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1.
Microvasc Res ; 140: 104310, 2022 03.
Article in English | MEDLINE | ID: covidwho-1586954

ABSTRACT

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.


Subject(s)
COVID-19/physiopathology , Diabetic Angiopathies/physiopathology , Endothelium, Vascular/pathology , Microcirculation , Pandemics , SARS-CoV-2 , Thrombophilia/etiology , Albuminuria/etiology , COVID-19/complications , Capillary Permeability , Delivery of Health Care , Diabetic Angiopathies/complications , Diabetic Nephropathies/complications , Diabetic Nephropathies/physiopathology , Diabetic Neuropathies/complications , Diabetic Neuropathies/physiopathology , Diabetic Retinopathy/complications , Diabetic Retinopathy/physiopathology , Endothelium, Vascular/injuries , Humans , Obesity/complications , Obesity/physiopathology , Pulmonary Circulation , Pulmonary Edema/etiology , Pulmonary Edema/physiopathology , Severity of Illness Index , Thrombophilia/physiopathology , Treatment Outcome
2.
J Mol Cell Cardiol ; 164: 69-82, 2022 03.
Article in English | MEDLINE | ID: covidwho-1531870

ABSTRACT

The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection. In addition, we discuss potential biomarkers that might indicate the disease severity, particularly related to the abnormal development of thrombosis that is a fatal vascular complication of severe COVID-19. Furthermore, we summarize clinical trials targeting the direct and indirect pathological pathways after SARS-CoV-2 infection to prevent or inhibit the virus induced endothelial disorders.


Subject(s)
COVID-19/pathology , Endothelium, Vascular/pathology , SARS-CoV-2 , Adolescent , Adult , Aged , Angiotensin-Converting Enzyme 2/physiology , Animals , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , COVID-19/therapy , Clinical Trials as Topic , Endothelial Cells/pathology , Endothelial Cells/virology , Endothelium, Vascular/immunology , Endothelium, Vascular/physiopathology , HMGB1 Protein/physiology , Humans , Macaca mulatta , Mice , Neuropilin-1/physiology , Oxidative Stress , Reactive Oxygen Species , Receptors, Virus/physiology , Scavenger Receptors, Class B/physiology , Severity of Illness Index , Signal Transduction , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/physiopathology , Thrombophilia/etiology , Thrombophilia/physiopathology , Vascular Endothelial Growth Factor A/physiology , Vasculitis/etiology , Vasculitis/immunology , Vasculitis/physiopathology , Young Adult
3.
Inflammopharmacology ; 29(4): 1017-1031, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1286160

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-COV-2) is the culprit of the Coronavirus Disease (COVID-19), which has infected approximately 173 million people and killed more than 3.73 million. At risk groups including diabetic and obese patients are more vulnerable to COVID-19-related complications and poor outcomes. Substantial evidence points to hypovitaminosis D as a risk factor for severe disease, the need for ICU, and mortality. 1,25(OH)D, a key regulator of calcium homeostasis, is believed to have various immune-regulatory roles including; promoting anti-inflammatory cytokines, down regulating pro-inflammatory cytokines, dampening entry and replication of SARS-COV-2, and the production of antimicrobial peptides. In addition, there are strong connections which suggest that dysregulated 1,25(OH)D levels play a mechanistic and pathophysiologic role in several disease processes that are shared with COVID-19 including: diabetes, obesity, acute respiratory distress syndrome (ARDS), cytokine storm, and even hypercoagulable states. With evidence continuing to grow for the case that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, there is a need now to address the public health efforts set in place to minimize infection, such as lock down orders, which may have inadvertently increased hypovitaminosis D in the general population and those already at risk (elderly, obese, and disabled). Moreover, there is a need to address the implications of this evidence and how we may apply the use of cheaply available supplementation, which has yet to overcome the near global concern of hypovitaminosis D. In our review, we exhaustively scope these shared pathophysiologic connections between COVID-19 and hypovitaminosis D.


