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1.
Acta Med Indones ; 53(3): 308-314, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34611070

RESUMEN

COVID-19 became a widespread infectious disease in late 2019. Indonesia currently has the highest COVID-19 mortality rate in Asia, between 4-5 percent. Interestingly, COVID-19-associated coagulopathy characterized by an increase of several procoagulant factor levels, including fibrinogen and D-dimer, that has been associated with higher mortality and unfavorable outcomes. We report a case of a 30-year-old male admitted to the hospital with a profuse vomiting and worsening fever, cough and shortness of breath, and was diagnosed with COVID-19-associated coagulopathy. Seven days after admission, he became deteriorated with significant reduction of oxygen saturation and his coagulation parameter levels were increased with highly suspicion of pulmonary embolism. He was treated with azithromycin, isoprinosine, lopinavir, and fondaparinux with thromboprophylaxis dosage since admission. The role of increased fondaparinux dosage at the time of clinical deterioration was then followed by clinical improvement and reduced D-dimer level. Anticoagulant therapy, mainly with fondaparinux, showed a better prognosis in patients with markedly elevated D-Dimer. Fondaparinux needs to be monitored appropriately to prevent bleeding and adverse. The patient was discharged from the hospital in an improved condition and normal D-Dimer levels. There was no bleeding event nor other major side effects had been found in this case. The decision for increasing dose of anticoagulant may be determined on individual basis, considering risks, benefits, and also the most important is clinical findings.


Asunto(s)
COVID-19 , Fondaparinux , Hemorragia/prevención & control , Embolia Pulmonar , SARS-CoV-2/aislamiento & purificación , Trombofilia , Adulto , Antivirales , Azitromicina/administración & dosificación , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/tratamiento farmacológico , COVID-19/fisiopatología , Deterioro Clínico , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/efectos adversos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fondaparinux/administración & dosificación , Fondaparinux/efectos adversos , Hemorragia/inducido químicamente , Humanos , Inosina Pranobex/administración & dosificación , Lopinavir/administración & dosificación , Masculino , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/etiología , Trombofilia/complicaciones , Trombofilia/diagnóstico , Trombofilia/tratamiento farmacológico , Trombofilia/etiología , Resultado del Tratamiento
2.
Sci Rep ; 11(1): 19979, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620968

RESUMEN

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p < 0.001 Sens. 83.9% and Spec. 86.7%) with presence, extent and severity of the disease. Moreover, CA 15.3 appeared significantly increased in COVID-19 severe lung fibrosis (ICU vs NON-ICU patients 42.6 ± 3.3 vs 25.7 ± 1.5 U/mL, p < 0.0001) and was associated with lung damage severity grade (ROC AUC 0.958, decision threshold > 24.8 U/mL, p < 0.0001, Sens. 88.4% and Spec. 91.8%). In conclusion, serum levels of sFlt-1 and CA 15.3 appeared useful tools for categorizing COVID-19 clinical stage and may represent a valid aid for clinicians to better personalise treatment.


Asunto(s)
COVID-19/sangre , Mucina-1/sangre , Fibrosis Pulmonar/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Anciano , Biomarcadores/sangre , COVID-19/complicaciones , COVID-19/patología , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/patología , SARS-CoV-2/aislamiento & purificación
3.
J Clin Invest ; 131(17)2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34623327

RESUMEN

Defining the correlates of protection necessary to manage the COVID-19 pandemic requires the analysis of both antibody and T cell parameters, but the complexity of traditional tests limits virus-specific T cell measurements. We tested the sensitivity and performance of a simple and rapid SARS-CoV-2 spike protein-specific T cell test based on the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2-vaccinated individuals (n = 112), convalescent asymptomatic and symptomatic COVID-19 patients (n = 130), and SARS-CoV-1-convalescent individuals (n = 12). The sensitivity of this rapid test is comparable to that of traditional methods of T cell analysis (ELISPOT, activation-induced marker). Using this test, we observed a similar mean magnitude of T cell responses between the vaccinees and SARS-CoV-2 convalescents 3 months after vaccination or virus priming. However, a wide heterogeneity of the magnitude of spike-specific T cell responses characterized the individual responses, irrespective of the time of analysis. The magnitude of these spike-specific T cell responses cannot be predicted from the neutralizing antibody levels. Hence, both humoral and cellular spike-specific immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.


