RESUMEN

COVID-19's long-lasting and complex impacts have become a global concern, with diverse clinical outcomes. This study evaluated 226 participants to understand the clinical spectrum of COVID-19/Long COVID (LC), exploring how disease severity correlates with sociodemographic factors and biomarkers. Determinants related to COVID-19 severity included age (P < 0.001), lower education (P < 0.001), ethnicity (P = 0.003), overweight (P < 0.001), MTHFR gene rs1801133 (P = 0.035), cardiovascular diseases (P = 0.002), diabetes mellitus (DM) (P = 0.006), Factor VIII (FVIII) (P = 0.046), von Willebrand factor (VWF) (P = 0.002), and dimer D (DD) (P < 0.001). Six months later, in a portion of the monitored participants, a significant reduction in FVIII (P < 0.001), VWF (P = 0.002), and DD (P < 0.001) levels was observed, with only DD returning to normal values. Different systemic sequelae were identified, with higher incidences of joint pain and myalgia in participants with a clinical history of DM, chronic lung disease (CLD) and sustained high interleukin 6 values in the convalescent phase. CLD, COVID-19 severity and high DD levels increased the risk of developing dyspnea and palpitations. Women were more likely to develop lower limb phlebitis long-term, while sustained elevated FVIII in the convalescent phase was associated with an increased risk of swelling. Regular physical activity had a protective effect against swelling. This study highlights factors contributing to COVID-19 severity/LC, emphasizing endothelial cell activation as a potential mechanism.

Asunto(s)

Biomarcadores , COVID-19 , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factor de von Willebrand , Humanos , COVID-19/sangre , Femenino , Masculino , Biomarcadores/sangre , Persona de Mediana Edad , Pronóstico , Factor de von Willebrand/metabolismo , Factor de von Willebrand/análisis , Adulto , Anciano , SARS-CoV-2/aislamiento & purificación , Factor VIII/metabolismo , Factor VIII/análisis , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo

RESUMEN

Acute respiratory distress syndrome is a significant complication in critical care patients. COVID-19 (C19)-associated severe respiratory failure is related to it, and d-dimer rise predicts a worse outcome. To investigate the association between d-dimer and the severity of this respiratory syndrome, we conducted a study in C19 intubated patients. A retrospective, single-center observational study was conducted with 64 C19 adult intubated patients. Strata of d-dimer results between patients was evaluated using survival analysis. Survival was higher in mild respiratory distress patients. D-dimer showed poor sensitivity and specificity in predicting respiratory failure severity. Risk assessment for death showed a higher prevalence of admission d-dimer results (HR 1.335; 95% CI 0.695-2.564). Our sample confidently represented the medical profile of C19 severe patients. Sepsis development in C19 is associated with the inflammatory storm in respiratory distress syndrome. As the receiver operating curves show, the increase in d-dimer results is consistent with inflammation rather than a prognostic biomarker. As expected, severe respiratory distress patients presented higher mortality. In summary, d-dimer results are not associated with the prognosis of C19 respiratory distress syndrome patients.

Asunto(s)

Biomarcadores , COVID-19 , Productos de Degradación de Fibrina-Fibrinógeno , Síndrome de Dificultad Respiratoria , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , COVID-19/sangre , COVID-19/complicaciones , COVID-19/mortalidad , Masculino , Biomarcadores/sangre , Estudios Retrospectivos , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/mortalidad , Femenino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Anciano , Pronóstico , SARS-CoV-2 , Adulto , Sensibilidad y Especificidad

RESUMEN

INTRODUCTION: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil. METHODS: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays. RESULTS: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination. CONCLUSIONS: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.

Asunto(s)

COVID-19 , Productos de Degradación de Fibrina-Fibrinógeno , Activación Plaquetaria , Factor Plaquetario 4 , Humanos , Femenino , Masculino , Brasil/epidemiología , Adulto , Factor Plaquetario 4/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Persona de Mediana Edad , Trombocitopenia/inducido químicamente , SARS-CoV-2/inmunología , Adulto Joven , Ad26COVS1 , Recuento de Plaquetas , Vacunación , Estudios Retrospectivos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Adolescente , Trombosis/inmunología , Trombosis/prevención & control

