11
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Martin-Martinez A, Ortega O, Viñas P, Arreola V, Nascimento W, Costa A, Riera SA, Alarcón C, Clavé P. COVID-19 is associated with oropharyngeal dysphagia and malnutrition in hospitalized patients during the spring 2020 wave of the pandemic. Clin Nutr 2022; 41:2996-3006. [PMID: 34187698 PMCID: PMC8205257 DOI: 10.1016/j.clnu.2021.06.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 06/08/2021] [Accepted: 06/08/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND & AIMS Prevalence and complications of oropharyngeal dysphagia (OD) and malnutrition (MN) in COVID-19 patients is unknown. Our aim was to assess the prevalence, risk factors and clinical outcomes of OD and MN in a general hospital during the first wave of the COVID-19 pandemic. METHODS This was a prospective, observational study involving clinical assessment of OD (Volume-Viscosity Swallowing Test), and nutritional screening (NRS2002) and assessment (GLIM criteria) in COVID-19 patients hospitalized in general wards at the Consorci Sanitari del Maresme, Catalonia, Spain. The clinical characteristics and outcomes of patients were assessed at pre-admission, admission and discharge, and after 3 and 6-months follow-up. RESULTS We included 205 consecutive patients (69.28 ± 17.52 years, Charlson 3.74 ± 2.62, mean hospital stay 16.8 ± 13.0 days). At admission, Barthel Index was 81.3 ± 30.3; BMI 28.5 ± 5.4 kg/m2; OD prevalence 51.7% (44.1% impaired safety of swallow); and 45.5% developed MN with a mean weight loss of 10.1 ± 5.0 kg during hospitalization. OD was an independent risk factor for MN during hospitalization (OR 3.96 [1.45-10.75]), and hospitalization was prolonged in patients with MN compared with those without (21.9 ± 14.8 vs 11.9 ± 8.9 days, respectively; p < 0.0001). OD was independently associated with comorbidities, neurological symptoms, and low functionality. At 6-month follow-up, prevalence of OD was still 23.3% and that of MN only 7.1%. Patients with OD at discharge showed reduced 6-month survival than those without OD at discharge (71.6% vs 92.9%, p < 0.001); in contrast, those with MN at discharge did not show 6-month survival differences compared to those without (85.4% vs 83.8%, p = 0.8). CONCLUSIONS Prevalence and burden of OD and MN in patients hospitalized in COVID-19 wards is very high. Our results suggest that optimizing the management of MN might shorten the hospitalization period but optimizing the management of OD will likely impact the nutritional status of COVID-19 patients and improve their clinical outcomes and survival after hospital discharge. CLINICALTRIALS gov Identifier: NCT04346212.
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Affiliation(s)
- Alberto Martin-Martinez
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Omar Ortega
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Paula Viñas
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - Viridiana Arreola
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - Weslania Nascimento
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - Alícia Costa
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - Stephanie A Riera
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - Claudia Alarcón
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain
| | - Pere Clavé
- Gastrointestinal Physiology Laboratory, Hospital de Mataró, Universitat Autònoma de Barcelona, Mataró, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
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12
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Holdiman A, Rogus-Pulia N, Pulia MS, Stalter L, Thibeault SL. Risk Factors for Dysphagia in Patients Hospitalized with COVID-19. Dysphagia 2022; 38:933-942. [PMID: 36109398 PMCID: PMC9483550 DOI: 10.1007/s00455-022-10518-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 08/26/2022] [Indexed: 11/29/2022]
Abstract
Patients hospitalized with COVID-19 may be at risk for dysphagia and vulnerable to associated consequences. We investigated predictors for dysphagia and its severity in a cohort of patients hospitalized with COVID-19 at a single hospital center. A large level I trauma center database was queried for all patients hospitalized with COVID-19. Demographics, medical information associated with COVID-19, specific to dysphagia, and interventions were collected. 947 patients with confirmed COVID-19 met the criteria. 118 (12%) were seen for a swallow evaluation. Individuals referred for evaluation were significantly older, had a lower BMI, more severe COVID-19, and higher rates of intubation, pneumonia, mechanical ventilation, tracheostomy placements, prone positioning, and ARDS. Pneumonia (OR 3.57, p = 0.004), ARDS (OR 3.57, p = 0.029), prone positioning (OR 3.99, p = 0.036), ventilation (OR 4.01, p = 0.006), and intubation (OR 4.75, p = 0.007) were significant risk factors for dysphagia. Older patients were more likely to have more severe dysphagia such that for every 1-year increase in age, the odds of severe dysphagia were 1.04 times greater (OR 1.04, p = 0.028). Patients hospitalized with COVID-19 are at risk for dysphagia. We show predictive variables that should be considered when referring COVID-19 patients for dysphagia services to reduce time to intervention/evaluation.
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Affiliation(s)
- Anna Holdiman
- Division of Otolaryngology, Department of Surgery, UW-Madison, 5103 WIMR, 1111 Highland Ave., Madison, WI, 53705, USA
| | - Nicole Rogus-Pulia
- Division of Geriatrics and Gerontology, Department of Medicine, UW-Madison, Madison, WI, USA
| | - Michael S Pulia
- Department of Emergency Medicine, UW-Madison, Madison, WI, USA
| | - Lily Stalter
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, UW-Madison, Madison, WI, USA
| | - Susan L Thibeault
- Division of Otolaryngology, Department of Surgery, UW-Madison, 5103 WIMR, 1111 Highland Ave., Madison, WI, 53705, USA.
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13
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Russo V, Caputo A, Imbalzano E, Di Micco P, Frontera A, Uccello A, Orlando L, Galimberti P, Golino P, D'Andrea A. The pharmacology of anticoagulant drug treatment options in COVID-19 patients: reviewing real-world evidence in clinical practice. Expert Rev Clin Pharmacol 2022; 15:1095-1105. [PMID: 36017645 DOI: 10.1080/17512433.2022.2117154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION The optimal anticoagulation strategy for venous thromboembolism (VTE) prevention among COVID-19 patients, hospitalized or in the community setting, is still challenging and largely based on real-world evidence. AREAS COVERED We analyzed real-world data regarding the safety and effectiveness of anticoagulant treatment, both parenteral and oral, for VTE prevention or atrial fibrillation (AF)/VTE treatment among COVID-19 patients. EXPERT OPINION The efficacy of low-molecular-weight heparin (LMWH) doses for VTE prevention correlates with COVID-19 disease status. LMWH prophylactic dose may be useful in COVID-19 patients at the early stage of the disease. LMWH intermediate or therapeutic dose is recommended in COVID-19 patients with an advanced stage of the disease. COVID-19 patients on VKAs therapy for atrial fibrillation (AF) and VTE should switch to NOACs in the community setting or LMWH in the hospital setting. No definitive data on de-novo starting of NOACs or VKAs therapy for VTE prevention in COVID-19 outpatients are available. In patients at high risk discharged after hospitalization due to COVID-19, thromboprophylaxis with NOACs may be considered.
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Affiliation(s)
- Vincenzo Russo
- Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli", Monaldi Hospital, Naples, Italy
| | - Adriano Caputo
- Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli", Monaldi Hospital, Naples, Italy
| | - Egidio Imbalzano
- Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy
| | - Pierpaolo Di Micco
- Department of Internal Medicine and Cardiology, Fatebenefratelli Hospital, Naples, Italy
| | - Antonio Frontera
- Arrhythmology Department, IRCCS Humanitas Research Hospital, Rozzano (MI), Italy
| | - Ambra Uccello
- Department of Internal Medicine and Cardiology, Fatebenefratelli Hospital, Naples, Italy
| | - Luana Orlando
- Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy
| | - Paola Galimberti
- Arrhythmology Department, IRCCS Humanitas Research Hospital, Rozzano (MI), Italy
| | - Paolo Golino
- Department of Medical Translational Sciences, University of Campania "Luigi Vanvitelli", Monaldi Hospital, Naples, Italy
| | - Antonello D'Andrea
- Department of Cardiology, Umberto I Hospital, 84014 Nocera Inferiore, Italy
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14
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Louis DW, Kennedy KF, Saad M, Salber G, Imran H, Wark T, Soares C, Ghosalkar D, Cherala R, Poppas A, Abbott JD, Aronow HD. Preadmission Oral Anticoagulation for Atrial Fibrillation/Flutter and Death or Thrombotic Events During COVID-19 Admission. Am J Cardiol 2022; 181:38-44. [PMID: 35970632 PMCID: PMC9374502 DOI: 10.1016/j.amjcard.2022.07.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 06/30/2022] [Accepted: 07/05/2022] [Indexed: 11/16/2022]
Abstract
Atrial fibrillation/flutter (AF) and COVID-19 are associated with an elevated risk of arterial and venous thrombosis. Whether preadmission oral anticoagulation (OAC) for AF reduces the incidence of in-hospital death or thrombotic events among patients with COVID-19 is unknown. We identified 630 patients with pre-existing AF and a hospitalization diagnosis of COVID-19 and stratified them according to preadmission OAC use. Multivariable logistic regression was employed to relate preadmission OAC to composite in-hospital mortality or thrombotic events. Unadjusted composite in-hospital mortality or thrombotic complications occurred less often in those on than not on preadmission OAC (27.1% vs 46.8%, p <0.001). After adjustment, the incidence of composite in-hospital all-cause mortality or thrombotic complications remained lower with preadmission OAC (odds ratio 0.37, confidence interval 0.25 to 0.53, p <0.0001). Secondary outcomes including all-cause mortality (16.3% vs 24.9%, p = 0.007), intensive care unit admission (14.7% vs 29.0%, p <0.001), intubation (6.4% vs 18.6%, p <0.001), and noninvasive ventilation (18.6% vs 27.5%, p = 0.007) occurred less frequently, and length of stay was shorter (6 vs 7 days, p <0.001) in patients on than those not on preadmission OAC. A higher CHA2DS2-VASc score was associated with an increased risk of thrombotic events. In conclusion, among patients with baseline AF who were hospitalized with COVID-19, those on preadmission OAC had lower rates of death, arterial and venous thrombotic events, and less severe COVID-19.
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Affiliation(s)
- David W Louis
- Lifespan Cardiovascular Institute, Providence, Rhode Island; Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - Kevin F Kennedy
- Saint Luke's Mid America Heart Institute, Kansas City, Missouri
| | - Marwan Saad
- Lifespan Cardiovascular Institute, Providence, Rhode Island; Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - Greg Salber
- Lifespan Cardiovascular Institute, Providence, Rhode Island; Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - Hafiz Imran
- Lifespan Cardiovascular Institute, Providence, Rhode Island; Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - Tyler Wark
- Department of Cardiology, University of Vermont, Burlington, Vermont
| | - Cullen Soares
- Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Dhairyasheel Ghosalkar
- Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - Rasan Cherala
- Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - Athena Poppas
- Lifespan Cardiovascular Institute, Providence, Rhode Island; Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - J Dawn Abbott
- Lifespan Cardiovascular Institute, Providence, Rhode Island; Division of Cardiology, Department of Medicine,, Alpert Medical School of Brown University, Providence, Rhode Island
| | - Herbert D Aronow
- Division of Cardiology, Henry Ford Heart & Vascular Institute, Detroit, Michigan.
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15
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Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ. Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study. Br J Gen Pract 2022; 72:e456-e463. [PMID: 35440465 PMCID: PMC9037187 DOI: 10.3399/bjgp.2021.0689] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/06/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited. AIM To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2. DESIGN AND SETTING On behalf of NHS England, a population-based cohort study was conducted. METHOD The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice. RESULTS Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use. CONCLUSION Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.
