Background: It is imperative to identify drugs that allow treating symptoms of severe COVID-19. Respiratory failure is the main cause of death in severe COVID-19 patients, and the host inflammatory response at the lungs remains poorly understood.Methods: Therefore, we retrieved data from post-mortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, and shortest pathways to physiological phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials.Results: Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, blood coagulation, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF-κB, TNF, oncostatin M signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis.Conclusion: We propose three small molecules (baricitinib, eritoran, and montelukast) that can be considered for treating severe COVID-19 symptoms after being thoroughly evaluated in COVID-19 clinical trials.

There is pressing urgency to identify drugs that allow treating COVID-19 patients effectively. Respiratory failure is the leading cause of death in patients with severe COVID-19, and the host inflammatory response at the lungs remains poorly understood. Therefore, we retrieved data from postmortem lungs from COVID-19 patients and performed in-depth in silico analyses of single-nucleus RNA sequencing data, inflammatory protein interactome network, functional enrichment, and shortest pathways to cancer hallmark phenotypes to reveal potential therapeutic targets and drugs in advanced-stage COVID-19 clinical trials. Herein, we analyzed transcriptomics data of 719 inflammatory response genes across 19 cell types (116,313 nuclei) from lung autopsies. The functional enrichment analysis of the 233 significantly expressed genes showed that the most relevant biological annotations were: inflammatory response, innate immune response, cytokine production, interferon production, macrophage activation, thymic stromal lymphopoietin, blood coagulation, IL-1 and megakaryocytes in obesity, NLRP3 inflammasome complex, and the TLR, JAK-STAT, NF-κB, TNF, oncostatin M, AGE-RAGE signaling pathways. Subsequently, we identified 34 essential inflammatory proteins with both high-confidence protein interactions and shortest pathways to inflammation, cell death, glycolysis, and angiogenesis. Lastly, we propose five small molecules involved in advanced-stage COVID-19 clinical trials: baricitinib, pacritinib, and ruxolitinib are tyrosine-protein kinase JAK2 inhibitors, losmapimod is a MAP kinase p38 alpha inhibitor, and eritoran is a TLR4/MD-2 antagonist. After being thoroughly analyzed in COVID-19 clinical trials, these drugs can be considered for treating severe COVID-19 patients.

More than 600 healthcare workers died due to COVID-19 infection until January 2022 in Ecuador. Even though the COVID-19 vaccines are safe, local and systemic reactions were reported among physicians. This study aims to analyze the adverse events of COVID-19 with an emphasis on comparing the homologous and heterologous booster doses in physicians that received three approved vaccines in Ecuador. An electronic survey was performed in Quito, Ecuador, directed at physicians who were vaccinated with the three doses of COVID-19 vaccines. A total of 210 participants were analyzed after administering any dose of the vaccines. At least one AE was identified in 60.0% (126/210) of the sample after the first dose, 52.40% (110/210) after the second dose, and 75.2% (158/210) after the booster dose. The most frequent AEs were localized pain, myalgia, headache, and fever. At least one drug was used in 44.3% of the population after the first dose, 37.1% after the second dose, and 63.8% in the booster dose. Heterologous booster produces more AEs compared with homologous booster (80.1% vs. 53.8%), and 77.3% of participants reported that interfered with daily activities. Similar studies agree that reactogenicity occurs mainly with heterologous vaccination compared to homologous vaccination. This situation affected physicians’ performance in daily activities and led them to use medication for the symptoms. In the future, it is recommended to perform cohort studies, where adverse events that are associated with vaccine boosters in the general population can be analyzed longitudinally, thus improving the level of evidence of the results.

More than 600 Healthcare workers died due to COVID-19 infection until January 2022 in Ecuador. Even though the COVID-19 vaccines are safe, local, and systemic reactions were reported among physicians. This study aims to analyze the Adverse events (AEs) of COVID-19 vaccines with an emphasis on homologous and heterologous booster doses. An electronic survey was performed in Quito- Ecuador, directed to physicians who were vaccinated with the three doses of COVID-19 vaccines. 210 participants were analyzed after administering any doses of the vaccines. At least one AE was identified in 60.0% (126/210) of the sample after the first dose, 52.40% (110/210) after the second dose, and 75.2% (158/210) after the booster dose. The most frequent AEs were localized pain, myalgia, headache, and fever. At least one drug was used in 44.3% of the population after the first dose, 37.1% after the second dose, and 63.8% in the booster dose. Heterol-ogous booster produces more AEs compared with homologous booster (80.1% vs. 53.8%), and 77.3% of participants reported that interfered with daily activities. Similar studies agree that reactogenicity occurs mainly with heterologous vaccination compared to ho-mologous vaccination. This situation affected physicians’ performance in daily activities and led them to use medication for the symptoms

En la actualidad, ha cobrado una gran importancia la relación que la microbiota intestinal mantiene con varios órganos y sistemas del cuerpo humano. Particularmente importante, son las relaciones de la microbiota con el Sistema Nervioso Central, el comportamiento y  el  desarrollo  y  tratamiento  de  varias  enfermedades.  La  relación  existente  entre  la  microbiota  intestinal  y  el  cerebro  se  produce gracias a la actividad de estímulos neuroendocrinos y neuroinmunes que pueden actuar de forma bilateral, llegando incluso a generar modificaciones en el comportamiento del ser humano. Del mismo modo, a través de la realización de estudios clínicos y paraclínicos, se ha conseguido demostrar la asociación entre el eje microbiota-intestino-cerebro y trastornos neurológicos como la enfermedad de Parkinson o el trastorno depresivo. El objetivo del presente artículo es realizar un análisis de los principales estudios identificados en relación a la función del eje microbiota-intestino-cerebro (MIC) así como identificar la nueva evidencia acerca del uso de probióticos en el tratamiento coadyuvante de varios trastornos neuro-psiquiátricos. Se realizó una búsqueda sistemática de la bibliografía utilizando palabras claves y términos MeSH y se presentó en formato de discusión de acuerdo a los subtemas: eje microbiota-intestino-cerebro, mecanismos de acción, microbiota y su relación con el comportamiento y regulación sobre probióticos. Se concluyó que existe evidencia que demuestra la relación entre el eje microbiota-intestino-cerebro y varios trastornos neuropsiquiátricos en el ser humano. Además, que la administración de probióticos puede modificar el eje MIC y pueden constituir una alternativa de terapia coadyuvante en estos trastornos del comportamiento.