RESUMEN

OBJECTIVE: The study aimed at analyzing the serum expression of Immature Granulocyte percentage (IG %) and D-Dimer (D-D) in patients with severe pancreatitis and exploring their clinical diagnostic value. METHODS: Eighty-four cases with severe pancreatitis received in Shengjing Hospital, China Medical University from July 2020 to July 2023 were regarded as the study group and conducted for retrospective analysis. They were divided into a survival group (n = 62) and a death group (n = 22) based on the prognosis. Another 80 patients diagnosed with mild and moderate pancreatitis were selected as the control group. Serum IG % and D-D levels of all subjects were analyzed and the value of IG % and D-D in the evaluation of severe pancreatitis and its prognosis was conducted by Receiver Operating Characteristic (ROC) curve. RESULTS: The IG % and D-D levels in the study group were markedly higher than the control group (p < 0.05). The IG % and D-D level in the death group were observably higher than the survival group (p < 0.05). The Area Under the Curve (AUC) of IG % and D-D combined assessment for severe pancreatitis was 0.963, and the sensitivity and specificity were 98.75 %, 82.14 %, respectively. The AUC of IG % and D-D combined assessment for prognosis of severe pancreatitis was 0.814 with a sensitivity of 79.03 % and a specificity of 77.27 %. The efficiency of joint evaluation of the two indicators is superior to the individual evaluation. CONCLUSION: Serum IG % and D-D are highly expressed in patients with severe pancreatitis, which has important clinical value for the evaluation of severe pancreatitis and its prognosis.

Asunto(s)

Productos de Degradación de Fibrina-Fibrinógeno , Granulocitos , Pancreatitis , Curva ROC , Índice de Severidad de la Enfermedad , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Pancreatitis/sangre , Pancreatitis/mortalidad , Pancreatitis/diagnóstico , Adulto , Sensibilidad y Especificidad , Anciano , Biomarcadores/sangre , Recuento de Leucocitos , Estudios de Casos y Controles

RESUMEN

This study aimed to investigate the immunomodulatory behavior of soluble immune checkpoints (sICPs) and other biomarkers in the pathophysiology of SARS-CoV-2 infection. The study included 59 adult participants, 43 of whom tested positive for SARS-CoV-2. Patients were divided into three cohorts: those with moderate disease (n = 16), recovered patients with severe disease (n = 13), and deceased patients with severe disease (n = 16). In addition, 16 participants were pre-pandemic subjects negative for SARS-CoV-2. The relative activity of neutralizing antibodies (rNAbs) against SARS-CoV-2 and the values of 14 sICPs in peripheral blood were compared between the four groups. Because the increase of markers values of inflammation [NLR > 12; CRP > 150 mg/L] and venous thromboembolism [D-dimer > 0.5 mg/L] has been associated with mortality from COVID-19, the total and differential leukocyte counts, the NLR, and CRP and D-dimer values were obtained in patients with severe disease. No differences in rNAbs were observed between the cohorts. Only the levels of five sICPs, sCD27, sHVEM sTIM-3, sPD-1, and sPDL-1, were significantly higher in patients with severe rather than moderate disease. The sPDL-2 level and NLR were higher in deceased patients than in recovered patients. However, there was no difference in CRP and D-dimer values between the two groups. Of the five soluble biomarkers compared among patients with severe disease, only sPDL-2 was higher in deceased patients than in recovered patients. This suggests that immuno-inhibitory sICPs might be used as indicators for severe COVID-19, with sPDL-2 used to assess individual risk for fatality.IMPORTANCECOVID-19, the disease caused by a SARS-CoV-2 infection, generates a broad spectrum of clinical symptoms, progressing to multiorgan failure in the most severe cases. As activation of the immune system is pivotal to eradicating the virus, future research should focus on identifying reliable biomarkers to efficiently predict the outcome in severe COVID-19 cases. Soluble immune checkpoints represent the function of the immune system and are easily determined in peripheral blood. This research could lead to implementing more effective severity biomarkers for COVID-19, which could increase patients' survival rate and quality of life.

Asunto(s)

Biomarcadores , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/sangre , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , SARS-CoV-2/inmunología , Anciano , Adulto , Índice de Severidad de la Enfermedad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Proteínas de Punto de Control Inmunitario/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Anciano de 80 o más Años

RESUMEN

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Asunto(s)

COVID-19 , Productos de Degradación de Fibrina-Fibrinógeno , Hemorragia , Trombosis , Humanos , COVID-19/sangre , COVID-19/complicaciones , COVID-19/diagnóstico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Hemorragia/sangre , Hemorragia/diagnóstico , Hemorragia/etiología , Hemorragia/inducido químicamente , Masculino , Femenino , Trombosis/sangre , Trombosis/etiología , Trombosis/diagnóstico , Anciano , Persona de Mediana Edad , Hospitalización , Factores de Riesgo , SARS-CoV-2 , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos

