An old foe on peculiar paths: severe falciparum malaria in a Syrian refugee, possibly infected during migrant smuggling from Türkiye to Germany.

Infectious diseases and their imperative awareness gain major relevance through global warming and multi-continent refugee crises. Here, we demonstrate the challenges of malaria diagnosis, disease course, and treatment, including post-artesunate hemolysis in a Syrian refugee with severe falciparum malaria, most probably infected during migrant smuggling from Türkiye to Germany.

Humoral immune response to SARS-CoV-2 mRNA vaccines is associated with choice of vaccine and systemic adverse reactions.

Purpose: Although the fast development of safe and effective messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 has been a success, waning humoral immunity has led to the recommendation of booster immunization. However, knowledge of the humoral immune response to different booster strategies and the association with adverse reactions is limited. Materials and Methods: We investigated adverse reactions and anti-spike protein immunoglobulin G (IgG) concentrations among health care workers who received primary immunization with mRNA-1273 and booster immunization with mRNA-1273 or BNT162b2. Results: Adverse reactions were reported by 85.1% after the first dose, 94.7% after the second dose, 87.5% after a third dose of BNT162b2, and 86.0% after a third dose of mRNA-1273. They lasted for a median of 1.8, 2.0, 2.5, and 1.8 days, respectively; 6.4%, 43.6%, and 21.0% of the participants were unable to work after the first, second, and third vaccination, respectively, which should be considered when scheduling vaccinations among essential workers. Booster immunization induced a 13.75-fold (interquartile range, 9.30-24.47) increase of anti-spike protein IgG concentrations with significantly higher concentrations after homologous compared to heterologous vaccination. We found an association between fever, chills, and arthralgia after the second vaccination and anti-spike protein IgG concentrations indicating a linkage between adverse reactions, inflammation, and humoral immune response. Conclusion: Further investigations should focus on the possible advantages of homologous and heterologous booster vaccinations and their capability of stimulating memory B-cells. Additionally, understanding inflammatory processes induced by mRNA vaccines might help to improve reactogenicity while maintaining immunogenicity and efficacy.

Severity of adverse reactions is associated with T-cell response in mRNA-1273 vaccinated health care workers.

Knowledge about mRNA-1273 elicited T-cell response is limited. We investigated adverse reactions and interferon gamma release by specific T-cells among mRNA-1273 vaccinated health care workers. Seven to 13 weeks after complete vaccination low levels of specific T-cells were detected not correlating with antibody response. Severity of symptoms after first and number of symptoms after second immunization were associated with T-cell response. Assessment of T-cell response in addition to antibody response is crucial because even few specific T-cells could add to protection against infection. Investigation of mRNA-1273 induced inflammatory processes might help improve reactogenicity and immunogenicity.

Two novel SARS-CoV-2 surrogate virus neutralization assays are suitable for assessing successful immunization with mRNA-1273.

BACKGROUND: Due to large vaccination efforts with novel vaccines there is an increasing need for laboratory tests assessing successful immunizations with SARS-CoV-2 vaccines. Unfortunately classical neutralization assays are laborious, time-consuming and require an adequate biosafety level laboratory. Recently, convenient ELISA-based surrogate neutralization assays (sVNTs) for determination of neutralizing SARS-CoV-2 antibodies have been developed. STUDY DESIGN: Our study compares the two novel ELISA-based SARS-CoV-2 surrogate neutralization assays "cPass SARS-CoV-2 Surrogate Virus Neutralization Test Kit" (GenScript Biotech, USA) and the "TECO SARS-CoV-2 Neutralization Antibody Assay" (TECOmedical, Switzerland) using 93 sera drawn from health care workers (HCVs) 2-3 weeks following the second vaccination with mRNA-1273 and 40 control sera from the pre-SARS-CoV-2 era before 2019. RESULTS: We found a sensitivity of 100% and 91,4% and a specificity of 100% and 100% for the GenScript assay and the TECO assay, respectively. Both sVNTs show a high correlation with anti-S IgG. Moreover, both sVNTs correlate well with each other. CONCLUSIONS: Surrogate neutralization assays based on the RBD as bait feature a high specificity and sensitivity for identifying humoral neutralizing activity in individuals vaccinated with the spike-based vaccine mRNA-1273. Although these assays appear well-suited for confirming successful vaccinations with spike-based vaccines, additional studies should compare both assays regarding other purposes such as screening COVID-recovered patients or individuals vaccinated with inactivated whole virus vaccines.

Evaluation of the QuantiFERON SARS-CoV-2 interferon-É£ release assay in mRNA-1273 vaccinated health care workers.

Current studies focus on cellular and humoral immunity induced by novel SARS-CoV-2 vaccines. Non-responders to vaccinations are not uncommonly encountered in clinical medicine (e.g. in the field of hepatitis B). Whereas vaccine-induced humoral immunity against SARS-CoV-2 is compromised by emerging Variants of Concern (VOCs), cellular immunity against SARS-CoV-2 is emerging as resilient against VOCs. Thus commercially available test kits for diagnostic laboratories designed to evaluate cellular immune responses to SARS-CoV-2 are urgently needed. Here we evaluated the novel QuantiFERON SARS-CoV-2 assay (Qiagen) measuring INF-É£ release induced by two spike-derived peptide pools (Ag1 and Ag2) in a cohort of health care workers vaccinated with the mRNA-1273 vaccine and confirmed humoral response. Our study indicates the usefulness of this novel assay for routine laboratories to evaluate cellular immunity against SARS-CoV-2 in response to mRNA-1273 vaccination.