Asunto(s)
Vacunas contra la COVID-19/administración & dosificación , COVID-19 , Inmunidad Celular/efectos de los fármacos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Linfocitos T , Adulto , COVID-19/sangre , COVID-19/inmunología , COVID-19/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo
4.
PLoS One ; 16(10): e0258255, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34624024

RESUMEN

This study aimed to assess the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) total antibodies in the north, middle, and south regions of West Bank and the prevalence of SARS-CoV-2 specific antibodies (IgA, IgM, and IgG) in the Palestinian population. This was a cross-sectional study. The serological and epidemiological data of 1269 persons were assessed. Participants were selected randomly among primary health care center attendees in Palestine between November 1, 2020 and December 31, 2020. All serum samples were tested for total antibodies using an enzyme-linked immunosorbent assay (ELISA) test. IgM, IgG, and IgA-specific antibody titers were measured using ELISA. The overall prevalence (with 95% confidence intervals [CIs]) of SARS-CoV-2 total antibodies and specific antibodies were estimated. A multivariate regression model was used to assess the predictive factors for SARS-CoV-2-specific antibodies. The overall seroprevalence of SARS-CoV-2 antibodies was 24·0% (95% CI, 21·7%-26·5%). Seroprevalence was significantly higher among people living in south West Bank (adjusted Odds ratio [aOR], 2·22; 95% CI: 1·58-3·11), people who had COVID-19 symptoms (aOR, 3·92; 95% CI, 2·83-5·43), people with a COVID-19 contact history (aOR, 1·44; 95% CI, 1·03-2·03), patients with hypertension (aOR, 1·57; 95% CI, 1·06-2·33), and non-smokers (aOR, 0·47; 95% CI, 0·31-0·72). A total of 171 blood samples from SARS-CoV-2-positive patients were chosen at random for additional serological testing. Specific IgM, IgG, and IgA antibodies were positive in 14·0% (95% CI, 9·2%-20·2%), 88·3% (82·5%-92·7%), and 42·1% (34·6%-59·9%) of the samples, respectively. SARS-CoV-2 antibodies were common among PHC center attendees and were significantly associated to sex, smoking, and COVID-19 contact history. However, considering that almost three-quarters of this population remains susceptible, maintaining public health measures and encouraging access to immunization is critical in protecting this population.


Asunto(s)
Anticuerpos Antivirales/sangre , Árabes , Prueba Serológica para COVID-19 , COVID-19 , SARS-CoV-2/metabolismo , Adulto , Anciano , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia
5.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34638539

RESUMEN

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient's outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.


Asunto(s)
COVID-19/sangre , Esfingolípidos/sangre , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/diagnóstico , Femenino , Humanos , Lipidómica , Masculino , Persona de Mediana Edad , Pronóstico , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Esfingolípidos/análisis , Esfingomielinas/análisis , Esfingomielinas/sangre , Adulto Joven
6.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34638523

RESUMEN

The transmissible respiratory disease COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide since its first reported outbreak in December of 2019 in Wuhan, China. Since then, multiple studies have shown an inverse correlation between the levels of high-density lipoprotein (HDL) particles and the severity of COVID-19, with low HDL levels being associated with an increased risk of severe outcomes. Some studies revealed that HDL binds to SARS-CoV-2 particles via the virus's spike protein and, under certain conditions, such as low HDL particle concentrations, it facilitates SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) and infection of host cells. Other studies, however, reported that HDL suppressed SARS-CoV-2 infection. In both cases, the ability of HDL to enhance or suppress virus infection appears to be dependent on the expression of the HDL receptor, namely, the Scavenger Receptor Class B type 1 (SR-B1), in the target cells. SR-B1 and HDL represent crucial mediators of cholesterol metabolism. Herein, we review the complex role of HDL and SR-B1 in SARS-CoV-2-induced disease. We also review recent advances in our understanding of HDL structure, properties, and function during SARS-CoV-2 infection and the resulting COVID-19 disease.


