Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Serum concentrations of apoptosis-associated molecules in septic children with leukemia, neutropenia and fever.

It has been shown that Fas, Fas-L, TNF and TNFR-1 display high serum concentrations in subjects with sepsis. This suggests that these are potential severity markers. However, the serum concentration of these molecules in children with leukemia and suspected sepsis has to be established before proposing their use as diagnostic biomarkers. We included children <17 years of age diagnosed with acute lymphoblastic leukemia with neutropenia and fever (NF). The subjects were divided into two groups: (1) leukemia and NF with sepsis, (2) leukemia and NF without sepsis. Determination of serum levels of TNF-α, TNFR-1, Fas and Fas-L was performed using ELISA tests, and apoptosis percentage using flow cytometry. Seventy-two subjects with ALL and NF were included in the two groups. The highest serum levels of TNF-α (35.2 ± 7.6 pg/ml) and TNF-R1 (4102 ± 2440) and the lowest levels of Fas-L (19.4 ± 7.3 pg/ml) were found in group 2: however, the difference in comparison with patients without sepsis was not statistically significant. Low levels of Fas-L and low percentage of apoptotic cells are observed in septic subjects. This pattern may reflect the presence of sepsis among subjects with NF secondary to leukemia.

[Procalcitonin as a diagnostic biomarker of sepsis in children with cancer, fever and neutropenia: literature review]. / Procalcitonina como biomarcador diagnóstico de sepsis en el niño con cáncer, neutropenia y fiebre: revisión de la literatura.

Among cancer and septic patients, there is a deregulation of common events such as inflammation. This fact limits the use of biomarkers to diagnose sepsis. Through a search in the PubMed database, we identified the clinical studies that evaluated procalcitonin as a biomarker among children with cancer and sepsis; we analyzed its characteristics, advantages and disadvantages. Most of the studies suggest that with a cut-off point between 0.5 ng/dl and 1 mg/dl, procalcitonin displays a sensitivity of 59-78%, a specificity of 76%, a predictive value of 93% and a negative predictive value of 45% to diagnose sepsis. The procalcitonin values were not modified by the use of chemotherapy or steroids. In the past few years, encouraging results have been obtained when using it as a biomarker in children with cancer, particularly with neutropenia and fever.

Procalcitonina como biomarcador diagnóstico de sepsis en el niño con cáncer, neutropenia y fiebre: revisión de la literatura / Procalcitonin as a diagnostic biomarker of sepsis in children with cancer, fever and neutropenia: literature review

En los enfermos de cáncer, al igual que en los sujetos sépticos, existe desregulación de eventos comunes, como la inflamación, lo que limita el uso de biomarcadores para diagnosticarles sepsis. Mediante una búsqueda en la base de datos PubMed, identificamos los estudios clínicos que evaluaron la procalcitonina como biomarcador en niños con cáncer y sepsis, y analizamos sus características, ventajas y desventajas. La mayoría de los estudios sugieren que, con un punto de corte de 0,5 ng/dl a 1 mg/dl, la procalcitonina presenta una sensibilidad de 59-78%, especificidad de 76%, valor predictivo positivo de 93% y valor predictivo negativo de 45% para el diagnóstico de sepsis. Los valores de procalcitonina no se modifican con el uso de la quimioterapia o el uso de esteroides y, en los últimos años, se han obtenido resultados alentadores en su uso como biomarcador en el niño con cáncer y, particularmente, con neutropenia y fiebre.(AU)

Among cancer and septic patients, there is a deregulation of common events such as inflammation. This fact limits the use of biomarkers to diagnose sepsis. Through a search in the PubMed database, we identified the clinical studies that evaluated procalcitonin as a biomarker among children with cancer and sepsis; we analyzed its characteristics, advantages and disadvantages. Most of the studies suggest that with a cut-off point between 0.5 ng/dl and 1 mg/dl, procalcitonin displays a sensitivity of 59-78%, a specificity of 76%, a predictive value of 93% and a negative predictive value of 45% to diagnose sepsis. The procalcitonin values were not modified by the use of chemotherapy or steroids. In the past few years, encouraging results have been obtained when using it as a biomarker in children with cancer, particularly with neutropenia and fever.(AU)

Procalcitonina como biomarcador diagnóstico de sepsis en el niño con cáncer, neutropenia y fiebre: revisión de la literatura / Procalcitonin as a diagnostic biomarker of sepsis in children with cancer, fever and neutropenia: literature review

