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1.
Nat Commun ; 12(1): 4117, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226537

RESUMO

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.


Assuntos
COVID-19/complicações , COVID-19/imunologia , Síndrome da Liberação de Citocina/complicações , Monócitos/patologia , Ativação de Neutrófilo , Idoso , Células Apresentadoras de Antígenos/imunologia , COVID-19/sangue , COVID-19/virologia , Estudos de Casos e Controles , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Armadilhas Extracelulares/metabolismo , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
2.
PLoS One ; 16(7): e0254367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242356

RESUMO

COVID-19 serological test must have high sensitivity as well as specificity to rule out cross-reactivity with common coronaviruses (HCoVs). We have developed a quantitative multiplex test, measuring antibodies against spike (S) proteins of SARS-CoV-2, SARS-CoV, MERS-CoV, and common human coronavirus strains (229E, NL63, OC43, HKU1), and nucleocapsid (N) protein of SARS-CoV viruses. Receptor binding domain of S protein of SARS-CoV-2 (S-RBD), and N protein, demonstrated sensitivity (94% and 92.5%, respectively) in COVID-19 patients (n = 53), with 98% specificity in non-COVID-19 respiratory-disease (n = 98), and healthy-controls (n = 129). Anti S-RBD and N antibodies appeared five to ten days post-onset of symptoms, peaking at approximately four weeks. The appearance of IgG and IgM coincided while IgG subtypes, IgG1 and IgG3 appeared soon after the total IgG; IgG2 and IgG4 remained undetectable. Several inflammatory cytokines/chemokines were found to be elevated in many COVID-19 patients (e.g., Eotaxin, Gro-α, CXCL-10 (IP-10), RANTES (CCL5), IL-2Rα, MCP-1, and SCGF-b); CXCL-10 was elevated in all. In contrast to antibody titers, levels of CXCL-10 decreased with the improvement in patient health suggesting it as a candidate for disease resolution. Importantly, anti-N antibodies appear before S-RBD and differentiate between vaccinated and infected people-current vaccines (and several in the pipeline) are S protein-based.


Assuntos
Anticorpos Antivirais , COVID-19 , Quimiocinas , Proteínas do Nucleocapsídeo de Coronavírus , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Adulto , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , Quimiocinas/sangue , Quimiocinas/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/sangue , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Fosfoproteínas/imunologia , Coelhos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/sangue , Glicoproteína da Espícula de Coronavírus/imunologia
3.
Nutr J ; 20(1): 66, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243781

RESUMO

There are limited proven therapeutic options for the prevention and treatment of COVID-19. We underwent an observational study with the aim of measure plasma vitamin C levels in a population of critically ill COVID-19 adult patients who met ARDS criteria according to the Berlin definition. This epidemiological study brings to light that up to 82% had low Vitamin C values. Notwithstanding the limitation that this is a single-center study, it nevertheless shows an important issue. Given the potential role of vitamin C in sepsis and ARDS, there is gathering interest of whether supplementation could be beneficial in COVID-19.


Assuntos
Ácido Ascórbico/sangue , COVID-19/sangue , Adulto , Idoso , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Vitaminas/sangue
4.
Eur J Med Res ; 26(1): 75, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256840