Subject(s)
COVID-19/metabolism , Cytokine Release Syndrome/metabolism , Thrombophilia/metabolism , Vitamin D Deficiency/metabolism , Vitamin D/administration & dosage , Vitamin D/metabolism , COVID-19/complications , COVID-19/drug therapy , COVID-19/physiopathology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/physiopathology , Humans , Obesity/epidemiology , Obesity/metabolism , Obesity/physiopathology , Risk Factors , Thrombophilia/drug therapy , Thrombophilia/physiopathology , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/physiopathology
5.
Stroke ; 52(5): 1885-1894, 2021 05.
Article in English | MEDLINE | ID: covidwho-1166635

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 or coronavirus disease 2019 (COVID-19) pandemic has raised concerns about the correlation with this viral illness and increased risk of stroke. Although it is too early in the pandemic to know the strength of the association between COVID-19 and stroke, it is an opportune time to review the relationship between acute viral illnesses and stroke. Here, we summarize pathophysiological principles and available literature to guide understanding of how viruses may contribute to ischemic stroke. After a review of inflammatory mechanisms, we summarize relevant pathophysiological principles of vasculopathy, hypercoagulability, and hemodynamic instability. We will end by discussing mechanisms by which several well-known viruses may cause stroke in an effort to inform our understanding of the relationship between COVID-19 and stroke.


Subject(s)
Brain Ischemia/complications , Brain Ischemia/physiopathology , COVID-19/complications , COVID-19/epidemiology , Ischemic Stroke/complications , Ischemic Stroke/physiopathology , Acute Disease , Blood Coagulation , Brain Ischemia/virology , Hemodynamics , Herpesvirus 3, Human , Humans , Inflammation/physiopathology , Ischemic Stroke/virology , Pandemics , Plaque, Atherosclerotic/physiopathology , Risk , Thrombophilia/physiopathology , Thrombosis/physiopathology , Vascular Diseases/physiopathology , Virus Diseases/physiopathology
6.
Eur J Clin Invest ; 51(5): e13546, 2021 May.
Article in English | MEDLINE | ID: covidwho-1142880
7.
Int J Hematol ; 113(1): 45-57, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1064611

ABSTRACT

The pathology of coronavirus disease 2019 (COVID-19) is exacerbated by the progression of thrombosis, and disseminated intravascular coagulation (DIC), and cytokine storms. The most frequently reported coagulation/fibrinolytic abnormality in COVID-19 is the increase in D-dimer, and its relationship with prognosis has been discussed. However, limits exist to the utility of evaluation by D-dimer alone. In addition, since the coagulation/fibrinolytic condition sometimes fluctuates within a short period of time, regular examinations in recognition of the significance of the examination are desirable. The pathophysiology of disseminated intravascular coagulation (DIC) associated with COVID-19 is very different from that of septic DIC, and both thrombotic and hemorrhagic pathologies should be noted. COVID-19 thrombosis includes macro- and microthrombosis, with diagnosis of the latter depending on markers of coagulation and fibrinolysis. Treatment of COVID-19 is classified into antiviral treatment, cytokine storm treatment, and thrombosis treatment. Rather than providing uniform treatment, the treatment method most suitable for the severity and stage should be selected. Combination therapy with heparin and nafamostat is expected to develop in the future. Fibrinolytic therapy and adsorption therapy require further study.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19/blood , Pandemics , SARS-CoV-2 , Adult , Anticoagulants/therapeutic use , Benzamidines , Blood Coagulation Disorders/physiopathology , Blood Coagulation Tests , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/physiopathology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysis , Guanidines/pharmacology , Guanidines/therapeutic use , Humans , Lymphopenia/etiology , Male , Middle Aged , Prognosis , Pulmonary Circulation , SARS-CoV-2/drug effects , Survivors , Thrombocytopenia/etiology , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombophilia/physiopathology
8.
Turk J Haematol ; 38(1): 15-21, 2021 02 25.
Article in English | MEDLINE | ID: covidwho-1045314

ABSTRACT

Objective: The defective interplay between coagulation and inflammation may be the leading cause of intravascular coagulation and organ dysfunction in coronavirus disease-19 (COVID-19) patients. Abnormal coagulation profiles were reported to be associated with poor outcomes. In this study, we assessed the prognostic values of antithrombin (AT) activity levels and the impact of fresh frozen plasma (FFP) treatment on outcome. Materials and Methods: Conventional coagulation parameters as well as AT activity levels and outcomes of 104 consecutive critically ill acute respiratory distress syndrome (ARDS) patients with laboratory-confirmed COVID-19 disease were retrospectively analyzed. Patients with AT activity below 75% were treated with FFP. Maximum AT activity levels achieved in those patients were recorded. Results: AT activity levels at admission were significantly lower in nonsurvivors than survivors (73% vs. 81%). The cutoff level for admission AT activity was 79% and 58% was the lowest AT for survival. The outcome in those patients who had AT activity levels above 75% after FFP treatment was better than that of the nonresponding group. As well as AT, admission values of D-dimer, C-reactive protein, and procalcitonin were coagulation and inflammatory parameters among the mortality risk factors. Conclusion: AT activity could be used as a prognostic marker for survival and organ failure in COVID-19-associated ARDS patients. AT supplementation therapy with FFP in patients with COVID-19-induced hypercoagulopathy may improve thrombosis prophylaxis and thus have an impact on survival.


