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1.
Br J Community Nurs ; 26(10): 474-480, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34632792

RESUMO

Despite its many devastating effects, the COVID-19 pandemic has had a positive impact in the ways in which society, scientific institutions, governing bodies, businesses, educational organisations, and communication have functioned unchallenged over the years. Rapid advancement in science enabled identification and characterisation of the virus and in developing vaccines to combat the disease. The mysterious ways in which the virus attacks the vital organs that lead on to multiorgan failure and thrombosis of the arterial and venous system have also been revealed. The ability to study the microcirculatory changes at the bedside and predict prognosis is a way forward. All the evidence suggests that the outcome of COVID-19 infection is related to the severity of the disease seen in the intensive care unit setting. This article discusses microcirculatory changes and immune coagulopathy caused by COVID-19.


Assuntos
COVID-19 , Microcirculação , Trombose , COVID-19/complicações , COVID-19/enfermagem , Humanos , Trombose/virologia
2.
Clin Appl Thromb Hemost ; 27: 10760296211042940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34693754

RESUMO

The world is in a hard battle against COVID-19. Endothelial cells are among the most critical targets of SARS-CoV-2. Dysfunction of endothelium leads to vascular injury following by coagulopathies and thrombotic conditions in the vital organs increasing the risk of life-threatening events. Growing evidences revealed that endothelial dysfunction and consequent thrombotic conditions are associated with the severity of outcomes. It is not yet fully clear that these devastating sequels originate directly from the virus or a side effect of virus-induced cytokine storm. Due to endothelial dysfunction, plasma levels of some biomarkers are changed and relevant clinical manifestations appear as well. Stabilization of endothelial integrity and supporting its function are among the promising therapeutic strategies. Other than respiratory, COVID-19 could be called a systemic vascular disease and this aspect should be scrutinized in more detail in order to reduce related mortality. In the present investigation, the effects of COVID-19 on endothelial function and thrombosis formation are discussed. In this regard, critical players, laboratory findings, clinical manifestation, and suggestive therapies are presented.


Assuntos
Coagulação Sanguínea , COVID-19/virologia , Células Endoteliais/virologia , Endotélio Vascular/virologia , SARS-CoV-2/patogenicidade , Trombose/virologia , Animais , COVID-19/sangue , COVID-19/patologia , COVID-19/fisiopatologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Interações Hospedeiro-Patógeno , Humanos , Transdução de Sinais , Trombose/sangue , Trombose/patologia , Trombose/fisiopatologia
3.
Med Sci Monit ; 27: e930776, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34635632

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients presented with COVID-19 pneumonia of varying severity. The phenomenon of severe hypoxemia without signs of respiratory distress is also known as silent or hidden hypoxemia. Although silent hypoxemia is not unique to pneumonia due to SARS-CoV-2 infection, this phenomenon is now recognized to be associated with severe COVID-19 pneumonia. Proper management of critically ill patients is the key to reducing mortality. Herein, we summarize the possible and rare factors contributing to silent hypoxemia in patients with COVID-19. Microvascular thrombosis causes dead space ventilation in the lungs, and the flow of pulmonary capillaries is reduced, which leads to an imbalance in the V/Q ratio. The dissociation curve of oxyhemoglobin shifts to the left and limits the release of oxygen to the tissue. SARS-CoV-2 interferes with the synthesis of hemoglobin and reduces the ability to carry oxygen. The accumulation of endogenous carbon monoxide and carboxyhemoglobin will reduce the total oxygen carrying capacity and interfere with pulse oxygen saturation readings. There are also some non-specific factors that cause the difference between pulse oximetry and oxygen partial pressure. We propose some potentially more effective clinical alternatives and recommendations for optimizing the clinical management processes of patients with COVID-19. This review aims to describe the prevalence of silent hypoxemia in COVID-19 pneumonia, to provide an update on what is known of the pathophysiology, and to highlight the importance of diagnosing silent hypoxemia in patients with COVID-19 pneumonia.