RESUMO

BACKGROUND: The aim of this study was to evaluate the expression of four up/down-regulated inflammatory miRNAs and their mRNA targets in the serum samples of COVID-19 patients with different grades. Also, we investigated the relative expression of these miRNAs and mRNAs during hospitalization. METHODS: In this cross-sectional study, 5 mL of blood sample were taken from COVID-19 patients with different grades and during hospitalization from several health centers of Yazd, Tehran, and Zahedan province of Iran from December 20, 2020 to March 2, 2021. The relative expression of miRNAs and mRNAs was evaluated by q-PCR. RESULTS: We found that the relative expression of hsa-miR-31-3p, hsa-miR-29a-3p, and hsa-miR-126-3p was significantly decreased and the relative expression of their mRNA targets (ZMYM5, COL5A3, and CAMSAP1) was significantly increased with the increase of disease grade. Conversely, the relative expression of hsa-miR-17-3p was significantly increased and its mRNA target (DICER1) was significantly decreased with the increase of disease grade. This pattern was exactly seen during hospitalization of COVID-19 patients who did not respond to treatment. In COVID-19 patients who responded to treatment, the expression of selected miRNAs and their mRNA targets returned to the normal level. A negative significant correlation was seen between (1) the expression of hsa-miR-31-3p and ZMYM5, (2) hsa-miR-29a-3p and COL5A3, (3) hsa-miR-126-3p and CAMSAP1, and (4) hsa-miR-17-3p and DICER1 in COVID-19 patients with any grade (P < 0.05) and during hospitalization. CONCLUSIONS: In this study, we gained a more accurate understanding of the expression of up/down-regulated inflammatory miRNAs in the blood of COVID-19 patients. The obtained data may help us in the diagnosis and prognosis of COVID-19. TRIAL REGISTRATION: The ethics committee of Zahedan University of Medical Sciences, Zahedan, Iran. (Ethical Code: IR.ZAUMS.REC.1399.316) was registered for this project.


Assuntos
COVID-19/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , RNA Mensageiro/genética , COVID-19/sangue , COVID-19/virologia , Proteínas de Transporte/genética , Colágeno/genética , Estudos Transversais , RNA Helicases DEAD-box/genética , Hospitalização/estatística & dados numéricos , Humanos , Irã (Geográfico) , Proteínas Associadas aos Microtúbulos/genética , Proteínas Nucleares/genética , Ribonuclease III/genética , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
5.
Sci Rep ; 11(1): 14471, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262116

RESUMO

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Assistência Ambulatorial , Biomarcadores/sangue , Proteína C-Reativa/análise , Diagnóstico Precoce , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Seguimentos , Hospitalização , Humanos , Interleucina-6/sangue , Estudos Longitudinais , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Medicina de Precisão , Prognóstico , Quarentena , SARS-CoV-2 , Índice de Gravidade de Doença , Troponina I/sangue
6.
Signal Transduct Target Ther ; 6(1): 271, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267185

RESUMO

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Adolescente , Adulto , COVID-19/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Pak J Pharm Sci ; 34(1(Special)): 429-433, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275790

RESUMO

SARS-Covid-19 infection got spread in many countries and WHO declared it as a serious global Pandemic. Pro-inflammatory cytokines storm generated by Covid-19 infection hyper-activates inflammatory response in host body, resulting in elevated release of inflammatory biomarkers. Present article describes the characteristic profile of these inflammatory and related biomarkers in a total of 48 critically ill Covid-19 patients, (Male = 38, F = 10), with mildly ill to severe, critically ill status and thus grouped accordingly. Inflammatory Biomarkers, Ferritin, ProCalcitonin, C-Reactive Protein, coagulation marker-D-Dimer, chemical analytes, Protein, Albumin, BUN, Bilirubin, Creatinine, and enzymes, Lactate Dehydrogenase, γ-Glutamyl transpeptidases, Alkaline phosphatase were routine analyzed by standard methods described earlier. D-dimer, Ferritin, CRP and Procalcitonin exhibited variable alterations (P<0.05 to P<0.001), more markedly in critically ill patients than in the mild and severe. Biochemical analytes and enzymatic parameters showed elevated levels (P<0.05 to P<0.01) mostly in critically ill category of patients when compared with mild or severe, except total protein and albumin, which remained non-significant. It is concluded that cytokine, chemokines and pro-inflammatory markers, which released in abnormally high concentrations in Covid-19 patients of variable syndrome intensity, are significant indicators of disease severity, progression and success of treatments. As the pharmacological options may vary with the different stages of the disease therefore identifying the correct stage of the disease may be very useful in selecting the best option.


