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1.
Eur Heart J ; 41(19): 1810-1817, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-629506

ABSTRACT

AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heart Failure/blood , Mineralocorticoid Receptor Antagonists/therapeutic use , Peptidyl-Dipeptidase A/blood , Renin-Angiotensin System/drug effects , Aged , Betacoronavirus , Coronavirus Infections , Europe , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral , Sex Factors
4.
Medwave ; 20(7): e8008, 2020 Aug 28.
Article in Spanish | MEDLINE | ID: covidwho-740553

ABSTRACT

In December 2019, a new strain of the SARS-CoV-2 coronavirus was reported in Wuhan, China, which produced severe lung involvement and progressed to respiratory distress. To date, more than seventeen million confirmed cases and more than half a million died worldwide from COVID-19. Patients with cardiovascular disease are more susceptible to contracting this disease and presenting more complications. We did a literature search on the association of cardiovascular disease and COVID-19 in databases such as Scopus, PubMed/MEDLINE, and the Cochrane Library. The purpose of this review is to provide updated information for health professionals who care for patients with COVID-19 and cardiovascular disease, given that they have a high risk of complications and mortality. Treatment with angiotensin-converting enzyme inhibitors and receptor blockers is controversial, and there is no evidence not to use these medications in patients with COVID-19. Regarding treatment with hydroxychloroquine associated or not with azithromycin, there is evidence of a higher risk with its use than clinical benefit and decreased mortality. Likewise, patients with heart failure are an important risk group due to their condition per se. Patients with heart failure and COVID-19 are a diagnostic dilemma because the signs of acute heart failure could be masked. On the other hand, in patients with acute coronary syndrome, the initial therapeutic approach could change in the context of the pandemic, although only based on expert opinions. Nonetheless, many controversial issues will be the subject of future research.


Subject(s)
Betacoronavirus , Cardiovascular Diseases/complications , Coronavirus Infections/complications , Pneumonia, Viral/complications , Acute Coronary Syndrome/etiology , Acute Coronary Syndrome/therapy , Algorithms , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiviral Agents/adverse effects , Azithromycin/adverse effects , Coronavirus Infections/drug therapy , Drug Therapy, Combination , Electrocardiography/drug effects , Heart Failure/etiology , Heart Failure/therapy , Humans , Hydroxychloroquine/adverse effects , Hypertension/complications , Hypertension/drug therapy , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Prognosis , Renin-Angiotensin System/physiology
5.
J Bras Nefrol ; 42(2 suppl 1): 47-48, 2020 Aug 26.
Article in English, Portuguese | MEDLINE | ID: covidwho-740467

ABSTRACT

This position statement of the Department of Hypertension of the Brazilian Society of Nephrology (SBN) addresses the controversy surrounding the use or suspension/replacement of the renin-angiotensin-aldosterone system blockers (particularly inhibitors of the angiotensin-converting enzyme or angiotensin II AT1 receptor blockers) prophylactically in individuals using these drugs, due to the possibility of allegedly worsening the prognosis of hypertensive patients infected with SARS-CoV-2. The SBN Hypertension Department recommends individualizing treatment and maintaining these medications until better scientific evidence is available.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Hypertension/drug therapy , Pneumonia, Viral/epidemiology , Brazil , Humans , Nephrology , Pandemics , Withholding Treatment
6.
Curr Atheroscler Rep ; 22(10): 61, 2020 08 24.
Article in English | MEDLINE | ID: covidwho-728266