Assuntos
COVID-19/metabolismo , Hipóxia/virologia , Pneumonia Viral/virologia , Doenças Assintomáticas/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Hipóxia/epidemiologia , Hipóxia/metabolismo , Pulmão/citologia , Pulmão/metabolismo , Pulmão/virologia , Microvasos/metabolismo , Oximetria , Oxigênio/metabolismo , Pneumonia Viral/metabolismo , Prevalência , SARS-CoV-2/isolamento & purificação , Trombose/metabolismo , Trombose/virologia
4.
Reumatol Clin (Engl Ed) ; 17(8): 431-436, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34625144

RESUMO

The novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). Acute respiratory distress syndrome (ARDS), multiorgan dysfunction and thrombotic events are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a "cytokine storm", also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. In addition to anti-viral therapy and supportive treatment in critically ill patients, unique medications for this condition are also under investigation. Here we reviewed therapeutic options, including the antibody therapy that might be an immediate strategy for SARS-CoV-2 therapy.


Assuntos
COVID-19/terapia , Síndrome da Liberação de Citocina/terapia , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/imunologia , Cloroquina/uso terapêutico , Terapia Combinada , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Fibrinolíticos/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Troca Plasmática , Inibidores de Proteínas Quinases/uso terapêutico , Terapia Respiratória , Reumatologia , Índice de Gravidade de Doença , Trombose/tratamento farmacológico , Trombose/virologia
5.
Int J Biol Macromol ; 192: 1040-1057, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656540

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent responsible for the Coronavirus Disease-2019 (COVID-19) pandemic, has infected over 185 million individuals across 200 countries since December 2019 resulting in 4.0 million deaths. While COVID-19 is primarily associated with respiratory illnesses, an increasing number of clinical reports indicate that severely ill patients often develop thrombotic complications that are associated with increased mortality. As a consequence, treatment strategies that target COVID-associated thrombosis are of utmost clinical importance. An array of pharmacologically active compounds from natural products exhibit effects on blood coagulation pathways, and have generated interest for their potential therapeutic applications towards thrombotic diseases. In particular, a number of snake venom compounds exhibit high specificity on different blood coagulation factors and represent excellent tools that could be utilized to treat thrombosis. The aim of this review is to provide a brief summary of the current understanding of COVID-19 associated thrombosis, and highlight several snake venom compounds that could be utilized as antithrombotic agents to target this disease.


Assuntos
COVID-19/sangue , Fibrinolíticos/farmacologia , Venenos de Serpentes/farmacologia , Trombose/tratamento farmacológico , Trombose/virologia , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/patologia , Humanos , Pandemias , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade
6.
PLoS One ; 16(9): e0256988, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34478452

RESUMO

Epidemiological studies suggest that individuals with comorbid conditions including diabetes, chronic lung, inflammatory and vascular disease, are at higher risk of adverse COVID-19 outcomes. Genome-wide association studies have identified several loci associated with increased susceptibility and severity for COVID-19. However, it is not clear whether these associations are genetically determined or not. We used a Phenome-Wide Association (PheWAS) approach to investigate the role of genetically determined COVID-19 susceptibility on disease related outcomes. PheWAS analyses were performed in order to identify traits and diseases related to COVID-19 susceptibility and severity, evaluated through a predictive COVID-19 risk score. We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR = 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10). Our study identifies significant association of genetically determined COVID-19 with increased blood clot events in leg and lungs. The reported associations between both COVID-19 susceptibility and severity and other diseases adds to the identification and stratification of individuals at increased risk, adverse outcomes and long-term effects.


Assuntos
COVID-19/genética , Obesidade/genética , Tromboflebite/genética , Trombose/genética , COVID-19/epidemiologia , COVID-19/virologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/virologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Análise da Randomização Mendeliana , Obesidade/epidemiologia , Obesidade/virologia , Fenômica , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , SARS-CoV-2/patogenicidade , Tromboflebite/epidemiologia , Tromboflebite/virologia , Trombose/epidemiologia , Trombose/virologia
7.
J Thromb Thrombolysis ; 52(3): 708-714, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34519015

