Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

The Impact of the COVID-19 Pandemic in Postoperative Neurosurgical Infections at a Reference Center in México.

The COVID-19 pandemic has had a major global impact on the treatment of hospitalized surgical patients. Our study retrospectively evaluates the impact of the COVID-19 pandemic at a neurosurgical reference center in Mexico City. We compared the number of neurosurgeries, the rate and type of postoperative infections, the causative microorganisms and in-hospital mortality rates in a 4-year period, from the pre-pandemic year 2019 until 2022. A total of 4150 neurosurgical procedures were registered. In 2020 the total number of surgeries was reduced by 36% compared to 2019 OR = 0.689 (95% CI 0.566-0.834) p ≤ 0.001, transnasal/trans sphenoidal pituitary resections decreased by 53%, and spinal surgeries by 52%. The rate of neurosurgical infections increased from 3.5% in 2019 to 5.6% in 2020 (p = 0.002). Regarding the microorganisms that caused infections, gram positive cocci accounted for 43.5% of isolates, Klebsiella spp. and Pseudomonas spp. caused one third of the infections. No significant differences were found for in-hospital mortality nor patterns of resistance to antibiotics. The number of surgeries increased in the last two years, although the infection rate has returned to pre-pandemic levels. We observed a lower impact from subsequent waves of COVID-19 and despite an increase in the number of surgeries, the surgeries have not amounted to the full pre-pandemic levels.

Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients.

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.gov NCT04513184 . 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.

High-flow nasal cannula therapy for hypoxemic respiratory failure in patients with COVID-19.

INTRODUCTION: High-flow nasal cannula (HFNC) therapy in patients with hypoxemic respiratory failure due to COVID-19 is poorly understood and remains controversial. METHODS: We evaluated a large cohort of patients with COVID-19-related hypoxemic respiratory failure at the temporary COVID-19 hospital in Mexico City. The primary outcome was the success rate of HFNC to prevent the progression to invasive mechanical ventilation (IMV). We also evaluated the risk factors associated with HFNC success or failure. RESULTS: HFNC use effectively prevented IMV in 71.4% of patients [270 of 378 patients; 95% confidence interval (CI) 66.6-75.8%]. Factors that were significantly different at admission included age, the presence of hypertension, and the Charlson comorbidity index. Predictors of therapy failure (adjusted hazard ratio, 95% CI) included the comorbidity-age-lymphocyte count-lactate dehydrogenase (CALL) score at admission (1.27, 1.09-1.47; p < 0.01), Rox index at 1 hour (0.82, 0.7-0.96; p = 0.02), and no prior steroid treatment (0.34, 95% CI 0.19-0.62; p < 0.0001). Patients with HFNC success rarely required admission to the intensive care unit and had shorter lengths of hospital stay [19/270 (7.0%) and 15.0 (interquartile range, 11-20) days, respectively] than those who required IMV [104/108 (96.3%) and 26.5 (20-36) days, respectively]. CONCLUSION: Treating patients with HFNC at admission led to improvement in respiratory parameters in many patients with COVID-19.

Impact of preemptive hospitalization on health outcomes at the temporary COVID-19 hospital in Mexico City: a prospective observational study.

INTRODUCTION: In response to the evolution of the coronavirus disease 2019 (COVID-19) pandemic, the admission protocol for the temporary COVID-19 hospital in Mexico City has been updated to hospitalize patients preemptively with an oxygen saturation (SpO2) of >90%. METHODS: This prospective, observational, single-center study compared the progression and outcomes of patients who were preemptively hospitalized versus those who were hospitalized based on an SpO2 ⩽90%. We recorded patient demographics, clinical characteristics, COVID-19 symptoms, and oxygen requirement at admission. We calculated the risk of disease progression and the benefit of preemptive hospitalization, stratified by CALL Score: age, lymphocyte count, and lactate dehydrogenase (<8 and ⩾8) at admission. RESULTS: Preemptive hospitalization significantly reduced the requirement for oxygen therapy (odds ratio 0.45, 95% confidence interval 0.31-0.66), admission to the intensive care unit (ICU) (0.37, 0.23-0.60), requirement for invasive mechanical ventilation (IMV) (0.40, 0.25-0.64), and mortality (0.22, 0.10-0.50). Stratification by CALL score at admission showed that the benefit of preemptive hospitalization remained significant for patients requiring oxygen therapy (0.51, 0.31-0.83), admission to the ICU (0.48, 0.27-0.86), and IMV (0.51, 0.28-0.92). Mortality risk remained significantly reduced (0.19, 0.07-0.48). CONCLUSION: Preemptive hospitalization reduced the rate of disease progression and may be beneficial for improving COVID-19 patient outcomes.