Macrophage activation syndrome in a patient with adult-onset Still’s disease following first COVID-19 vaccination with BNT162b2

Background: Adult-onset Still's disease (AOSD) is an autoinflammatory multi-systemic syndrome. Macrophage activation syndrome (MAS) is a potentially life-threatening complication of AOSD with a mortality rate of 10-20%. Especially viral infection is thought to be a common trigger for development of MAS. On the other hand, the occurrence of MAS following vaccinations is extremely rare and has been described in a few cases after measles or influenza vaccinations and more recently after ChAdOx1 nCoV-19 (COVID-19 viral vector vaccine, Oxford-AZ). Case presentation: We report the case of a twenty-year-old female with adult-onset Still's disease (AOSD), who developed a MAS six days after receiving her first COVID-19 vaccine dose of BNT162b2 (mRNA vaccine, BioNTech/Pfizer) with ferritin levels of 136,680 mu g/l (ref.: 13-150 mu g/l). Conclusions: To the best of our knowledge, this is the first case report of development of MAS in a patient with preexisting AOSD after vaccination in general, and SARS-CoV-2 vaccination in particular. The new mRNA vaccines have generally shown a reassuring safety profile, but it has been shown that nucleic acids in general, including mRNA can act as pathogen-associated molecular patterns that activate toll-like receptors with extensive production of pro-inflammatory cytokines and further activation of immune cells. Proving an interferon 1 response in our patient directly after vaccination, we think that in this particular case the vaccination might have acted as trigger for the development of MAS. Even if it remains difficult to establish causality in the case of rare adverse events, especially in patients with autoimmune or autoinflammatory conditions, these complications are important to monitor and register, but do not at all diminish the overwhelming positive benefit-risk ratio of licensed COVID-19 vaccines

Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses

Clinical trials on the use of COVID-19 convalescent plasma remain inconclusive. While data on safety is increasingly available, evidence for efficacy is still sparse. Subgroup analyses hint to a dose-response relationship between convalescent plasma neutralizing antibody levels and mortality. In particular, patients with primary and secondary antibody deficiency might benefit from this approach. However, testing of neutralizing antibodies is limited to specialized biosafety level 3 laboratories and is a time- and labor-intense procedure. In this single center study of 206 COVID-19 convalescent patients, clinical data, results of commercially available ELISA testing of SARS-CoV-2 spike-IgG and -IgA, and levels of neutralizing antibodies, determined by plaque reduction neutralization testing (PRNT), were analyzed. At a medium time point of 58 days after symptom onset, only 12.6% of potential plasma donors showed high levels of neutralizing antibodies (PRNT50 >= 1:320). Multivariable proportional odds logistic regression analysis revealed need for hospitalization due to COVID-19 (odds ratio 6.87; p-value 0.0004) and fever (odds ratio 3.00; p-value 0.0001) as leading factors affecting levels of SARS-CoV-2 neutralizing antibody titers in convalescent plasma donors. Using penalized estimation, a predictive proportional odds logistic regression model including the most important variables hospitalization, fever, age, sex, and anosmia or dysgeusia was developed. The predictive discrimination for PRNT50 >= 1:320 was reasonably good with AUC: 0.86 (with 95% CI: 0.79-0.92). Combining clinical and ELISA-based pre-screening, assessment of neutralizing antibodies could be spared in 75% of potential donors with a maximal loss of 10% of true positives (PRNT50 >= 1:320)

Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines - A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design

Разработка мероприятий по улучшению условий труда на примере предприятия ООО "Юргинский машиностроительный завод"

Abstract IL-6 is known to play a crucial role in the pathogenesis of chronic intestinal inflammation by modulating T cell functions. In this study, we investigated the role of gp130, the common signal transducer for all IL-6 cytokines, in a murine model of acute T cell independent colitis to better characterize the impact of gp130 on innate immune cells and the early stages of inflammation. Experimental colitis was induced by dextran sulfate sodium treatment of mice with inducible systemic deletion of gp130 (MxCre/gp130−/−), macrophage/neutrophil-specific gp130-deficiency (LysCre/gp130−/−), or bone marrow chimeric mice and compared with wild-type controls (gp130f/f). Systemic deletion of gp130 (MxCre/gp130−/−) protected mice from severe colitis and wasting and attenuated the mucosal inflammatory infiltrate as well as local cytokine, chemokine, and adhesion molecule expression. Experiments in newly generated macrophage/neutrophil-specific gp130-deleted animals (LysCre/gp130−/−) and gp130 bone marrow chimeric mice, revealed a dual mechanism of proinflammatory effects mediated by gp130. Leukocyte recruitment was impaired in gp130-deleted animals and gp130-deleted recipients of wild-type bone marrow, demonstrating a central role of gp130-dependent signals in nonmyeloid cells for directing leukocytes to sites of inflammation, which was further confirmed in a model of sterile peritonitis. In contrast, macrophage/neutrophil-specific gp130 deficiency delayed and attenuated the disease but only marginally affected the inflammatory infiltrate, indicating a defective activation of mucosal leukocytes. We provide evidence that IL-6 cytokines acting via gp130 are required in the acute stages of intestinal inflammation by modulating the dynamics of innate immune cell recruitment and activation.</jats:p