RESUMO

Coronavirus disease 2019 (Covid-19) is associated with a high incidence of venous and arterial thromboembolic events. Currently, there are no clinical or laboratory markers that predict thrombotic risk. Circulating immature platelets are hyper-reactive platelets, which are associated with arterial thrombotic events. The aim of this study was to assess whether the proportion of circulating immature platelets is associated with disease severity in Covid-19 patients. Patients admitted with Covid-19 disease were prospectively assessed. Immature platelet count (IPC) and immature platelet fraction (IPF) were measured at admission and at additional time points during the hospital course using the Sysmex XN-3000 auto-analyzer. A total of 136 consecutive patients with Covid-19 were recruited [mean age 60 ± 19 years, 49% woman, 56 (41%) had mild-moderate disease and 80 (59%) had severe disease at presentation]. The median IPF% was higher in patients with severe compared to mild-moderate disease [5.8 (3.9-8.7) vs. 4.2 (2.73-6.45), respectively, p = 0.01]. The maximal IPC value was also higher in patients with severe disease [15 (10.03-21.56), vs 10.9 (IQR 6.79-15.62), respectively, p = 0.001]. Increased IPC was associated with increased length of hospital stay. Patients with severe Covid-19 have higher levels of IPF than patients with mild-moderate disease. IPF may serve as a prognostic marker for disease severity in Covid-19 patients.


Assuntos
Plaquetas/virologia , COVID-19/virologia , SARS-CoV-2/patogenicidade , Trombose/virologia , Adulto , Idoso , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico , Fatores de Tempo
8.
Sci Immunol ; 6(59)2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-34446527

RESUMO

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers: Washington University School of Medicine (n=134) and Yale School of Medicine (n=49). We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza (n=54), and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV, n=22). We demonstrate that circulating markers of complement activation are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., angiopoietin-2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials.


Assuntos
COVID-19/imunologia , Ativação do Complemento , Idoso , Biomarcadores/sangue , COVID-19/complicações , COVID-19/patologia , Estudos de Coortes , Estado Terminal , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Estudos Prospectivos , Trombose/patologia , Trombose/virologia , Resultado do Tratamento
9.
Front Immunol ; 12: 700184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408749

RESUMO

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states. Upon viral infections, cellular lncRNAs directly regulate viral genes and influence viral replication and pathology through virus-mediated changes in the host transcriptome. Additionally, several host lncRNAs could help the occurrence of viral immune escape by inhibiting type I interferons (IFN-1), while others could up-regulate IFN-1 production to play an antiviral role. Consequently, understanding the expression and function of lncRNAs during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection will provide insights into the development of lncRNA-based methods. In this review, we summarized the current findings of lncRNAs in the regulation of the strong inflammatory response, immune dysfunction and thrombosis induced by SARS-CoV-2 infection, discussed the underlying mechanisms, and highlighted the therapeutic challenges of COVID-19 treatment and its future research directions.


Assuntos
COVID-19/imunologia , Interações entre Hospedeiro e Microrganismos/genética , Imunidade Inata/genética , RNA Longo não Codificante/metabolismo , Trombose/imunologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Biomarcadores/análise , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/genética , Teste para COVID-19/métodos , Citocinas/genética , Citocinas/metabolismo , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/imunologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Evasão da Resposta Imune/genética , Pandemias/prevenção & controle , RNA Longo não Codificante/análise , RNA Longo não Codificante/antagonistas & inibidores , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Trombose/genética , Trombose/virologia , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética , Replicação Viral/imunologia
10.
Ann Clin Lab Sci ; 51(4): 570-572, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452898

RESUMO

COVID-19 has affected patients of all ages and demographics, not excluding pregnant women. The effects of COVID-19 on pregnant women are still largely unknown. Several adverse perinatal outcomes have been reported in COVID-19-positive pregnant women, including pre-eclampsia, miscarriage, pre-term labor, and stillbirth. Histopathological examination of COVID-19 placentas can contribute significant data regarding maternal and fetal health and can elucidate more findings in this novel disease. A 23-year-old female with morbid obesity and scant antenatal care presented to the emergency department complaining of shortness of breath and fever; she was found to be positive for COVID-19. Grossly, her placenta showed no abnormalities. Histological examination of her placenta showed chronic lymphoplasmacytic deciduitis, villous fibrosis, loss of capillarization, extravasation of erythrocytes, chorangiosis, and thrombosis of upstream stem vessels, including large fetal vessels on the chorionic plate. These changes were deemed to be consistent with fetal thrombotic vasculopathy (FTV). In conclusion, this case of FTV in the placenta of a patient with COVID-19 is a significant finding, as it can be critical to clinicians in the management of prenatal care for expecting mothers during this pandemic.This case was presented at the annual meeting of the Association of Clinical Scientists (ACS) on May 13, 2021.