ABSTRACT

PURPOSE OF REVIEW: The role of renin-angiotensin-aldosterone system (RAAS) inhibitors, notably angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), in the COVID-19 pandemic has not been fully evaluated. With an increasing number of COVID-19 cases worldwide, it is imperative to better understand the impact of RAAS inhibitors in hypertensive COVID patients. PubMed, Embase and the pre-print database Medrxiv were searched, and studies with data on patients on ACEi/ARB with COVID-19 were included. Random effects models were used to estimate the pooled mean difference with 95% confidence interval using Open Meta[Analyst] software. RECENT FINDINGS: A total of 28,872 patients were included in this meta-analysis. The use of any RAAS inhibition for any conditions showed a trend to lower risk of death/critical events (OR 0.671, CI 0.435 to 1.034, p = 0.071). Within the hypertensive cohort, however, there was a significant lower association with deaths (OR 0.664, CI 0.458 to 0.964, p = 0.031) or the combination of death/critical outcomes (OR 0.670, CI 0.495 to 0.908, p = 0.010). There was no significant association of critical/death outcomes within ACEi vs non-ACEi (OR 1.008, CI 0.822 to 1.235, p = 0.941) and ARB vs non-ARB (OR 0.946, CI 0.735 to 1.218, p = 0.668). This is the largest meta-analysis including critical events and mortality data on patients prescribed ACEi/ARB and found evidence of beneficial effects of chronic ACEi/ARB use especially in hypertensive cohort with COVID-19. As such, we would strongly encourage patients to continue with RAAS inhibitor pharmacotherapy during the COVID-19 pandemic.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Renin-Angiotensin System/drug effects , Humans , Hypertension/drug therapy , Pandemics
7.
Diabetes Metab J ; 44(4): 602-613, 2020 08.
Article in English | MEDLINE | ID: covidwho-721570

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. METHODS: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. RESULTS: Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. CONCLUSION: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.


Subject(s)
Coronavirus Infections/mortality , Diabetes Mellitus/epidemiology , Pneumonia, Viral/mortality , Adult , Aged , Aged, 80 and over , Alanine Transaminase/metabolism , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Aspartate Aminotransferases/metabolism , Betacoronavirus , C-Reactive Protein/metabolism , Case-Control Studies , Comorbidity , Coronavirus Infections/metabolism , Coronavirus Infections/physiopathology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Female , Humans , Length of Stay/statistics & numerical data , Logistic Models , Lymphocytosis , Male , Middle Aged , Multivariate Analysis , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/physiopathology , Prognosis , Propensity Score , Proportional Hazards Models , Quarantine/statistics & numerical data , Republic of Korea/epidemiology , Risk Factors , Severity of Illness Index , Thrombocytopenia
8.
Int J Mol Sci ; 21(16)2020 Aug 07.
Article in English | MEDLINE | ID: covidwho-713058

ABSTRACT

Gitelman's syndrome (GS) and Bartter's syndrome (BS) are rare inherited salt-losing tubulopathies whose variations in genotype do not correlate well with either clinical course or electrolyte requirements. Using GS/BS patients as nature's experiments, we found them to be a human model of endogenous Ang II antagonism with activated Renin-Angiotensin System (RAS), resulting in high Ang II levels with blunted cardiovascular effects. These patients are also characterized by increased and directly correlated levels of both Angiotensin Converting Enzyme 2 (ACE2) and Ang 1-7. Understanding the myriad of distinctive and frequently overlapping clinical presentations of GS/BS arises remains challenging. Efforts to find a treatment for COVID-19 has fueled a recent surge in interest in chloroquine/hydroxychloroquine and its effects. Of specific interest are chloroquine/hydroxychloroquine's ability to inhibit SARS-CoV infection by impairing ACE2, the SARS-CoV2 entry point, through terminal glycosylation via effects on TGN/post-Golgi pH homeostasis. Several different studies with a GS or a BS phenotype, along with a nonsyndromic form of X-linked intellectual disability linked to a mutated SLC9A7, provide additional evidence that specific gene defects can act via misregulation of TGN/post-Golgi pH homeostasis, which leads to a common mechanistic basis resulting in overlapping phenotypes. We suggest that linkage between the specific gene defects identified in GS and BS and the myriad of distinctive and frequently overlapping clinical findings may be the result of aberrant glycosylation of ACE2 driven by altered TGN/endosome system acidification caused by the metabolic alkalosis brought about by these salt-losing tubulopathies in addition to their altered intracellular calcium signaling due to a blunted second messenger induced intracellular calcium release that is, in turn, amplified by the RAS system.