RESUMEN

BACKGROUND: Hemodialysis (HD) per se is a risk factor for thrombosis. Considering the growing body of evidence on blood-flow restriction (BFR) exercise in HD patients, identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model. The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise (RE) with BFR on this molecule. METHODS: Two hundred and six HD patients volunteered for this study (all with a glomerular filtration rate of <15 mL/min/1.73 m2). The RE + BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD (intradialytic exercise). RE repetitions included concentric and eccentric lifting phases (each lasting 2 s) and were supervised by a strength and conditioning specialist. RESULTS: Several variables were associated with elevated levels of D-dimer, including higher blood glucose, citrate use, recent cardiovascular events, recent intercurrents, higher inflammatory status, catheter as vascular access, older patients (>70 years old), and HD vintage. Furthermore, RE + BFR significantly increases D-dimer after 4 h. Patients with borderline baseline D-dimer levels (400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range (≥500 ng/mL). CONCLUSION: These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE + BFR. D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE + BFR.

Asunto(s)

Productos de Degradación de Fibrina-Fibrinógeno , Diálisis Renal , Entrenamiento de Fuerza , Trombosis , Humanos , Diálisis Renal/efectos adversos , Entrenamiento de Fuerza/métodos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Masculino , Trombosis/etiología , Trombosis/sangre , Femenino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Glucemia/metabolismo , Flujo Sanguíneo Regional , Factores de Edad

RESUMEN

BACKGROUND: Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are eicosanoids involved in modulation of the antiviral immune response. Recent studies have identified increased levels of several eicosanoids in the plasma and bronchoalveolar lavage of patients with coronavirus disease (COVID-19). This study investigated correlations between plasma levels of PGE2 and LTB4 and clinical severity of COVID-19. METHODS: This cross-sectional study involved non-infected (n = 10) individuals and COVID-19 patients classified as cured (n = 13), oligosymptomatic (n = 29), severe (n = 15) or deceased (n = 11). Levels of D-dimer a, known COVID-19 severity marker, PGE2 and LTB4 were measured by ELISAs and data were analysed with respect to viral load. RESULTS: PGE2 plasma levels were decreased in COVID-19 patients compared to the non-infected group. Changes in PGE2 and LTB4 levels did not correlate with any particular clinical presentations of COVID-19. However, LTB4 was related to decreased SARS-CoV-2 burden in patients, suggesting that only LTB4 is associated with control of viral load. CONCLUSIONS: Our data indicate that PGE2/LTB4 plasma levels are not associated with COVID-19 clinical severity. Hospitalized patients with COVID-19 are treated with corticosteroids, which may influence the observed eicosanoid imbalance. Additional analyses are required to fully understand the participation of PGE2 receptors in the pathophysiology of COVID-19.

Asunto(s)

COVID-19 , Dinoprostona , Leucotrieno B4 , SARS-CoV-2 , Carga Viral , Humanos , COVID-19/sangre , COVID-19/virología , COVID-19/inmunología , Leucotrieno B4/sangre , Estudios Transversales , Dinoprostona/sangre , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/fisiología , Anciano , Adulto , Índice de Severidad de la Enfermedad , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/análisis

RESUMEN

Plaque rupture triggers a prothrombotic response that is counterbalanced by a fibrinolytic response. d -dimer serves as a marker of both processes. Inflammatory mediators are also released, evidenced with the rise of high-sensitive C reactive protein (hsCRP). Current evidence with these biomarkers has shown conflicting results. Determine an association between d -dimer and hsCRP within hospital and 1-year mortality in patients with acute coronary syndromes. In total, 127 patients were included. In-hospital mortality was 5.7%, and 1-year all-cause and cardiovascular mortality were 14.6 and 9.7%, respectively. The median of admission d -dimer for patients who died during hospital stay was higher than those who survived [4.59 (interquartile ranges (IQR) 1.94-6.05 µg/ml fibrinogen equivalent units (FEU)) vs. 0.56 (IQR 0.31-1.12 µg/ml FEU), P  = 0.001]. At 1-year follow-up, the median of admission d -dimer for patients who died was significantly higher than those who survived: 1.55 (IQR 0.91-5.08 µg/ml FEU) vs. 0.53 (IQR 0.29-0.90 µg/ml FEU), P  < 0.001. Positive d -dimer vs. negative d -dimer at admission analysis evidenced that almost 25% of the positive patients were dead at 1-year follow-up (22.4 vs. 2.4% negative d -dimer, P  = 0.011). Multivariate logistic regression analysis showed that d -dimer has an independent association with 1-year mortality [odds ratio 1.06 (95% confidence interval 1.02-1.10), P  = 0.006]. Positive significative correlations between d -dimer and hsCRP levels ( R  = 0.56, P  < 0.001) were found. High levels of admission d -dimer were strongly associated with in-hospital and 1-year mortality. Significant correlations with hsCRP could explain the inflammatory nature that led to poorer outcomes. d -dimer could be useful in risk stratification in acute coronary syndromes; however, a specific threshold should be defined for this type of patient.

