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DOI: 10.1016/j.medin.2020.08.004
Available online 26 September 2020
HLA genetic polymorphisms and prognosis of patients with COVID-19
Polimorfismos genéticos de los HLA y pronóstico de pacientes con COVID-19
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L. Lorentea,
Corresponding author
lorentemartin@msn.com

Corresponding author.
, M.M. Martínb, A. Francoc, Y. Barriosd, J.J. Cácerese, J. Solé-Violánf, A. Perezg, J.A. Marcos y Ramosh, L. Ramos-Gómezi, N. Ojedaj, A. Jiménezk, Working Group on COVID-19 Canary ICU
a Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Santa Cruz de Tenerife, Spain
b Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Crta del Rosario s/n., Santa Cruz de Tenerife 38010, Spain
c Immunology Unit of Laboratory Department, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Santa Cruz de Tenerife, Spain
d Immunology Unit of Laboratory Department, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Santa Cruz de Tenerife, Spain
e Intensive Care Unit, Hospital Insular, Plaza Dr. Pasteur s/n., Las Palmas de Gran Canaria 35016, Spain
f Intensive Care Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n., Las Palmas de Gran Canaria 35010, Spain
g Internal Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Santa Cruz de Tenerife, Spain
h Intensive Care Unit, Hospital Doctor José Molina Orosa, Ctra. Arrecife-Tinajo, km 1.300, Arrecife, Lanzarote 35550, Spain
i Intensive Care Unit, Hospital General La Palma, Buenavista de Arriba s/n, Breña Alta, La Palma 38713, Spain
j Department of Anesthesiology, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n., Las Palmas de Gran Canaria 35010, Spain
k Research Unit, Hospital Universitario de Canarias, Ofra, s/n., La Laguna 38320, Santa Cruz de Tenerife, Spain
Annex. Members of the BIOMEPOC group
Received 09 June 2020. Accepted 07 August 2020
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Tables (3)
Table 1. Demographic and clinical data of non-surviving and surviving patients.
Table 2. Treatment of non-surviving and surviving patients.
Table 3. Multiple logistic regression analyses to predict mortality at 30 days.
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Additional material (1)
Abstract
Objective

Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients.

Design

Observational and prospective study.

Setting

Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain).

Patients

COVID-19 patients admitted in ICU and healthy subjects.

Interventions

Determination of HLA genetic polymorphisms.

Main variable of interest

Mortality at 30 days.

Results

A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p=0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p=0.02) and HLA-C*16 (p=0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR=7.693; 95% CI=1.063–55.650; p=0.04) or APACHE-II (OR=11.858; 95% CI=1.524–92.273; p=0.02), the allele HLA-C*01 after controlling for SOFA (OR=11.182; 95% CI=1.053–118.700; p=0.04) or APACHE-II (OR=17.604; 95% CI=1.629–190.211; p=0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR=9.963; 95% CI=1.235–80.358; p=0.03).

Conclusions

The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Keywords:
HLA
Genetic polymorphisms
COVID-19
Mortality
Outcome
Resumen
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 la UCI y sujetos sanos.

Intervenciones

Se determinaron los polimorfismos genéticos de los HLA.

Variable de interés principal

Mortalidad a los 30 días.

Resultados

Se incluyeron 3.886 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; IC del 95%=1.063-55.650; p=0,04) o APACHE-II (OR=11.858; IC del 95%=1.524-92.273; p=0,02), el alelo HLA-C*01 controlando por SOFA (OR=11.182; IC del 95%=1.053-118.700; p=0,04) o APACHE-II (OR=17.604; IC del 95%=1.629-190.211; p=0,02) y el alelo HLA-DQB1*04 controlando por SOFA (OR=9.963; IC del 95%=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 los HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, son necesarios estudios de mayor tamaño muestral para concluirlo definitivamente.

Palabras clave:
HLA
Polimorfismos genéticos
COVID-19
Mortalidad
Pronóstico

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