Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients
Authors: Cárdenas Graciela , Chávez-Canales María , Espinosa Ana María , Jordán-Ríos Antonio , Malagon Daniel Anica , Murillo Manlio Fabio Márquez , Araujo Laura Victoria Torres , Campos Ricardo Leopoldo Barajas , Wong-Chew Rosa María , González Luis Esteban Ramirez , Cresencio Karent Ibet , Velázquez Enrique García , de la Cerda Mariana Rodriguez , Leyva Yoana , Hernández-Ruiz Joselin , Hernández-Medel María Luisa , León-Hernández Mireya , Quero Karen Medina , Monciváis Anahí Sánchez , Díaz Sergio Hernández , Martínez Ignacia Rosalia Zeron , Martínez-Cuazitl Adriana , Salazar Iván Noé Martínez , Sarmiento Eduardo Beltrán , Peña Aldo Figueroa , Hernández Patricia Saraí , Reynoso Rafel Ignacio Aguilar , Reyes Daniela Murillo , del Río Ambriz Luis Rodrigo , Bonilla Rogelio Antonio Alfaro , Cruz Jocelyn , Huerta Leonor , Fierro Nora Alma , Hernández Marisela , Pérez-Tapia Mayra , Meneses Gabriela , Espíndola-Arriaga Erick , Rosas Gabriela , Chinney Alberto , Mendoza Sergio Rosales , Hernández-Aceves Juan Alberto , Cervantes-Torres Jaquelynne , Rodríguez Anai Fuentes , Alor Roxana Olguin , Francisco Sandra Ortega , Salazar Evelyn Alvarez , Besedovsky Hugo , Romano Marta C. , Bobes Raúl J. , Jung Helgi , Soldevila Gloria , López-Alvarenga Juan , Fragoso Gladis , Laclette Juan Pedro , Sciutto Edda 
Published: February 2022

Abstract
Background
By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses.

Methods
This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization.

Conclusions
This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients.

Trial registration
ClinicalTrials.govNCT04513184. Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.

Graphical abstract