Serial measurement of circulating calprotectin as a prognostic biomarker in COVID-19 patients in intensive care setting.

OBJECTIVES: Circulating calprotectin (cCLP) has been shown to be a promising prognostic marker for COVID-19 severity. We aimed to investigate the prognostic value of serial measurements of cCLP in COVID-19 patients admitted to an intensive care unit (ICU). METHODS: From November 2020 to May 2021, patients with COVID-19, admitted at the ICU of the OLV Hospital, Aalst, Belgium, were prospectively included. For sixty-six (66) patients, blood samples were collected at admission and subsequently every 48 h during ICU stay. On every sample (total n=301), a cCLP (EliA™ Calprotectin 2, Phadia 200, Thermo Fisher Scientific; serum/plasma protocol (for Research Use Only, -RUO-) and C-reactive protein (CRP; cobas c501/c503, Roche Diagnostics) analysis were performed. Linear mixed models were used to associate biomarkers levels with mortality, need for mechanical ventilation, length of stay at ICU (LOS-ICU) and medication use (antibiotics, corticosteroids, antiviral and immune suppressant/modulatory drugs). RESULTS: Longitudinally higher levels of all biomarkers were associated with LOS-ICU and with the need for mechanical ventilation. Medication use and LOS-ICU were not associated with variations in cCLP and CRP levels. cCLP levels increased significantly during ICU hospitalization in the deceased group (n=21/66) but decreased in the non-deceased group (n=45/66). In contrast, CRP levels decreased non-significantly in both patient groups, although significantly longitudinally higher CRP levels were obtained in the deceased subgroup. CONCLUSIONS: Serial measurements of cCLP provides prognostic information which can be useful to guide clinical management of COVID-19 patients in ICU setting.

Prognostic value of circulating calprotectin levels on the clinical course of COVID-19 differs between serum, heparin, EDTA and citrate sample types.

INTRODUCTION: During the recent SARS-CoV-2 pandemic, circulating calprotectin (cCLP) gained interest as biomarker to predict the severity of COVID-19. We aimed to investigate the prognostic value of cCLP measured in serum, heparin, EDTA and citrate plasma. MATERIALS AND METHODS: COVID-19 patients were prospectively included, in parallel with two SARS-CoV-2 negative control populations. The prognostic value of cCLP was compared with IL-6, CRP, LDH, procalcitonin, and the 4C-mortality score by AUROC analysis. RESULTS: For the 136 COVID-19 patients, cCLP levels were higher compared to the respective control populations, with significantly higher cCLP levels in serum and heparin than in EDTA or citrate. Higher cCLP levels were obtained for COVID-19 patients with i) severe/critical illness (n = 70), ii) ICU admission (n = 66) and iii) need for mechanical ventilation/ECMO (n = 25), but iv) not in patients who deceased within 30 days (n = 41). The highest discriminatory power (AUC [95% CI]) for each defined outcome was i) CRP (0.835 [0.755-0.914]); ii) EDTA cCLP (0.780 [0.688-0.873]); iii) EDTA cCLP (0.842 [0.758-0.925]) and iv) the 4C-mortality score (0.713 [0.608-0.818]). CONCLUSION: Measuring cCLP in COVID-19 patients helps the clinician to predict the clinical course of COVID-19. The discriminatory power of EDTA and citrate plasma cCLP levels often outperforms heparin plasma cCLP levels.

Factors influencing the immune response after a single-dose 3-visit pre-exposure rabies intradermal vaccination schedule: A retrospective multivariate analysis.

BACKGROUND: The World Health Organization (WHO) recommends intradermal (ID) rabies vaccination as a safe and immunogenic alternative to intramuscular administration. The aim of this study is to determine which factors influence the levels of rabies virus neutralizing antibodies (RVNA) after a 3-visit ID rabies vaccination. METHODS: This is a retrospective secondary data analysis study based on electronic health record vaccination data of Belgian military subjects who received ID rabies Pre-exposure prophylaxis (PrEP) with a single-dose 3-visit regimen during the period 2014-2017. Logistic regression was performed to identify predictive factors of RVNA level ≥3.0 IU/mL and >10 IU/mL. RESULTS: The second analysis performed on the 2025 subjects (100% seroconverted with a RVNA ≥ 0.5 IU/mL) shows a significantly better immune response in subjects younger than 30 years compared to all other age-groups, a gender-difference to predict RVNA ≥ 3.0 IU/mL (OR 2.30 [1.26-4.22] comparing "female" to "male") and the influence of the vaccination schedule (OR 2.28 [1.15-4.53] comparing "late - very variable" to "correct" schedule) to predict > 10 IU/ml. Multivariate analysis also demonstrates that a postponed serology control significantly influences the Rapid Fluorescent Focus Inhibition Test (RFFIT). CONCLUSION: Gender and age significantly influence the response to ID rabies vaccine. Timing of RVNA determination is important to correctly assess the response to vaccination. A single-dose 3-visit ID rabies PrEP schedule is a dose-sparing effective alternative to the double-dose 2-visit ID schedule. When the minimum time interval between doses is respected, RVNA determination is not necessary.

Timing of Intradermal Rabies Pre-exposure Prophylaxis Injections: Immunological Effect on Vaccination Response.

INTRODUCTION: Rabies remains a global threat, with annually over 59,000 deaths. Intradermal (ID) pre-exposure prophylaxis (PrEP) is very efficient and reduces the need for rabies immunoglobulins. Not much is known about factors that influence the immune response to ID administered rabies vaccine. The aim of this study is to determine if variations in timing of vaccine administration and serology determination, age and gender have an influence on the levels of rabies virus neutralizing antibody (RVNA) after ID rabies vaccination. MATERIALS AND METHODS: This is a retrospective study based on electronic health record vaccination data of Belgian military personnel who received ID rabies PrEP with a three injections regimen during the period 2014-2017. Serology was determined by using the RFFIT method. Fischer's exacts tests were used to evaluate the effect of each independent variable on RVNA levels. RESULTS: In this study, 2,112 subjects were included. All but one seroconverted with a RVNA level ≥0.5 IU/mL. About 48% of subjects developed an antibody titer of >10 IU/mL, 36% had antibody levels 3-10 IU/mL and 16% had an antibody level 0.5-2.99 IU/mL. Statistically significant (p = 0.0018) higher RVNA levels are observed in the groups that received vaccination doses later as planned. Timing of serology determination also influenced RVNA levels significantly (p = 0.000). Antibody levels were significantly higher in females than in males (p = 0.000). Age did influence RVNA levels significantly (p = 0.022). CONCLUSIONS: Timing of vaccine dose administration, timing of serology testing, sex and age do significantly influence the humoral B-cell response to ID administered rabies vaccine.