RESUMO
Resumen Introducción: los cuadros clínicos más graves y los desenlaces fatales resultantes de la infección por SARS-CoV-2 han sido asociados con una hiperactivación del sistema inmune con inmunotrombosis, proceso caracterizado por una respuesta inflamatoria exacerbada y de hipercoagulabilidad. Diferentes comorbilidades y factores genéticos de cada individuo podrían estar involucrados en un peor pronóstico. El objetivo de este estudio fue analizar si distintos biomarcadores relacionados con inflamación y coagulación, así como ciertas variables clínicas, identificadas al momento de la admisiónhospitalaria, podrían ser factores de riesgo asociados con una evolución clínica desfavorable. Asimismo, investigar la posible asociación entre la portación de las variantes genéticas factor V Leiden, la variante G20210A del gen del factor II y las variantes alélicas 10034C/T del gen del fibrinógeno gamma y 7872C/T del gen del factor XI con el desenlace clínico de pacientes COVID-19. Materiales y métodos: se incluyeron 204 pacientes adultos con diagnóstico confirmado de COVID-19+, hospitalizados durante la primera ola de la pandemia. Se registraron variables demográficas y clínicas incluyendo comorbilidades y se midieron diversos parámetros bioquímicos plasmáticos. Los pacientes se dividieron en dos grupos (sobrevida: n=141 y muerte: n=63) para comparar su evolución clínica. Resultados: se observó que los pacientes fallecidos eran de mayor edad y presentaban un índice de masa corporal más alto. Además, tenían recuentos de plaquetas y linfocitos más bajos, recuentos totales de leucocitos y neutrófilos más altos, una mayor relación neutrófilos/linfocitos y niveles más elevados de dímero D, ferritina y LDH en comparación con los supervivientes (p<0.05). Estableciendo puntos de corte, se encontró que un recuento de plaquetas <200.103/ul [OR=2.81, IC 95% (1.51-5.23)], un recuento de leucocitos >10.103/ul [OR=2.54, IC 95% (1.32-5.23)], un porcentaje de linfocitos <10% [OR=3.48, IC 95% (1.85-6.54]), un porcentaje de neutrófilos >70% [OR=2.82, IC 95% (1.43-5.59)], una relación neutrófilos/linfocitos >4 [OR=2.77, IC 95% (1.40-5.40)], niveles de dímero D >1500 ng/ml FEU [OR=2.67 IC 95% (1.33-5.37)] y ferritina >1000 ng/ml [OR=2.33, IC 95%(1.214.49)] al momento de la admisión hospitalaria estarían asociados con mayores posibilidades de sufrir un desenlace fatal. No se encontraron diferencias significativas en las distribuciones genotípicas de las variantes genéticas estudiadas entre ambos grupos. Discusión: acorde a investigaciones previas, se encontró que la edad, la obesidad y los niveles de marcadores hematológicos/plasmáticos medidos al momento de la admisión hospitalaria serían predictores de mal pronóstico en pacientes no inmunizados. Pese a la típica exacerbación de los mecanismos de coagulación en casos de COVID-19 severo, la portación de las variantes genéticas protrombóticas estudiadas no estaría asociada a un peor pronóstico.
Abstract Introduction: the most severe clinical presentations and the fatal outcomes resulting from SARS-CoV-2 infection have been associated with hyperactivation of the immune system with immunothrombosis, a process characterized by an exacerbated inflammatory response and hypercoagulability. Different comorbidities and genetic factors of each individual could be involved in a worse prognosis. The objective of this study was to analyze whether different biomarkers related to inflammation and coagulation, as well as certain clinical variables, addressed at the time of hospital admission, could be risk factors associated with an adverse clinical outcome. Likewise, to investigate the possible association between the carriage of the genetic variants factor V Leiden, G20210A variant in the factor II gene and the allelic variants 10034C/T in the fibrinogen gamma gene and 7872C/T in the factor XI gene and the clinical outcome of COVID-19 patients. Materials and methods: 204 adult patients with a confirmed diagnosis of COVID-19+, hospitalized during the first wave of the pandemic, were included. Demographic and clinical variables including comorbidities were recorded and various plasma biochemical parameters were measured. The patients were divided into two groups (survival: n=141 and death: n=63) to compare their clinical evolution. Results: it was found that the deceased patients were older and had a higher body mass index. They also had lower platelet and lymphocyte counts, higher total leukocyte and neutrophil counts, higher neutrophil/lymphocyte ratio, and higher levels of D-dimer, ferritin, and LDH compared to survivors (p<0.05). Establishing cut-off points, it was found that a platelet count <200.103/ul [OR=2.81, IC 95% (1.515.23)], a leukocyte count >10.103/ul [OR=2.54, IC 95% (1.32-5.23)], a percentage of lymphocytes <10% [OR=3.48, IC 95% (1.85-6.54]), a percentage of neutrophils >70% [OR=2.82, IC 95% (1.43-5.59)] a relationship neutrophils/lymphocytes >4 [OR=2.77, IC 95% (1.40-5.40)], D-dimer levels >1500 ng/ml FEU [OR=2.67 IC 95% (1.33-5.37)] and ferritin >1000 ng/ml [OR=2.33, IC 95%(1.21-4.49)] at the time of hospital admission would be associated with greater chances of suffering a fatal outcome. No significant differences were found in the genotypic distributions of the genetic variants studied between both groups. Discussion: according to previous investigations, it was found that age, obesity and the levels of hematological/plasma markers measured at the time of hospital admission, would be predictors of poor prognosis in non-immunized patients. Despite the typical exacerbation of coagulation mechanisms in cases of severe COVID-19, the carriage of the prothrombotic genetic variants studied would not be associated with a worse prognosis.
RESUMO
The case of a man with diagnosis of Kikuchi-Fujimoto disease (KFD) and catastrophic antiphospholipid syndrome (CAPS) is reported. He presented prolonged fever, lymphadenopathies, arthralgia, weight loss, hepatosplenomegaly and positive IgM for cytomegalovirus. While he was empirically treated with tuberculostatic drugs, he suddenly developed systemic inflammatory response syndrome, multiple organ failure and distal necrosis. On suspicion of severe sepsis, antibiotics, corticoids and recombinant human activated protein C (XIGRIS) were administrated. Exhaustive laboratory searching was negative. Histopathologic examinations of lymph node first disclosed malignant lymphoma but later KFD was confirmed. One month later, laboratory tests showed the presence of antiphospholipid antibodies (aPL). The patient was discharged after two months of hospitalization. This case exhibits a KFD complicated by definite CAPS. Cytomegalovirus could be involved in the development of both CAPS and KFD. Because of the severity of the case, we believe that XIGRIS noticeable improved the altered coagulation profile associated with CAPS.