Asunto(s)

Síndrome Coronario Agudo , Proteína C-Reactiva , Humanos , Proteína C-Reactiva/análisis , Síndrome Coronario Agudo/diagnóstico , Biomarcadores , Inflamación , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hemostasis

RESUMEN

Resumen Introducción: El aumento de la concentración de dímero-D en pacientes COVID-19 se ha asociado a mayor gravedad y peor pronóstico; sin embargo, su rol en predecir el diagnóstico de tromboembolismo pulmonar (TEP), aún es incierto. Objetivo: Evaluar la utilidad del dímero-D plasmático en el diagnóstico de TEP en pacientes con COVID-19. Pacientes y Métodos: Estudio observacional analítico. Se incluyó a pacientes COVID-19 que tenían una angiotomografía computada de tórax (AngioTAC). Se registraron datos clínicos, niveles plasmáticos de dímero-D de ingreso y previo al momento de realizar la AngioTAC. Se identificó la presencia o ausencia de TEP. Resultados: Se incluyeron 163 pacientes; 37(23%) presentaron TEP. Al comparar la serie de pacientes con TEP versus sin TEP, no se encontraron diferencias significativas en características clínicas, ni mortalidad. Hubo diferencias significativas en el nivel plasmático del dímero-D previo a realizar la AngioTAC (3.929 versus 1.912 μg/L; p = 0,005). El área bajo la curva ROC del dímero-D para TEPfue de 0,65. El mejor punto de corte del dímero-D fue de 2.000 μg/L, con una baja sensibilidad y valor predictivo positivo. El valor de corte con el mejor valor predictivo negativo (VPN)fue de 900 μg/L (96%), el cual fue mejor que la estrategia de corte de dímero D ajustado por edad (VPN 90%). Conclusión: La capacidad discriminativa del dímero D para diagnosticar TEP fue baja. En cambio, el dímero D mantiene un alto valor predictivo negativo para descartar TEP, el cual es mayor al valor descrito clásicamente en los pacientes no COVID.

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Introduction: Increased D-dimer concentration in COVID-19 patients has been associated with greater severity and worse prognosis; however its role in predicting the diagnosis of pulmonary thromboembolism (PTE), is still uncertain. Objective: To evaluate the usefulness of plasma D-dimer in the diagnosis of PTE in patients with COVID-19. Method: Analytical observational study. COVID-19 patients who had a chest computed tomography angiography (CTA) were included. Clinical data, Ddimer plasma levels on admission and prior to CTA were recorded. The presence or absence of PTE was identified. Results: 163 patients were included, 37 (23%) presented PTE. After comparing the series of patients with PTE versus the series without PTE, no significant differences were found in clinical characteristics or mortality. There were significant differences in the plasma level of D-dimer prior to performing CTA (3,929 μg/L versus. 1,912 μg/L; p = 0.005). The area under the D-dimer ROC curve for PTEprediction was 0.65. The best D-dimer cutoffpoint was 2.000μg/L, with a low sensitivity and positivepredictive value. The cutoff value with the best negativepredictive value (NPV) was 900 μg/L (96%), which was better than the age-adjusted D-dimer cutoff strategy (NPV 90%). Conclusion: The discriminative ability of D-dimer to diagnose PTE was low. In contrast, D-dimer maintains a high negative predictive value to rule out PTE, which is higher than the value classically described in non-COVID patients.

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , COVID-19/complicaciones , Embolia Pulmonar/diagnóstico por imagen , Biomarcadores/análisis , Valor Predictivo de las Pruebas , Curva ROC , Sensibilidad y Especificidad , Angiografía por Tomografía Computarizada

RESUMEN

BACKGROUND: Peru is the country with the world's highest COVID-19 death rate per capita. Characteristics associated with increased mortality among adult patients with COVID-19 pneumonia in this setting are not well described. METHODS: Retrospective, single-center cohort study including 1537 adult patients hospitalized with a diagnosis of SARS-CoV-2 pneumonia between May 2020 and August 2020 at a national hospital in Lima, Peru. The primary outcome measure was in-hospital mortality. RESULTS: In-hospital mortality was 49.71%. The mean age was 60 ± 14.25 years, and 68.38% were males. We found an association between mortality and inflammatory markers, mainly leukocytes, D-dimer, lactate dehydrogenase, C-reactive protein and ferritin. A multivariate model adjusted for age, hypertension, diabetes mellitus, and corticosteroid use demonstrated that in-hospital mortality was associated with greater age (RR: 2.01, 95%CI: 1.59-2.52) and a higher level of oxygen requirement (RR: 2.77, 95%CI: 2.13-3.62). Conclusions: In-hospital mortality among COVID-19 patients in Peru is high and is associated with greater age and higher oxygen requirements.