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Affiliation(s)
- Angel Ys Wong
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Laurie Tomlinson
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Jeremy P Brown
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - William Elson
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Alex J Walker
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - Anna Schultze
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Caroline E Morton
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - David Evans
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - Peter Inglesby
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - Brian MacKenna
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - Krishnan Bhaskaran
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Christopher T Rentsch
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Emma Powell
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Elizabeth Williamson
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Richard Croker
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - Seb Bacon
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - William Hulme
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | | | - Helen J Curtis
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - Amir Mehrkar
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | | | - Helen I McDonald
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London and NIHR Health Protection Research Unit (HPRU) in Immunisation, London School of Hygiene and Tropical Medicine, London
| | - Rohini Mathur
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Kevin Wing
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | | | - Rosalind M Eggo
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Stephen Jw Evans
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
| | - Liam Smeeth
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London and NIHR Health Protection Research Unit (HPRU) in Immunisation, London School of Hygiene and Tropical Medicine, London
| | - Ben Goldacre
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford
| | - Ian J Douglas
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London
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16
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Fung KW, Baik SH, Baye F, Zheng Z, Huser V, McDonald CJ. Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients. PLoS One 2022; 17:e0266922. [PMID: 35436293 PMCID: PMC9015134 DOI: 10.1371/journal.pone.0266922] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 03/29/2022] [Indexed: 02/08/2023] Open
Abstract
Background Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. Methods Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. Results Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI, ARB, statins, warfarin, direct factor Xa inhibitors and P2Y12 inhibitors were associated with reduced risks, compared to never users. Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters. Conclusion Maintenance use of ACEI, ARB, warfarin, statins, direct factor Xa inhibitors and P2Y12 inhibitors was associated with reduction in risk of acquiring COVID-19 and dying from it.
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Affiliation(s)
- Kin Wah Fung
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
- * E-mail:
| | - Seo H. Baik
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Fitsum Baye
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Zhaonian Zheng
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Vojtech Huser
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Clement J. McDonald
- Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America
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17
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Adomi M, Kuno T, Komiyama J, Taniguchi Y, Abe T, Miyawaki A, Imai S, Morita K, Saito M, Ohbe H, Kamio T, Tamiya N, Iwagami M. Association between pre-admission anticoagulation and in-hospital death, venous thromboembolism, and major bleeding among hospitalized COVID-19 patients in Japan. Pharmacoepidemiol Drug Saf 2022; 31:680-688. [PMID: 35324035 PMCID: PMC9088474 DOI: 10.1002/pds.5433] [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: 08/11/2021] [Revised: 01/11/2022] [Accepted: 03/18/2022] [Indexed: 11/18/2022]
Abstract
Purpose The coagulation activation leads to thrombotic complications such as venous thromboembolism (VTE) in patients with coronavirus disease‐2019 (COVID‐19). Prophylactic anticoagulation therapy has been recommended for hospitalized COVID‐19 patients in clinical guidelines. This retrospective cohort study aimed to examine the association between pre‐admission anticoagulation treatment and three outcomes: in‐hospital death, VTE, and major bleeding among hospitalized COVID‐19 patients in Japan. Methods Using a large‐scale claims database built by the Medical Data Vision Co. in Japan, we identified patients hospitalized for COVID‐19 who had outpatient prescription data at least once within 3 months before being hospitalized. Exposure was set as pre‐admission anticoagulation treatment (direct oral anticoagulant or vitamin K antagonist), and outcomes were in‐hospital death, VTE, and major bleeding. We conducted multivariable logistic regression analyses, adjusting for a single summarized score (a propensity score of receiving pre‐admission anticoagulation) for VTE and major bleeding, due to the small number of outcomes. Results Among the 2612 analytic patients, 179 (6.9%) had pre‐admission anticoagulation. Crude incidence proportions were 13.4% versus 8.5% for in‐hospital death, 0.56% versus 0.58% for VTE, and 2.2% versus 1.1% for major bleeding among patients with and without pre‐admission anticoagulation, respectively. Adjusted odds ratios (95% confidence intervals) were 1.25 (0.75–2.08) for in‐hospital death, 0.21 (0.02–1.97) for VTE, and 2.63 (0.80–8.65) for major bleeding. Several sensitivity analyses did not change the results. Conclusions We found no evidence that pre‐admission anticoagulation treatment was associated with in‐hospital death. However, a larger sample size may be needed to conclude its effect on VTE and major bleeding.
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Affiliation(s)
- Motohiko Adomi
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.,Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Toshiki Kuno
- Department of Cardiology, Montefiore Medical Center/Albert Einstein Medical College, NY, USA
| | - Jun Komiyama
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.,Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yuta Taniguchi
- Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.,Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Toshikazu Abe
- Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan.,Department of Emergency and Critical Care Medicine, Tsukuba Memorial Hospital, Tokyo, Japan
| | - Atsushi Miyawaki
- Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan.,Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shinobu Imai
- Department of Drug Safety and Risk Management, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Kojiro Morita
- Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Makoto Saito
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hiroyuki Ohbe
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Japan
| | - Tadashi Kamio
- Division of Critical Care, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa, Japan
| | - Nanako Tamiya
- Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.,Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan
| | - Masao Iwagami
- Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.,Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan
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18
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Abdel-Qadir H, Austin PC, Pang A, Fang J, Udell JA, Geerts WH, McNaughton CD, Jackevicius CA, Kwong JC, Yeh CH, Cox JL, Lee DS, Ko DT, Atzema CL. The association between anticoagulation and adverse outcomes after a positive SARS-CoV-2 test among older outpatients: A population-based cohort study. Thromb Res 2022; 211:114-122. [PMID: 35149396 PMCID: PMC8667561 DOI: 10.1016/j.thromres.2021.12.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 11/24/2021] [Accepted: 12/09/2021] [Indexed: 01/08/2023]
Abstract
Introduction Anticoagulation may improve outcomes in patients with COVID-19 when started early in the course of illness. Materials and methods This was a population-based cohort study using linked administrative datasets of outpatients aged ≥65 years old testing positive for SARS-CoV-2 between January 1 and December 31, 2020 in Ontario, Canada. The key exposure was anticoagulation with warfarin or direct oral anticoagulants before COVID-19 diagnosis. We calculated propensity scores and used matching weights (MWs) to reduce baseline differences between anticoagulated and non-anticoagulated patients. The primary outcome was a composite of death or hospitalization within 60 days of a positive SARS-CoV-2 test. We used the Kaplan-Meier method and cumulative incidence functions to estimate risk of the primary and component outcomes at 60 days. Results We studied 23,159 outpatients (mean age 78.5 years; 13,474 [58.2%] female), among whom 3200 (13.8%) deaths and 3183 (13.7%) hospitalizations occurred within 60 days of the SARS-CoV-2 test. After application of MWs, the 60-day risk of death or hospitalization was 29.2% (95% CI 27.4%–31.2%) for anticoagulated individuals and 32.1% (95% CI 30.7%–33.5%) without anticoagulation (absolute risk difference [ARD], −2.9%; p = 0.005). Anticoagulation was also associated with a lower risk of death: 18.6% (95% CI 17.0%–20.2%) with anticoagulation and 20.9% (95% CI 19.7%–22.2%) in non-anticoagulated patients (ARD -2.3%; p = 0.005). Conclusions Among outpatients aged ≥65 years, oral anticoagulation at the time of a positive SARS-CoV-2 test was associated with a lower risk of a composite of death or hospitalization within 60 days.
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Affiliation(s)
- Husam Abdel-Qadir
- Women's College Hospital, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
| | - Peter C Austin
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Andrea Pang
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada
| | - Jiming Fang
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada
| | - Jacob A Udell
- Women's College Hospital, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - William H Geerts
- Department of Medicine, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Candace D McNaughton
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Cynthia A Jackevicius
- University Health Network, Toronto, ON, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Western University of Health Sciences, Pomona, CA, United States of America
| | - Jeffrey C Kwong
- University Health Network, Toronto, ON, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Public Health Ontario, Toronto, ON, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
| | - Calvin H Yeh
- Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada; Department of Medicine, Division of Emergency Medicine, Hamilton Health Sciences, Hamilton, ON, Canada
| | - Jafna L Cox
- Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Douglas S Lee
- University Health Network, Toronto, ON, Canada; ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Dennis T Ko
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Clare L Atzema
- ICES (formerly known as the Institute for Clinical Evaluative Sciences), Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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19
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Rieder M, Gauchel N, Kaier K, Jakob C, Borgmann S, Classen AY, Schneider J, Eberwein L, Lablans M, Rüthrich M, Dolff S, Wille K, Haselberger M, Heuzeroth H, Bode C, von Zur Mühlen C, Rieg S, Duerschmied D. Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities. Clin Res Cardiol 2022; 111:322-332. [PMID: 34546427 PMCID: PMC8453472 DOI: 10.1007/s00392-021-01939-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 09/06/2021] [Indexed: 12/15/2022]
Abstract
AIMS Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. METHODS AND RESULTS We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). CONCLUSIONS Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.
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Affiliation(s)
- Marina Rieder
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
| | - Nadine Gauchel
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany.
| | - Klaus Kaier
- Institute of Medical Biometry and Statistics, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
| | - Carolin Jakob
- Department I for Internal Medicine, Faculty of Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Stefan Borgmann
- Department of Infectious Diseases and Infection Control, Ingolstadt Hospital, Ingolstadt, Germany
| | - Annika Y Classen
- Department I for Internal Medicine, Faculty of Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Jochen Schneider
- School of Medicine, Technical University of Munich, University Hospital Rechts der Isar, Munich, Germany
| | - Lukas Eberwein
- 4Th Department of Internal Medicine, Klinikum Leverkusen, Leverkusen, Germany
| | - Martin Lablans
- Federated Information Systems, German Cancer Research Center, Heidelberg, Germany
- University Medical Center Mannheim, Mannheim, Germany
| | - Maria Rüthrich
- Department for Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, Germany
- Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute, Jena, Germany
| | - Sebastian Dolff
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Kai Wille
- University Clinic for Haematology, Oncology, Haemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, University of Bochum, Bochum, Germany
| | | | - Hanno Heuzeroth
- Department of Emergency and Intensive Care Medicine, Klinikum Ernst-Von-Bergmann, Potsdam, Germany
| | - Christoph Bode
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
| | - Constantin von Zur Mühlen
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
| | - Siegbert Rieg
- Division of Infectious Diseases, Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Daniel Duerschmied
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
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20
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Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions. J Pers Med 2022; 12:jpm12030349. [PMID: 35330349 PMCID: PMC8955701 DOI: 10.3390/jpm12030349] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 02/12/2022] [Accepted: 02/14/2022] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is now being investigated for its distinctive patterns in the course of disease development which can be indicated with miscellaneous immune responses in infected individuals. Besides this series of investigations on the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant fundamental immunological and physiological processes are indispensable to address clinical markers of COVID-19 disease and essential to identify or design effective therapeutics. Recent developments in the literature suggest that deficiency of type I interferon (IFN) in serum samples can be used to represent a severe progression of COVID-19 disease and can be used as the basis to develop combined immunotherapeutic strategies. Precise control over inflammatory response is a significant aspect of targeting viral infections. This account presents a brief review of the pathophysiological characteristics of the SARS-CoV-2 virus and the understanding of the immune status of infected patients. We further discuss the immune system’s interaction with the SARS-CoV-2 virus and their subsequent involvement of dysfunctional immune responses during the progression of the disease. Finally, we highlight some of the implications of the different approaches applicable in developing promising therapeutic interventions that redirect immunoregulation and viral infection.
