Laboratory parameters predicting mortality of adult in-patients with COVID-19 associated cytokine release syndrome treated with high-dose tocilizumab

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.

Gemtuzumab-Ozogamicin-Related Impaired Hemoglobin-Haptoglobin Scavenging as On-Target/Off-Tumor Toxicity of Anti-CD33 AML Therapy: A Report of Two Cases

Gemtuzumab-ozogamicin (GO) is a humanized anti-CD33 antibody, which is conjugated to a cytotoxic calicheamicin. It is used to treat acute myeloid leukemia (AML) in combination with chemotherapy. We describe here two GO-treated acute myeloid leukemia (AML) cases: both patients suffered from a toxic syndrome, which manifested as impaired hemoglobin-haptoglobin scavenging and accumulation of hemolysis-related products. Our observations and earlier reports indicated that the reaction was caused by GO-targeted destruction of CD33 + CD163+ monocytes/macrophages, which are responsible for the clearance of hemoglobin-haptoglobin complexes. The rise of plasma lactate dehydrogenase was an early sign of the reaction, and both patients had high levels of free plasma hemoglobin, but plasma haptoglobin and bilirubin levels were paradoxically normal. Symptoms included septic fever and abnormalities in cardiac tests and in the case of the first patient, severe neurological symptoms which required intensive care unit admittance. Therapeutic plasma exchanges supported the patients until the recovery of normal hematopoiesis. The symptoms may be easily confounded with infectious complications-related organ damage. Regarding the increasing use of gemtuzumab-ozogamicin and other emerging CD33-targeted cell therapies, we want to highlight this mostly unknown and probably underdiagnosed toxicity.

1029. Outcome of Candida Graft Vascular Infection: Results From a Prospective Cohort

Background Candida graft vascular infections (CGVI) are rare events and little data are available in the literature. The aim of this study was to describe the characteristics and outcome of patients admitted for fungal graft vascular infections, in a reference center for CGVI treatment. Methods Patients admitted for a CGVI in our center from 1 January 2000 to 1 February 2018 were prospectively included. Clinical, biological, and outcome data were recorded. Results Two hundred patients were admitted with graft vascular infections (GVI) in our center, and 11 of them (6%) presented CGVI. They were mainly men (7; 64%), and median age was 74 years old [min–max: 39–83]. All patients had benefited from prosthetic bypass surgery prior to CGVI, and infection was considered as an early disease in six patients (55%). Candida albicans was found in 72% of cases. Infection was plurimicrobial in 10 patients (92%), involving Staphyloccocus aureus in only one case and Bacille gram negatif in six (55%) cases. The management consisted in a total or partial graft replacement for five patients (45%), and surgical revision was required in four of them (30%). The empirical antifungal therapy included an echinocandin (Caspofungine) for eight patients (73%), and was changed to fluconazole or voriconazole according to antifungigram. Two patients received Amphotericin B therapy, complicated by acute kidney injury. Intensive care unit admittance was required for nine patients (82%). After the curative treatment period, antifungal therapy could not be removed in two patients and was long-continued using fluconazole. Finally, six patients (55%) died, all within the year after CGVI. Conclusion To our knowledge, we report here the biggest CGVI cohort. CGVI resulted in very high morbidity and mortality, requiring ICU admission for a long time. Despite multidisciplinary management involving anesthesiologists, surgeons, intensive care, and infectious disease physicians, outcome of CGVI patients remains poor. Disclosures All authors: No reported disclosures.

Molecular Inflammatory Responses Measured in Blood of Patients with Severe Community-Acquired Pneumonia

ABSTRACT In order to analyze the characteristics of the inflammatory response occurring in blood during pneumonia, we studied 38 patients with severe community-acquired pneumonia. Venous and arterial blood samples were collected at study entry and on days 1, 2, 3, 5, and 7 after inclusion. The concentrations of proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin 1β [IL-1β], IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines were determined in order to detect differences related to the origin of the sample, the causative organism, the clinical variables, and the final outcome of the episode. Legionella pneumonia infections showed higher concentrations of TNF-α, IL-6, IL-8, and IL-10. After 24 h, plasma IL-6, IL-8, and IL-10 concentrations in pneumococcal episodes increased, whereas in the same time interval, cytokine concentrations in Legionella episodes markedly decreased. The characteristics of the inflammatory response in bacteremic pneumococcal episodes were different from those in nonbacteremic episodes, as indicated by the higher plasma cytokine concentrations in the former group. Finally, our analysis of cytokine concentrations with regard to the outcome—in terms of the need for intensive care unit admittance and/or mechanical ventilation as well as mortality—suggests that there is a direct relationship between the intensity of the inflammatory response measured in blood and the severity of the episode.