Assuntos
COVID-19/complicações , Doenças Fetais/patologia , Feto/patologia , Doenças Placentárias/patologia , Placenta/patologia , SARS-CoV-2/isolamento & purificação , Trombose/patologia , Adulto , COVID-19/transmissão , COVID-19/virologia , Feminino , Doenças Fetais/virologia , Feto/virologia , Humanos , Placenta/virologia , Doenças Placentárias/virologia , Gravidez , Prognóstico , Trombose/virologia , Adulto Jovem
12.
Curr Opin Hematol ; 28(6): 445-453, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232139

RESUMO

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2. Over the past year, COVID-19 has posed a significant threat to global health. Although the infection is associated with mild symptoms in many patients, a significant proportion of patients develop a prothrombotic state due to a combination of alterations in coagulation and immune cell function. The purpose of this review is to discuss the pathophysiological characteristics of COVID-19 that contribute to the immunothrombosis. RECENT FINDINGS: Endotheliopathy during COVID-19 results in increased multimeric von Willebrand factor release and the potential for increased platelet adhesion to the endothelium. In addition, decreased anticoagulant proteins on the surface of endothelial cells further alters the hemostatic balance. Soluble coagulation markers are also markedly dysregulated, including plasminogen activator inhibitor-1 and tissue factor, leading to COVID-19 induced coagulopathy. Platelet hyperreactivity results in increased platelet-neutrophil and -monocyte aggregates further exacerbating the coagulopathy observed during COVID-19. Finally, the COVID-19-induced cytokine storm primes neutrophils to release neutrophil extracellular traps, which trap platelets and prothrombotic proteins contributing to pulmonary thrombotic complications. SUMMARY: Immunothrombosis significantly contributes to the pathophysiology of COVID-19. Understanding the mechanisms behind COVID-19-induced coagulopathy will lead to future therapies for patients.


Assuntos
Transtornos da Coagulação Sanguínea/patologia , COVID-19/complicações , SARS-CoV-2/isolamento & purificação , Trombose/patologia , Transtornos da Coagulação Sanguínea/epidemiologia , Transtornos da Coagulação Sanguínea/virologia , COVID-19/transmissão , COVID-19/virologia , Humanos , Prognóstico , Trombose/epidemiologia , Trombose/virologia
13.
Radiologia (Engl Ed) ; 63(4): 370-383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34246427

RESUMO

In March 2020, the World Health Organization declared a global pandemic of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); epidemic conditions continue in nearly all countries today. Although the symptoms and imaging manifestations of COVID-19 predominantly involve the respiratory system, it is fundamental to know the manifestations of the disease and its possible complications in other organs to help in diagnosis and orient the prognosis. To improve the diagnostic process without increasing the risk of contagion unnecessarily, it is crucial to know when extrathoracic imaging tests are indicated and which tests are best in each situation. This paper aims to provide answers to these questions. To this end, we describe and illustrate the extrathoracic imaging manifestations of COVID-19 in adults as well as the entire spectrum of imaging findings in children.


Assuntos
COVID-19/diagnóstico por imagem , Adulto , COVID-19/complicações , Criança , Cardiopatias/virologia , Humanos , Doenças do Sistema Nervoso/virologia , Síndrome de Resposta Inflamatória Sistêmica , Trombose/virologia
14.
Biosci Rep ; 41(8)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34328172

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients. Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation. Using platelet-poor plasma (PPP), we show that spike protein may interfere with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to ß and γ fibrin(ogen), complement 3, and prothrombin. These proteins were substantially resistant to trypsinization, in the presence of spike protein S1. Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis. Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients. This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.