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21
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Hamad AS. Non-vitamin K antagonist oral anticoagulants for COVID-19 thrombosis. JOURNAL OF ACUTE DISEASE 2022. [DOI: 10.4103/2221-6189.362812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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22
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Wardhana A, Ghea C, Nugroho A, Assilmi F. The effect of oral anticoagulant use before visit for patients with COVID-19 on mortality: A meta-analysis. Tzu Chi Med J 2022. [PMID: 37545792 PMCID: PMC10399847 DOI: 10.4103/tcmj.tcmj_199_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objectives Anticoagulants have been used as therapeutic or prophylactic agents in COVID-19 and seem to be more beneficial. However, the advantage of oral anticoagulant (OAC) consumption before visit in lowering mortality in COVID-19 patients remains debatable. This meta-analysis aimed to evaluate the effect of OAC use before visit on mortality using the hazard ratio (HR) to estimate the effect of time-to-event endpoints. Materials and Methods We conducted a literature search in the PubMed and ProQuest databases for any studies comparing groups consuming OAC to no-OAC before visit for mortality in patients with COVID-19. We calculated the overall HRs and their variances across the studies using the random-effects model to obtain pooled estimates. Results We included 12 studies which had sample sizes ranging from 70 to 459,402 patients. A meta-analysis comparing OAC therapy and non-OAC consumption in COVID-19 patients before visit revealed no decrease in all-cause mortality (HR = 0.92, 95% confidence interval [CI]: 0.83-1.02, P = 0.12; I2 = 68%). However, subgroup analysis of laboratory-confirmed populations revealed that OAC use before visit had a beneficial effect on mortality (HR = 0.84, 95% CI: 0.73-0.98, P = 0.02; I2 = 56%). Conclusion The use of OAC before visit had no beneficial effect on all-cause mortality in COVID-19 patients.
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23
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Senderovich H, Vinoraj D, Stever M, Waicus S. Efficacy of COVID-19 treatments among geriatric patients: a systematic review. Ther Adv Infect Dis 2022; 9:20499361221095666. [PMID: 35677110 PMCID: PMC9168946 DOI: 10.1177/20499361221095666] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 03/29/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction A majority of the fatalities due to COVID-19 have been observed in those over the age of 60. There is no approved and universally accepted treatment for geriatric patients. The aim of this review is to assess the current literature on efficacy of COVID-19 treatments in geriatric populations. Methods A systematic review search was conducted in PubMed, MedRxiv, and JAMA databases with the keywords COVID-19, geriatric, hydroxychloroquine, dexamethasone, budesonide, remdesivir, favipiravir, ritonavir, molnupiravir, tocilizumab, bamlanivimab, baricitinib, sotrovimab, fluvoxamine, convalescent plasma, prone position, or anticoagulation. Articles published from January 2019 to January 2022 with a population greater than or equal to 60 years of age were included. Interventions examined included hydroxychloroquine, remdesivir, favipiravir, dexamethasone, budesonide, tocilizumab, bamlanivimab, baricitinib, sotrovimab, convalescent plasma, prone position, and anticoagulation therapy. Outcome measures included viral load, viral markers, ventilator-free days, or clinical improvement. Results The search revealed 302 articles, 52 met inclusion criteria. Hydroxychloroquine, dexamethasone, and remdesivir revealed greater side effects or inefficiency in geriatric patients with COVID-19. Favipiravir, bamlanivimab, baricitinib, and supportive therapy showed a decrease in viral load and improvement of clinical symptoms. There is conflicting evidence with tocilizumab, convalescent plasma, and anticoagulant therapy in reducing mortality, ventilator-free days, and clinical improvements. In addition, there was limited evidence and lack of data due to ongoing trials for treatments with sotrovimab and budesonide. Conclusion No agent is known to be effective for preventing COVID-19 after exposure to the virus. Further research is needed to ensure safety and efficacy of each of the reviewed interventions for older adults.
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Affiliation(s)
- Helen Senderovich
- Baycrest, 3560 Bathurst Street, Toronto, ON M6A
2E1, Canada
- Department of Family and Community Medicine,
University of Toronto, Toronto, ON, Canada
- Division of Palliative Care, University of
Toronto, Toronto, ON, Canada
| | - Danusha Vinoraj
- Department of Psychiatry, Faculty of Medicine,
University of Ottawa, Ottawa, ON, Canada
| | | | - Sarah Waicus
- School of Medicine, Trinity College Dublin, The
University of Dublin, Dublin, Ireland
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24
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Rivera-Caravaca JM, Núñez-Gil IJ, Lip GYH, Uribarri A, Viana-Llamas MC, Gonzalez A, Castro-Mejía AF, Alonso González B, Alfonso E, García Prieto JF, Cavallino C, Cortese B, Feltes G, Fernández-Rozas I, Signes-Costa J, Huang J, García Aguado M, Pepe M, Romero R, Cerrato E, Becerra-Muñoz VM, Raposeiras Roubin S, Santoro F, Bagur R, Sposato L, El-Battrawy I, López Masjuan A, Fernandez-Ortiz A, Estrada V, Macaya C, Marín F. Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry. Int J Clin Pract 2022; 2022:7325060. [PMID: 35685504 PMCID: PMC9158796 DOI: 10.1155/2022/7325060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/21/2022] [Accepted: 04/21/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. METHODS Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. RESULTS 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. CONCLUSION Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399.
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Affiliation(s)
- José Miguel Rivera-Caravaca
- Department of Cardiology, Hospital Clínico UniversitarioVirgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, Murcia, Spain
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart & Chest Hospital, Liverpool, UK
| | - Iván J. Núñez-Gil
- Hospital Clínico San Carlos Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Gregory Y. H. Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart & Chest Hospital, Liverpool, UK
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Aitor Uribarri
- Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | | | - Adelina Gonzalez
- Hospital Universitario Infanta Sofía, San Sebastian de los Reyes, Madrid, Spain
| | | | | | - Emilio Alfonso
- Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba
| | | | | | | | | | | | - Jaime Signes-Costa
- Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, Valencia, Spain
| | - Jia Huang
- The Second People's Hospital of Shenzhen, Shenzhen, China
| | | | - Martino Pepe
- Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari, Bari, Italy
| | | | - Enrico Cerrato
- San Luigi Gonzaga University Hospital, Rivoli, Turin, Italy
| | - Víctor Manuel Becerra-Muñoz
- Unidad de Gestión Clínica Área del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Málaga, Spain
| | | | - Francesco Santoro
- Azienda Sanitaria Locale della Provincia di Barletta-Andria-Trani, Andria, Italy
- Department of Medical and Surgery Sciences, University of Foggia, Foggia, Italy
| | - Rodrigo Bagur
- London Health Sciences Centre, London, Ontario, Canada
| | - Luciano Sposato
- London Health Sciences Centre, London, Ontario, Canada
- Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
- Lawson Health Research Institute, London, Ontario, Canada
- Robarts Research Institute, London, Ontario, Canada
| | | | | | - Antonio Fernandez-Ortiz
- Hospital Clínico San Carlos Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Vicente Estrada
- Hospital Clínico San Carlos Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Carlos Macaya
- Hospital Clínico San Carlos Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Francisco Marín
- Department of Cardiology, Hospital Clínico UniversitarioVirgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, Murcia, Spain
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Venturelli A, Vitolo M, Albini A, Boriani G. How did COVID-19 affect medical and cardiology journals? A pandemic in literature. J Cardiovasc Med (Hagerstown) 2021; 22:840-847. [PMID: 34482327 PMCID: PMC10100635 DOI: 10.2459/jcm.0000000000001245] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/28/2021] [Accepted: 08/03/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS The spreading speed of the COVID-19 pandemic forced the medical community to produce efforts in updating and sharing the evidence about this new disease, trying to preserve the accuracy of the data but at the same time avoiding the potentially harmful delay from discovery to implementation. The aim of our analysis was to assess the impact of the COVID-19 pandemic on medical literature in terms of proportion of COVID-19-related published papers and temporal patterns of publications within a sample of general/internal medicine and cardiology journals. METHODS We searched through PubMed scientific papers published from 1 January 2020 to 31 January 2021 about COVID-19 in ten major medical journals, of which five were in general/internal medicine and five in the cardiology field. We analyzed the proportion of COVID-19-related papers, and we examined temporal trends in the number of published papers. RESULTS Overall, the proportion of COVID-19-related papers was 18.5% (1986/10 756). This proportion was higher among the five selected general/internal medicine journals, compared with cardiology journals (23.8% vs 9.5%). The vast majority of papers were not original articles; in particular, in cardiology journals, there were 28% 'original articles', 17% 'review articles' and 55.1% 'miscellaneous', compared with 20.2%, 5.1% and 74.7% in general/internal medicine journals, respectively. CONCLUSIONS Our analysis highlights the big impact of the COVID-19 pandemic on international scientific literature. General and internal medicine journals were mainly involved, with cardiology journals only at a later time.
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Affiliation(s)
- Andrea Venturelli
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena
| | - Marco Vitolo
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandro Albini
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena
| | - Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena
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Hozayen SM, Zychowski D, Benson S, Lutsey PL, Haslbauer J, Tzankov A, Kaltenborn Z, Usher M, Shah S, Tignanelli CJ, Demmer RT. Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients. EClinicalMedicine 2021; 41:101139. [PMID: 34585129 PMCID: PMC8461367 DOI: 10.1016/j.eclinm.2021.101139] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/27/2021] [Accepted: 09/07/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING No funding was obtained for this study.
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Key Words
- %, percentage
- (n), number
- ACEi, angiotensin-converting enzyme inhibitors
- ARBs, angiotensin receptor blockers
- Anticoagulation
- CI, confidence intervals
- CKD, chronic kidney disease
- CO2, carbon dioxide
- COPD, chronic obstructive pulmonary disease
- COVID-19
- COVID-19, coronavirus disease 2019
- D-dimer
- DIC, disseminated intravascular coagulation
- DOAC, direct oral anticoagulant
- EHR, electronic health records
- EMR, electronic medical records
- HCT, hematocrit
- HIT, heparin-induced thrombocytopenia
- HR, hazard ratio
- Hospitalization
- IPAC, inpatient anticoagulation therapy
- IRB, institutional review board
- Inpatient
- MI, prior myocardial infarction
- Mortality
- OPAC, outpatient persistent anticoagulation therapy
- Outpatient
- RDW, red blood cell distribution width
- SARS-CoV-2, severe Acute Respiratory Syndrome Coronavirus-2
- SBP, systolic blood pressure
- SBP-min, minimum systolic blood pressure
- SD, standard deviations
- SE, standard errors
- SpO2-min, minimum oxygen saturation
- T1DM, type 1 diabetes mellitus
- T2DM, type 2 diabetes mellitus
- VTE, venous thromboembolism
- WBC, white blood cell
- mg/dl, milligram per deciliter
- rt-PCR, reverse transcriptase-polymerase chain reaction
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Affiliation(s)
- Sameh M. Hozayen
- Department of Medicine, Division of General Internal Medicine, Assistant Professor of Medicine, Hospitalist, University of Minnesota, Mayo Building, 420 Delaware Street, SE, 6 Floor, Room D694, Minneapolis, MN 55455, United States
- Corresponding author.
