Comprehensive antibody and cytokine profiling in hospitalized COVID-19 patients in relation to clinical outcomes in a large Belgian cohort.

The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-ß and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-ß, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality.

Epidural neostigmine and clonidine improves the quality of combined spinal epidural analgesia in labour: a randomised, double-blind controlled trial.

BACKGROUND: In labour analgesia, the combination of epidural clonidine and neostigmine as adjuvants to local anaesthetics and opioids is under investigation to provide a longer duration of initial spinal analgesia with local anaesthetics and/or opioids. OBJECTIVES: To evaluate the quality of analgesia with epidural neostigmine and clonidine, added to initial spinal analgesia, and to test the hypothesis that the incidence of breakthrough pain could be reduced and patient satisfaction improved. DESIGN: Randomised double-blind controlled trial. SETTING: University Hospital of Leuven in Belgium. PARTICIPANTS: One hundred healthy, term (≥37 weeks) parturients. INTERVENTION: All patients received initial spinal analgesia with ropivacaine and sufentanil. Fifteen minutes after spinal injection, 10 ml of a solution containing neostigmine 500 µg and clonidine 75 µg, or 10 ml physiological saline alone was injected epidurally. Patient-controlled analgesia with ropivacaine and sufentanil was then made available. MAIN OUTCOME MEASURES: The incidence of breakthrough pain, patient satisfaction and hourly ropivacaine use. RESULTS: Ropivacaine use decreased significantly by 32.6% in the neostigmine/clonidine (NC) group [11.6 ±â€Š4.2 vs. 17.2 ±â€Š5.3 mg h in the NC group and placebo (P) group, respectively] and a significant difference in breakthrough pain was noted; only 3% in group NC had breakthrough pain compared with 36% in group P. Patient satisfaction was better after 1 h in group NC compared with group P (P <0.05) but not different after 24 h (visual analogue scale score 97 ±â€Š5 vs. 88 ±â€Š11 mm after 1 h; 92 ±â€Š10 vs. 90 ±â€Š14 mm after 24 h). CONCLUSION: The administration of epidural clonidine and neostigmine as adjuvants, following spinal injection of local anaesthetic, improves the quality of analgesia with less ropivacaine consumption, higher patient satisfaction 1 h after administration and a decrease in breakthrough pain compared to standard combined spinal and epidural analgesia and patient-controlled epidural analgesia with ropivacaine and sufentanil.