Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis.

BACKGROUND: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance. METHODS: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA). Patients with pre-existing cognitive impairment were excluded. Laboratory results at hospital admission were clustered by principal component analysis (PCA) and included in a path analysis model evaluating the causal relationship between age, comorbidities, hypoxemia, invasive mechanical ventilation (IMV) requirement, in-hospital delirium, and cognitive performance. RESULTS: We studied 92 patients: 54 (58.7%) men and 38 (41.3%) women, with median age of 50 years (interquartile range 42-55), among whom 50 (54.4%) tested positive for cognitive impairment at 6-month follow-up. Path analysis revealed a direct link between the thrombo-inflammatory component of PCA (C-reactive protein, fibrinogen, and neutrophils) and hypoxemia severity at hospital admission. Our model showed that low PaO2/FiO2 ratio values, unlike the thrombo-inflammatory component, had a direct effect on cognitive performance, independent from age, in-hospital delirium, and invasive mechanical ventilation. CONCLUSION: In this study, biomarkers of thrombo-inflammation in COVID-19 and low PaO2/FiO2 had a negative effect on cognitive performance 6 months after hospital discharge. These results highlight the critical role of hypoxemia as a driver for impaired cognition in the mid-term.

Delirium and Associated Factors in a Cohort of Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic dramatically increased the number of patients requiring treatment in an intensive care unit or invasive mechanical ventilation worldwide. Delirium is a well-known neuropsychiatric complication of patients with acute respiratory diseases, representing the most frequent clinical expression of acute brain dysfunction in critically ill patients, especially in those undergoing invasive mechanical ventilation. Among hospitalized patients with COVID-19, delirium incidence ranges from 11% to 80%, depending on the studied population and hospital setting. OBJECTIVE: To determine risk factors for the development of delirium in hospitalized patients with COVID-19 pneumonia. METHODS: We retrospectively studied consecutive hospitalized adult (≥18 y) patients with confirmed COVID-19 pneumonia from March 15 to July 15, 2020, in a tertiary-care hospital in Mexico City. Delirium was assessed by the attending physician or trained nurse, with either the Confusion Assessment Method for the Intensive Care Unit or the Confusion Assessment Method brief version, according to the appropriate diagnostic tool for each hospital setting. Consultation-liaison psychiatrists and neurologists confirmed all diagnoses. We calculated adjusted hazard ratios (aHR) with 95% confidence interval (CI) using a Cox proportional-hazards regression model. RESULTS: We studied 1017 (64.2% men; median age, 54 y; interquartile range 44-64), of whom 166 (16.3%) developed delirium (hyperactive in 75.3%); 78.9% of our delirium cases were detected in patients under invasive mechanical ventilation. The median of days from admission to diagnosis was 14 (interquartile range 8-21) days. Unadjusted mortality rates between delirium and no delirium groups were similar (23.3% vs. 24.1; risk ratio 0.962, 95% CI 0.70-1.33). Age (aHR 1.02, 95% CI 1.01-1.04; P = 0.006), an initial neutrophil-to-lymphocyte ratio ≥9 (aHR 1.81, 95% CI 1.23-2.65; P = 0.003), and requirement of invasive mechanical ventilation (aHR 3.39, 95% CI 1.47-7.84; P = 0.004) were independent risk factors for in-hospital delirium development. CONCLUSIONS: Delirium is a common in-hospital complication of patients with COVID-19 pneumonia, associated with disease severity; given the extensive number of active COVID-19 cases worldwide, it is essential to detect patients who are most likely to develop delirium during hospitalization. Improving its preventive measures may reduce the risk of the long-term cognitive and functional sequelae associated with this neuropsychiatric complication.