Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients.

The SARS-CoV-2 disease presents different phenotypes of severity. Comorbidities, age, and being overweight are well established risk factors for severe disease. However, innate immunity plays a key role in the early control of viral infections and may condition the gravity of COVID-19. Natural Killer (NK) cells are part of innate immunity and are important in the control of virus infection by killing infected cells and participating in the development of adaptive immunity. Therefore, we studied the short tandem repeat (STR) transmembrane polymorphisms of the major histocompatibility complex class I chain-related A (MICA), an NKG2D ligand that induces activation of NK cells, among other cells. We compared the alleles and genotypes of MICA in COVID-19 patients versus healthy controls and analyzed their relation to disease severity. Our results indicate that the MICA*A9 allele is related to infection as well as to symptomatic disease but not to severe disease. The MICA*A9 allele may be a risk factor for SARS-CoV-2 infection and symptomatic disease.

[Usefulness of COVID-19 patients first analysis made at the Emergency Department as a prediction tool for mortality (PMCovid Score).] / Utilidad de la primera analítica de Urgencias realizada en pacientes con COVID-19 como predictora de mortalidad (PMCOVID SCORE).

OBJECTIVE: The COVID-19 pandemic has generated a high demand for hospital resources taking the national health system to its limit. In order to reduce this over burden and to avoid a potential system collapse, it would be beneficial to generate scientific evidence for the prognosis of the disease and to count with models that are able to forecast the mortality and progression of the disease. Identify mortality risk factors in COVID-19 patients from analytic data obtained from the Emergency Service at our hospital and to elaborate a prognostic score for predicting 30-day mortality (PMCovid Score) that will be included in the report submitted by the Emergency Clinic Laboratory. METHODS: Transversal descriptive study in a population that came to the Emergency Service at the University Hospital of Jaén between March 8th and April 7th 2020. We obtained the variables for the prognosis by a univariate data analysis. On this basis, we applied a multivariate analysis of the logistical regression of the mortality after 30 days in order to generate a prognostic score which was validated subsequently by the TRIPOD method. RESULTS: 298 patients were included. PMCovid Score assigns 1 point to patients age ≥77 years old; 1 point to patients with a urea level ≥49 mg/dL, 1 point to erythrocyte values <4.6x106/µL, 2 points to platelet values <165x103/µL; 1 point to patients with a percentage of lymphocytes below 18.1%; 1 point to those with a % of monocytes <6.8% and 2 points if the % of eosinophils is <0.4%.Our score had a predictive accuracy of 88.6% (AUC 0.886 IC at 95%; 0.842-0.931), with a sensibility of 91.7% (IC at 95% 82.810-100) and a specificity of 69.7% (IC at 95% 63.840-75.680). CONCLUSIONS: PMCovid Score provides the doctor with information on the prognosis of the positive COVID-19 patient along with the usual first analysis data, the necessary parameters for the calculations are available at all Emergency Laboratory Clinics. This information can be very useful for the management of this kind of patients and their classification based on the risk supplied by the PMCovid Score.

OBJETIVO: La pandemia por COVID-19 ha generado una alta demanda de recursos hospitalarios llevando al límite al sistema nacional de salud. Es por ello que para reducir dicha sobrecarga y el posible colapso del sistema, sería beneficioso generar evidencia científica sobre el pronóstico de la enfermedad y disponer de modelos que permitan predecir la mortalidad y la progresión de la enfermedad. El objetivo de este trabajo fue identificar factores de riesgo de mortalidad en pacientes COVID-19 a partir de los datos analíticos solicitados por el Servicio de Urgencias del hospital y elaborar un score pronóstico de mortalidad a 30 días. METODOS: Estudio transversal descriptivo en pacientes con COVID-19 que acudieron al Servicio de Urgencias del Hospital Universitario de Jaén entre el 8 de marzo y el 7 de abril de 2020. Las variables con utilidad para el pronóstico se obtuvieron mediante un análisis univariante de los datos, a partir de ellas se aplicó un análisis multivariante de regresión logística de mortalidad a los 30 días para generar el score pronóstico que posteriormente fue validado mediante el método TRIPOD. RESULTADOS: Se incluyeron 298 pacientes. PMCovid Score asigna 1 punto a pacientes con edad ≥77 años; 1 punto a los pacientes con niveles de urea ≥49 mg/dL, 1 punto a valores de hematíes <4,6x106/µL, 2 puntos a valores de plaquetas <165x103/µL; 1 punto a pacientes con un porcentaje de linfocitos inferior al 18,1%; 1 punto a los que tenga un porcentaje de monocitos menores a 6,8% y 2 puntos si el porcentaje de eosinófilos es menor del 0,4%. La capacidad pronóstica de nuestro score fue del 88,6% (AUC 0,886 IC al 95%; 0,842-0,931), con una sensibilidad del 91,7% (IC al 95% 82,810-100) y una especificidad del 69,7% (IC al 95% 63,840-75,680). CONCLUSIONES: PMCovid Score proporciona al clínico información acerca del pronóstico del paciente con COVID-19 positivo con los datos habituales de la primera analítica, los parámetros necesarios para el cálculo están disponibles en la totalidad de los Laboratorios Clínicos de Urgencias.

