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Latent Epstein-Barr virus (EBV) infection can clinically reactivate in immunosuppressed individuals causing lymphoproliferative disease and rarely hepatitis. In this study, we provide in vivo and in vitro evidence that Treponema pallidum infection can cause EBV reactivation with hepatitis in an immunocompetent patient. We report the diagnostic challenges and immunological findings of coinciding syphilis and EBV-associated hepatitis. Using an in vitro EBV-reactivation assay, we demonstrate that T pallidum reactivates latent EBV in a Toll-like receptor (TLR)2/B-cell receptor signaling-dependent manner. Epstein-Barr virus-associated reactivation or lymphoproliferation should be considered in infections with pathogens that activate TLR2.

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We report the occurrence of immune thrombocytopenia (ITP) in a 77-year-old man a few days after receiving the first dose of the COVID-19 mRNA vaccine tozinameran (Comirnaty®). The patient was treated with systemic corticosteroids, intravenous immunoglobulins and eltrombopag. He elected to proceed with the second dose of tozinameran 14 weeks after the first and his platelet count remained stable under a tapered eltrombopag dose. To our knowledge, this is the first case in which a second tozinameran dose has been administered to a patient who developed presumed secondary ITP after the first vaccination. We also report global pharmacovigilance data for the occurrence of ITP after vaccination with tozinameran.

Vaccines against SARS-CoV-2 are the most effective measure against the COVID-19 pandemic. The safety profile of mRNA vaccines in patients with rare diseases has not been assessed systematically in the clinical trials, as these patients were typically excluded. This report describes the occurrence of agranulocytosis within days following the first dose of an mRNA-1273 vaccination against COVID-19 in a previously healthy older adult. The patient was diagnosed with a suspected STAT3 wild-type T-cell large granular lymphocytic leukaemia (T-LGL). Neutropenia was successfully treated with IVIG, glucocorticoids, and G-CSF. In vitro experiments aimed at elucidating the pathways potentially causing the mRNA vaccine-associated neutropenia indicated that the mRNA, but not the adenoviral Ad26.COV2.S vector vaccine, triggered strong IL-6/STAT3 activation in vitro, resulting in excessive T-cell activation and neutrophil degranulation in the patient but not in controls. mRNA-1273 activated TLR-3 suggesting TLR mediated IL-6/STAT3 pathway activation. To complete the primary series of COVID-19 immunization, we used a single dose of Ad26.COV2.S vector vaccine without reoccurrence of neutropenia. The T-LGL clone remained stable during the follow-up of more than 12 months without ongoing therapy. Our data suggest that switching the immunization platform may be a reasonable approach in subjects with rare associated hematologic side effects due to excess STAT3-mediated stimulation following mRNA vaccination. Using in vitro testing before re-administration of a (COVID) vaccine also has relevance for other rare immune events after (mRNA) vaccination.

IgE Western blotCommercially available pasteurized (75°C for 15 seconds), and ultra-high temperature (140°C for 1-2 seconds) processed CM, pasteurized SM (72-73°C for 15 seconds), and GM (122°C for 5 second) were used. Additionally, we used fresh, unpasteurized SM from a Lacaune sheep (Furter-Farm, Bubendorf, Switzerland). We incubated 40 ml of milk with 100 l goat rennet (Labextrakt La Chevrette, Winkler AG, Konolfingen, Switzerland) at 45°C for 60 min. to separate the whey from the casein (curd) fraction.Milk protein concentrations were determined by Bicinchoninic Acid Assay (BCA) using the Pierce TM BCA protein assay kit (ThermoFisher) according to the manufacturer's instructions. We used 1 ng of CM, SM, or GM total protein diluted in 4x Laemmli buffer, incubated at 95°C with 1000 rpm for 10 min, and run on a 4-20% Mini-PROTEAN® TGX Stain-Free TM 1-D polyacrylamide gel (Bio-Rad Laboratories). Following electrophoresis, gels were transferred on a 0.2 um nitrocellulose Trans-Blot Turbo membrane (Bio-Rad Laboratories, Inc.). To prevent unspecific binding, membranes were incubated with TBS/T with 5% SureBlock TM (Lubio Sciences) for 1h at RT. Then, blots were incubated with 1/100 of human serum from patients and controls in TBS/T rotating overnight at 4°C. Bound IgE was detected using a biotin mouse anti-human IgE (Biolegend) for one hour, followed by a streptavidinhorseradish peroxidase complex (Biolegend) for one hour. The bands were visualized by Pierce™ ECL Western Blotting Substrate (ThermoFisher) and analyzed using Image Lab (v.6.0.1, Bio-Rad Laboratories, Inc.). Cow casein pre-adsorption experimentsWe did a pre-adsorption experiment to test for cross-reactivity between CM casein-specific IgE and IgE against SM or GM. We coated 1 ng or 10 ng CM casein (Fluka) on Magnetic MagPlex-microspheres (Luminex). Empty beads served as the negative control. To pull down casein antibodies, serum samples were incubated with the casein-coated beads or empty beads for 2 h under constant rotation. Then, samples were placed in a magnet for 1 min to remove the cow casein-specific antibodies. The cow casein antibody-depleted sera were then analyzed by Western blotting.