Chronic Comorbidities in Middle Aged Patients Contribute to Ineffective Emergency Hematopoiesis in Covid-19 Fatal Outcomes.

BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.

[Allergies as a target of interest in the era of immunotherapy]. / Las alergias como blanco de interés en la era de la inmunoterapia.

Exacerbated immune system reactions often trigger allergy pathologies, which include asthma, rhinitis, urticaria, food and drug allergies, insect bites, and may sometimes have fatal outcomes. In Mexico, more than 20% of open population, present allergic symptoms with notable increase in the last twenty years, especially in children. The Mexican Institute for Social Security (IMSS, according to its initials in Spanish) provides attention to around 7000 patients per year, mainly due to allergies deriving from therapeutic drugs and certain foods. Pharmacotherapy has been effective in reducing classical allergy symptoms, although treatment does not stop disease progression. In addition, the constant use of drugs represents a remarkable socioeconomic impact. Strategies based on the modification of immune responses in the course of allergic reactions through immunotherapy started more than 100 years ago, and some have provided cure to the disease. On the occasion of the Nobel Prize in Physiology or Medicine 2018, it was awarded to James P. Allison and Tasuku Honjo for their contributions in the regulation of the immune system against cancer, through a new generation of immunotherapy. In this review we analyzed current immunotherapeutic options, including its benefits, limitations and perspectives for the best clinical management of allergies.

Las reacciones exacerbadas del sistema inmunológico a menudo disparan patologías por cuadros alérgicos que, entre otros, incluyen asma, rinitis, urticaria, alergia a alimentos, fármacos y picaduras de insectos, y en ocasiones tienen desenlaces fatales. En México, más del 20% de la población general presenta cuadros alérgicos, con un notable incremento en los últimos veinte años, especialmente en la población pediátrica. Tan solo el Instituto Mexicano del Seguro Social (IMSS) atiende alrededor de 7000 pacientes por año, principalmente por alergias a medicamentos y algunos alimentos. La farmacoterapia ha sido muy efectiva en la disminución de los síntomas, aunque el tratamiento no detiene la progresión de la enfermedad. Además, el uso constante de fármacos representa un remarcable impacto socioeconómico. Las estrategias basadas en la modificación de respuestas inmunes en el curso de las reacciones alérgicas a través de inmunoterapia comenzaron hace más de 100 años y algunas de ellas han dado solución a este grupo de padecimientos. En ocasión de la entrega del Premio Nobel de Medicina y Fisiología 2018, este fue otorgado a los doctores James P. Allison y Tasuku Honjo por sus contribuciones en la regulación del sistema inmune contra el cáncer, por medio de una nueva generación de inmunoterapia. En esta revisión analizamos las opciones inmunoterapéuticas actuales e incluimos sus beneficios, limitantes y perspectivas para el mejor manejo clínico de las alergias.