Perfusion-related changes in intestinal diffusion detected by NMR-MOUSE® monitoring in minipigs.

OBJECTIVE: The aim was to investigate perfusion-related changes in the intestinal diffusion assessed by NMR-MOUSE monitoring in minipigs. This was a follow-up study of previous experiments on landrace pigs demonstrating the feasibility of NMR-MOUSE monitoring in large animals. METHODS: 5 mature female minipigs (mean body weight 50 ±â€¯2 kg) underwent laparotomy with exposition of several small intestinal loops and their feeding vessels. The loops were examined consecutively using NMR-MOUSE monitoring for assessment of intestinal proton diffusion (fast diffusion component [FC] and slow diffusion component [SC]) and oxygen to see monitoring (O2C, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory evaluation. Following a baseline measurement on each loop under physiological perfusion, measurements were continued as one of the following main treatments were performed per loop: method 1 - ischemia; method 2 - flow reduction; method 3 - intraluminal glucose followed by ischemia; method 4 - intraluminal glucose followed by flow reduction. Perioperative monitoring was supplemented by blood gas analyses and histopathological assessment of H.E. stained intestinal biopsies. RESULTS: The NMR-MOUSE measurement showed a significant difference in the change to baseline values in the FC during flow reduction compared to the other treatments according to the unadjusted (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0005, pM2 vs. M4 = 0.0005) and the adjusted p-values (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0030, pM2 vs. M4 = 0.0030). In the SC, the difference between ischemia and flow reduction was significant according to the unadjusted p-values (pM2 vs. M1 = 0.0397). Whereas the FC showed a trend towards ongoing increase during ischemia but towards ongoing decrease during flow reduction, the SC showed contrary trends. These effects seemed to be attenuated by prior glucose application. According to the results of O2C monitoring, ischemia as well as flow reduction caused a significant decrease of microcirculatory oxygen saturation (inner probe: methods 1-4 and outer probe methods 1, 2: p < 0.0001; outer probe: pM2 = 0.0001), velocity (inner probe: pM1 < 0.0001, pM2 = 0.0155, pM3 = 0.0027; outer probe: pM1 < 0.0001, pM2 = 0.0045, pM3 = 0.0047, pM4 = 0.0037) and serosal flow (outer probe, methods 1 and 2: p < 0.0001; pM3 = 0.0009, pM4 = 0.0008). The histopathological analysis showed a significant association with time (p = 0.003) but not with the experimental method (p = 0.1386). CONCLUSIONS: Intestinal diffusion is affected significantly by perfusion changes in mature minipigs. As shown by NMR-MOUSE monitoring, ischemia and flow reduction have contrary effects on intestinal diffusion and, additionally, the fast and slow diffusion components show opposite trends during each of those pathological perfusion states. Prior intraluminal glucose application seems to attenuate the effects of malperfusion on intestinal diffusion.

Evaluation of the NMR-MOUSE as a new method for continuous functional monitoring of the small intestine during different perfusion states in a porcine model.

OBJECTIVE: The study aim was to evaluate a small low-field NMR (nuclear magnetic resonance) scanner, the NMR-MOUSE®, for detecting changes in intestinal diffusion under different (patho-) physiological perfusion states. METHODS: Laparotomy was performed on 8 female landrace pigs (body weight 70±6 kg) and the feeding vessels of several intestinal loops were dissected. Successively, the intestinal loops were examined using O2C (oxygen to see, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory monitoring and the NMR-MOUSE® for diffusion measurement (fast and slow components). On each loop the baseline measurement (physiological perfusion) was followed by one of the following main procedures: method 1 -ischemia; method 2 -flow reduction; method 3 -intraluminal glucose followed by ischemia; method 4 -intraluminal glucose followed by flow reduction. Additionally, standard perioperative monitoring (blood pressure, ECG, blood gas analyses) and histological assessment of intestinal biopsies was performed. RESULTS: There was no statistical overall time and method effect in the NMR-MOUSE measurement (fast component: ptime = 0.6368, pmethod = 0.9766, slow component: ptime = 0.8216, pmethod = 0.7863). Yet, the fast component of the NMR-MOUSE measurement showed contrary trends during ischemia (increase) versus flow reduction (decrease). The slow-to-fast diffusion ratio shifted slightly towards slow diffusion during flow reduction. The O2C measurement showed a significant decrease of oxygen saturation and microcirculatory blood flow during ischemia and flow reduction (p < .0001). The local microcirculatory blood amount (rHb) showed a significant mucosal increase (pClamping(method 1) = 0.0007, pClamping(method 3) = 0.0119), but a serosal decrease (pClamping(method 1) = 0.0119, pClamping(method 3) = 0.0078) during ischemia. The histopathological damage was significantly higher with increasing experimental duration and at the end of methods 3 and 4 (p < .0001,Fisher-test). CONCLUSION: Monitoring intestinal diffusion changes due to different perfusion states using the NMR-MOUSE is feasible under experimental conditions. Despite the lack of statistical significance, this technique reflects perfusion changes and therefore seems promising for the evaluation of different intestinal perfusion states in the future. Beforehand however, an optimization of this technology, including the optimization of the penetration depth, as well as further validation studies under physiological conditions and including older animals are required.