From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.

Inhibidores del NF-kB en la dieta y su papel en las enfermedades alérgicas / NF-kB inhibitors from diet and their role in allergic diseases

Resumen El NF-kB tiene un papel central como regulador de las respuestas inflamatoria e inmune. Se encuentra en forma inactiva en el citoplasma de las células. Después de la activación de estas, el NF-kB se disocia de su proteína inhibidora y se transloca al núcleo, donde participa en la transcripción de genes como los de las citoquinas inflamatorias, moléculas de adhesión, inmunoglobulinas y diversos receptores presentes en células de la respuesta inmune, entre otros. Este factor de transcripción posee un grupo de inhibidores fisiológicos y no fisiológicos. Dentro de los no fisiológicos se destacan algunos presentes en la dieta, como los carotenoides y los polifenoles, que reducen su actividad como inductor transcripcional. Diversos estudios epidemiológicos muestran que el consumo de frutas y verduras protege del desarrollo de alergias. Se ha postulado que este efecto protector se debe al contenido de polifenoles y carotenoides presentes en estos alimentos. Estos compuestos actúan en diversos niveles de la respuesta inmune de tipo alérgico. Inhibiendo las citoquinas Th2, el infiltrado de células inflamatorias en los tejidos, la síntesis de IgE y la liberación de mediadores farmacológicos, entre otras. Esto debido al efecto de estos compuestos sobre la fosforilación, ubiquitinación y degradación de diversas proteínas que participan en los procesos de inhibición y/o activación del NF-kB. En esta revisión analizamos aspectos moleculares del NF-kB y describimos inhibidores presentes en la dieta, como polifenoles y carotenoides, su papel en los procesos inflamatorios de tipo alérgico y en el desarrollo de enfermedades alérgicas.

Abstract The NF-kB plays a central role as a regulator of the inflammatory and immune responses. It is found in inactive form in the cytoplasm of cells. After its activation, the NF-kB dissociates from an inhibitory protein and translocate to the nucleus where it participates in the transcription of genes such as inflammatory cytokines, adhesion molecules, immunoglobulins and various receptors on immune cells, among others. This transcription factor has a group of physiological and non-physiological inhibitors. Among the non-physiological, those present in the diet such as carotenoids and polyphenols reduce their activity as a transcriptional inducer. Epidemiological studies have shown that consumption of fruits and vegetables protect against development of allergies. It has been postulated that this protective effect is due to polyphenol and carotenoids present in those foods. These compounds act at various levels of the allergic immune response. Inhibiting Th2 cytokines, inflammatory cell infiltration into tissues, IgE synthesis and the release of pharmacological mediators among others. This is due to their effect on phosphorylation, ubiquitination and degradation of various proteins involved in the processes of inhibition and/or activation of NF-kB. In this review, we analyze molecular aspects of NF-kB and described inhibitors present in the diet, such as polyphenols and carotenoids, their role in allergic inflammatory process and the development of allergic diseases.