Subject(s)
Antithrombins/blood , COVID-19/blood , COVID-19/therapy , Critical Illness/mortality , Aged , Aged, 80 and over , Antithrombins/physiology , Antithrombins/therapeutic use , Blood Coagulation Tests/methods , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/mortality , Case-Control Studies , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/prevention & control , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , Plasma , Procalcitonin/analysis , Prognosis , Retrospective Studies , SARS-CoV-2/genetics , Thrombophilia/complications , Thrombophilia/physiopathology , Turkey/epidemiology
9.
Expert Rev Hematol ; 14(2): 155-173, 2021 02.
Article in English | MEDLINE | ID: covidwho-1044433

ABSTRACT

INTRODUCTION: COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management. AREAS COVERED: Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer. EXPERT OPINION: A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19/complications , Complement Activation , SARS-CoV-2 , Animals , Anticoagulants/therapeutic use , Biomarkers , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/immunology , Blood Coagulation Disorders/physiopathology , Blood Coagulation Tests , COVID-19/blood , COVID-19/immunology , COVID-19/therapy , China/epidemiology , Comorbidity , Coronavirus Infections/blood , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/epidemiology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/physiopathology , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Forecasting , Humans , Immunization, Passive , Inflammation/etiology , Inflammation/physiopathology , Iron Chelating Agents/therapeutic use , Ischemia/blood , Ischemia/etiology , Ischemia/physiopathology , Mice , Prevalence , Severe Acute Respiratory Syndrome/blood , Severity of Illness Index , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombophilia/physiopathology , Venous Thromboembolism/blood , Venous Thromboembolism/etiology , Venous Thromboembolism/physiopathology
11.
Rev Neurosci ; 32(3): 341-349, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1021723

ABSTRACT

Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan city, China in December 2019 and rapidly spread to other countries. The most common reported symptoms are fever, dry cough, myalgia and fatigue, headache, anorexia, and breathlessness. Anosmia and dysgeusia as well as gastrointestinal symptoms including nausea and diarrhea are other notable symptoms. This virus also can exhibit neurotropic properties and may also cause neurological diseases, including epileptic seizures, cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. In this study, we discuss stroke as a complication of the new coronavirus and its possible mechanisms of damage.


Subject(s)
COVID-19/physiopathology , Endothelium, Vascular/physiopathology , Hypoxia/physiopathology , Stroke/physiopathology , Thrombophilia/physiopathology , Angiotensin-Converting Enzyme 2/metabolism , Blood Viscosity , COVID-19/blood , COVID-19/complications , COVID-19/metabolism , Humans , Hypoxia/complications , Myocarditis/complications , Myocarditis/physiopathology , Renin-Angiotensin System , Risk , SARS-CoV-2/metabolism , Stroke/blood , Stroke/etiology , Stroke/metabolism , Thrombophilia/blood , Thrombophilia/etiology
12.
S Afr Med J ; 110(12): 1180-1185, 2020 10 23.
Article in English | MEDLINE | ID: covidwho-994155

ABSTRACT

COVID-19 severity appears to lie in its propensity to cause a hyperinflammatory response, attributed to the cytokine release syndrome (CRS) or 'cytokine storm', although the exact role of the CRS remains to be fully elucidated. Hyperinflammation triggers a hypercoagulable state, also thought to play a key role in COVID-19 pathogenesis. Disease severity is linked to age, sex and comorbid conditions, which in turn may be linked to oxidative stress and pre-existing depletion of nicotinamide adenine dinucleotide (NAD+). There is increasing evidence that the host genome may determine disease outcome. Since most information pertaining to COVID-19 has thus far been extrapolated from the 'global North', similar studies in African populations are warranted. Many studies are aimed at finding a therapeutic strategy based on scientific rationale. Some promising results have emerged, e.g. the use of corticosteroids in severe acute respiratory distress syndrome (ARDS).