Assuntos
COVID-19/patologia , Fibrina/metabolismo , Fibrinólise/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Trombose/patologia , Adulto , Idoso , Amiloide/metabolismo , Plaquetas/metabolismo , Complemento C3/metabolismo , Feminino , Fibrinogênio/metabolismo , Humanos , Pulmão/patologia , Masculino , Técnicas Analíticas Microfluídicas , Pessoa de Meia-Idade , Protrombina/metabolismo , SARS-CoV-2/metabolismo , Trombose/virologia , Tripsina/metabolismo
15.
Nutrients ; 13(7)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203190

RESUMO

SARS-CoV-2 infects the respiratory tract and leads to the disease entity, COVID-19. Accordingly, the lungs bear the greatest pathologic burden with the major cause of death being respiratory failure. However, organs remote from the initial site of infection (e.g., kidney, heart) are not spared, particularly in severe and fatal cases. Emerging evidence indicates that an excessive inflammatory response coupled with a diminished antiviral defense is pivotal in the initiation and development of COVID-19. A common finding in autopsy specimens is the presence of thrombi in the lungs as well as remote organs, indicative of immunothrombosis. Herein, the role of SARS-CoV-2 in lung inflammation and associated sequelae are reviewed with an emphasis on immunothrombosis. In as much as vitamin D is touted as a supplement to conventional therapies of COVID-19, the impact of this vitamin at various junctures of COVID-19 pathogenesis is also addressed.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/imunologia , Inflamação/virologia , Pneumonia/virologia , Vitamina D/uso terapêutico , Animais , COVID-19/virologia , Armadilhas Extracelulares , Humanos , Inflamação/tratamento farmacológico , Pulmão/patologia , Camundongos , Insuficiência de Múltiplos Órgãos/virologia , Pneumonia/tratamento farmacológico , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2 , Trombose/imunologia , Trombose/virologia , Vitaminas/uso terapêutico
16.
Blood ; 138(16): 1481-1489, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34315173

RESUMO

A subset of patients with coronavirus disease 2019 (COVID-19) become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill patients with COVID-19 are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesized that platelets might be susceptible to activation by anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies and might contribute to thrombosis. We found that immune complexes containing recombinant SARS-CoV-2 spike protein and anti-spike immunoglobulin G enhanced platelet-mediated thrombosis on von Willebrand factor in vitro, but only when the glycosylation state of the Fc domain was modified to correspond with the aberrant glycosylation previously identified in patients with severe COVID-19. Furthermore, we found that activation was dependent on FcγRIIA, and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by the therapeutic small molecules R406 (fostamatinib) and ibrutinib, which inhibit tyrosine kinases Syk and Btk, respectively, or by the P2Y12 antagonist cangrelor.


Assuntos
Plaquetas/patologia , COVID-19/complicações , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Trombose/patologia , Fator de von Willebrand/metabolismo , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Complexo Antígeno-Anticorpo/imunologia , Plaquetas/imunologia , Plaquetas/metabolismo , COVID-19/imunologia , COVID-19/virologia , Glicosilação , Humanos , Ativação Plaquetária/imunologia , Trombose/imunologia , Trombose/virologia , Fator de von Willebrand/genética
17.
Am J Med Sci ; 362(4): 418-423, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34161825

RESUMO

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of venous and arterial thrombotic disease. Although pulmonary embolism has been the most common thrombotic complication, there have been recent reports of COVID-19-associated large-vessel ischemic stroke, acute upper- and lower-limb ischemia, as well as infarctions of the abdominal viscera, including renal, splenic, and small bowel infarctions. Here, we describe a case of splenic infarction (SI) associated with aortic thrombosis, which evolved despite the prophylactic use of low-molecular-weight heparin (LMWH), in a 60-year-old female patient with COVID-19. The patient was treated clinically with a therapeutic dose of LMWH, followed by warfarin, and eventually presented a favorable outcome. We also present a review of the literature regarding SI in patients with COVID-19.