| | - Diana Zychowski
- Department of Medical Education, University of Minnesota, United States
| | - Sydney Benson
- Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States
| | - Pamela L. Lutsey
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States
| | - Jasmin Haslbauer
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland
| | - Alexandar Tzankov
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland
| | - Zachary Kaltenborn
- Department of Medicine, Division of General Internal Medicine, Assistant Professor of Medicine, Hospitalist, University of Minnesota, Mayo Building, 420 Delaware Street, SE, 6 Floor, Room D694, Minneapolis, MN 55455, United States
| | - Michael Usher
- Department of Medicine, Division of General Internal Medicine, Assistant Professor of Medicine, Hospitalist, University of Minnesota, Mayo Building, 420 Delaware Street, SE, 6 Floor, Room D694, Minneapolis, MN 55455, United States
| | - Surbhi Shah
- Department of Hematology and oncology, Mayo Clinic, Arizona, United States
| | - Christopher J. Tignanelli
- Department of Surgery, University of Minnesota, Minneapolis, MN, United States
- Institute for Health Informatics, University of Minnesota, Minneapolis, MN, United States
- Department of Surgery, North Memorial Health Hospital, Robbinsdale, MN, United States
| | - Ryan T. Demmer
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States
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Wong AYS, Tomlinson LA, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJW, Smeeth L, Goldacre B, Douglas IJ. Association between warfarin and COVID-19-related outcomes compared with direct oral anticoagulants: population-based cohort study. J Hematol Oncol 2021; 14:172. [PMID: 34666811 PMCID: PMC8525065 DOI: 10.1186/s13045-021-01185-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/04/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Thromboembolism has been reported as a consequence of severe COVID-19. Although warfarin is a commonly used anticoagulant, it acts by antagonising vitamin K, which is low in patients with severe COVID-19. To date, the clinical evidence on the impact of regular use of warfarin on COVID-19-related thromboembolism is lacking. METHODS On behalf of NHS England, we conducted a population-based cohort study investigating the association between warfarin and COVID-19 outcomes compared with direct oral anticoagulants (DOACs). We used the OpenSAFELY platform to analyse primary care data and pseudonymously linked SARS-CoV-2 antigen testing data, hospital admissions and death records from England. We used Cox regression to estimate hazard ratios (HRs) for COVID-19-related outcomes comparing warfarin with DOACs in people with non-valvular atrial fibrillation. We also conducted negative control outcome analyses (being tested for SARS-CoV-2 and non-COVID-19 death) to assess the potential impact of confounding. RESULTS A total of 92,339 warfarin users and 280,407 DOAC users were included. We observed a lower risk of all outcomes associated with warfarin versus DOACs [testing positive for SARS-CoV-2, HR 0.73 (95% CI 0.68-0.79); COVID-19-related hospital admission, HR 0.75 (95% CI 0.68-0.83); COVID-19-related deaths, HR 0.74 (95% CI 0.66-0.83)]. A lower risk of negative control outcomes associated with warfarin versus DOACs was also observed [being tested for SARS-CoV-2, HR 0.80 (95% CI 0.79-0.81); non-COVID-19 deaths, HR 0.79 (95% CI 0.76-0.83)]. CONCLUSIONS Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease.
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Affiliation(s)
| | - Angel Y S Wong
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
| | - Laurie A Tomlinson
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Jeremy P Brown
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - William Elson
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Alex J Walker
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Anna Schultze
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Caroline E Morton
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - David Evans
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Peter Inglesby
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Brian MacKenna
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Krishnan Bhaskaran
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Christopher T Rentsch
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Emma Powell
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Elizabeth Williamson
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Richard Croker
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Seb Bacon
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - William Hulme
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | | | - Helen J Curtis
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Amir Mehrkar
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | | | - Helen I McDonald
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.,NIHR Health Protection Research Unit (HPRU) in Immunisation, London, UK
| | - Rohini Mathur
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Kevin Wing
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Harriet Forbes
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Rosalind M Eggo
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Stephen J W Evans
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Liam Smeeth
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.,NIHR Health Protection Research Unit (HPRU) in Immunisation, London, UK
| | - Ben Goldacre
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Ian J Douglas
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
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Raschi E, Fusaroli M, Diemberger I, Poluzzi E. Direct Oral Anticoagulants and Interstitial Lung Disease: Emerging Clues from Pharmacovigilance. Drug Saf 2021; 43:1191-1194. [PMID: 32845443 PMCID: PMC7447592 DOI: 10.1007/s40264-020-00990-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Emanuel Raschi
- Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
| | - Michele Fusaroli
- Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Via Irnerio 48, 40126, Bologna, Italy
| | - Igor Diemberger
- Cardiology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Elisabetta Poluzzi
- Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Via Irnerio 48, 40126, Bologna, Italy
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Aslan B, Akyüz A, Işık F, Çap M, İnci Ü, Kaya İ, Karahan MZ, Aktan A, Bilge Ö, Özbek M, Altıntaş B, Boyraz B. The effect of chronic DOAC treatment on clinical outcomes of hospitalized patients with COVID-19. Int J Clin Pract 2021; 75:e14467. [PMID: 34107130 PMCID: PMC8237002 DOI: 10.1111/ijcp.14467] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/24/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Recent findings indicate that thrombosis is one of the underlying pathophysiology and complication of COVID-19 infection. Therefore, the prognosis of the disease may be more favourable in people who were under oral anticoagulant treatment before the COVID-19 diagnosis. This study aims to evaluate the effects of chronic DOAC use on ICU admission and mortality in hospitalized patients due to COVID-19 infection. METHOD Between 1 September and 30 November 2020, 2760 patients hospitalized in our hospital due to COVID-19 were screened. A total of 1710 patients who met the inclusion criteria were included in the study. The patients were divided into two groups as those who use DOAC due to any cardiovascular disease before the COVID-19 infection and those who do not. RESULTS Seventy-nine patients were enrolled in the DOAC group and 1631 patients in the non-DOAC group. Median age of all study patient was 62 (52-71 IQR) and 860 (50.5%) of them were female. The need for intensive care, in-hospital stay, and mechanical ventilation were observed at higher rates in the DOAC group. Mortality was observed in 23 patients (29%) in the DOAC group, and it was statistically higher in the DOAC group (P = .002). In the multivariable analysis, age (OR: 1.047, CI: 1.02-1.06, P < .001), male gender (OR: 1.8, CI: 1.3-2.7, P = .02), lymphocyte count (OR: 0.45, CI: 0.30-0.69, P < .001), procalcitonin (OR: 1.12, CI: 1.02-1.23, P = .015), SaO2 (OR: 0.8, CI: 0.77-0.82, P < .001) and creatinine (OR: 2.59, CI: 1.3-5.1, P = .006) were found to be associated with in-hospital mortality. DOAC treatment was not found to be associated with lower in-hospital mortality in multivariable analysis (OR:1.17, CI: 0.20-6.60, P = .850). CONCLUSION Our study showed that the use of DOAC prior to hospitalization had no protective effect on in-hospital mortality and intensive care need in hospitalized COVID-19 patients.
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Affiliation(s)
- Burhan Aslan
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - Abdurrahman Akyüz
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - Ferhat Işık
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - Murat Çap
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - Ümit İnci
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - İlyas Kaya
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - Mehmet Zülküf Karahan
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - Adem Aktan
- Department of CardiologyMardin State HospitalMardinTurkey
| | - Önder Bilge
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
| | - Mehmet Özbek
- Department of CardiologyDiyarbakır Dicle UniversityDiyarbakırTurkey
| | - Bernas Altıntaş
- Department of CardiologyDiyarbakır Gazi Yaşargil Education and Research HospitalHealth and Science UniversityDiyarbakırTurkey
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30
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Lip GYH, Genaidy A, Tran G, Marroquin P, Estes C. Incident atrial fibrillation and its risk prediction in patients developing COVID-19: A machine learning based algorithm approach. Eur J Intern Med 2021; 91:53-58. [PMID: 34023150 PMCID: PMC8118660 DOI: 10.1016/j.ejim.2021.04.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 04/20/2021] [Accepted: 04/22/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The elderly multi-morbid patient is at high risk of adverse outcomes with COVID-19 complications, and in the general population, the development of incident AF is associated with worse outcomes in such patients. There is therefore the need to identify those patients with COVID-19 who are at highest risk of developing incident AF. We therefore investigated incident AF risks in a large prospective population of elderly patients with/without incident COVID-19 cases and baseline cardiovascular/non-cardiovascular multi-morbidities. We used two approaches: main effect modeling and secondly, a machine-learning (ML) approach, accounting for the complex dynamic relationships among comorbidity variables. METHODS We studied a prospective elderly US cohort of 280,592 patients from medical databases in an 8-month investigation of with/without newly incident COVID19 cases. Incident AF outcomes were examined in relationship to diverse multi-morbid conditions, COVID-19 status and demographic variables, with ML accounting for the dynamic nature of changing multimorbidity risk factors. RESULTS Multi-morbidity contributed to the onset of confirmed COVID-19 cases with cognitive impairment (OR 1.69; 95%CI 1.52-1.88), anemia (OR 1.41; 95%CI 1.32-1.50), diabetes mellitus (OR 1.35; 95%CI 1.27-1.44) and vascular disease (OR 1.30; 95%CI 1.21-1.39) having the highest associations. A main effect model (C-index value 0.718) showed that COVID-19 had the highest association with incident AF cases (OR 3.12; 95%CI 2.61-3.710, followed by congestive heart failure (1.72; 95%CI 1.50-1.96), then coronary artery disease (OR 1.43; 95%CI 1.27-1.60) and valvular disease (1.42; 95%CI 1.26-1.60). The ML algorithm demonstrated improved discriminatory validity incrementally over the statistical main effect model (training: C-index 0.729, 95%CI 0.718-0.740; validation: C-index 0.704, 95%CI 0.687-0.72). Calibration of the ML based formulation was satisfactory and better than the main-effect model. Decision curve analysis demonstrated that the clinical utility for the ML based formulation was better than the 'treat all' strategy and the main effect model. CONCLUSION COVID-19 status has major implications for incident AF in a cohort with diverse cardiovascular/non-cardiovascular multi-morbidities. Our ML approach accounting for dynamic multimorbidity changes had good prediction for new onset AF amongst incident COVID19 cases.
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Affiliation(s)
- Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom.
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Kaptein F, Stals M, Huisman M, Klok F. Prophylaxis and treatment of COVID-19 related venous thromboembolism. Postgrad Med 2021; 133:27-35. [PMID: 33657964 PMCID: PMC7938649 DOI: 10.1080/00325481.2021.1891788] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 02/15/2021] [Indexed: 01/08/2023]
Abstract
COVID-19 pneumonia has been associated with high rates of thrombo-embolic complications, mostly venous thromboembolism (VTE), which is thought to be a combination of conventional VTE and in situ immunothrombosis in the pulmonary vascular tree. The incidence of thrombotic complications is dependent on setting (intensive care unit (ICU) versus general ward) and the threshold for performing diagnostic tests (screening versus diagnostic algorithms triggered by symptoms). Since these thrombotic complications are associated with in-hospital mortality, all current guidelines and consensus papers propose pharmacological thromboprophylaxis in all hospitalized patients with COVID-19. Several trials are ongoing to study the optimal intensity of anticoagulation for this purpose. As for the management of thrombotic complications, treatment regimens from non-COVID-19 guidelines can be adapted, with choice of anticoagulant drug class dependent on the situation. Parenteral anticoagulation is preferred for patients on ICUs or with impending clinical deterioration, while oral treatment can be started in stable patients. This review describes current knowledge on incidence and pathophysiology of COVID-19 associated VTE and provides an overview of guideline recommendations on thromboprophylaxis and treatment of established VTE in COVID-19 patients.