Asunto(s)

COVID-19/mortalidad , Hospitalización/estadística & datos numéricos , Factores de Edad , Anciano , Proteína C-Reactiva/análisis , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/virología , Comorbilidad , Femenino , Ferritinas/análisis , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Perú/epidemiología , Respiración Artificial , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación

RESUMEN

Aim: Pulmonary disease burden and biomarkers are possible predictors of outcomes in patients with COVID-19 and provide complementary information. In this study, the prognostic value of adding quantitative chest computed tomography (CT) to a multiple biomarker approach was evaluated among 148 hospitalized patients with confirmed COVID-19. Materials & methods: Patients admitted between March and July 2020 who were submitted to chest CT and biomarker measurement (troponin I, D-dimer and C-reactive protein) were retrospectively analyzed. Biomarker and tomographic data were compared and associated with death and intensive care unit admission. Results: The number of elevated biomarkers was significantly associated with greater opacification percentages, lower lung volumes and higher death and intensive care unit admission rates. Total lung volume <3.0 l provided further stratification for mortality when combined with biomarker evaluation. Conclusion: Adding automated CT data to a multiple biomarker approach may provide a simple strategy for enhancing risk stratification of patients with COVID-19.

Asunto(s)

Biomarcadores/análisis , COVID-19/diagnóstico , Tórax/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteína C-Reactiva/análisis , COVID-19/mortalidad , COVID-19/virología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Tomografía Computarizada por Rayos X , Troponina I/sangre

RESUMEN

Objectives: To analyze the association of inflammatory and coagulation biomarkers with mortality in geriatric patients with COVID-19. Methods: This is a retrospective cohort study of 206 patients aged 60 years or older who were hospitalized with COVID-19 at an intensive care unit. The analyzed variables were age, sex, length of hospital stay, and inflammatory biomarkers (C-reactive protein, neutrophil-to-lymphocyte ratio, procalcitonin, fibrinogen, ferritin, and d-dimer). We constructed a receiver operating characteristic curve and analyzed the area under the curve to evaluate the accuracy of biomarkers associated with mortality in patients with COVID-19. Results: Mean age was 72 (± 8) years. There were 101 deaths (49% of the total sample), which were significantly more frequent (p = 0.006) in the older age groups and were distributed as follows: 37.50% (60 ­ 69 years old); 50% (70 ­ 79 years old); 67.50% (80 ­ 89 years old); and 75% (over 90 years old). Mortality was associated with increased serum levels of procalcitonin, neutrophil-to-lymphocyte ratio, C-reactive protein, and d-dimer, and decreased fibrinogen levels. Neutrophil-to-lymphocyte ratio occupied the largest area under the receiver operating characteristic curve (area under the curve 0.859) in this group. Conclusions: In this study, inflammatory biomarkers neutrophil-to-lymphocyte ratio, procalcitonin, C-reactive protein, and d-dimer were associated with mortality in older patients with COVID-19 hospitalized at an intensive care unit, and neutrophil-to-lymphocyte ratio presented the best accuracy.

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Objetivos: Analisar associação de biomarcadores inflamatórios e da coagulação com mortalidade em pacientes geriátricos com COVID-19. Metodologia: Estudo do tipo coorte retrospectiva de 206 pacientes com 60 anos de idade ou mais internados em unidade de terapia intensiva (UTI) com COVID-19. As variáveis analisadas foram idade, sexo, tempo de permanência hospitalar e biomarcadores inflamatórios, sendo esses proteína C reativa (PCR), relação neutrófilo-linfócitos (RNL), procalcitonina, fibrinogênio, ferritina e D-dímero. Empregou-se a curva ROC, com análise da área sob a curva (ACR), para avaliar a acurácia dos biomarcadores associados à mortalidade nos pacientes com COVID-19. Resultados: A média de idade foi de 72 (± 8) anos. Ocorreram 101 óbitos (49,02% da amostra total), significativamente mais frequente (p = 0,006) nas faixas etárias mais elevadas, distribuídos por faixa etária: 37,50% (60 ­ 69 anos); 50% (70 ­ 79 anos); 67,50% (80 ­ 89 anos); e 75% (nos maiores de 90 anos). A mortalidade foi associada a aumento dos níveis séricos dos biomarcadores procalcitonina, relação neutrófiloslinfócitos (RNL), proteína C reativa (PCR) e D-dímero, bem como diminuição dos níveis de fibrinogênio. A RNL ocupou a maior área sob a curva ROC (ACR 0,859) nesse grupo. Conclusões: Neste estudo, os biomarcadores inflamatórios RNL, procalcitonina, PCR e D-dímero foram associados com mortalidade em pacientes idosos portadores de COVID-19 internados em UTI, e a RNL foi a que apresentou a melhor acurácia.