Asunto(s)
COVID-19/metabolismo , Colesterol/metabolismo , Lipoproteínas HDL/metabolismo , SARS-CoV-2/fisiología , Animales , COVID-19/sangre , COVID-19/diagnóstico , Colesterol/sangre , Interacciones Huésped-Patógeno , Humanos , Lipoproteínas HDL/sangre , Receptores de Lipoproteína/metabolismo , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/metabolismo
7.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-34638691

RESUMEN

A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure (n = 11) and severe respiratory failure (n = 10) at an acute stage (day 0-3) and in the later course of the disease (>7 days). All patients needed supplemental oxygen and severe patients were defined by the requirement of positive pressure ventilation (intubation). Levels of D-dimers, activated partial thromboplastin time (aPTT), C-reactive protein (CRP), and interleukin (IL)-6 were significantly higher in patients with severe compared with moderate respiratory failure. Concurrently, next generation sequencing (NGS) analysis demonstrated increased dysregulation of miRNA expression with progression of disease severity connected to extreme downregulation of miR-320a, miR-320b and miR-320c. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed involvement in the Hippo signaling pathway, the transforming growth factor (TGF)-ß signaling pathway and in the regulation of adherens junctions. The expression of all miR-320 family members was significantly correlated with CRP, IL-6, and D-dimer levels. In conclusion, our analysis underlines the importance of thromboembolic processes in patients with respiratory failure and emphasizes miRNA-320s as potential biomarkers for severe progressive SARS-CoV-2 infection.


Asunto(s)
COVID-19/complicaciones , COVID-19/genética , MicroARNs/genética , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/genética , Anciano , Anciano de 80 o más Años , Coagulación Sanguínea , COVID-19/sangre , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Humanos , Inflamación/sangre , Inflamación/etiología , Inflamación/genética , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Insuficiencia Respiratoria/sangre , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad
8.
JAMA Netw Open ; 4(10): e2127172, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34605919

RESUMEN

Importance: Serum ferritin, an acute phase marker of inflammation, has several physiologic functions, including limiting intracellular oxidative stress. Whether the effectiveness of corticosteroids differs according to serum ferritin level in COVID-19 has not been reported. Objective: To examine the association between admission serum ferritin level and methylprednisolone treatment outcomes in nonintubated patients with severe COVID-19. Design, Setting, and Participants: This retrospective cohort study included patients with severe COVID-19 admitted to an academic referral center in Stony Brook, New York, from March 1 to April 15, 2020, receiving high-flow oxygen therapy (fraction of inspired oxygen, ≥50%). The outcomes of treatment with methylprednisolone were estimated using inverse probability of treatment weights, based on a propensity score comprised of clinical and laboratory variables. Patients were followed up for 28 days. Data were analyzed from December 19, 2020, to July 22, 2021. Exposures: Systemic methylprednisolone administered per the discretion of the treating physician. Main Outcomes and Measures: The primary outcome was mortality, and the secondary outcome was a composite of death or mechanical ventilation at 28 days. Results: Among 380 patients with available ferritin data (median [IQR] age, 60 years [49-72] years; 130 [34.2%] women; 250 [65.8%] men; 310 White patients [81.6%]; 47 Black patients [12.4%]; 23 Asian patients [6.1%]), 142 patients (37.4%) received methylprednisolone (median [IQR] daily dose, 160 [120-240] mg). Ferritin levels were similar in patients who received methylprednisolone vs those who did not (median [IQR], 992 [509-1610] ng/mL vs 893 [474-1467] ng/mL; P = .32). In weighted analyses using tertiles of ferritin values (lower: 29-619 ng/mL; middle: 623-1316 ng/mL; upper: 1322-13 418 ng/mL), methylprednisolone was associated with lower mortality in patients with ferritin in the upper tertile (HR, 0.16; 95% CI, 0.06-0.45) and higher mortality in those with ferritin in the middle (HR, 2.46; 95% CI, 1.15-5.28) and lower (HR, 2.43; 95% CI, 1.13-5.22) tertiles (P for interaction < .001). Composite end point rates were lower with methylprednisolone in patients with ferritin in the upper tertile (HR, 0.45; 95% CI, 0.25-0.80) but not in those with ferritin in the middle (HR, 0.83; 95% CI, 0.50-1.39) and lower (HR, 0.89; 95% CI, 0.51-1.55) tertiles (P for interaction = .11). Conclusions and Relevance: In this cohort study of nonintubated patients with severe COVID-19, methylprednisolone was associated with improved clinical outcomes only among patients with admission ferritin in the upper tertile of values.