Assuntos
Doenças da Aorta/virologia , COVID-19/complicações , Infarto do Baço/virologia , Trombose/virologia , COVID-19/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Pessoa de Meia-Idade , Infarto do Baço/diagnóstico por imagem
18.
Angiogenesis ; 24(4): 755-788, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34184164

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 ARDS and its perfusion defect differs from ARDS induced by other causes. Beside pro-inflammatory cytokines (such as interleukin-1 ß [IL-1ß] or IL-6), several main pathological phenomena have been seen because of endothelial cell (EC) dysfunction: hypercoagulation reflected by fibrin degradation products called D-dimers, micro- and macrothrombosis and pathological angiogenesis. Direct endothelial infection by SARS-CoV-2 is not likely to occur and ACE-2 expression by EC is a matter of debate. Indeed, endothelial damage reported in severely ill patients with COVID-19 could be more likely secondary to infection of neighboring cells and/or a consequence of inflammation. Endotheliopathy could give rise to hypercoagulation by alteration in the levels of different factors such as von Willebrand factor. Other than thrombotic events, pathological angiogenesis is among the recent findings. Overexpression of different proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) or placental growth factors (PlGF) have been found in plasma or lung biopsies of COVID-19 patients. Finally, SARS-CoV-2 infection induces an emergency myelopoiesis associated to deregulated immunity and mobilization of endothelial progenitor cells, leading to features of acquired hematological malignancies or cardiovascular disease, which are discussed in this review. Altogether, this review will try to elucidate the pathophysiology of thrombotic complications, pathological angiogenesis and EC dysfunction, allowing better insight in new targets and antithrombotic protocols to better address vascular system dysfunction. Since treating SARS-CoV-2 infection and its potential long-term effects involves targeting the vascular compartment and/or mobilization of immature immune cells, we propose to define COVID-19 and its complications as a systemic vascular acquired hemopathy.


Assuntos
COVID-19/metabolismo , Mielopoese , Neovascularização Patológica/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , SARS-CoV-2/metabolismo , Trombose/metabolismo , COVID-19/patologia , COVID-19/terapia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais/virologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Proteínas de Membrana/metabolismo , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia , Neovascularização Patológica/virologia , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , Trombose/patologia , Trombose/terapia , Trombose/virologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismo
19.
Front Immunol ; 12: 651545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149692

RESUMO

COVID-19 is an acute, complex disorder that was caused by a new ß-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on current reports, it was surprising that the characteristics of many patients with COVID-19, who fulfil the Berlin criteria for acute respiratory distress syndrome (ARDS), are not always like those of patients with typical ARDS and can change over time. While the mechanisms of COVID-19-related respiratory dysfunction in COVID-19 have not yet been fully elucidated, pulmonary microvascular thrombosis is speculated to be involved. Considering that thrombosis is highly related to other inflammatory lung diseases, immunothrombosis, a two-way process that links coagulation and inflammation, seems to be involved in the pathophysiology of COVID-19, including respiratory dysfunction. Thus, the current manuscript will describe the proinflammatory milieu in COVID-19, summarize current evidence of thrombosis in COVID-19, and discuss possible interactions between these two.


Assuntos
COVID-19/imunologia , COVID-19/patologia , Inflamação/virologia , Síndrome do Desconforto Respiratório/virologia , Trombose/virologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/patologia , SARS-CoV-2 , Trombose/imunologia , Trombose/patologia
20.
Semin Vasc Surg ; 34(2): 8-12, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34144749

RESUMO

This literature review discusses the current evidence on acute limb ischemia (ALI) in patients with COVID-19. Throughout the pandemic, these patients have been at increased risk of arterial thrombotic events and subsequent mortality as a result of a hypercoagulable state. The exact mechanism of thrombosis is unknown; however arterial thrombosis may be due to invasion of endothelial cells via angiotensin-converting enzyme 2 (ACE2) receptors, endothelial injury from inflammation, or even free-floating aortic thrombus. Multiple studies have been performed evaluating the medical and surgical management of these patients; the decision to proceed with operative intervention is dependent on the patient's clinical status as it relates to COVID-19 and morbidity of that disease. The interventions afforded typically include anticoagulation in patients undergoing palliation; alternatively, thrombectomy (endovascular and open) is utilized in other patients. There is a high risk of rethrombosis, despite anticoagulation, given persistent endothelial injury from the virus. Postoperative mortality can be high in these patients.


Assuntos
COVID-19/complicações , Isquemia/terapia , Isquemia/virologia , Extremidade Inferior/irrigação sanguínea , Trombose/terapia , Trombose/virologia , Anticoagulantes/uso terapêutico , COVID-19/diagnóstico , COVID-19/terapia , Humanos , Isquemia/diagnóstico , Trombectomia , Trombose/diagnóstico
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