Subject(s)
Bartter Syndrome/genetics , Coronavirus Infections/drug therapy , Gitelman Syndrome/genetics , Peptidyl-Dipeptidase A/metabolism , Phenotype , Pneumonia, Viral/drug therapy , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Bartter Syndrome/metabolism , Bartter Syndrome/pathology , Endosomes/drug effects , Endosomes/metabolism , Gitelman Syndrome/metabolism , Gitelman Syndrome/pathology , Humans , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Pandemics
9.
EBioMedicine ; 58: 102907, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-704827

ABSTRACT

BACKGROUND: SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful. METHODS: Animal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed. FINDINGS AND INTERPRETATION: SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Coronavirus Infections/drug therapy , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Betacoronavirus/pathogenicity , Coronavirus Infections/metabolism , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Kallikrein-Kinin System/drug effects , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Renin-Angiotensin System/drug effects
11.
Eur J Heart Fail ; 22(6): 967-974, 2020 06.
Article in English | MEDLINE | ID: covidwho-702780

ABSTRACT

AIMS: The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection. METHODS AND RESULTS: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01). CONCLUSIONS: There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Heart Failure/drug therapy , Pneumonia, Viral/epidemiology , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Comorbidity , Coronavirus Infections/drug therapy , Disease Progression , Female , Follow-Up Studies , Heart Failure/epidemiology , Humans , Male , Pandemics , Pneumonia, Viral/drug therapy , Severity of Illness Index , Treatment Outcome , United Kingdom/epidemiology
14.
Diabetes Metab Syndr ; 14(4): 303-310, 2020.
Article in English | MEDLINE | ID: covidwho-676723

ABSTRACT

BACKGROUND AND AIMS: High prevalence of diabetes makes it an important comorbidity in patients with COVID-19. We sought to review and analyze the data regarding the association between diabetes and COVID-19, pathophysiology of the disease in diabetes and management of patients with diabetes who develop COVID-19 infection. METHODS: PubMed database and Google Scholar were searched using the key terms 'COVID-19', 'SARS-CoV-2', 'diabetes', 'antidiabetic therapy' up to April 2, 2020. Full texts of the retrieved articles were accessed. RESULTS: There is evidence of increased incidence and severity of COVID-19 in patients with diabetes. COVID-19 could have effect on the pathophysiology of diabetes. Blood glucose control is important not only for patients who are infected with COVID-19, but also for those without the disease. Innovations like telemedicine are useful to treat patients with diabetes in today's times.


Subject(s)
Betacoronavirus , Comorbidity , Coronavirus Infections/epidemiology , Diabetes Mellitus/epidemiology , Pneumonia, Viral/epidemiology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Blood Glucose/analysis , Blood Glucose/metabolism , Coronavirus Infections/mortality , Diabetes Mellitus/physiopathology , Diabetes Mellitus/therapy , Dipeptidyl Peptidase 4 , Humans , Hypoglycemic Agents/therapeutic use , Interleukin-6 , Mice , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral/mortality , Prognosis , PubMed , Risk Factors , Telemedicine
15.
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 , 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, Adult/etiology , Thrombolytic Therapy/instrumentation , Thrombolytic Therapy/methods , Thrombophilia/physiopathology , Thrombophilia/therapy , Venous Thrombosis/etiology , Venous Thrombosis/physiopathology , Venous Thrombosis/virology , Virus Internalization/drug effects
18.
Front Immunol ; 11: 1472, 2020.
Article in English | MEDLINE | ID: covidwho-643141

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 has spread rapidly around the globe. However, despite its high pathogenicity and transmissibility, the severity of the associated disease, COVID-19, varies widely. While the prognosis is favorable in most patients, critical illness, manifested by respiratory distress, thromboembolism, shock, and multi-organ failure, has been reported in about 5% of cases. Several studies have associated poor COVID-19 outcomes with the exhaustion of natural killer cells and cytotoxic T cells, lymphopenia, and elevated serum levels of D-dimer. In this article, we propose a common pathophysiological denominator for these negative prognostic markers, endogenous, angiotensin II toxicity. We hypothesize that, like in avian influenza, the outlook of COVID-19 is negatively correlated with the intracellular accumulation of angiotensin II promoted by the viral blockade of its degrading enzyme receptors. In this model, upregulated angiotensin II causes premature vascular senescence, leading to dysfunctional coagulation, and immunity. We further hypothesize that angiotensin II blockers and immune checkpoint inhibitors may be salutary for COVID-19 patients with critical illness by reversing both the clotting and immune defects (Graphical Abstract).