Asunto(s)
Antiinflamatorios/uso terapéutico , COVID-19/tratamiento farmacológico , Ferritinas/sangre , Inflamación/sangre , Metilprednisolona/uso terapéutico , Índice de Severidad de la Enfermedad , Afroamericanos , Anciano , Grupo de Ascendencia Continental Asiática , COVID-19/sangre , COVID-19/mortalidad , COVID-19/terapia , Grupo de Ascendencia Continental Europea , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , New York , Terapia por Inhalación de Oxígeno , Neumonía , Respiración Artificial , Estudios Retrospectivos , SARS-CoV-2 , Resultado del Tratamiento
9.
Front Immunol ; 12: 739037, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34594341

RESUMEN

Background: Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients. Methods: Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients. Results: Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients. Conclusion: Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.


Asunto(s)
COVID-19/terapia , Convalecencia , SARS-CoV-2/inmunología , Seroconversión , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Antígenos Virales/sangre , Donantes de Sangre , COVID-19/sangre , COVID-19/inmunología , Femenino , Humanos , Inmunización Pasiva , Cinética , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , ARN Viral/sangre
10.
Tohoku J Exp Med ; 255(2): 127-134, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34645738

RESUMEN

Vitamin D attenuates inflammatory responses to viral respiratory infections. Hence, vitamin D deficiency may be a highly significant prognostic factor for severity and mortality in COVID-19 patients. To evaluate the complications and mortality in different vitamin D status groups in COVID-19 hospitalized patients, we conducted this retrospective study on 646 laboratory-confirmed COVID-19 patients who were hospitalized in Shahid Modarres Hospital, Tehran, Iran from 16th March 2020 until 25th February 2021. Overall, patients with vitamin D deficiency, insufficiency and sufficiency were 16.9%, 43.6% and 39.5%, respectively. The presence of comorbidity, length of hospitalization, ICU admission, and invasive mechanical ventilation requirement and overall complications were significantly more in patients with vitamin D deficiency (p-value < 0.001). 46.8% (51/109) of vitamin D deficient patients died due to the disease, whilst the mortality rate among insufficient and sufficient vitamin D groups was 29.4% (83/282) and 5.5% (14/255), respectively. In univariate analysis, age > 60 years (odds ratio (OR) = 6.1), presence of comorbidity (OR = 10.7), insufficient vitamin D status (OR = 7.2), and deficient vitamin D status (OR = 15.1) were associated with increase in COVID-19 mortality (p-value < 0.001). Finally, the multivariate analysis adjusted for age, sex, and comorbidities indicated vitamin D deficiency as an independent risk factor for mortality (OR = 3.3, p-value = 0.002). Vitamin D deficiency is a strong risk factor for mortality and severity of SARS-CoV-2 infection. Vitamin D supplementation may be able to prevent or improve the prognosis of COVID-19 during this pandemic.


Asunto(s)
COVID-19/complicaciones , Hospitalización , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , COVID-19/sangre , COVID-19/mortalidad , COVID-19/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , SARS-CoV-2/fisiología , Resultado del Tratamiento , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/virología
11.
Mediators Inflamm ; 2021: 9924542, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34602859

RESUMEN

Compared with other deadly diseases, the coronavirus disease 2019 (COVID-19) is highly infectious with a relatively low mortality rate. Although critical cases account for only 5% of cases, the mortality rate for the same is nearly 50%. Therefore, the key to the COVID-19 treatment is to effectively treat severe patients and reduce the transition from severe to critical cases. A retrospective study was carried out to evaluate outcomes of treatment in patients with severe and critical COVID-19 admitted to a COVID-19 special hospital in Wuhan, China. A total of 75 severe and critical COVID-19 patients were admitted and treated with immunomodulation as the main strategy combined with anti-inflammatory therapy and appropriate anticoagulation. Leukocyte levels in patients with 7-14 days of onset to diagnosis were significantly lower than in those with >14 days. Higher levels of globulin and D-dimer and lower lymphocyte levels were found in the older age group (>65 years) than in the middle-aged group (50-64 years). Patients with comorbidity had higher levels of inflammatory indicators. After treatment, 65 (86.67%) patients were cured, 7 (9.33%) had improved, and 3 (4.00%) had died. Median hospitalization duration was 23 days. Fatal cases showed continuously increased levels of globulin, dehydrogenase (LDH), hypersensitive C-reactive protein (hs-CRP), D-dimer, and cytokines during treatment. Time from onset to diagnosis, age, and comorbidity are important influencing factors on treatment effects. The occurrence of immunosuppression, "cytokine storm," and thrombosis may be an important cause of death in severely infected cases. In conclusion, high cure rate and low mortality suggested that immunomodulation combined with anti-inflammatory therapy and appropriate anticoagulant therapy is a good strategy for treatment of patients with severe and critical COVID-19.