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Inflammation/immunology , Thrombophilia/blood , Adrenal Cortex Hormones/therapeutic use , Age Factors , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/drug therapy , COVID-19/physiopathology , COVID-19/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , HLA Antigens/genetics , Humans , Immunization, Passive , Inflammation/blood , Inflammation/drug therapy , NAD , Oxidative Stress , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/physiopathology , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/therapy , Thrombophilia/drug therapy , Thrombophilia/physiopathology , Vitamins/therapeutic use
13.
Int J Hematol ; 113(1): 45-57, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-915246

ABSTRACT

The pathology of coronavirus disease 2019 (COVID-19) is exacerbated by the progression of thrombosis, and disseminated intravascular coagulation (DIC), and cytokine storms. The most frequently reported coagulation/fibrinolytic abnormality in COVID-19 is the increase in D-dimer, and its relationship with prognosis has been discussed. However, limits exist to the utility of evaluation by D-dimer alone. In addition, since the coagulation/fibrinolytic condition sometimes fluctuates within a short period of time, regular examinations in recognition of the significance of the examination are desirable. The pathophysiology of disseminated intravascular coagulation (DIC) associated with COVID-19 is very different from that of septic DIC, and both thrombotic and hemorrhagic pathologies should be noted. COVID-19 thrombosis includes macro- and microthrombosis, with diagnosis of the latter depending on markers of coagulation and fibrinolysis. Treatment of COVID-19 is classified into antiviral treatment, cytokine storm treatment, and thrombosis treatment. Rather than providing uniform treatment, the treatment method most suitable for the severity and stage should be selected. Combination therapy with heparin and nafamostat is expected to develop in the future. Fibrinolytic therapy and adsorption therapy require further study.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19/blood , Pandemics , SARS-CoV-2 , Adult , Anticoagulants/therapeutic use , Benzamidines , Blood Coagulation Disorders/physiopathology , Blood Coagulation Tests , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/physiopathology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysis , Guanidines/pharmacology , Guanidines/therapeutic use , Humans , Lymphopenia/etiology , Male , Middle Aged , Prognosis , Pulmonary Circulation , SARS-CoV-2/drug effects , Survivors , Thrombocytopenia/etiology , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombophilia/physiopathology
15.
Surg Innov ; 28(2): 236-238, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-806393

ABSTRACT

Aim. The disease caused by the 2019 novel coronavirus is known predominantly for its respiratory outcomes; a subset of critically ill patients demonstrates clinically remarkable hypercoagulability in which thrombotic events range from acute pulmonary embolism in patients with COVID-19 pneumonia to extremity ischemia. Our observational study aimed to describe the incidence and characteristics, as well as clinical outcomes, of patients presenting and treated for mesenteric ischemia during the COVID-19 pandemic. Material and Methods. Between March 13 and May 13, 2020, 60 patients operated for emergency reasons were analyzed, and it was noticed that 5 of the 6 COVID-positive patients were operated due to mesenteric ischemia. Results. Five of sixty patients (83.3%) applied to our emergency clinic with COVID-19 positive and acute abdomen. Two of them (40%) did not have any comorbidities. All of them (%100) were male. There were no complications and only 1 death (20%). Mean leukocyte, neutrophil, and platelet levels were within the normal range, while the lymphocyte level was near the lower limit. C-Reactive Protein was above the limit in all patients. The mean levels of International Normalized Ratio, Platelet, and Activated Partial Thromboplastin Time were above the limits. While D-dimer levels were close to the upper limit; fibrinogen levels were above the normal limit for each patient. Conclusion. The presence of hypercoagulation status in critical COVID-19 patients should be observed closely, and anticoagulation therapy can be considered in selected patients. More clinical data are needed to examine the role of anticoagulation in COVID-19 treatment.


Subject(s)
COVID-19 , Mesenteric Ischemia , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/physiopathology , Critical Illness , Humans , Male , Mesenteric Ischemia/physiopathology , Mesenteric Ischemia/virology , Middle Aged , SARS-CoV-2 , Thrombophilia/physiopathology , Thrombophilia/virology
17.
Front Endocrinol (Lausanne) ; 11: 530, 2020.
Article in English | MEDLINE | ID: covidwho-719724

ABSTRACT

COVID-19, caused by SARS-CoV-2, is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Several reports from around the world have identified obesity and severe obesity as one of the strongest risk factors for COVID-19 hospitalization and mechanical ventilation. Moreover, countries with greater obesity prevalence have a higher morbidity and mortality risk of developing serious outcomes from COVID-19. The understanding of how this increased susceptibility of the people with obesity to develop severe forms of the SARS-CoV-2 infection occurs is crucial for implementing appropriate public health and therapeutic strategies to avoid COVID-19 severe symptoms and complications in people living with obesity. We hypothesize here that increased ACE2 expression in adipose tissue displayed by people with obesity may increase SARS-CoV-2 infection and accessibility to this tissue. Individuals with obesity have increased white adipose tissue, which may act as a reservoir for a more extensive viral spread with increased shedding, immune activation and pro-inflammatory cytokine amplification. Here we discuss how obesity is related to a pro-inflammatory and metabolic dysregulation, increased SARS-CoV-2 host cell entry in adipose tissue and induction of hypercoagulopathy, leading people with obesity to develop severe forms of COVID-19 and also death. Taken together, it may be crucial to better explore the role of visceral adipose tissue in the inflammatory response to SARS-CoV-2 infection and investigate the potential therapeutic effect of using specific target anti-inflammatories (canakinumab or anakinra for IL-1ß inhibition; anti-IL-6 antibodies for IL-6 inhibition), anticoagulant or anti-diabetic drugs in COVID-19 treatment of people with obesity. Defining the immunopathological changes in COVID-19 patients with obesity can provide prominent targets for drug discovery and clinical management improvement.


