Por favor, use este identificador para citar o enlazar este ítem:
http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/2221| Targeting the catecholamine-cytokine axis to prevent SARS-CoV-2 cytokine storm syndrome | |
| Maximilian F Konig. Mike Powell. Verena Staedtke. Ren-Yuan Bai. David L Thomas. Nicole Fischer. Sakibul Huq. Adham M Khalafallah. Allison Koenecke. Nickolas Papadopoulos. Kenneth W Kinzler. Bert Vogelstein. Joshua T Vogelstein. Susan Athey. Shibin Zhou. Chetan Bettegowda. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.04.02.20051565 | |
| The mortality of Coronavirus disease 2019 (COVID-19) appears to be driven by acute respiratory distress syndrome (ARDS) and a dysregulated immune response to SARS-CoV-2. Emerging evidence suggests that a subset of COVID-19 is characterized by the development of a cytokine storm syndrome (CSS), and interleukin (IL)-6 levels are predictors of COVID-19 severity and in-hospital mortality. Targeting hyper-inflammation in COVID-19 may be critical for reducing mortality. Catecholamines enhance inflammatory injury by augmenting the production of IL-6 and other cytokines through a self-amplifying feed-forward loop in immune cells that requires alpha-1 adrenergic receptor (1-AR) signaling. Prophylactic inhibition of catecholamine synthesis with the 1-AR antagonist prazosin reduced catecholamines and cytokine responses in mice, and resulted in markedly increased survival following various hyper-inflammatory stimuli. These findings offer a rationale for studying 1-AR antagonists in the prophylaxis of patients with COVID-19-CSS and ARDS. As high infection rates threaten to overwhelm hospital capacity during this pandemic, preventative approaches that ameliorate COVID-19 severity and reduce excessive mortality are desperately needed. We hypothesize that treatment with prazosin of individuals who test positive for SARS-CoV-2 could reduce catecholamine surges, secondary cytokine dysregulation, and mortality. To investigate a potential role for 1-AR antagonists in preventing poor outcomes in ARDS, we conducted a retrospective analysis of hospitalized patients diagnosed with ARDS. Using data from the Truven Health MarketScan Research Database (2010-2017), we identified 12,673 men (age 45-64) with ARDS, of whom 1,189 patients (9.4%) were prescribed 1-AR antagonists in the previous year. Applying logistic regression models, we found that patients with prior use of 1-AR antagonists had lower odds of the composite of need for invasive mechanical ventilation and mortality compared to non-users (AOR 0.80, 95% CI 0.69-0.94, p=0.008). Mirroring findings from pre-clinical models, these data support a clinical rationale to study 1-AR antagonists in the prophylaxis of ARDS and states of local and systemic immune dysregulation. Prospective, randomized clinical trials of alpha-1 receptor antagonists (e.g. prazosin) administered prior to the onset of severe symptoms are needed to assess their efficacy in preventing CSS and reducing mortality in COVID-19. | |
| www.medrxiv.org | |
| 2020 | |
| Artículo | |
| https://www.medrxiv.org/content/10.1101/2020.04.02.20051565v2.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
Cargar archivos:
| Fichero | Tamaño | Formato | |
|---|---|---|---|
| 1101293.pdf | 284.5 kB | Adobe PDF | Visualizar/Abrir |