Asunto(s)
COVID-19/tratamiento farmacológico , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/uso terapéutico , COVID-19/sangre , COVID-19/diagnóstico por imagen , COVID-19/inmunología , Femenino , Humanos , Inmunomodulación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
12.
Front Immunol ; 12: 741765, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34567007

RESUMEN

The long-term impact of COVID-19 on transplant recipients remains unknown. We describe the case of a 30-year-old male kidney transplant recipient from Wuhan, China that was treated for severe COVID-19 in February 2020. He suffered an acute lung and renal injury and required systemic treatment including adjustment of his immunosuppressant regime. He was followed up to 1-year after discharge. No chronic lung fibrosis or deterioration of his pulmonary function was observed. Despite COVID-19 mediated damage to his renal tubular cells, no transplant rejection occurred. His immunological profile demonstrated both cellular anti-SARS-CoV-2 reactivity and specific humoral immunity, indicating that it is beneficial for the transplanted patients to be immunized with SARS-CoV-2 virus vaccine. This case will help guide clinical decision making for immunocompromised individuals that become infected with SARS-CoV-2.


Asunto(s)
COVID-19 , Trasplante de Riñón , SARS-CoV-2 , Adulto , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/terapia , Citocinas/sangre , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/terapia , Recuento de Leucocitos , Masculino , Oxígeno/uso terapéutico , ARN Viral/análisis , SARS-CoV-2/genética , Receptores de Trasplantes
13.
Biomolecules ; 11(9)2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34572581

RESUMEN

Systemic vascular damage with micro/macro-thrombosis is a typical feature of severe COVID-19. However, the pathogenesis of this damage and its predictive biomarkers remain poorly defined. For this reason, in this study, serum monocyte chemotactic protein (MCP)-2 and P- and E-selectin levels were analyzed in 204 patients with COVID-19. Serum MCP-2 and P-selectin were significantly higher in hospitalized patients compared with asymptomatic patients. Furthermore, MCP-2 increased with the WHO stage in hospitalized patients. After 1 week of hospitalization, MCP-2 levels were significantly reduced, while P-selectin increased in patients in WHO stage 3 and decreased in patients in WHO stages 5-7. Serum E-selectin was not significantly different between asymptomatic and hospitalized patients. The lower MCP-2 levels after 1 week suggest that endothelial damage triggered by monocytes occurs early in COVID-19 disease progression. MCP-2 may also predict COVID-19 severity. The increase in P-selectin levels, which further increased in mild patients and reduced in severe patients after 1 week of hospitalization, suggests that the inactive form of the protein produced by the cleavage of the active protein from the platelet membrane is present. This may be used to identify a subset of patients that would benefit from targeted therapies. The unchanged levels of E-selectin in these patients suggest that endothelial damage is less relevant.


Asunto(s)
COVID-19 , Quimiocina CCL8/sangre , Selectina E/sangre , Endotelio Vascular , Selectina-P/sangre , SARS-CoV-2/metabolismo , Adulto , Anciano , COVID-19/sangre , COVID-19/patología , Endotelio Vascular/lesiones , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Monocitos/patología
14.
BMC Pregnancy Childbirth ; 21(1): 658, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34583679

