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.

Proton 1H- and Phosphorus 31P-MR spectroscopy (MRS) in asymptomatic HIV-positive patients.

INTRODUCTION: HIV infection is accompanied by a variety of neurological disorders. Depression of cell-mediated immunity is followed by the development of central nervous system opportunistic infections/tumours, and frequently by the occurrence of the AIDS dementia complex (ADC). However, the pathophysiology of the emergence of neuro-AIDS is still unknown. Despite the development of cognitive impairments, the early diagnosis, objectification and quantification of the existence and extent of this impairment during infection are difficult to recognize in each individual case. To support the early diagnosis of ADC, there is a need for additional, non-invasive diagnostic methods. In this study, it is of interest to answer the clinically relevant question of whether magnetic resonance spectroscopy can detect changes in the cerebral metabolism of asymptomatic HIV-positive patients and is possibly suitable for the early diagnosis and prevention of HIV encephalopathy. METHODS: A group of 13 asymptomatic, HIV-positive patients with combined antiretroviral therapy (cART) and 13 healthy controls were examined with 2D 1H-MRS and 3D 31P-MRS at 3T. The patients were treated with cART for at least 12 months. Changes in the absolute concentrations of phosphorylated metabolites (ATP), N-acetyl-aspartate, creatine, myo-Isonitol, glutamate/glutamine and choline-containing compounds were compared with that of control subjects. RESULTS: Asymptomatic HIV-positive patients had significantly lower N-acetyl-aspartate in the white matter in a frontal and parietal target region. The other evaluated metabolites in the 1H MRS showed no significant difference between the HIV-positive patients and healthy controls. The 31P-MRS detected significant elevated values regarding the choline-containing compounds PEth, GPE and PCho. CONCLUSIONS: This spectroscopic study revealed a significantly lower N-acetyl-aspartate in the white matter in a frontal and parietal cerebral target region in asymptomatic, HIV-positive patients as an early sign of neuronal disintegration. The 31P-MRS detected significant elevated values regarding the choline-containing compounds PEth, GPE and PCho as an early sign of gliosis. Furthermore we could show that with the use of 1H-MRS and 31P-MRS cerebral metabolites can be reliably detected and measured in HIV-positive patients. The 1H-MRS and 31P-MRS is therefore suited as a diagnostic tool for early cerebral metabolic changes in HIV-positive patients.

Autologous stem cell transplantation in HIV-related lymphoma in the rituximab era - a feasibility study in a monocentric cohort.

INTRODUCTION: Since the introduction of highly active antiretroviral therapy (HAART) (1) and later on the availability of anti-CD20 monoclonal antibody treatment (2), the therapeutic options as well as the prognosis of AIDS related lymphoma (ARL) have been improved. There is however no uniform agreement on how to treat patients who do not achieve a partial remission, who experience a relapse or who have very aggressive subtypes. Autologous hematopoietic stem cell transplantation (ASCT) has become an option for those patients. We retrospectively examined ARL patients to elucidate the feasibility of high-dose chemotherapy and autologous stem cell transplantation. PATIENTS AND METHODS: Data of seven male and one female HIV+ patients with ARL was collected and informed consent was obtained. Age, HIV disease characteristics (CD4 count, HIV-RNA-PCR, ART) and transplantation-related details (histopathology, myeloablative therapy, neutrophil engraftment and NCI-CTCAE during/after transplantation as well as follow up and survival) were obtained from the patients' medical records. RESULTS: Eight patients were treated with the intent of ASCT. The median age was at 64 years. Four patients had experienced prior AIDS. The median CD4 NADIR was at 157/µl, the median CD4 count at diagnosis of lymphoma at 81/µl. Five patients were receiving combination antiretroviral therapy (cART) at the time of lymphoma diagnosis, four of which had achieved a viral load of less than 50/µl. Two patients have died, due to (Nr. 8) a transplant-related complication (non-infectious leukoencephalophathy). The other patient died of an unknown reason (351 days after transplantation). The median survival is at 345 days to date. The time until engraftment was well at 11 days. Grade 3/4 haematological toxicity was present in all patients. Five out of three patients developed infectious complications, but there were no infection-related deaths. One patients (Nr. 4) developed a Kaposi Sarcoma reactivation that necessitated further chemotherapy. CONCLUSIONS: ASCT is feasible in high risk ARL with good engraftment. Toxicity was substantial and studies are needed to define which patients have an unduly high risk of toxicity.