Assuntos
COVID-19/sangue , Citocinas/sangue , Mediadores da Inflamação/sangue , Biomarcadores/sangue , COVID-19/virologia , Estado Terminal , Feminino , Humanos , Masculino , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
9.
Sci Rep ; 11(1): 14250, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244563

RESUMO

Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9-95.8%; Sensitivity: 55.5-77.8%; Specificity: 91.5-98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.


Assuntos
Teste para COVID-19 , COVID-19 , Aprendizado de Máquina , Modelos Biológicos , SARS-CoV-2/metabolismo , Adolescente , Adulto , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tórax/diagnóstico por imagem
10.
Sci Rep ; 11(1): 14232, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244584

RESUMO

COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus's spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients' serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.


Assuntos
Ceramidase Ácida/sangue , COVID-19 , Portador Sadio , Metabolismo dos Lipídeos , SARS-CoV-2/metabolismo , Esfingolipídeos/sangue , Esfingosina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , Portador Sadio/sangue , Portador Sadio/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
BMC Infect Dis ; 21(1): 678, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256733

RESUMO

BACKGROUND: In this case report, we presented a rare case of maternal death with massive vulvar edema and Covid-19 diagnosis. CASE PRESENTATION: The case was a 20-year-old woman who was referred to with pain and massive vulvar edema by passing 7 days from her labor. The laboratory tests showed leukocytosis, lymphopenia, and elevated C-reactive protein levels. The high-resolution computed tomography was in favor of Covid-19 changes. Finally, she died because of respiratory distress, ON the 8th day postpartum. CONCLUSION: Given the increasing prevalence of Covid-19, it is important and vital to be aware of its potential complications and then to try prevent and manage them, especially during high-risk periods such as pregnancy and postpartum.


Assuntos
COVID-19/complicações , Edema/complicações , Edema/diagnóstico por imagem , Morte Materna , Período Pós-Parto , SARS-CoV-2/genética , Doenças da Vulva/complicações , Doenças da Vulva/diagnóstico por imagem , COVID-19/sangue , COVID-19/virologia , Teste para COVID-19/métodos , Evolução Fatal , Feminino , Humanos , Linfopenia , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
12.
BMC Infect Dis ; 21(1): 677, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256735

RESUMO

BACKGROUND: SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. METHODS: Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677 . RESULTS: We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90-174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. CONCLUSIONS: Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677 .


Assuntos
Bancos de Espécimes Biológicos , Teste para COVID-19/métodos , COVID-19/complicações , SARS-CoV-2/genética , Sobreviventes , Adulto , Idoso , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Colorado/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Manejo de Espécimes , Adulto Jovem
13.
Nutrients ; 13(7)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202697

RESUMO

COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01-30.26]; p = 0.048) and mortality (OR 5.21 [1.06-25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.


Assuntos
COVID-19/sangue , Vitamina A/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/mortalidade , Cromatografia Líquida/métodos , Estado Terminal , Estudos Transversais , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Ferritinas/sangue , Hospitalização , Humanos , Inflamação/epidemiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome do Desconforto Respiratório/epidemiologia , SARS-CoV-2 , Índice de Gravidade de Doença
14.
Rev Cardiovasc Med ; 22(2): 277-286, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258896

RESUMO

Emerging evidences prove that the ongoing pandemic of coronavirus disease 2019 (COVID-19) is strictly linked to coagulopathy even if pneumonia appears as the major clinical manifestation. The exact incidence of thromboembolic events is largely unknown, so that a relative significant number of studies have been performed in order to explore thrombotic risk in COVID-19 patients. Cytokine storm, mediated by pro-inflammatory interleukins, tumor necrosis factor α and elevated acute phase reactants, is primarily responsible for COVID-19-associated hypercoagulopathy. Also comorbidities, promoting endothelial dysfunction, contribute to a higher thromboembolic risk. In this review we aim to investigate epidemiology and clarify the pathophysiological pathways underlying hypercoagulability in COVID-19 patients, providing indications on the prevention of thromboembolic events in COVID-19. Furthermore we aim to reassume the pathophysiological paths involved in COVID-19 infection.