RESUMEN

BACKGROUND: Whilst the impact of Covid-19 infection in pregnant women has been examined, there is a scarcity of data on pregnant women in the Middle East. Thus, the aim of this study was to examine the impact of Covid-19 infection on pregnant women in the United Arab Emirates population. METHODS: A case-control study was carried out to compare the clinical course and outcome of pregnancy in 79 pregnant women with Covid-19 and 85 non-pregnant women with Covid-19 admitted to Latifa Hospital in Dubai between March and June 2020. RESULTS: Although Pregnant women presented with fewer symptoms such as fever, cough, sore throat, and shortness of breath compared to non-pregnant women; yet they ran a much more severe course of illness. On admission, 12/79 (15.2%) Vs 2/85 (2.4%) had a chest radiograph score [on a scale 1-6] of ≥3 (p-value = 0.0039). On discharge, 6/79 (7.6%) Vs 1/85 (1.2%) had a score ≥3 (p-value = 0.0438). They also had much higher levels of laboratory indicators of severity with values above reference ranges for C-Reactive Protein [(28 (38.3%) Vs 13 (17.6%)] with p < 0.004; and for D-dimer [32 (50.8%) Vs 3(6%)]; with p < 0.001. They required more ICU admissions: 10/79 (12.6%) Vs 1/85 (1.2%) with p=0.0036; and suffered more complications: 9/79 (11.4%) Vs 1/85 (1.2%) with p=0.0066; of Covid-19 infection, particularly in late pregnancy. CONCLUSIONS: Pregnant women presented with fewer Covid-19 symptoms but ran a much more severe course of illness compared to non-pregnant women with the disease. They had worse chest radiograph scores and much higher levels of laboratory indicators of disease severity. They had more ICU admissions and suffered more complications of Covid-19 infection, such as risk for miscarriage and preterm deliveries. Pregnancy with Covid-19 infection, could, therefore, be categorised as high-risk pregnancy and requires management by an obstetric and medical multidisciplinary team.


Asunto(s)
COVID-19 , Unidades de Cuidados Intensivos/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Radiografía Torácica , Evaluación de Síntomas , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Proteína C-Reactiva/análisis , COVID-19/sangre , COVID-19/epidemiología , COVID-19/terapia , COVID-19/transmisión , Estudios de Casos y Controles , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/fisiopatología , Complicaciones Infecciosas del Embarazo/terapia , Complicaciones Infecciosas del Embarazo/virología , Resultado del Embarazo/epidemiología , Embarazo de Alto Riesgo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Radiografía Torácica/métodos , Radiografía Torácica/estadística & datos numéricos , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Evaluación de Síntomas/métodos , Evaluación de Síntomas/estadística & datos numéricos , Emiratos Árabes Unidos/epidemiología
16.
Cells ; 10(9)2021 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-34571855

RESUMEN

The cellular immune response plays an important role in COVID-19, caused by SARS-CoV-2. This feature makes use of in vitro models' useful tools to evaluate vaccines and biopharmaceutical effects. Here, we developed a two-step model to evaluate the cellular immune response after SARS-CoV-2 infection-induced or spike protein stimulation in peripheral blood mononuclear cells (PBMC) from both unexposed and COVID-19 (primo-infected) individuals (Step1). Moreover, the supernatants of these cultures were used to evaluate its effects on lung cell lines (A549) (Step2). When PBMC from the unexposed were infected by SARS-CoV-2, cytotoxic natural killer and nonclassical monocytes expressing inflammatory cytokines genes were raised. The supernatant of these cells can induce apoptosis of A549 cells (mock vs. Step2 [mean]: 6.4% × 17.7%). Meanwhile, PBMCs from primo-infected presented their memory CD4+ T cells activated with a high production of IFNG and antiviral genes. Supernatant from past COVID-19 subjects contributed to reduce apoptosis (mock vs. Step2 [ratio]: 7.2 × 1.4) and to elevate the antiviral activity (iNOS) of A549 cells (mock vs. Step2 [mean]: 31.5% × 55.7%). Our findings showed features of immune primary cells and lung cell lines response after SARS-CoV-2 or spike protein stimulation that can be used as an in vitro model to study the immunity effects after SARS-CoV-2 antigen exposure.


Asunto(s)
COVID-19/inmunología , COVID-19/virología , Inmunidad Celular , Modelos Biológicos , SARS-CoV-2/fisiología , Adulto , Células Epiteliales Alveolares/virología , COVID-19/sangre , COVID-19/genética , Citocinas/genética , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Memoria Inmunológica/inmunología , Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Fenotipo , Linfocitos T/inmunología , Replicación Viral/fisiología , Adulto Joven
17.
Front Endocrinol (Lausanne) ; 12: 727419, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34589058

RESUMEN

Background: Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup. Methods: We conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters. Results: Of 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090-0.507; HR: 1.066, 95% CI 1.030-1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128-0.612) and 4.458 (1.817-10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity. Conclusion: Lower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.