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Affiliation(s)
- F.H.J. Kaptein
- Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
| | - M.A.M. Stals
- Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
| | - M.V. Huisman
- Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
| | - F.A. Klok
- Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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Alves M, Fernandes MA, Bahat G, Benetos A, Clemente H, Grodzicki T, Martínez-Sellés M, Mattace-Raso F, Rajkumar C, Ungar A, Werner N, Strandberg TE. Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications. Eur Geriatr Med 2021; 12:725-739. [PMID: 34031865 PMCID: PMC8143992 DOI: 10.1007/s41999-021-00504-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 04/15/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE In the pathogenesis of severe COVID-19 complications, derangements of renin-angiotensin-aldosterone system (RAAS), vascular endothelial dysfunction leading to inflammation and coagulopathy, and arrhythmias play an important role. Therefore, it is worth considering the use of currently available drugs to protect COVID-19 patients with cardiovascular diseases. METHODS We review the current experience of conventional cardiovascular drugs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, anticoagulants, acetosalicylic acid, antiarrhythmic drugs, statins] as well as some other drug classes (antidiabetic drugs, vitamin D and NSAIDs) frequently used by older patients with cardiovascular diseases. Data were sought from clinical databases for COVID-19 and appropriate key words. Conclusions and recommendations are based on a consensus among all authors. RESULTS Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on retrospective, observational studies. Despite propensity score adjustments used in many analyses observational studies are not equivalent to randomised controlled trials (RCTs). Ongoing RCTs include treatment with antithrombotics, pulmonary vasodilators, RAAS-related drugs, and colchicine. RCTs in the acute phase of COVID-19 may not, however, recognise the benefits of long term anti-atherogenic therapies, such as statins. CONCLUSIONS Most current cardiovascular drugs can be safely continued during COVID-19. Some drug classes may even be protective. Age-specific data are scarce, though, and conditions which are common in older patients (frailty, comorbidities, polypharmacy) must be individually considered for each drug group.
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Affiliation(s)
- Mariana Alves
- Faculty of Medicine, Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Serviço de Medicina III, Hospital Pulido Valente, CHULNUniversity of LisbonUniversidade de Lisboa, Lisbon, Portugal
| | - Marília Andreia Fernandes
- Department of Internal Medicine, Hospital Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Gülistan Bahat
- Istanbul Medical School, Department of Internal Medicine, Division of Geriatrics, Istanbul University, Capa, 34093, Istanbul, Turkey
| | - Athanase Benetos
- Department of Geriatrics and FHU CARTAGE-PROFILES, CHRU de Nancy and INSERM 1116, Université de Lorraine, Vandoeuvre-lès-Nancy, France
| | - Hugo Clemente
- Department of Geriatrics, Centre Hospitalier de Wallonie Picarde, Tournai, Belgium
| | - Tomasz Grodzicki
- Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Cracow, Poland
| | - Manuel Martínez-Sellés
- Department of Cardiology, Hospital General Universitario Gregorio Marañón, CIBER-CV. Universidad Europea, Universidad Complutense, Madrid, Spain
| | - Francesco Mattace-Raso
- Division of Geriatrics, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | | | - Andrea Ungar
- Department of Geriatrics and Intensive Care Unit, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy
| | - Nikos Werner
- Heart Center Trier, Krankenhaus der Barmherzigen Brüder, Trier, Germany
| | - Timo E Strandberg
- Helsinki University and Helsinki University Hospital, Haartmaninkatu 4, PO Box 340, N00029, Helsinki, Finland.
- University of Oulu, Center for Life Course Health Research, Oulu, Finland.
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Rivera-Caravaca JM, Buckley BJR, Harrison SL, Fazio-Eynullayeva E, Underhill P, Marín F, Lip GYH. Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes. Thromb Res 2021; 205:1-7. [PMID: 34218058 PMCID: PMC8236305 DOI: 10.1016/j.thromres.2021.06.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 12/23/2022]
Abstract
Background It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis. Methods We used data from TriNetX, a global federated health research network. Patients aged ≥18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH). Results 738,423 patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 ± 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12–1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64–1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91–5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54–1.51; Log-Rank test p = 0.513). Conclusion In COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.
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Affiliation(s)
- José Miguel Rivera-Caravaca
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, Murcia, Spain
| | - Benjamin J R Buckley
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Stephanie L Harrison
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
| | | | | | - Francisco Marín
- Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, Murcia, Spain
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
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34
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Corrochano M, Acosta-Isaac R, Mojal S, Miqueleiz S, Rodriguez D, Quijada-Manuitt MÁ, Fraga E, Castillo-Ocaña M, Amaro-Hosey K, Albiol N, Soria JM, Antonijoan RM, Souto JC. Impact of pre-admission antithrombotic therapy on disease severity and mortality in patients hospitalized for COVID-19. J Thromb Thrombolysis 2021; 53:96-102. [PMID: 34138399 PMCID: PMC8210515 DOI: 10.1007/s11239-021-02507-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2021] [Indexed: 12/15/2022]
Abstract
Anticoagulant therapy is a cornerstone treatment for coronavirus disease 2019 (COVID-19) due to the high rates of thromboembolic complications associated with this disease. We hypothesized that chronic antithrombotic therapy could play a protective role in patients hospitalized for COVID-19. Retrospective, observational study of all patients admitted to our hospital for ≥ 24 h from March 1 to May 31, 2020 with SARS-CoV-2. The objective was to evaluate clinical outcomes and mortality in COVID-19 patients receiving chronic anticoagulation (AC) or antiplatelet therapy (AP) prior to hospital admission. A total of 1612 patients were evaluated. The mean (standard deviation; SD) age was 66.5 (17.1) years. Patients were divided into three groups according to the use of antithrombotic therapy prior to admission (AP, AC, or no-antithrombotic treatment). At admission, 9.6% of the patients were taking anticoagulants and 19.1% antiplatelet therapy. The overall mortality rate was 19.3%. On the multivariate analysis there were no significant differences in mortality between the antithrombotic groups (AC or AP) and the no-antithrombotic group (control group). Patients on AC had lower ICU admission rates than the control group (OR: 0.41, 95% CI, 0.18–0.93). Anticoagulation therapy prior to hospitalization for COVID-19 was associated with lower ICU admission rates. However, there were no significant differences in mortality between the patients receiving chronic antithrombotic therapy and patients not taking antithrombotic medications. These findings suggest that chronic anticoagulation therapy at the time of COVID-19 infection may reduce disease severity and thus the need for ICU admission.
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Affiliation(s)
- Mariana Corrochano
- Haemostasis and Thrombosis Unit, Hospital de La Santa Creu I Sant Pau. Carrer de Sant Quintí 89, 08041, Barcelona, Spain.
| | - René Acosta-Isaac
- Haemostasis and Thrombosis Unit, Hospital de La Santa Creu I Sant Pau. Carrer de Sant Quintí 89, 08041, Barcelona, Spain
| | - Sergi Mojal
- Haemostasis and Thrombosis Unit, Hospital de La Santa Creu I Sant Pau. Carrer de Sant Quintí 89, 08041, Barcelona, Spain
| | - Sara Miqueleiz
- Clinical Trials Unit (AGDAC), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Diana Rodriguez
- Clinical Trials Unit (AGDAC), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | | | | | - Marta Castillo-Ocaña
- Clinical Pharmacology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | | | - Nil Albiol
- Haemostasis and Thrombosis Unit, Hospital de La Santa Creu I Sant Pau. Carrer de Sant Quintí 89, 08041, Barcelona, Spain
| | - José Manuel Soria
- Unit of Genomics of Complex Diseases, Institut d'Investigació Biomèdica Sant Pau, IIB-Sant Pau, Barcelona, Spain
| | - Rosa Maria Antonijoan
- Clinical Pharmacology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Drug Research Center, Institut d'Investigació Biomèdica Sant Pau, IIB-Sant Pau, Barcelona, Spain
| | - Joan Carles Souto
- Haemostasis and Thrombosis Unit, Hospital de La Santa Creu I Sant Pau. Carrer de Sant Quintí 89, 08041, Barcelona, Spain
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35
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Goswami J, MacArthur TA, Sridharan M, Pruthi RK, McBane RD, Witzig TE, Park MS. A Review of Pathophysiology, Clinical Features, and Management Options of COVID-19 Associated Coagulopathy. Shock 2021; 55:700-716. [PMID: 33378321 PMCID: PMC8122038 DOI: 10.1097/shk.0000000000001680] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ABSTRACT There is increasing evidence that novel coronavirus disease 2019 (COVID-19) leads to a significant coagulopathy, a phenomenon termed "COVID-19 associated coagulopathy." COVID-19 has been associated with increased rates of both venous and arterial thromboembolic events, a source of significant morbidity and mortality in this disease. Further evidence suggests a link between the inflammatory response and coagulopathy associated with COVID-19. This presents a unique set of challenges for diagnosis, prevention, and treatment of thrombotic complications. In this review, we summarize and discuss the current literature on laboratory coagulation disruptions associated with COVID-19 and the clinical effects of thromboembolic events including pulmonary embolism, deep vein thrombosis, peripheral arterial thrombosis, and acute ischemic stroke in COVID-19. Endothelial injury and augmented innate immune response are implicated in the development of diffuse macro- and microvascular thrombosis in COVID-19. The pathophysiology of COVID-19 associated coagulopathy is an important determinant of appropriate treatment and monitoring of these complications. We highlight the importance of diagnosis and management of dysregulated coagulation in COVID-19 to improve outcomes in COVID-19 patients with thromboembolic complications.
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Affiliation(s)
- Julie Goswami
- Division of Trauma, Critical Care, and General Surgery, Department of Surgery, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
| | - Taleen A. MacArthur
- Division of Trauma, Critical Care, and General Surgery, Department of Surgery, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
| | - Meera Sridharan
- Department of Hematology, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
| | - Rajiv K. Pruthi
- Department of Hematology, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
| | - Robert D. McBane
- Department of Hematology, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
- Division of Vascular Cardiology, Department of Cardiovascular Disease, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
| | - Thomas E. Witzig
- Department of Hematology, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
| | - Myung S. Park
- Division of Trauma, Critical Care, and General Surgery, Department of Surgery, Mayo Clinic, 200 1 St. SW, Rochester, MN, 55905
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36
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Buenen AG, Sinkeldam M, Maas ML, Verdonschot M, Wever PC. Prior use of anticoagulation is associated with a better survival in COVID-19. J Thromb Thrombolysis 2021; 52:1207-1211. [PMID: 34061283 PMCID: PMC8166893 DOI: 10.1007/s11239-021-02486-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/18/2021] [Indexed: 01/06/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is associated with a high incidence of venous and arterial thromboembolic events. The role of anticoagulation (AC) prior to hospital admission and how different types of oral AC influences the outcome of COVID-19 is currently unknown. This observational study compares the outcome in COVID-19 patients with prior use of direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA), and without prior use of AC. We collected the baseline characteristics and outcomes of COVID-19 patients presented to the emergency department of Bernhoven Hospital, the Netherlands. The primary outcome was all-cause mortality within 30 days and analyzed in a multivariable Cox proportional hazards model including age, sex, symptom duration, home medication, and comorbidities. We included 497 patients, including 57 patients with DOAC (11%) and 53 patients with VKA (11%). Patients with AC had a lower body temperature and lower C-reactive protein levels. Comparing the primary outcome in patients with AC (DOAC or VKA) and no AC, the adjusted hazard ratio (aHR) was 0.64 (95% CI 0.42–0.96, P = 0.03). Comparing DOAC and no AC, the aHR was 0.53 (95% CI 0.32–0.89, P = 0.02) and comparing VKA and no AC, the aHR was 0.77 (95% CI 0.47–1.27, P = 0.30). In a subgroup analysis of DOAC, all nine patients with prior use of dabigatran survived within 30 days. In this observational study, the prior use of AC is associated with a better survival of COVID-19. DOAC, especially dabigatran, might have additional beneficial effects.