TH1 and TH2 Cytokine Profiles as Predictors of Severity in Acute Pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is severe in up to 20% of patients, with a high mortality rate. Quantification of serum TH1 and TH2 cytokines may provide objective evidence to assess the severity of AP and predict its course. METHODS: One hundred seventeen patients were studied, measuring serum concentrations of interleukin (IL)1ß, IL2, IL4, IL5, IL6, IL10, IL12p70, IL13, IL18, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN) γ, and tumor necrosis factor (TNF) α. RESULTS: Significant differences were found between patients with severe AP and those with mild or moderately severe AP in IFN-γ (P < 0.001), IL6 (P < 0.001), TNF-α (P = 0.002), GM-CSF (P < 0.001), IL4 (P = 0.002), IL1b (P = 0.017), and IL13 (P < 0.001) concentrations. Interferon-γ, IL6, and TNF-α were associated with severe AP, whereas GM-CSF, IL4, IL1b, and IL13 were associated with mild or moderately severe AP. The IL13/IFNγ ratio was significantly higher in patients with mild AP (P = 7.36 × 10). CONCLUSIONS: A TH1 profile was associated with severe AP and a TH2 profile with mild or moderately severe AP. We report an IL13/IFNγ ratio of potential value to predict the prognosis in AP.

Epistatic interaction between TLR4 and NOD2 in patients with Crohn's Disease: relation with risk and phenotype in a Spanish cohort.

Crohn's Disease is one of the two major forms of the Inflammatory Bowel Diseases and, although the etiology is not completely understood, the confluence of environmental and genetic factors has been demonstrated. The aim of this study was to determine the distribution of TLR4 variants in a Spanish cohort of Crohn's Disease patients and their relation with phenotype and common NOD2 variants. A total of 371 Crohn's Disease (CD) patients and 636 healthy controls (HC) were included. Single Nucleotide Polimorphisms (SNPs) in TLR4 (D299G and T399I) and NOD2 (R702W and G908R) detection was performed by a Taqman(®) Allelic Discrimination Assay. 1007insC NOD2 variant was analyzed using a PCR combined with fluorescent technology and the different alleles were determined depending on the PCR products size. D299G and T399I were related to CD only in patients carrying NOD2 variants (NOD2+/TLR4+ haplotype) (p=0.036; OR=1.924), increasing the risk to develop CD when 1007insC and TLR4 variants were both present (OR=4.886). We also described a strong association between mutant NOD2 and CD risk (p<0.001, OR=3.214). R702W, G908R and 1007insC were associated when they were considered separately (p<0.001; p=0.002; p<0.001, respectively). Moreover, the patients carrying any mutant D299G or T399I polymorphisms were predisposed to develop a stricturing disease (p=0.013; OR=2.391), especially in the presence of NOD2 mutation (p=0.002; OR=4.989). In this study, ileal disease was also associated with the presence of at least one NOD2 susceptibility allele (p=0.001; OR=3.838) and, the risk of ileal CD was increased if TLR4 variants were presents (p<0.050; OR=4.160). TLR4 variants were related to bowel perforation, independently of NOD2.

The role of Toll-like receptor polymorphisms in acute pancreatitis occurrence and severity.

OBJECTIVES: Toll-like receptors (TLRs) are damage-associated molecular patterns receptors, which are essential in the activation of the inflammasome cascade, required for the initiation of inflammation. We hypothesized that changes in the function of these receptors caused by genetic polymorphisms in their encoding genes could determine acute pancreatitis (AP) incidence or severity. METHODS: Two hundred sixty-nine patients and 269 controls were included. Acute pancreatitis diagnosis criteria were abdominal pain, increased serum amylase levels, and positive findings on abdominal imaging. The patients were observed until discharge. Blood samples were obtained, determining the following TLRs: TLR1 rs5743611, TLR2 rs5743704, TLR3 rs3775291, TLR3 rs5743305, TLR4 rs4986790, TLR4 rs4986791, TLR5 rs5744174, TLR6 rs5743795, TLR7 rs2302267, TLR9 rs352140, and TLR10 rs4129009. RESULTS: No TLR polymorphism was related to AP incidence. Regarding severity, CC genotype patients in TLR3 rs3775291 had an increased risk for severe pancreatitis (CC odds ratio [OR], 2.426; P = 0.015). In addition, TLR6 rs5743795 GG genotype patients had a lower risk for severe AP (GG OR, 0.909; P < 0.05). Intensive care unit admission was related to TLR5 rs5744174 homozygote TT carriers (TT OR, 3.367; P = 0.036). CONCLUSIONS: Our article points to genetic polymorphisms in TLR3 and TLR6 as having a plausible role in the occurrence of severe AP.