Asunto(s)
COVID-19/sangre , HDL-Colesterol/sangre , Diabetes Mellitus/sangre , Anciano , Biomarcadores/sangre , COVID-19/diagnóstico , COVID-19/mortalidad , China , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Leucocitos/citología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
18.
BMC Nephrol ; 22(1): 297, 2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34465289

RESUMEN

BACKGROUND: Kidney disease and renal failure are associated with hospital deaths in patients with COVID - 19. We aimed to test if contrast enhancement affects short-term renal function in hospitalized COVID - 19 patients. METHODS: Plasma creatinine (P-creatinine) was measured on the day of computed tomography (CT) and 24 h, 48 h, and 4-10 days after CT. Contrast-enhanced (n = 142) and unenhanced (n = 24) groups were subdivided, based on estimated glomerular filtration rates (eGFR), > 60 and ≤ 60 ml/min/1.73 m2. Contrast-induced acute renal failure (CI-AKI) was defined as ≥27 µmol/L increase or a > 50% rise in P-creatinine from CT or initiation of renal replacement therapy during follow-up. Patients with renal replacement therapy were studied separately. We evaluated factors associated with a > 50% rise in P-creatinine at 48 h and at 4-10 days after contrast-enhanced CT. RESULTS: Median P-creatinine at 24-48 h and days 4-10 post-CT in patients with eGFR> 60 and eGFR≥30-60 in contrast-enhanced and unenhanced groups did not differ from basal values. CI-AKI was observed at 48 h and at 4-10 days post contrast administration in 24 and 36% (n = 5/14) of patients with eGFR≥30-60. Corresponding figures in the eGFR> 60 contrast-enhanced CT group were 5 and 5% respectively, (p < 0.037 and p < 0.001, Pearson χ2 test). In the former group, four of the five patients died within 30 days. Odds ratio analysis showed that an eGFR≥30-60 and 30-day mortality were associated with CK-AKI both at 48 h and 4-10 days after contrast-enhanced CT. CONCLUSION: Patients with COVID - 19 and eGFR≥30-60 had a high frequency of CK-AKI at 48 h and at 4-10 days after contrast administration, which was associated with increased 30-day mortality. For patients with eGFR≥30-60, we recommend strict indications are practiced for contrast-enhanced CT. Contrast-enhanced CT had a modest effect in patients with eGFR> 60.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , COVID-19/complicaciones , Medios de Contraste/efectos adversos , Creatinina/sangre , Yodo/efectos adversos , Riñón/efectos de los fármacos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Anciano , COVID-19/sangre , COVID-19/mortalidad , COVID-19/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/diagnóstico por imagen , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Análisis de Regresión , Terapia de Reemplazo Renal , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X
19.
Front Immunol ; 12: 700921, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34539631