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Affiliation(s)
- A G Buenen
- Department of Emergency Medicine, Maxima MC, Postbus 7777, 5500 MB, Veldhoven, The Netherlands. .,Department of Emergency Medicine, Bernhoven Hospital, Uden, The Netherlands.
| | - Marijn Sinkeldam
- Department of Intensive Care, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Martje L Maas
- Department of Internal Medicine, Bernhoven Hospital, Uden, The Netherlands
| | | | - Peter C Wever
- Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands
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Russo V, Bottino R, D'Andrea A, Silverio A, Di Maio M, Golino P, Nigro G, Valsecchi O, Attena E, Canonico ME, Galasso G, Parodi G, Scudiero F. Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients. Cardiovasc Drugs Ther 2021; 36:705-712. [PMID: 33988835 PMCID: PMC8120255 DOI: 10.1007/s10557-021-07194-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/14/2021] [Indexed: 01/08/2023]
Abstract
PURPOSE The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19. METHODS This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants. RESULTS Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients CONCLUSION: Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.
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Affiliation(s)
- Vincenzo Russo
- Cardiology Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli" - Monaldi Hospital, Via. Bianchi, 80131, Naples, Italy
| | - Roberta Bottino
- Cardiology Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli" - Monaldi Hospital, Via. Bianchi, 80131, Naples, Italy.
| | - Antonello D'Andrea
- Department of Cardiology, Umberto I Hospital, 84014, Nocera Inferiore, Italy
| | - Angelo Silverio
- Cardiovascolar and Thoracic Department, Division of Cardiology, San Giovanni di Dio e Ruggi d'Aragona University Hospital, Salerno, Italy
| | - Marco Di Maio
- Cardiovascolar and Thoracic Department, Division of Cardiology, San Giovanni di Dio e Ruggi d'Aragona University Hospital, Salerno, Italy.,Division of Cardiology, Maria SS. Addolorata Hospital, Eboli, Salerno, Italy
| | - Paolo Golino
- Cardiology Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli" - Monaldi Hospital, Via. Bianchi, 80131, Naples, Italy
| | - Gerardo Nigro
- Cardiology Unit, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli" - Monaldi Hospital, Via. Bianchi, 80131, Naples, Italy
| | - Orazio Valsecchi
- Division of Cardiology, "Bolognini" Hospital, ASST Bergamo Est, Seriate, BG, Italy
| | - Emilio Attena
- Department of Cardiology, Monaldi Hospital, Naples, Italy
| | | | - Gennaro Galasso
- Cardiovascolar and Thoracic Department, Division of Cardiology, San Giovanni di Dio e Ruggi d'Aragona University Hospital, Salerno, Italy
| | - Guido Parodi
- Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy
| | - Fernando Scudiero
- Division of Cardiology, "Bolognini" Hospital, ASST Bergamo Est, Seriate, BG, Italy
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38
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Kamel AM, Sobhy M, Magdy N, Sabry N, Farid S. Anticoagulation outcomes in hospitalized Covid-19 patients: A systematic review and meta-analysis of case-control and cohort studies. Rev Med Virol 2021; 31:e2180. [PMID: 33022834 PMCID: PMC7646049 DOI: 10.1002/rmv.2180] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/22/2020] [Accepted: 09/24/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Coagulopathy and thromboembolic events are common in Covid-19 patients and are poor prognostic factors. Controversy exists regarding the potential of anticoagulation (AC) to reduce mortality and incidence of thromboembolic events in Covid-19 patients. The current systematic review and meta-analysis investigated the association between anticoagulants and mortality in adult hospitalized COVID-19 patients using the available published non-randomized studies. METHODS Google Scholar, PubMed, Scopus, the Cochrane Library and Clinical Trials.gov were searched for relevant studies. A meta-analysis of adjusted and unadjusted estimates was performed. The relative risk was used as a measure of effect. The random-effects model was used to pool estimates using the generic inverse variance method. RESULTS Sixteen studies were included in the quantitative data synthesis. Results showed a statistically significant association between AC and mortality (RR = 0.56, 95% CI 0.36; 0.92, p = 0.02). Both therapeutic (Relative risk [RR] = 0.4, 95% CI 0.27; 0.57) and prophylactic AC (RR = 0.54, 95% CI 0.41; 0.71) were associated with lower risk of mortality. Pre-admission AC was not associated with mortality (RR = 0.84, 95% CI 0.49; 1.43, p > 0.05) while prophylactic AC was associated with higher risk of mortality compared to therapeutic AC (RR = 1.58, 95% CI 1.34; 1.87, p < 0.001). CONCLUSION Findings support the association of AC with mortality in Covid-19 patients. The results, synthesized from mostly low-quality studies, show that prophylactic and therapeutic AC might reduce mortality in Covid-19 patients. Findings suggest that therapeutic doses might be associated with better survival compared to prophylactic doses.
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Affiliation(s)
- Ahmed M. Kamel
- Clinical Pharmacy DepartmentCollege of PharmacyCairo UniversityCairoEgypt
| | - Mona Sobhy
- Clinical Pharmacy DepartmentCollege of PharmacyCairo UniversityCairoEgypt
| | - Nada Magdy
- Clinical Pharmacy DepartmentCollege of PharmacyCairo UniversityCairoEgypt
| | - Nirmeen Sabry
- Clinical Pharmacy DepartmentCollege of PharmacyCairo UniversityCairoEgypt
| | - Samar Farid
- Clinical Pharmacy DepartmentCollege of PharmacyCairo UniversityCairoEgypt
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39
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Spiegelenberg JP, van Gelder MMHJ, Maas ML, Hovens MMC, Esselink A, Dofferhoff ASM, Janssen R, van de Maat J, Janssen N, Blaauw M, Hassing RJ, van Apeldoorn M, Kerckhoffs A, Veerman K, Hoogerwerf J, Kramers C, Leentjens J. Prior use of therapeutic anticoagulation does not protect against COVID-19 related clinical outcomes in hospitalized patients: A propensity score-matched cohort study. Br J Clin Pharmacol 2021; 87:4839-4847. [PMID: 33899226 PMCID: PMC8250934 DOI: 10.1111/bcp.14877] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/21/2021] [Accepted: 04/11/2021] [Indexed: 02/06/2023] Open
Abstract
The hypercoagulable state observed in COVID‐19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID‐19 patients. This study included 1154 COVID‐19 patients admitted to 6 hospitals in the Netherlands between March and May 2020. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. In total, 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (risk ratio 1.02 [95% confidence interval; 0.80–1.30]) or length of hospital stay (7.0 [4–12] vs. 7.0 [4–12] days, P = .69), although we observed a lower risk of pulmonary embolism (0.19 [0.05–0.80]). This study shows that prior use of therapeutic anticoagulation is not associated with improved clinical outcome in hospitalized COVID‐19 patients.
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Affiliation(s)
- Janneke P Spiegelenberg
- Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.,Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
| | - Marleen M H J van Gelder
- Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, the Netherlands.,Radboud REshape Innovation Center, Radboud university medical center, Nijmegen, the Netherlands
| | - Martje L Maas
- Department of Internal Medicine, Bernhoven, Uden, the Netherlands
| | - Marcel M C Hovens
- Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands
| | - Anne Esselink
- Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Anton S M Dofferhoff
- Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Rob Janssen
- Department of Pulmonary Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Josephine van de Maat
- Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.,Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
| | - Nico Janssen
- Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.,Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
| | - Marc Blaauw
- Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.,Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
| | - Robert-Jan Hassing
- Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands
| | - Marjan van Apeldoorn
- Department of Internal Medicin and Geriatricts, Jeroen Bosch Hospital, GZ,'s-Hertogenbosch, the Netherlands
| | - Angèle Kerckhoffs
- Department of Internal Medicin and Geriatricts, Jeroen Bosch Hospital, GZ,'s-Hertogenbosch, the Netherlands
| | - Karin Veerman
- Department of Internal Medicine, St. Maartenskliniek, Ubbergen, The Netherlands
| | - Jacobien Hoogerwerf
- Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.,Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
| | - Cornelis Kramers
- Department of Pharmacology-Toxicology, Radboud university medical center, Nijmegen, the Netherlands.,Department of Pharmacy, Canisius Willhelmina Hospital, Nijmegen, the Netherlands
| | - Jenneke Leentjens
- Department of Internal Medicine, Radboud university medical center, Nijmegen, the Netherlands.,Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
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40
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The pleiotropic effects of antithrombotic drugs in the metabolic-cardiovascular-neurodegenerative disease continuum: impact beyond reduced clotting. Clin Sci (Lond) 2021; 135:1015-1051. [PMID: 33881143 DOI: 10.1042/cs20201445] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 04/07/2021] [Accepted: 04/13/2021] [Indexed: 12/25/2022]
Abstract
Antithrombotic drugs are widely used for primary and secondary prevention, as well as treatment of many cardiovascular disorders. Over the past few decades, major advances in the pharmacology of these agents have been made with the introduction of new drug classes as novel therapeutic options. Accumulating evidence indicates that the beneficial outcomes of some of these antithrombotic agents are not solely related to their ability to reduce thrombosis. Here, we review the evidence supporting established and potential pleiotropic effects of four novel classes of antithrombotic drugs, adenosine diphosphate (ADP) P2Y12-receptor antagonists, Glycoprotein IIb/IIIa receptor Inhibitors, and Direct Oral Anticoagulants (DOACs), which include Direct Factor Xa (FXa) and Direct Thrombin Inhibitors. Specifically, we discuss the molecular evidence supporting such pleiotropic effects in the context of cardiovascular disease (CVD) including endothelial dysfunction (ED), atherosclerosis, cardiac injury, stroke, and arrhythmia. Importantly, we highlight the role of DOACs in mitigating metabolic dysfunction-associated cardiovascular derangements. We also postulate that DOACs modulate perivascular adipose tissue inflammation and thus, may reverse cardiovascular dysfunction early in the course of the metabolic syndrome. In this regard, we argue that some antithrombotic agents can reverse the neurovascular damage in Alzheimer's and Parkinson's brain and following traumatic brain injury (TBI). Overall, we attempt to provide an up-to-date comprehensive review of the less-recognized, beneficial molecular aspects of antithrombotic therapy beyond reduced thrombus formation. We also make a solid argument for the need of further mechanistic analysis of the pleiotropic effects of antithrombotic drugs in the future.
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41
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Tieleman RG, Klok FA, Belfroid E, Hoogervorst-Schilp J, Schalkers I, Jansen CW, Siebelink HJ. Effect of anticoagulant therapy in COVID-19 patients. Neth Heart J 2021; 29:35-44. [PMID: 33861430 PMCID: PMC8050812 DOI: 10.1007/s12471-021-01574-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND In patients hospitalised with COVID-19, an increased incidence of thromboembolic events, such as pulmonary embolism, deep vein thrombosis and stroke, has been reported. It is unknown whether anticoagulation can prevent these complications and improve outcome. METHODS A systematic literature search was performed to answer the question: What is the effect of (prophylactic and therapeutic dose) anticoagulation therapy in COVID-19 patients on cardiovascular and thromboembolic complications and clinical outcome? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Medline and Embase databases were searched with relevant search terms until 17 July 2020. After systematic analysis, eight studies were included. Analysis was stratified for the start of anticoagulation before or during hospital admission. RESULTS There was insufficient evidence that therapeutic anticoagulation could improve the outcome in patients hospitalised with COVID-19. None of the studies demonstrated improved mortality, except for one very small Italian study. Furthermore, none of the studies showed a positive effect of anticoagulation on other outcome measures in COVID-19, such as ICU admission, length of hospital stay, thromboembolic complications, need for mechanical ventilation, acute kidney failure or need for renal replacement therapy, except for two studies demonstrating an association between anticoagulation and a lower incidence of pulmonary embolism. However, the level of evidence of all studies varied from 'low' to 'very low', according to the GRADE methodology. CONCLUSION Analysis of the literature showed that there was insufficient evidence to answer our objective on the effect of anticoagulation on outcome in COVID-19 patients, especially due to the low scientific quality of the described studies. Randomised controlled studies are needed to answer this question.
