Inmunodeficiencias en contexto de infección por SARS-CoV-2 / Immunodeficiencies in the context of SARS-CoV-2 infection

SARS-CoV-2 infection in the people has been characterized by great variability in the clinical manifestations, ranging from an asymptomatic infection in some individuals to a fatal disease in others. Recently, the importance of human genetics in determining clinical response has been highlighted. Within this context there are patients who don't become infected despite viral exposure and others who, being young without comorbidities, develop a severe disease.On the other hand, it's under constant investigation whether the presence of a concomitant primary or secondary immunodeficiency determines a different clinical course. (AU)

Características de los coronavirus, origen del SARS-CoV-2, características estructurales, proteínas y factores de virulencia, variantes genéticas / Characteristics of coronaviruses, origin of SARS-CoV-2, characteristics structural, proteins and factors of virulence, genetic variants

Coronaviruses (CoVs) were identified in 1937, they were considered innocuous viruses until the appearance of three highly pathogenic variants, SARS-CoV, MERS-CoV and SARS-CoV-2 causing the current pandemic of Covid-19, so far it is known that its origin is zoonotic, the main reservoir could be bats considering the high homology of CoVs that inhabit this species. Its transmissibility is much higher than that of previous CoVs, possibly in the process of natural selection; it has acquired some or all the mutations necessary for a much more efficient transmission in our species. This condition is specifically attributed to unique characteristics of the SARS-CoV-2 Spike protein that allow it greater affinity and therefore greater infectivity by binding to the angiotensin receptor 2 (ACE-2) present in the host cells. Since the Covid-19 outbreak began at the end of 2019, more than 1,500 mutations have been detected throughout the SARS-CoV-2 genome, however the most significant are those that occur near or in the receptor binding domain (RBD) that could provide variations between 4x to 100x greater infectivity, such is the case of the new variants identified in the United Kingdom, South Africa, Brazil and Japan that force us to take extreme preventive measures and continue research to elucidate strategies to combat the current crisis. (AU)

Prevalencia de resistencia transmitida a drogas antirretrovirales en pacientes con infección por VIH en Chile (2014-2018)

Background: Transmitted drug resistance (TDR) occurs in patients with HIV infection who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. Aim: To determine the prevalence of TDR and characterize HIV reverse transcriptase and protease mutation patterns. Material and Methods: HIV infected antiretroviral treatment-naive patients treated in three centers between 2014 and 2018 were studied. A genotyping study was carried out. The HIVdb Program (Stanford University) and the World Health Organization (WHO) TDR surveillance mutation list were used to register resistance-associated mutations. Results: We enrolled 220 patients aged a median of 29 (interquartile range (IQR) 24-34) years, 99% men. Median CD4 count was 365 cells/μL (IQR 250-499 cells/μL) and median viral load was 39.150 copies/mL (IQR 9,270 −120,000). The overall prevalence of RTD was 10.45% (95% CI 6.7-15.2, N = 23/220). The higher frequency of TDR was against non-nucleoside reverse transcriptase inhibitors, reaching 9.0% (95% CI 5.6-13.6), followed by nucleoside reverse transcriptase inhibitors reaching 1.8% (95% CI 0.49-4.5) and protease inhibitors reaching 0.45% (95% CI 0.01-2.5). The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. Conclusions: These results should prompt a change in recommendations for starting antiretoviral therapy, especially in first-line regimens that include non-nucleoside reverse transcriptase inhibitors.

Enfermedad granulomatosa crónica: tres casos clínicos con diferentes formas de presentación / Chronic granulomatous disease: three cases with different presentations

Introducción: La enfermedad granulomatosa crónica (EGC) es una forma infrecuente de inmunodeficiencia primaria que se caracteriza por una sensibilidad anormal a infecciones bacterianas y fúngicas, debida a un déficit en el complejo nicotinamida adenina dinucleótida fosfato oxidasa (NADPH) en los fagocitos. Objetivo: Describir tres casos de EGC con énfasis en su forma de presentación y realizar una revisión del tema. Casos Clínicos: Se presentan tres casos clínicos, dos de ellos con relación de parentesco (primos en primer grado). Se llegó a diagnóstico molecular en uno de los casos. Se destacan las manifestaciones clínicas: infecciones recurrentes, abscesos, adenitis y granulomas, y complicaciones, con la finalidad de facilitar la sospecha diagnóstica de EGC, debido a la importancia del diagnóstico temprano y el consejo genético. Conclusiones: La EGC es un trastorno inmunológico primario congénito infrecuente, con herencia ligada a X en su mayoría, pero también con formas autosómicas recesivas, con una forma de presentación característica y cuyo diagnóstico debe ser oportuno para evitar complicaciones, realizar profilaxis y tratamiento agresivo de las infecciones y consejo genético.

Introduction: Chronic granulomatous disease (CGD) is a rare form of primary immunodeficiency disease, characterized by an abnormal susceptibility to bacterial and fungal infections, and it is caused by a deficit in the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex (NADPH), resulting in the inability to generate reactive oxygen species that destroy micro-organisms. The diagnosis is based on clinical characteristics and analysis of phagocytes, and later confirmed by molecular studies. Its management should consider antimicrobial prophylaxis, a search for infections and aggressive management of these. Objective: To describe three cases of CGD emphasizing their forms of presentation and to conduct a review of the condition. Case reports: Three case reports, two of them first cousins, are presented. Molecular diagnosis was reached in one of the cases. Recurrent infections, abscesses, adenitis, granulomas and complications are identified to facilitate the suspected diagnosis of CGD, bearing in mind the importance of early diagnosis and genetic counseling. Conclusions: EGC is a rare congenital primary immunodeficiency disorder, mostly with X-linked inheritance, autosomal recessive form, and a specific presentation form. Its diagnosis should be timely to avoid complications. Prophylaxis and aggressive treatment of infections should be performed, as well as genetic counseling.