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Knowledge regarding the sustainability of immune responses after COVID-19 vaccination is important, e.g., to decide whom and when to booster. Thus, we analyzed antibody titers in firefighters six months after vaccination with the mRNA-based vaccine Comirnaty. SARS-CoV-2 spike-binding antibodies (bAb) were quantified and compared to peak responses determined in healthcare workers (HCW). For the firefighters, neutralizing antibodies (nAb) were also analyzed. Six months after the second vaccine dose, all analyzed firefighters had detectable bAb, and 91% exhibited nAb titers above 1:16. However, actual titers six months after vaccination were over 12-fold lower than in the HCW control group four weeks after vaccination. bAb and nAb responses showed a significant correlation, and age correlated inversely with antibody responses. Unexpectedly, participants with a body mass index over 25 had higher neutralization titers after six months. All participants with very low neutralization titers were offered booster vaccination. The booster vaccination improved the extent and sustainability of antibody responses.

Midazolam is a widely used short-acting benzodiazepine. However, midazolam is also criticized for its deliriogenic potential. Since delirium is associated with a malfunction of the neurotransmitter acetylcholine, midazolam appears to interfere with its proper metabolism, which can be triggered by epigenetic modifications. Consequently, we tested the hypothesis that midazolam indeed changes the expression and activity of cholinergic genes by acetylcholinesterase assay and qPCR. Furthermore, we investigated the occurrence of changes in the epigenetic landscape by methylation specific PCR, ChiP-Assay and histone ELISA. In an in-vitro model containing SH-SY5Y neuroblastoma cells, U343 glioblastoma cells, and human peripheral blood mononuclear cells, we found that midazolam altered the activity of acetylcholinesterase /buturylcholinesterase (AChE / BChE). Interestingly, the increased expression of the buturylcholinesterase evoked by midazolam was accompanied by a reduced methylation of the BCHE gene and the di-methylation of histone 3 lysine 4 and came along with an increased expression of the lysine specific demethylase KDM1A. Last, inflammatory cytokines were not induced by midazolam. In conclusion, we found a promising mechanistic link between midazolam treatment and delirium, due to a significant disruption in cholinesterase homeostasis. In addition, midazolam seems to provoke profound changes in the epigenetic landscape. Therefore, our results can contribute to a better understanding of the hitherto poorly understood interactions and risk factors of midazolam on delirium.

Hepatitis B virus infection results in the appearance of anti-HBc antibodies that normally persist lifelong. We analyzed the course of anti-HBc antibodies overtime, focusing on patients with a permanent loss or fluctuating anti-HBc antibodies. From 120,531 patients tested for anti-HBc antibodies (Architect, Abbott) from January 2006 to December 2020, ≥4 serial values were available in 8098 and permanent or intermittent anti-HBc loss was observed in 139 patients. It was relatively frequent in baseline anti-HBc positive, immunocompromised patients with available serial measurements of anti-HBc overtime (13% of hematologic/oncologic patients, 10% of solid organ transplant recipients, and 6% of HIV patients compared to 3% in patients with other diseases). In the same period, 12,607 samples were tested for HBsAg, anti-HBc antibodies, and HBV DNA—in nine cases we detected HBV DNA with undetectable anti-HBc and HBsAg. In four out of nine cases contamination of the PCR during processing was the likeliest cause, in another four, no further data were available, while in one the HBV DNA was later followed by a temporary anti-HBc seroconversion. In conclusion, permanent or intermittent anti-HBc loss is more common in immunocompromised hosts than in patients with other underlying diseases. Furthermore, anti-HBc and HBsAg assays can be safely used to exclude an active HBV infection, even in immunocompromised hosts.