Assuntos
Coagulação Sanguínea , COVID-19/sangue , Embolia Pulmonar/sangue , Tromboembolia Venosa/sangue , Trombose Venosa/sangue , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Interações Hospedeiro-Patógeno , Humanos , Prognóstico , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/prevenção & controle , Embolia Pulmonar/virologia , Medição de Risco , Fatores de Risco , SARS-CoV-2/patogenicidade , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/virologia , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle , Trombose Venosa/virologia
15.
J Coll Physicians Surg Pak ; 31(7): 93-98, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34271803

RESUMO

OBJECTIVE: To investigate the symptoms and laboratory results of children hospitalised with the diagnosis of COVID-19, aiming to reveal the characteristics of symptomatic cases. STUDY DESIGN: A descriptive cross-sectional study. PLACE AND DURATION OF STUDY: Department of Pediatrics, Kastamonu Training and Research Hospital, Kastamonu, Turkey from March to December 2020. METHODOLOGY: Seventy-nine children, hospitalised with the diagnosis of COVID-19, were included in the study and were divided into two groups as symptomatic and asymptomatic. The demographic data, laboratory results and clinics of the patients of the two groups were compared. RESULTS: The mean age of participants was 10.43 ± 5.91 (0-17) years, and 57% (n=45) of them were girls. Five patients in the symptomatic group had comorbidities (2 allergic asthma,  cerebral palsy, type-1 diabetes mellitus and anorexia nervosa). The most common symptom was fever (36.7%, n=29). It was noteworthy that everyone with an NLR >3.13 (high-NLR) was symptomatic. Significantly more patients in the high-NLR group were symptomatic compared with the low-NLR group (p=0.005). On the other hand, symptomatic children had significantly higher levels of C-reactive protein (2.8 (IQR: 1.2-10.0) mg/L vs. 1.4 (IQR: 0.4-2.0) mg/L, p=0.011); and procalcitonin (0.05 (IQR: 0.02-0.10) ng/mL vs. 0.01 (IQR: 0.00-0.03) ng/mL, p<0.001) than those without symptoms. One of the children with cerebral palsy died from pneumonia during the study. CONCLUSION: C-reactive protein, procalcitonin and NLR levels were found to be significantly higher in symptomatic children. NLR can be suggested as a potential marker associated with disease severity in COVID-19 patients, which needs to be supported by other studies. Key Words: COVID-19, Children, Neutrophil / lymphocyte ratio, C-reactive protein, Procalcitonin.


Assuntos
COVID-19 , Pediatria , Adolescente , COVID-19/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Linfócitos/metabolismo , Masculino , Neutrófilos/metabolismo , Estudos Retrospectivos , SARS-CoV-2 , Turquia/epidemiologia
16.
Front Immunol ; 12: 625732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194422

RESUMO

The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this ACE2 gene dysregulation mainly affects the monocytes, which also show a lower expression of membrane ACE2 protein. Moreover, soluble ACE2 (sACE2) plasma concentrations are lower in prolonged viral shedders than in healthy controls, while the concentration of sACE2 returns to normal levels in short viral shedders. In the plasma of prolonged viral shedders, we also found higher concentrations of Ang II and angiotensin I (Ang I). On the other hand, the plasma levels of Ang-(1-7) remains almost stable in prolonged viral shedders but seems insufficient to prevent the adverse effects of Ang II accumulation. Altogether, these data evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Enzima de Conversão de Angiotensina 2/sangue , COVID-19/sangue , Fragmentos de Peptídeos/sangue , Adulto , Enzima de Conversão de Angiotensina 2/genética , COVID-19/virologia , Feminino , Perfilação da Expressão Gênica , Antígenos HLA-DR , Humanos , Receptores de Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Projetos Piloto , Estudos Prospectivos , RNA Mensageiro , Eliminação de Partículas Virais
17.
J Clin Invest ; 131(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196300

RESUMO

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).