RESUMEN

Cytokines, chemokines and growth factors present different expression profiles related to the prognosis of COVID-19. We analyzed clinical parameters and assessed the expression of these biomarkers in patients with different disease severity in a hospitalized Peruvian cohort to determine those associated with worse prognosis. We measured anti-spike IgG antibodies by ELISA and 30 cytokines by quantitative suspension array technology in 123 sera samples. We analyzed differences between patients with moderate, severe and fatal COVID-19 by logistic regression at baseline and in longitudinal samples. Significant differences were found among the clinical parameters: hemoglobin, neutrophils, lymphocytes and C-reactive protein (CRP), creatinine and D-dimer levels. Higher anti-spike IgG antibody concentrations were associated to fatal patient outcomes. At hospitalization, IL-10, IL-6, MIP-1α, GM-CSF, MCP-1, IL-15, IL-5, IL1RA, TNFα and IL-8 levels were already increased in fatal patients´ group. Meanwhile, multivariable analysis revealed that increased GM-CSF, MCP-1, IL-15, and IL-8 values were associated with fatal outcomes. Moreover, longitudinal analysis identified IL-6 and MCP-1 as the main risk factors related to mortality in hospitalized COVID-19 patients. In this Peruvian cohort we identified and validated biomarkers related to COVID-19 outcomes. Further studies are needed to identify novel criteria for stratification of SARS-CoV-2 infected patients at hospital entry. Background: In the most severe forms of SARS-CoV-2 infection, large numbers of innate and adaptive immune cells become activated and begin to produce pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. Methods: A total of 55 patients with laboratory-confirmed COVID-19 admitted to the Hospital Nacional Guillermo Almenara Irigoyen in Lima, Peru were enrolled during August-October 2020. Of these, 21 had moderate disease, 24 severe diseases and 10 died. We measured 30 cytokines and chemokines by quantitative suspension array technology and anti-spike IgG antibodies using a commercial ELISA. We evaluated these parameters in peripheral blood every 2-5 days until patient discharge or death. Patient information and clinical parameters related were obtained from the respective clinical histories. Results: The frequency of obesity differed among the 3 groups, being most frequent in patients who died. There were also significant differences in clinical parameters: hemoglobin, segmented neutrophils, lymphocytes,C-reactive protein, creatinine and D-dimer levels. Greater anti-spike IgG antibody concentrations were associated to fatal outcomes. In univariate analyses, higher baseline concentrations of IL-6, MIP-1α, GM-CSF, MCP-1, IL-15, IL-5, IL1RA, TNFα, IL-8 and IL-12p70 correlated with severity, while multivariable analysis showed that increased concentrations in 4 biomarkers (GM-CSF, MCP-1, IL-15, IL-8) were associated with fatal outcomes. Longitudinal analysis showed IL-6 (hazard ratio [HR] 6.81, 95% confidence interval [CI] 1.6-28.7) and MCP-1 (HR 4.61, 95%CI 1.1-19.1) to be related to mortality in hospitalized COVID-19 patients. Conclusions: Cytokine, chemokine and growth factor profiles were identified and validated related to severity and outcomes of COVID-19. Our findings may be useful to identify novel criteria for COVID-19 patient stratification at hospital entry.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/sangre , COVID-19/mortalidad , Citocinas/sangre , Anticuerpos Antivirales/inmunología , Biomarcadores/sangre , COVID-19/inmunología , Comorbilidad , Ensayo de Inmunoadsorción Enzimática , Femenino , Hospitalización , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Perú/epidemiología , Pronóstico , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/inmunología
20.
Int J Immunopathol Pharmacol ; 35: 20587384211048026, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34569339

RESUMEN

COVID-19 is a highly heterogeneous and complex medical disorder; indeed, severe COVID-19 is probably amongst the most complex of medical conditions known to medical science. While enormous strides have been made in understanding the molecular pathways involved in patients infected with coronaviruses an overarching and comprehensive understanding of the pathogenesis of COVID-19 is lacking. Such an understanding is essential in the formulation of effective prophylactic and treatment strategies. Based on clinical, proteomic, and genomic studies as well as autopsy data severe COVID-19 disease can be considered to be the connection of three basic pathologic processes, namely a pulmonary macrophage activation syndrome with uncontrolled inflammation, a complement-mediated endothelialitis together with a procoagulant state with a thrombotic microangiopathy. In addition, platelet activation with the release of serotonin and the activation and degranulation of mast cells contributes to the hyper-inflammatory state. Auto-antibodies have been demonstrated in a large number of hospitalized patients which adds to the end-organ damage and pro-thrombotic state. This paper provides a clinical overview of the major pathogenetic mechanism leading to severe COVID-19 disease.


Asunto(s)
COVID-19/virología , SARS-CoV-2/patogenicidad , COVID-19/sangre , COVID-19/inmunología , COVID-19/fisiopatología , Activación de Complemento , Proteínas del Sistema Complemento/metabolismo , Citocinas/sangre , Progresión de la Enfermedad , Interacciones Huésped-Patógeno , Humanos , Inflamación/sangre , Inflamación/inmunología , Inflamación/fisiopatología , Inflamación/virología , Mediadores de Inflamación/sangre , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/inmunología , Síndrome de Activación Macrofágica/fisiopatología , Síndrome de Activación Macrofágica/virología , Activación Plaquetaria , SARS-CoV-2/inmunología , Serotonina/sangre , Índice de Severidad de la Enfermedad , Microangiopatías Trombóticas/sangre , Microangiopatías Trombóticas/inmunología , Microangiopatías Trombóticas/fisiopatología , Microangiopatías Trombóticas/virología
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