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Affiliation(s)
- R G Tieleman
- Department of Cardiology, Martini Hospital, Groningen, The Netherlands.
| | - F A Klok
- Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - E Belfroid
- Knowledge Institute of Medical Specialists, Utrecht, The Netherlands
| | | | | | - C W Jansen
- Netherlands Society of Cardiology, Utrecht, The Netherlands
| | - H J Siebelink
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
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42
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Sjöström A, Wersäll JD, Warnqvist A, Farm M, Magnusson M, Oldner A, Ågren A, Antovic J, Bruzelius M. Platelet Count Rose While D-Dimer Levels Dropped as Deaths and Thrombosis Declined-An Observational Study on Anticoagulation Shift in COVID-19. Thromb Haemost 2021; 121:1610-1621. [PMID: 33831964 DOI: 10.1055/a-1477-3829] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND High levels of D-dimer and low platelet counts are associated with poor outcome in coronavirus disease 2019 (COVID-19). As anticoagulation appeared to improve survival, hospital-wide recommendations regarding higher doses of anticoagulation were implemented on April 9, 2020. OBJECTIVES To investigate if trends in D-dimer levels and platelet counts were associated with death, thrombosis, and the shift in anticoagulation. METHODS Retrospective cohort study of 429 patients with COVID-19 at Karolinska University Hospital. Information on D-dimer levels and platelet counts was obtained from laboratory databases and clinical data from medical records. RESULTS Thirty-day mortality and thrombosis rates were 19% and 18%, respectively. Pulmonary embolism was common, 65/83 (78%). Increased D-dimer levels in the first week in hospital were significantly associated with death and thrombosis (odds ratio [OR]: 6.06; 95% confidence interval [CL]: 2.10-17.5 and 3.11; 95% CI: 1.20-8.10, respectively). If platelet count increased more than 35 × 109/L per day, the mortality and thrombotic risk decreased (OR: 0.16; 95% CI: 0.06-0.41, and OR: 0.36; 95% CI: 0.17-0.80). After implementation of updated hospital-wide recommendations, the daily mean significantly decreased regarding D-dimer levels while platelet counts rose; -1.93; 95% CI: -1.00-2.87 mg/L FEU (fibrinogen-equivalent unit) and 65; 95% CI: 54-76 ×109/L, and significant risk reductions for death and thrombosis were observed; OR: 0.48; 95% CI: 0.25-0.92 and 0.35; 95% CI: 0.17-0.72. CONCLUSION In contrast to D-dimer levels, increase of platelet count over the first week in hospital was associated with improved survival and reduced thrombotic risk. The daily mean levels of D-dimer dropped while the platelet counts rose, coinciding with increased anticoagulation and a decline in thrombotic burden and mortality.
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Affiliation(s)
- Anna Sjöström
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Clinical Chemistry, Karolinska University Laboratory, Stockholm, Sweden
| | | | - Anna Warnqvist
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Maria Farm
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Clinical Chemistry, Karolinska University Laboratory, Stockholm, Sweden
| | - Maria Magnusson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden
| | - Anders Oldner
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.,Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Ågren
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.,Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Jovan Antovic
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Clinical Chemistry, Karolinska University Laboratory, Stockholm, Sweden
| | - Maria Bruzelius
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
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43
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Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol 2021; 21:319-329. [PMID: 33824483 PMCID: PMC8023349 DOI: 10.1038/s41577-021-00536-9] [Citation(s) in RCA: 603] [Impact Index Per Article: 150.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2021] [Indexed: 02/07/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease. Here, the authors propose that SARS-CoV-2 induces a prothrombotic state, with dysregulated immunothrombosis in lung microvessels and endothelial injury, which drive the clinical manifestations of severe COVID-19. They discuss potential antithrombotic and immunomodulating drugs that are being considered in the treatment of patients with COVID-19.
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Vrotsou K, Rotaeche R, Mateo-Abad M, Machón M, Vergara I. Variables associated with COVID-19 severity: an observational study of non-paediatric confirmed cases from the general population of the Basque Country, Spain. BMJ Open 2021; 11:e049066. [PMID: 33795313 PMCID: PMC8024058 DOI: 10.1136/bmjopen-2021-049066] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/04/2021] [Accepted: 03/17/2021] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES To investigate which were the most relevant sociodemographic and clinical variables associated with COVID-19 severity, and uncover how their inter-relations may have affected such severity. DESIGN A retrospective observational study based on electronic health record data. PARTICIPANTS Individuals ≥14 years old with a positive PCR or serology test, between 28 February and 31 May 2020, belonging to the Basque Country (Spain) public health system. Institutionalised and individuals admitted to a hospital at home unit were excluded from the study. MAIN OUTCOME MEASURE Three severity categories were established: primary care, hospital/intensive care unit admission and death. RESULTS A total of n=14 197 cases fulfilled the inclusion criteria. Most variables presented statistically significant associations with the outcome (p<0.0001). The Classification and Regression Trees recursive partitioning methodology (based on n=13 792) suggested that among all associations, those with, age, sex, stratification of patient healthcare complexity, chronic consumption of blood and blood-forming organ, and nervous system drugs, as well as the total number of chronic Anatomical Therapeutic Chemical types were the most relevant. Psychosis also emerged as a potential factor. CONCLUSIONS Older cases are more likely to experience more severe outcomes. However, the sex, underlying health status and chronic drug consumption may interfere and alter the ageing effect. Understanding the factors related to the outcome severity is of key importance when designing and promoting public health intervention plans for the COVID-19 pandemic.
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Affiliation(s)
- Kalliopi Vrotsou
- Primary Care Group, Biodonostia Institute for Health Research, Donostia-San Sebastián, Spain
- Research Network in Health Services in Chronic Diseases (REDISSEC), Kronikgune Health Services Research Institute, Baracaldo, Spain
| | - Rafael Rotaeche
- Alza Health Center, Osakidetza-Basque Health Service, Donostia-San Sebastian, Spain
| | - Maider Mateo-Abad
- Research Network in Health Services in Chronic Diseases (REDISSEC), Kronikgune Health Services Research Institute, Baracaldo, Spain
| | - Mónica Machón
- Primary Care Group, Biodonostia Institute for Health Research, Donostia-San Sebastián, Spain
- Research Network in Health Services in Chronic Diseases (REDISSEC), Kronikgune Health Services Research Institute, Baracaldo, Spain
| | - Itziar Vergara
- Primary Care Group, Biodonostia Institute for Health Research, Donostia-San Sebastián, Spain
- Research Network in Health Services in Chronic Diseases (REDISSEC), Kronikgune Health Services Research Institute, Baracaldo, Spain
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Winkler MS, Skirecki T, Brunkhorst FM, Cajander S, Cavaillon JM, Ferrer R, Flohé SB, García-Salido A, Giamarellos-Bourboulis EJ, Girardis M, Kox M, Lachmann G, Martin-Loeches I, Netea MG, Spinetti T, Schefold JC, Torres A, Uhle F, Venet F, Weis S, Scherag A, Rubio I, Osuchowski MF. Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge. EBioMedicine 2021; 66:103291. [PMID: 33813139 PMCID: PMC8016444 DOI: 10.1016/j.ebiom.2021.103291] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 02/22/2021] [Accepted: 03/05/2021] [Indexed: 02/07/2023] Open
Abstract
Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge. In this review, we characterize the existing animal models exposing their relevance and limitations as well as outline their utility in COVID-19 drug and vaccine development. Concurrently, we summarize the status of clinical trial research and discuss the novel tactics utilized in the largest multi-center trials aiming to accelerate generation of reliable results that may subsequently shape COVID-19 clinical treatment practices. We also highlight areas of improvement for animal studies in order to elevate their translational utility. In pandemics, to optimize the use of strained resources in a short time-frame, optimizing and strengthening the synergy between the preclinical and clinical domains is pivotal.
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Affiliation(s)
- Martin S Winkler
- Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Robert-Koch-Str. 40, 37085 Göttingen, Germany
| | - Tomasz Skirecki
- Laboratory of Flow Cytometry, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Frank M Brunkhorst
- Dept. of Anesthesiology and Intensive Care Medicine & Center for Sepsis Control and Care (CSCC), Jena University Hospital-Friedrich Schiller University, Am Klinikum 1, 07747 Jena, Germany; Center for Clinical Studies, Jena University Hospital, 07747 Jena, Germany
| | - Sara Cajander
- Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Sweden
| | | | - Ricard Ferrer
- Intensive Care Department and Shock, Organ Dysfunction and Resuscitation Research Group, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, Barcelona, 08035, Spain; Centro de Investigación Biomedica En Red-Enfermedades Respiratorias (CibeRes, CB06/06/0028), Instituto de salud Carlos III (ISCIII), Av. de Monforte de Lemos, 5, 28029 Madrid, Spain
| | - Stefanie B Flohé
- Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
| | - Alberto García-Salido
- Pediatric Critical Care Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | | | - Massimo Girardis
- Department of Anesthesia and Intensive Care, University Hospital of Modena, Italy
| | - Matthijs Kox
- Department of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands
| | - Gunnar Lachmann
- Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany
| | - Ignacio Martin-Loeches
- Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, James's St N, Ushers, Dublin, D03 VX82, Ireland
| | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Thibaud Spinetti
- Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, 3010 Bern, Switzerland
| | - Joerg C Schefold
- Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, 3010 Bern, Switzerland
| | - Antoni Torres
- Pneumology Department, Respiratory Institute (ICR), Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - University of Barcelona (UB), Spain
| | - Florian Uhle
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
| | - Fabienne Venet
- Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, 5 Place d'Arsonval, 69003 Lyon, France; EA 7426 "Pathophysiology of Injury-Induced Immunosuppression - PI3", Université Claude Bernard Lyon 1/bioMérieux/Hospices Civils de Lyon, Edouard Herriot Hospital, 5 Place d'Arsonval, 69003 Lyon, France
| | - Sebastian Weis
- Dept. of Anesthesiology and Intensive Care Medicine & Center for Sepsis Control and Care (CSCC), Jena University Hospital-Friedrich Schiller University, Am Klinikum 1, 07747 Jena, Germany; Institute for Infectious Disease and Infection Control, Jena University Hospital-Friedrich Schiller University, Am Klinikum 1, 07747 Jena, Germany
| | - André Scherag
- Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital-Friedrich Schiller University, Bachstrasse 18, 07743 Jena, Germany
| | - Ignacio Rubio
- Dept. of Anesthesiology and Intensive Care Medicine & Center for Sepsis Control and Care (CSCC), Jena University Hospital-Friedrich Schiller University, Am Klinikum 1, 07747 Jena, Germany
| | - Marcin F Osuchowski
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA Research Center, Donaueschingenstrasse 13, 1200, Vienna, Austria.