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Mortalidad Hospitalaria , COVID-19/mortalidad , COVID-19/sangre , Proteína C-Reactiva/análisis , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Estudios Retrospectivos , Curva ROC , Estudios de Cohortes , Ferritinas/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre

RESUMEN

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Asunto(s)

Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Proteína C-Reactiva/análisis , COVID-19/mortalidad , COVID-19/patología , Relación Dosis-Respuesta a Droga , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Oportunidad Relativa , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tasa de Supervivencia

RESUMEN

INTRODUCTION: The multisystem inflammatory syndrome in children associated with SARS-CoV-2 (MIS-C) is cha racterized by a hyperinflammatory state resulting from a cytokine storm, evidenced by alterations in laboratory blood testing and acute-phase proteins. OBJECTIVE: to describe the clinical and labora tory characteristics of patients hospitalized due to MIS-C and identify predictive markers of severity. PATIENTS AND METHOD: Retrospective study of 32 patients. The group was divided into critical and non-critical according to clinical presentation and therapy used. Clinical and laboratory aspects were studied, including complete blood count, coagulation tests, and biomarkers. RESULTS: 18/32 were males, with a median age of 6.8 years. The most frequent manifestations were cardiovascular (84.3%), digestive (84%), and mucocutaneous (59%). The group of critical patients included 15 patients, 12 were males with a median age of 8.9 years, and the non-critical group included 17 patients, 6 were males with a median age of 5.4 years. The laboratory parameters at the admission in the global group showed increased C-reactive protein, D-dimer, leukocytes, neutrophils, ferritin, and fibrinogen. In contrast, albumin and blood sodium levels were decreased. At admission, the critical group was cha racterized by presenting thrombocytopenia, hypoalbuminemia, prolonged prothrombin time, and elevated ferritin. At the time of deterioration, there was an intensification of thrombocytopenia, in creased C-reactive protein together with increased neutrophils level. CONCLUSION: The blood count, C-reactive protein, and albuminemia at admission proved to be significantly important in the identi fication of patients at risk of clinical deterioration.

Asunto(s)

COVID-19/complicaciones , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Biomarcadores/sangre , Proteína C-Reactiva/análisis , COVID-19/clasificación , Niño , Deterioro Clínico , Enfermedad Crítica , Femenino , Ferritinas/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Humanos , Leucocitos , Masculino , Neutrófilos , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/clasificación , Trombocitopenia/sangre

RESUMEN

BACKGROUND: There is no effective therapy for the severe acute respiratory syndrome by coronavirus 2 (SARS-CoV2) responsible for the Coronavirus disease 2019 (Covid-19). To date, dexamethasone has shown a decrease in mortality in patients who require oxygen, especially those with invasive mechanical ventilation. However, it is unknown if another corticosteroid can be used, the optimal dose and its duration, to achieve a better clinical outcome. The objective of the study was to compare the differences in clinical outcome and laboratory results in hospitalized patients with severe SARS-CoV2 Pneumonia treated with dexamethasone at 6 mg doses versus patients treated with high-dose methylprednisolone. MATERIALS AND METHODS: Ambispective cohort study with survival analysis of 216 patients diagnosed with severe Covid-19 pneumonia confirmed by polymerase chain reaction for SARS-CoV2 by Berlin protocol, who were hospitalized in a high-complexity clinic in Medellín, Colombia. The patients should also have supplementary oxygen and radiological confirmation of Pneumonia by chest tomography. Sample size was not calculated since the total population that met the inclusion criteria was evaluated. 111 patients were treated with the institutional protocol with intravenous dexamethasone 6 mg QD for seven to 10 days if they required oxygen. Since September 15, 2020, the hospitalization protocol of the clinic was modified by the Infectious Diseases and Pulmonology service, recommending a high dose of methylprednisolone of 250 to 500 mg every day for three days with a subsequent change to oral prednisone 50 mg every day for 14 days. The protocol was not applied in the intensive care unit, where dexamethasone continued to be administered. The clinical outcome and differences in laboratory results of the patients who received dexamethasone vs. the prospective cohort that received methylprednisolone from September 15 to October 31, 2020, were evaluated. Follow-up was carried out by outpatient consultation one month after discharge or by telephone, inquiring about readmission or living-dead status. RESULTS: 216 patients had Covid-19 pneumonia documented by ground-glass imaging and alveolar pressure / inspired oxygen fraction (PaFi) less than 300. 111 patients received dexamethasone (DXM) and 105 received methylprednisolone (MTP). Patients in the DXM group evolved to severe ARDS in a higher proportion (26.1% vs 17.1% than the MTP group). Upon completion 4 days of treatment with parenteral corticosteroid, laboratory markers of severity decreased significantly in the group that received MTP, CRP 2.85 (2.3-3.8) vs 7.2 (5.4-9.8), (p-value < 0.0001), D-dimer 691 (612-847) vs 1083 (740-1565) (p-value = 0.04) and DHL 273 (244-289) vs 355 (270.6-422) (p-value = 0.01). After starting the corticosteroid, transfer to the intensive care unit (4.8% vs. 14.4%) and mortality (9,5% vs. 17.1%) was lower in the group that received MTP. Recovery time was shorter in patients treated with MTP, three days (3-4) vs. DXM 6 days (5-8) (p-value < 0.0001). At 30-day follow-up, 88 (92.6%) were alive in MTP vs 58 (63.1%) of those who received dexamethasone. CONCLUSIONS: In this study, the treatment of severe Covid-19 Pneumonia with high-dose methylprednisolone for three days followed by oral prednisone for 14 days, compared with 6 mg dexamethasone for 7 to 10 days, statistically significantly decreased the recovery time, the need for transfer to intensive care and the severity markers C-reactive protein (CRP), D-dimer and LDH. Randomized controlled studies with methylprednisolone are required to corroborate its effect, and studies in a population hospitalized in intensive care wards.

