Delirium in hospitalized COVID-19 patients: Predictors and implications for patient outcome.

INTRODUCTION: Delirium is recognized as a severe complication of coronavirus-disease-2019 (COVID-19). COVID-19-associated delirium has been linked to worse patient outcomes and is considered to be of multifactorial origin. Here we sought to evaluate the incidence and risk factors of delirium in hospitalized COVID-19 patients, along with its impact on clinical outcome. METHODS: Consecutive adult COVID-19 patients admitted to a tertiary academic referral hospital between March 1st and December 31st, 2020 were included. Potential risk factors for delirium were evaluated, including: age, gender, disease severity (as per the highest WHO grading reached during admission), laboratory parameters for infection and renal function (as per their most extreme values), and presence of comorbidities. To assess the relative strength of risk factors for predicting the occurrence of delirium, we performed a random-forest survival analysis. RESULTS: 347 patients with positive COVID-19 PCR test and median age 68.2 [IQR 55.5, 80.5] years were included. Of those, 79 patients (22.8%) developed delirium, 81 (23.3%) were transferred to ICU, 58 (16.7%) died. 163 (73.8%) patients were discharged home, 13 (5.9%) to another hospital, 32 (14.5%) to nursing homes, 13 (5.9%) to rehabilitation with an overall median admission-to-discharge time of 53 [IQR 14, 195] days. The strongest predictors for the occurrence of delirium were blood urea nitrogen (minimal depth value (MD): 3.33), age (MD: 3.75), disease severity (as captured by WHO grading; MD: 3.93), leukocyte count (MD: 4.22), the presence of a neurodegenerative history (MD: 4.43), ferritin (MD: 4.46) and creatinine (MD: 4.59) levels. CONCLUSION: The risk of delirium in COVID-19 can be stratified based on COVID-19 disease severity and-similar to delirium associated with other respiratory infections-the factors advanced age, neurodegenerative disease history, and presence of elevated infection and renal-retention parameters. Screening for these risk factors may facilitate early identification of patients at high-risk for COVID-19-associated delirium.

Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia.

Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2 peptides to the patients' HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Toward clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19.