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Patel NG, Bhasin A, Feinglass JM, Angarone MP, Cohen ER, Barsuk JH. Mortality, critical illness, and mechanical ventilation among hospitalized patients with COVID-19 on therapeutic anticoagulants. THROMBOSIS UPDATE 2021; 2:100027. [PMID: 38620459 PMCID: PMC7732225 DOI: 10.1016/j.tru.2020.100027] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 12/06/2020] [Accepted: 12/08/2020] [Indexed: 12/22/2022] Open
Abstract
Background COVID-19 is associated with hypercoagulability and increased incidence of thrombosis. We compared the clinical outcomes of adults hospitalized with COVID-19 who were on therapeutic anticoagulants to those on prophylactic anticoagulation. Materials and methods We performed an observational study of adult inpatients' with COVID-19 from March 9 to June 26, 2020. We compared patients who were continued on their outpatient prescribed therapeutic anticoagulation and those who were newly started on therapeutic anticoagulation for COVID-19 (without other indication) to those who were on prophylactic doses. The primary outcome was overall death while secondary outcomes were critical illness (World Health Organization Ordinal Scale for Clinical Improvement score ≥5), mechanical ventilation, and death among patients who first had critical illness. We adjusted for age, sex, race, body mass index (BMI), Charlson score, glucose on admission, and use of antiplatelet agents. Results Of 1716 inpatients with COVID-19, 171 patients were continued on their therapeutic anticoagulation and 78 were started on new therapeutic anticoagulation for COVID-19. In patients continued on home therapeutic anticoagulation, there were no differences in overall death, critical illness, mechanical ventilation, or death among patients with critical illness compared to patients on prophylactic anticoagulation. In patients receiving new therapeutic anticoagulation for COVID-19, there was increased death (OR 5.93; 95% CI 3.71-9.47), critical illness (OR 14.51; 95% CI 7.43-28.31), need mechanical ventilation (OR 11.22; 95% CI 6.67-18.86), and death after first having critical illness (OR 5.51; 95% CI 2.80-10.87). Conclusions Therapeutic anticoagulation for inpatients with COVID-19 was not associated with improved outcomes.
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Affiliation(s)
- Niti G Patel
- Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, IL, USA
| | - Ajay Bhasin
- Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, IL, USA
| | - Joseph M Feinglass
- Northwestern University Feinberg School of Medicine, Division of General Internal Medicine and Geriatrics, Chicago, IL, USA
| | - Michael P Angarone
- Northwestern University Feinberg School of Medicine, Division of Infectious Diseases, Department of Medicine, Chicago, IL, USA
| | - Elaine R Cohen
- Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, IL, USA
| | - Jeffrey H Barsuk
- Northwestern University Feinberg School of Medicine, Department of Medicine, Chicago, IL, USA
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Flam B, Wintzell V, Ludvigsson JF, Mårtensson J, Pasternak B. Direct oral anticoagulant use and risk of severe COVID-19. J Intern Med 2021; 289:411-419. [PMID: 33258156 PMCID: PMC7753564 DOI: 10.1111/joim.13205] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/03/2020] [Accepted: 11/09/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND Hypercoagulability and thromboembolism are prominent features of severe COVID-19, and ongoing anticoagulant use might be protective. METHODS We conducted a nationwide register-based cohort study in Sweden, February through May, 2020, to assess whether ongoing direct oral anticoagulant (DOAC) use was associated with reduced risk of hospital admission for laboratory-confirmed COVID-19, or a composite of intensive care unit (ICU) admission or death due to laboratory-confirmed COVID-19. RESULTS DOAC use (n = 103 703) was not associated with reduced risk of hospital admission for COVID-19 (adjusted hazard ratio [aHR] [95% confidence interval] 1.00 [0.75-1.33] vs. nonuse atrial fibrillation comparator [n = 36 875]; and aHR 0.94 [0.80-1.10] vs. nonuse cardiovascular disease comparator [n = 355 699]), or ICU admission or death due to COVID-19 (aHRs 0.76 [0.51-1.12], and 0.90 [0.71-1.15], respectively). CONCLUSION Ongoing DOAC use was not associated with reduced risk of severe COVID-19, indicating that prognosis would not be modified by early outpatient DOAC initiation.
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Affiliation(s)
- B Flam
- From the, Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.,Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - V Wintzell
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - J F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.,Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - J Mårtensson
- From the, Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.,Section of Anaesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - B Pasternak
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
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Rentsch CT, Beckman JA, Tomlinson L, Gellad WF, Alcorn C, Kidwai-Khan F, Skanderson M, Brittain E, King JT, Ho YL, Eden S, Kundu S, Lann MF, Greevy RA, Ho PM, Heidenreich PA, Jacobson DA, Douglas IJ, Tate JP, Evans SJW, Atkins D, Justice AC, Freiberg MS. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ 2021; 372:n311. [PMID: 33574135 PMCID: PMC7876672 DOI: 10.1136/bmj.n311] [Citation(s) in RCA: 147] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/01/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. DESIGN Observational cohort study. SETTING Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. PARTICIPANTS All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. MAIN OUTCOME MEASURES The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. RESULTS Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. CONCLUSIONS Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.
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Affiliation(s)
- Christopher T Rentsch
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
- VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT, USA
| | - Joshua A Beckman
- Cardiovascular Division, Vanderbilt University Medical Center and Vanderbilt Translational and Clinical Cardiovascular Research Center, Nashville, TN, USA
| | - Laurie Tomlinson
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
| | - Walid F Gellad
- Center for Pharmaceutical Policy and Prescribing, Health Policy Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Division of General Internal Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Veterans Affairs Pittsburgh Healthcare System, US Department of Veterans Affairs, Pittsburgh, PA, USA
| | - Charles Alcorn
- Center for Occupational Biostatistics and Epidemiology, Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Farah Kidwai-Khan
- VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT, USA
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Melissa Skanderson
- VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT, USA
| | - Evan Brittain
- Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Translational and Clinical Cardiovascular Research Center, Nashville, TN, USA
| | - Joseph T King
- VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT, USA
- Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA
| | - Yuk-Lam Ho
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA
| | - Svetlana Eden
- Faculty of Biostatistics, Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Suman Kundu
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael F Lann
- Center for Occupational Biostatistics and Epidemiology, Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Robert A Greevy
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - P Michael Ho
- Rocky Mountain Regional VA Medical Center, US Department of Veterans Affairs, Aurora, CO, USA
| | - Paul A Heidenreich
- VA Palo Alto Healthcare System, US Department of Veterans Affairs, Palo Alto, CA, USA
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Daniel A Jacobson
- Oak Ridge National Laboratory, Biosciences Division, Oak Ridge, TN, USA
| | - Ian J Douglas
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
| | - Janet P Tate
- VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT, USA
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Stephen J W Evans
- Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
| | - David Atkins
- Health Services Research and Development, US Department of Veterans Affairs, Washington, DC, USA
| | - Amy C Justice
- VA Connecticut Healthcare System, US Department of Veterans Affairs, West Haven, CT, USA
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
- Center for Interdisciplinary Research on AIDS, Yale School of Public Health, New Haven, CT, USA
| | - Matthew S Freiberg
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, US Department of Veterans Affairs, Nashville, TN, USA
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49
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Zuo Z, Wu T, Pan L, Zuo C, Hu Y, Luo X, Jiang L, Xia Z, Xiao X, Liu J, Ye M, Deng M. Modalities and Mechanisms of Treatment for Coronavirus Disease 2019. Front Pharmacol 2021; 11:583914. [PMID: 33643033 PMCID: PMC7908061 DOI: 10.3389/fphar.2020.583914] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 12/03/2020] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials underway. Current treatments could be divided into two major part: anti-viral agents and host system modulatory agents. On one hand, anti-viral agents focus on virus infection process. Umifenovir blocks virus recognizing host and entry. Remdesivir inhibits virus replication. Chloroquine and hydroxychloroquine involve preventing the whole infection process, including virus transcription and release. On the other hand, host system modulatory agents are associated with regulating the imbalanced inflammatory reaction and biased immune system. Corticosteroid is believed to be commonly used for repressing hyper-inflammation, which is one of the major pathologic mechanisms of COVID-19. Convalescent plasma and neutralizing antibodies provide essential elements for host immune system and create passive immunization. Thrombotic events are at high incidence in COVID-19 patients, thus anti-platelet and anti-coagulation are crucial, as well. Here, we summarized these current or reproposed agents to better understand the mechanisms of agents and give an update of present research situation.
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Affiliation(s)
- Zhihong Zuo
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Ting Wu
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
- Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Liangyu Pan
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
| | - Chenzhe Zuo
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Yingchuo Hu
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
| | - Xuan Luo
- Hunan Yuanpin Cell Biotechnology Co., Ltd., Changsha, China
| | - Liping Jiang
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Zanxian Xia
- Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China
- Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
| | - Xiaojuan Xiao
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
| | - Jing Liu
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
| | - Mao Ye
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China
| | - Meichun Deng
- Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
- Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
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50
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Schiavone M, Gasperetti A, Mancone M, Curnis A, Mascioli G, Mitacchione G, Busana M, Sabato F, Gobbi C, Antinori S, Galli M, Forleo GB. Oral anticoagulation and clinical outcomes in COVID-19: An Italian multicenter experience. Int J Cardiol 2021; 323:276-280. [PMID: 32911000 PMCID: PMC7476907 DOI: 10.1016/j.ijcard.2020.09.001] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 08/30/2020] [Accepted: 09/01/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND Since the body of evidence addressing the coagulation derangements caused by Coronavirus disease (COVID-19) has been constantly growing, we investigated whether pre-hospitalization oral anticoagulation (OAC) or in-hospital heparin treatment could have a protective role among COVID-19 patients. METHOD In this cohort study, consecutive COVID-19 patients admitted to four different Italian Institutions were enrolled. Baseline demographic, clinical, laboratory, and radiological characteristics, as well as in-hospital treatment and outcomes were evaluated. The primary outcome was mortality. RESULTS A total of 844 COVID-19 patients were enrolled as study cohort, n = 65 (7.7%) taking OACs prior to hospitalization. Regarding clinical outcomes, OAC patients developed acute hypoxemic respiratory failure (AHRF) more frequently than non-OAC patients as well as presenting a higher mortality rate (44.6% vs 19.8%, p < 0.001). At overall multivariate logistical regression, use of heparin (n = 394, 46.6%) was associated with a better chance of survival to hospital discharge (OR 0.60 [0.38-0.94], p < 0.001), in particular in patients with AHRF, with no association found with the use of OACs. In a sub-analysis, the highest mortality rate was found for AHRF patients when heparin was not administered. CONCLUSION In our cohort, OACs appeared to be ineffective in reducing mortality rate, while heparin resulted to be a useful treatment when lung disease was sufficiently severe, potentially suggesting a crucial role of microthrombosis in severe COVID-19. Due to the relatively small number of COVID-19 patients treated with OACs included in our analysis and their higher number of comorbidities, larger studies are needed in order to confirm our findings.
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Affiliation(s)
- Marco Schiavone
- Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy
| | - Alessio Gasperetti
- Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy
| | - Massimo Mancone
- Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Antonio Curnis
- Institute of Cardiology, ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
| | - Giosuè Mascioli
- Cardiovascular Department, Humanitas Gavazzeni Hospital, Bergamo, Italy
| | - Gianfranco Mitacchione
- Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy
| | - Mattia Busana
- Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany
| | - Federica Sabato
- Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy
| | | | - Spinello Antinori
- Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy; Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy
| | - Massimo Galli
- Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy; Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy
| | - Giovanni Battista Forleo
- Department of Cardiology, ASST-Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy.
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