Subject(s)
Adipose Tissue/physiopathology , Betacoronavirus/isolation & purification , Coronavirus Infections/mortality , Inflammation/physiopathology , Obesity/complications , Pneumonia, Viral/mortality , Thrombophilia/physiopathology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Prognosis , SARS-CoV-2 , Survival Rate
18.
Life Sci ; 258: 118166, 2020 Oct 01.
Article in English | MEDLINE | ID: covidwho-703163

ABSTRACT

In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. Activated macrophages secrete proinflammatory cytokines and chemokines and tend to polarise into the inflammatory M1 phenotype. These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS. Pulmonary activated platelets are also an important source of proinflammatory cytokines and ROS, as well as exacerbating pulmonary neutrophil-mediated inflammatory responses and contributing to systemic sepsis by binding to neutrophils to form platelet-neutrophil complexes (PNCs). PNC formation increases neutrophil recruitment, activation priming and extraversion of these immune cells into inflamed pulmonary tissue, thereby contributing to ARDS. Sequestered PNCs cause the development of a procoagulant and proinflammatory environment. The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Respiratory Distress Syndrome/physiopathology , Alveolar Epithelial Cells/immunology , Alveolar Epithelial Cells/pathology , Animals , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Humans , Immunity, Innate , Inflammation/etiology , Inflammation/immunology , Inflammation/physiopathology , Inflammation/therapy , Macrophage Activation , Macrophages, Alveolar/immunology , Macrophages, Alveolar/pathology , Neutrophil Activation , Pandemics , Platelet Activation , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Thrombophilia/etiology , Thrombophilia/immunology , Thrombophilia/physiopathology , Thrombophilia/therapy
19.
Clin Appl Thromb Hemost ; 26: 1076029620936776, 2020.
Article in English | MEDLINE | ID: covidwho-657787

ABSTRACT

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Pandemics , Pneumonia, Viral/complications , Thrombophilia/etiology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Anticoagulants/therapeutic use , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/physiopathology , Arterial Occlusive Diseases/virology , COVID-19 , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Catheterization, Swan-Ganz , Combined Modality Therapy , Coronavirus Infections/blood , Coronavirus Infections/drug therapy , Endothelium, Vascular/physiopathology , Endothelium, Vascular/virology , Fibrinolytic Agents/therapeutic use , Humans , Hyperbaric Oxygenation , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/blood , Pneumonia, Viral/drug therapy , Pulmonary Embolism/etiology , Pulmonary Embolism/therapy , Pulmonary Embolism/virology , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Thrombolytic Therapy/instrumentation , Thrombolytic Therapy/methods , Thrombophilia/physiopathology , Thrombophilia/therapy , Venous Thrombosis/etiology , Venous Thrombosis/physiopathology , Venous Thrombosis/virology , Virus Internalization/drug effects
20.
Thromb Res ; 194: 101-115, 2020 10.
Article in English | MEDLINE | ID: covidwho-608547

ABSTRACT

The 2019 coronavirus disease (COVID-19) presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death. While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis. Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death. Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis. At present, the pathophysiology underlying the hypercoagulable state is poorly understood. However, a growing body of data suggests that the initial events occur in the lung. A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy. This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro- and microvascular thrombosis. Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies. Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.


Subject(s)
Blood Coagulation , COVID-19 , Inflammation/drug therapy , Thrombophilia , Thrombosis , Venous Thromboembolism , Animals , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/physiopathology , Humans , Incidence , Inflammation/blood , Inflammation/epidemiology , Inflammation/physiopathology , Thrombophilia/blood , Thrombophilia/epidemiology , Thrombophilia/physiopathology , Thrombophilia/prevention & control , Thrombosis/blood , Thrombosis/epidemiology , Thrombosis/physiopathology , Thrombosis/therapy , Venous Thromboembolism/blood , Venous Thromboembolism/epidemiology , Venous Thromboembolism/physiopathology , Venous Thromboembolism/therapy
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