Asunto(s)

Tratamiento Farmacológico de COVID-19 , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Adulto , Proteína C-Reactiva/análisis , COVID-19/mortalidad , COVID-19/patología , COVID-19/virología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

OBJECTIVE: To investigate whether a simplified inflammation-based risk scoring system comprising three readily available biomarkers (albumin, C-reactive protein, and leukocytes) may predict major adverse outcomes in patients with COVID-19. METHODS: Upon admission to the emergency room, the inflammation-based risk scoring system was applied and patients were classified as having mild, moderate, or severe inflammation. In-hospital occurrence of thrombosis, need for mechanical ventilation, and death were recorded. RESULTS: One-hundred patients (55 ± 13 years; 71% men) were included and classified as having mild (29%), moderate (12%), or severe (59%) inflammation. The need for mechanical ventilation differed among patients in each group (16%, 50%, and 71%, respectively; P < 0.0001), yielding a 4.1-fold increased risk of requiring mechanical ventilation in patients with moderate inflammation and 5.4 for those with severe inflammation. On the contrary, there were no differences for the occurrence of thrombosis (10%, 8%, and 22%, respectively; P = 0.142) or death (21%, 42%, and 39%, respectively; P = 0.106). In the multivariate analysis, only severe inflammation (hazard ratio [HR] = 4.1), D-dimer > 574 ng/mL (HR = 3.0), and troponin I ≥ 6.7 ng/mL (HR = 2.4) at hospital admission were independent predictors of the need for mechanical ventilation. CONCLUSION: The inflammation-based risk scoring system predicts the need for mechanical ventilation in patients with severe COVID-19.

Asunto(s)

COVID-19/terapia , Respiración Artificial , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Adulto , Anciano , Biomarcadores/sangre , COVID-19/sangre , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hospitalización , Humanos , Inflamación/sangre , Inflamación/terapia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Troponina I/sangre

RESUMEN

BACKGROUND: Observational studies have suggested a higher risk of thrombotic events in patients with coronavirus disease 2019 (COVID-19). Moreover, elevated D-dimer levels have been identified as an important prognostic marker in COVID-19 directly associated with disease severity and progression. Prophylactic anticoagulation for hospitalized COVID-19 patients might not be enough to prevent thrombotic events; therefore, therapeutic anticoagulation regimens deserve clinical investigation. DESIGN: ACTION is an academic-led, pragmatic, multicenter, open-label, randomized, phase IV clinical trial that aims to enroll around 600 patients at 40 sites participating in the Coalition COVID-19 Brazil initiative. Eligible patients with a confirmed diagnosis of COVID-19 with symptoms up to 14 days and elevated D-dimer levels will be randomized to a strategy of full-dose anticoagulation for 30 days with rivaroxaban 20 mg once daily (or full-dose heparin if oral administration is not feasible) vs standard of care with any approved venous thromboembolism prophylaxis regimen during hospitalization. A confirmation of COVID-19 was mandatory for study entry, based on specific tests used in clinical practice (RT-PCR, antigen test, IgM test) collected before randomization, regardless of in the outpatient setting or not. Randomization will be stratified by clinical stability at presentation. The primary outcome is a hierarchical analysis of mortality, length of hospital stay, or duration of oxygen therapy at the end of 30 days. Secondary outcomes include the World Health Organization's 8-point ordinal scale at 30 days and the following efficacy outcomes: incidence of venous thromboembolism , acute myocardial infarction, stroke, systemic embolism, major adverse limb events, duration of oxygen therapy, disease progression, and biomarkers. The primary safety outcomes are major or clinically relevant non-major bleeding according to the International Society on Thrombosis and Haemostasis criteria. SUMMARY: The ACTION trial will evaluate whether in-hospital therapeutic anticoagulation with rivaroxaban for stable patients, or enoxaparin for unstable patients, followed by rivaroxaban through 30 days compared with standard prophylactic anticoagulation improves clinical outcomes in hospitalized patients with COVID-19 and elevated D-dimer levels.