Subject(s)
Angiotensin II/blood , Betacoronavirus/metabolism , Coronavirus Infections/blood , Coronavirus Infections/physiopathology , Pneumonia, Viral/blood , Pneumonia, Viral/physiopathology , Up-Regulation , Age Factors , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Brain/immunology , Brain/metabolism , Cellular Senescence/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Critical Illness , Cytokines/metabolism , Dopamine/metabolism , Down-Regulation , Humans , Immunotherapy/methods , Mitochondria/metabolism , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Prognosis , Renin-Angiotensin System/immunology
19.
Pharmacol Res Perspect ; 8(4): e00623, 2020 08.
Article in English | MEDLINE | ID: covidwho-641200

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 novel coronavirus, has spread worldwide causing high fatality rates. Neither a vaccine nor specific therapeutic approaches are available, hindering the fight against this disease and making better understanding of its pathogenesis essential. Despite similarities between SARS-CoV-2 and SARS-CoV, the former has unique characteristics which represent a great challenge to physicians. The mechanism of COVID-19 infection and pathogenesis is still poorly understood. In the present review, we highlight possible pathways involved in the pathogenesis of COVID-19 and potential therapeutic targets, focusing on the role of the renin-angiotensin-aldosterone system.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , Renin-Angiotensin System , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Evidence-Based Medicine , Host-Pathogen Interactions , Humans , Pandemics , Peptidyl-Dipeptidase A/therapeutic use , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Renin-Angiotensin System/drug effects
20.
Clin Rheumatol ; 39(9): 2529-2543, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-640445

ABSTRACT

The pathogenesis of Coronavirus disease 2019 (COVID-19) is gradually being comprehended. A high number of thrombotic episodes are reported, along with the mortality benefits of heparin. COVID-19 can be viewed as a prothrombotic disease. We overviewed the available evidence to explore this possibility. We identified various histopathology reports and clinical case series reporting thromboses in COVID-19. Also, multiple coagulation markers support this. COVID-19 can be regarded as a risk factor for thrombosis. Applying the principles of Virchow's triad, we described abnormalities in the vascular endothelium, altered blood flow, and platelet function abnormalities that lead to venous and arterial thromboses in COVID-19. Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19. Stratifying risk of COVID-19 thromboses should be based on age, presence of comorbidities, D-dimer, CT scoring, and various blood cell ratios. Isolated heparin therapy may not be sufficient to combat thrombosis in this disease. There is an urgent need to explore newer avenues like activated protein C, PAI-1 antagonists, and tissue plasminogen activators (tPA). These should be augmented with therapies targeting RAAS, antiplatelet drugs, repurposed antiinflammatory, and antirheumatic drugs. Key Points • Venous and arterial thromboses in COVID-19 can be viewed through the prism of Virchow's triad. • Endothelial dysfunction, platelet activation, hyperviscosity, and blood flow abnormalities due to hypoxia, immune reactions, and hypercoagulability lead to thrombogenesis in COVID-19. • There is an urgent need to stratify COVID-19 patients at risk for thrombosis using age, comorbidities, D-dimer, and CT scoring. • Patients with COVID-19 at high risk for thrombosis should be put on high dose heparin therapy.


Subject(s)
Coronavirus Infections/blood , Endothelium, Vascular/metabolism , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/blood , Thrombophilia/blood , Thrombosis/blood , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Anticoagulants/therapeutic use , Betacoronavirus/metabolism , Blood Platelets , Blood Viscosity , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Endothelium, Vascular/physiopathology , Fibrin Fibrinogen Degradation Products , Fibrinogen/metabolism , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Humans , Pandemics , Plasminogen Activator Inhibitor 1/blood , Platelet Activation , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Severity of Illness Index , Thrombophilia/etiology , Thrombophilia/metabolism , Thrombosis/drug therapy , Thrombosis/etiology , Tissue Plasminogen Activator/blood , Tissue Plasminogen Activator/therapeutic use
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