Assuntos
COVID-19/sangue , COVID-19/virologia , SARS-CoV-2 , Viremia/sangue , Viremia/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Pandemias , Prognóstico , Proteoma/metabolismo , Proteômica , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Internalização do Vírus
18.
Front Endocrinol (Lausanne) ; 12: 694083, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34226825

RESUMO

Background: Male sex is related to increased COVID-19 severity and fatality although confirmed infections are similarly distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19. Patients and Methods: We studied for effects of sex hormones on disease severity and immune activation in 377 patients (230 men, 147 women) with PCR-confirmed SARS-CoV-2 infections hospitalized at the Innsbruck University Hospital between February and December 2020. Results: Men had more severe COVID-19 with concomitant higher immune system activation upon hospital admission when compared to women. Men with a severe course of infection had lower serum total testosterone (tT) levels whereas luteinizing hormone (LH) and estradiol (E2) levels were within the normal range. tT deficiency was associated with elevated CRP (rs = - 0.567, p < 0.001), IL-6 levels (rs = - 0.563, p < 0.001), lower cholesterol levels (rs = 0.407, p < 0.001) and an increased morbidity and mortality. Men with tT levels < 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 - 144.639], p = 0.006) compared to men with tT levels > 230 ng/dL. Moreover, while morbidity and mortality showed a positive correlation with E2 levels at admission, we detected a negative correlation with the tT/E2 ratio upon hospital admission. Conclusion: Hospitalized men with COVID-19 present with rather low testosterone levels linked to more advanced immune activation, severe clinical manifestations translating into an increased risk for ICU admission or death. The underlying mechanisms remain elusive but may include infection driven hypogonadism as well as inflammation mediated cholesterol reduction causing gonadotropin suppression and impaired androgen formation. Finally, in elderly late onset hypogonadism might also contribute to lower testosterone levels.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico , Índice de Gravidade de Doença , Testosterona/sangue , Testosterona/deficiência , Idoso , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Testosterona/imunologia
19.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206357

RESUMO

In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1-60.0 µg/mL with regression coefficient (r2) = 0.9976. However, with acceptable r2, the calibration data's heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday's % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at -20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank.


Assuntos
Amidas/análise , Amidas/sangue , Antivirais/análise , Antivirais/sangue , Bioensaio/métodos , COVID-19/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos , Extração Líquido-Líquido/métodos , Pirazinas/análise , Pirazinas/sangue , Aciclovir/análise , Aciclovir/sangue , COVID-19/sangue , Calibragem , Estabilidade de Medicamentos , Congelamento , Humanos , Padrões de Referência , Reprodutibilidade dos Testes , Solventes/química
20.
Life Sci Alliance ; 4(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34226277

RESUMO

Here, we recorded serum proteome profiles of 33 severe COVID-19 patients admitted to respiratory and intensive care units because of respiratory failure. We received, for most patients, blood samples just after admission and at two more later time points. With the aim to predict treatment outcome, we focused on serum proteins different in abundance between the group of survivors and non-survivors. We observed that a small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, histidine-rich glycoprotein, and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3, and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also showed opposite trends in protein abundance during disease progression. We defined an optimal panel of nine proteins for mortality risk assessment. The prediction power of this mortality risk panel was evaluated against two recent COVID-19 serum proteomics studies on independent cohorts measured in other laboratories in different countries and observed to perform very well in predicting mortality also in these cohorts. This panel may not be unique for COVID-19 as some of the proteins in the panel have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria.


Assuntos
COVID-19/sangue , COVID-19/mortalidade , Proteoma/metabolismo , Índice de Gravidade de Doença , Idoso , COVID-19/virologia , Estudos de Coortes , Feminino , Hospitalização , Humanos , Imunoglobulinas/sangue , Masculino , SARS-CoV-2/fisiologia , Sobreviventes
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