En los enfermos de cáncer, al igual que en los sujetos sépticos, existe desregulación de eventos comunes, como la inflamación, lo que limita el uso de biomarcadores para diagnosticarles sepsis. Mediante una búsqueda en la base de datos PubMed, identificamos los estudios clínicos que evaluaron la procalcitonina como biomarcador en niños con cáncer y sepsis, y analizamos sus características, ventajas y desventajas. La mayoría de los estudios sugieren que, con un punto de corte de 0,5 ng/dl a 1 mg/dl, la procalcitonina presenta una sensibilidad de 59-78%, especificidad de 76%, valor predictivo positivo de 93% y valor predictivo negativo de 45% para el diagnóstico de sepsis. Los valores de procalcitonina no se modifican con el uso de la quimioterapia o el uso de esteroides y, en los últimos años, se han obtenido resultados alentadores en su uso como biomarcador en el niño con cáncer y, particularmente, con neutropenia y fiebre.(AU)

Among cancer and septic patients, there is a deregulation of common events such as inflammation. This fact limits the use of biomarkers to diagnose sepsis. Through a search in the PubMed database, we identified the clinical studies that evaluated procalcitonin as a biomarker among children with cancer and sepsis; we analyzed its characteristics, advantages and disadvantages. Most of the studies suggest that with a cut-off point between 0.5 ng/dl and 1 mg/dl, procalcitonin displays a sensitivity of 59-78%, a specificity of 76%, a predictive value of 93% and a negative predictive value of 45% to diagnose sepsis. The procalcitonin values were not modified by the use of chemotherapy or steroids. In the past few years, encouraging results have been obtained when using it as a biomarker in children with cancer, particularly with neutropenia and fever.(AU)

Procalcitonina como biomarcador diagnóstico de sepsis en el niño con cáncer, neutropenia y fiebre: revisión de la literatura / Procalcitonin as a diagnostic biomarker of sepsis in children with cancer, fever and neutropenia: literature review

En los enfermos de cáncer, al igual que en los sujetos sépticos, existe desregulación de eventos comunes, como la inflamación, lo que limita el uso de biomarcadores para diagnosticarles sepsis. Mediante una búsqueda en la base de datos PubMed, identificamos los estudios clínicos que evaluaron la procalcitonina como biomarcador en niños con cáncer y sepsis, y analizamos sus características, ventajas y desventajas. La mayoría de los estudios sugieren que, con un punto de corte de 0,5 ng/dl a 1 mg/dl, la procalcitonina presenta una sensibilidad de 59-78%, especificidad de 76%, valor predictivo positivo de 93% y valor predictivo negativo de 45% para el diagnóstico de sepsis. Los valores de procalcitonina no se modifican con el uso de la quimioterapia o el uso de esteroides y, en los últimos años, se han obtenido resultados alentadores en su uso como biomarcador en el niño con cáncer y, particularmente, con neutropenia y fiebre.

Among cancer and septic patients, there is a deregulation of common events such as inflammation. This fact limits the use of biomarkers to diagnose sepsis. Through a search in the PubMed database, we identified the clinical studies that evaluated procalcitonin as a biomarker among children with cancer and sepsis; we analyzed its characteristics, advantages and disadvantages. Most of the studies suggest that with a cut-off point between 0.5 ng/dl and 1 mg/dl, procalcitonin displays a sensitivity of 59-78%, a specificity of 76%, a predictive value of 93% and a negative predictive value of 45% to diagnose sepsis. The procalcitonin values were not modified by the use of chemotherapy or steroids. In the past few years, encouraging results have been obtained when using it as a biomarker in children with cancer, particularly with neutropenia and fever.

Procalcitonina como biomarcador diagnóstico de sepsis en el niño con cáncer, neutropenia y fiebre: revisión de la literatura. / [Procalcitonin as a diagnostic biomarker of sepsis in children with cancer, fever and neutropenia: literature review].

Among cancer and septic patients, there is a deregulation of common events such as inflammation. This fact limits the use of biomarkers to diagnose sepsis. Through a search in the PubMed database, we identified the clinical studies that evaluated procalcitonin as a biomarker among children with cancer and sepsis; we analyzed its characteristics, advantages and disadvantages. Most of the studies suggest that with a cut-off point between 0.5 ng/dl and 1 mg/dl, procalcitonin displays a sensitivity of 59-78

, a specificity of 76

, a predictive value of 93

and a negative predictive value of 45

to diagnose sepsis. The procalcitonin values were not modified by the use of chemotherapy or steroids. In the past few years, encouraging results have been obtained when using it as a biomarker in children with cancer, particularly with neutropenia and fever.