Asunto(s)

Anticoagulantes/uso terapéutico , COVID-19/complicaciones , Enoxaparina/uso terapéutico , Rivaroxabán/uso terapéutico , Trombosis/prevención & control , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Brasil , COVID-19/sangre , COVID-19/mortalidad , Esquema de Medicación , Enoxaparina/administración & dosificación , Enoxaparina/efectos adversos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hemorragia/inducido químicamente , Hospitalización , Humanos , Terapia por Inhalación de Oxígeno , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Trombosis/etiología , Factores de Tiempo

RESUMEN

Previous studies have suggested that COVID-19 pneumonia is associated with an increased risk of venous thromboembolism (VTE). This study aimed to investigate the incidence of VTE among mechanically ventilated adults with COVID-19 pneumonia, compared to patients with respiratory failure related to other causes. Prospective study that enrolled critically ill adults with suspected COVID-19 pneumonia between June 2, 2020 and August 11, 2020. Critically ill adults with suspected COVID-19 pneumonia who required mechanical ventilation within 24 h after hospital admission were followed until death or hospital discharge. Sequential ultrasonography screening of the lower extremities and catheter insertion sites, as well as testing for plasma biochemical markers, were performed at the intensive care unit admission, day 3, day 7, and day 14. The primary outcome was a composite of deep venous thrombosis, pulmonary embolism, and thrombosis at the central catheter insertion sites. We enrolled 70 patients, including 57 patients with COVID-19 and 13 patients without COVID-19, and all patients completed follow-up. The incidence of the primary outcome was higher among patients with COVID-19 than among patients with respiratory failure related to other etiologies (36.8% vs. 0%, p = 0.023). Multivariate regression analysis revealed that VTE was independently associated with a COVID-19 diagnosis (odds ratio: 6.28, 95% confidence interval: 1.19-68.07) and D-dimer concentration (1-ng/mL increase, odds ratio: 1.15, 95% confidence interval: 1.05-1.30). The incidence of VTE was higher among critically ill mechanically ventilated patients, relative to among patients with respiratory failure related to other causes.

Asunto(s)

COVID-19 , Enfermedad Crítica , Neumonía Viral , Embolia Pulmonar , Insuficiencia Respiratoria , Medición de Riesgo , Tromboembolia Venosa , Brasil/epidemiología , COVID-19/diagnóstico , COVID-19/fisiopatología , COVID-19/terapia , Prueba de COVID-19/métodos , Catéteres Venosos Centrales/efectos adversos , Enfermedad Crítica/epidemiología , Enfermedad Crítica/terapia , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neumonía Viral/etiología , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Estudios Prospectivos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Respiración Artificial/métodos , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Tromboembolia Venosa/sangre , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/terapia

RESUMEN

Thromboinflammation is a still not well-understood phenomenon, which has recently come to the foreground as a function of its relevance in the pathophysiology of coronavirus disease 2019 (COVID-19). The patient described in the present case report exhibited acute fever, giant urticaria, elevated acute phase reactants, and very high d-dimer levels, thus characterizing thromboinflammation. She was diagnosed as a COVID-19 suspect case, which was not confirmed; urticarial vasculitis was ruled out. Homeopathic treatment was started with the earliest clinical manifestations, resulting in rapid and drastic reduction of inflammation and hypercoagulability within the first 12 hours, and full recovery on 10-day follow-up assessment. This case demonstrates the effectiveness of homeopathy in a severe acute disorder, and points to the need to include laboratory testing in homeopathic clinical assessment to achieve an accurate picture of disease, and to avoid the risk of passing over life-threatening disorders.

Asunto(s)

Venenos de Abeja/uso terapéutico , Abejas , COVID-19/complicaciones , Homeopatía , Inflamación/terapia , Trombosis/terapia , Anciano , Animales , Proteína C-Reactiva/análisis , Femenino , Fiebre/virología , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Inflamación/virología , Trombosis/virología , Urticaria/virología