Background Homologous and heterologous SARS‐CoV‐2 vaccinations yield different spike protein‐directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods COV‐ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV‐19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV‐19/BNT162b2. We assessed humoral (anti‐spike‐RBD‐IgG, neutralizing antibodies, and avidity) and cellular (spike‐induced T‐cell interferon‐γ release) immune responses in blood samples up to 2 weeks before (T1) and 2–12 weeks following secondary immunization (T2). Results Initial vaccination with ChAdOx1 nCoV‐19 resulted in lower anti‐spike‐RBD‐IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV‐19 at T2 (anti‐spike‐RBD‐IgG: ChAdOx1 nCoV‐19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV‐19 413 ± 461 BAU/ml, both p < .001; spike‐induced T‐cell interferon‐γ release: ChAdOx1 nCoV‐19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV‐19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2‐boostered groups at T2. For ChAdOx1 nCoV‐19, no booster effect on T‐cell activation could be observed. We found associations between anti‐spike‐RBD‐IgG levels (ChAdOx1 nCoV‐19/BNT162b2 and homologous BNT162b2) and T‐cell responses (homologous ChAdOx1 nCoV‐19 and ChAdOx1 nCoV‐19/BNT162b2) from T1 to T2. Additionally, anti‐spike‐RBD‐IgG and T‐cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions Interdependencies between humoral and cellular immune responses differ between common SARS‐CoV‐2 vaccination regimes. T‐cell activation is unlikely to compensate for poor humoral responses.

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Among the increasing number of new psychoactive substances, 3′,4′‐methylenedioxy‐α‐pyrrolidinohexanophenone (MDPHP) belongs to the group of synthetic cathinones, which are the derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant. Currently, only limited data are available for MDPHP, and no information is available on its human metabolism. We describe the toxicological investigation of nine cases associated with the use of MDPHP during the period February–June 2019. Serum MDPHP concentrations showed a high variability ranging from 3.3 to 140 ng/mL (mean 30.3 ng/mL and median 16 ng/mL). Intoxication symptoms of the described cases could not be explained by the abuse of MDPHP alone because in all cases the co‐consumption of other psychotropic drugs with frequent occurrence of opiates and benzodiazepines could be verified. Therefore, the patients showed different clinical symptoms, including aggressive behaviour, delayed physical response, loss of consciousness and coma. Liquid chromatography–high‐resolution mass spectrometry was successfully used to investigate the human in vivo metabolism of MDPHP using authentic human urine samples. The metabolism data for MDPHP were further substantiated by the analysis of human urine using gas chromatography–mass spectrometry (GC–MS, a widely used systematic toxicological analysis method appropriate for the toxicological detection of MDPHP intake), which revealed the presence of seven phase I metabolites and three phase II metabolites as glucuronides. GC‐MS spectral data for MDPHP and metabolites are provided. The identified metabolite pattern corroborates the principal metabolic pathways of α‐pyrrolidinophenones in humans.

Metallothionein-II (MT-II) is an ubiquitously expressed small-molecular-weight protein and highly induced in various species and tissues upon stress, inflammation, and ischemia. MT-deficiency exacerbates ischemic injury in rodent stroke models in vitro and in vivo. However, there is conflicting data on the potential neuroprotective effect of exogenously applied metallothionein. Thus, we applied MT-II in an in vitro stroke model and intraperitoneally (i.p.) in two in vivo standard models of transient middle cerebral artery occlusion (MCAO) (a ‘stringent’ one [60min MCAO/48h reperfusion] and a ‘mild’ one [30min MCAO/72h reperfusion]), as well as i.v. together with recombinant tissue plasminogen activator (rtPA) to evaluate if exogenous MT-II-application protects against ischemic stroke. Whereas MT-II did not protect against 60min MCAO, there was a significant reduction of direct and indirect infarct volumes and neurological deficit in the MT-II (i.p.) treated animals in the ‘mild’ model at 3d after MCAO. Furthermore, MT-II also improved survival of the mice after MCAO, suppressed TNF-α mRNA induction in ischemic brain tissue, and protected primary neuronal cells against oxygen-glucose-deprivation in vitro. Thus, exogenous application of MT-II protects against ischemic injury in vitro and in vivo. However, long-term studies with different species and larger sampling sizes are required before a clinical use can be envisaged.