Objetivo: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19).
Diseño: Estudio observacional y prospectivo
Ámbito: Ocho Unidades de Cuidados Intensivos (UCI) de 6 hospitales de las islas canarias (España).
Pacientes: Pacientes COVID-19 ingresados en UCI y sujetos sanos.
Intervenciones: Se determinaron los polimorfismos genéticos de HLA
Variable de interés principal: Mortalidad a los 30 días
Resultados: Se incluyeron 3886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p=0.004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p=0.02) y HLA-C*16 (p=0.02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR=7.693; 95% CI=1.063-55.650; p=0.04) o APACHE-II (OR=11.858; 95% CI=1.524-92.273; p=0.02), el alelo HLA-C*01 controlando por SOFA (OR=11.182; 95% CI=1.053-118.700; p=0.04) o APACHE-II (OR=17.604; 95% CI=1.629-190.211; p=0.02), y el alelo HLA-DQB1*04 controlando por SOFA (OR=9.963; 95% CI=1.235-80.358; p=0.03).
Conclusiones: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, estudios de mayor tamaño muestral son necesarios para concluirlo definitivamente.
Highlights
Non-surviving showed higher RDW than surviving patients
There is an association between RDW and mortality
RDW could be used as mortality biomarker
Objective
To understand the anti-virus adaptive immune response occurring during SARS-Cov-2 infection is necessary to have methods to investigate cellular and humoral components. The goal of this study has been to investigate the utility of a specific spike-DTH test using a coronavirus recombinant protein in COVID-19 patients.
Methods
DTH studies were performed by intradermal injection of a commercial recombinant spike protein from SARS-CoV-2 along with conventional serology studies.
Results
Fifty-one COVID-19 patients were studied showing 84,3% of concordance with spike-DTH and anti-RBD-IgG. Spike-DTH was superior to identify seven more COVID-19 individuals. A high specificity was found with no positive spike DTH reactions in the non-sick individuals. The skin test also showed more stable results over time while specific anti-RBD-IgG decreased gradually. Clinical severity groups also showed a progressive gradient of larger positive spike-DTH.
Conclusion
Specific spike DTH test seems to be an easy method to study cell immune response.
Background: Monitoring cellular immune responses elicited in vaccinated individuals is highly complicated. Methods: 28 individuals participated during the vaccination process with 12 BNT162b2 mRNA (Pfizer) vaccine. Specific anti-RBD IgG using a classic ELISA was performed in days 10 and 20 (after one dose of the vaccine) and on day 35 (after two vaccine doses) in serum samples of all participants. In parallel, DTH (delayed-type hypersensitivity) Skin Test using S protein was performed before (11/28) and after two doses (28/28) of the vaccine. Results: 6/28 individuals were considered positive for the specific anti-RBD IgG positive at day 10, whereas all 28 individuals were positive at day 20. Moreover, 28/28 individuals increased the OD ratios at day 36 (2 doses). DTH cutaneous test was performed on 11/28 participants at day 20 (1 dose) showing 8/11 a positive reaction at 12 h. DTH of all participants was performed on day 36 (2 doses), showing 28/28 positive reactions at 12 h. Conclusion: This report describes the first publication of the results obtained using an in vivo method, the classical DTH response to the Spike protein to assess T-cell immune responses in vaccinated individuals. This affordable and simple test would help to answer basic immunogenicity questions on large-scale population vaccine studies.
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