Type of vaccine and immunosuppressive therapy but not diagnosis critically influence antibody response after COVID-19 vaccination in patients with rheumatic disease

Objective: The development of sufficient COVID-19 vaccines has been a big breakthrough in fighting the global SARS-CoV-2 pandemic. However, vaccination effectiveness can be reduced in patients with autoimmune rheumatic diseases (AIRD). The aim of this study was to identify factors that lead to a diminished humoral vaccination response in patients with AIRD. Methods: Vaccination response was measured with a surrogate virus neutralisation test and by testing for antibodies directed against the receptor-binding-domain (RBD) of SARS-CoV-2 in 308 fully vaccinated patients with AIRD. In addition, 296 immunocompetent participants were investigated as a control group. Statistical adjusted analysis included covariates with a possible influence on antibody response. Results: Patients with AIRD showed lower antibody responses compared with immunocompetent individuals (median neutralising capacity 90.8% vs 96.5%, p<0.001; median anti-RBD-IgG 5.6 S/CO vs 6.7 S/CO, p<0.001). Lower antibody response was significantly influenced by type of immunosuppressive therapy, but not by rheumatic diagnosis, with patients under rituximab therapy developing the lowest antibody levels. Patients receiving mycophenolate, methotrexate or janus kinase inhibitors also showed reduced vaccination responses. Additional negative influencing factors were vaccination with AZD1222, old age and shorter intervals between the first two vaccinations. Conclusion: Certain immunosuppressive therapies are associated with lower antibody responses after vaccination. Additional factors such as vaccine type, age and vaccination interval should be taken into account. We recommend antibody testing in at-risk patients with AIRD and emphasise the importance of booster vaccinations in these patients

Heart failure with preserved ejection fraction according to the HFA-PEFF score in COVID-19 patients: clinical correlates and echocardiographic findings

Aims: Viral-induced cardiac inflammation can induce heart failure with preserved ejection fraction (HFpEF)-like syndromes. COVID-19 can lead to myocardial damage and vascular injury. We hypothesised that COVID-19 patients frequently develop a HFpEF-like syndrome, and designed this study to explore this. Methods and results: Cardiac function was assessed in 64 consecutive, hospitalized, and clinically stable COVID-19 patients from April-November 2020 with left ventricular ejection fraction (LVEF) ≥50% (age 56 ± 19 years, females: 31%, severe COVID-19 disease: 69%). To investigate likelihood of HFpEF presence, we used the HFA-PEFF score. A low (0-1 points), intermediate (2-4 points), and high (5-6 points) HFA-PEFF score was observed in 42%, 33%, and 25% of patients, respectively. In comparison, 64 subjects of similar age, sex, and comorbidity status without COVID-19 showed these scores in 30%, 66%, and 4%, respectively (between groups: P = 0.0002). High HFA-PEFF scores were more frequent in COVID-19 patients than controls (25% vs. 4%, P = 0.001). In COVID-19 patients, the HFA-PEFF score significantly correlated with age, estimated glomerular filtration rate, high-sensitivity troponin T (hsTnT), haemoglobin, QTc interval, LVEF, mitral E/A ratio, and H2 FPEF score (all P < 0.05). In multivariate, ordinal regression analyses, higher age and hsTnT were significant predictors of increased HFA-PEFF scores. Patients with myocardial injury (hsTnT ≥14 ng/L: 31%) vs. patients without myocardial injury, showed higher HFA-PEFF scores [median 5 (interquartile range 3-6) vs. 1 (0-3), P < 0.001] and more often showed left ventricular diastolic dysfunction (75% vs. 27%, P < 0.001). Conclusion: Hospitalized COVID-19 patients frequently show high likelihood of presence of HFpEF that is associated with cardiac structural and functional alterations, and myocardial injury. Detailed cardiac assessments including echocardiographic determination of left ventricular diastolic function and biomarkers should become routine in the care of hospitalized COVID-19 patients

Wissenschaftliche Begründung der STIKO zur Implementierung der COVID-19-Impfung in die allgemeinen Empfehlungen der STIKO 2023

Die COVID-19-Impfempfehlungen der STIKO ha¬ben seit Beginn der Impfkampagne im Winter 2020/2021 das vordringliche Ziel, schwere Verläufe und Langzeit¬folgen von COVID-19 zu verhindern sowie Beschäf¬tigte in der medizinischen und pflegenden Versor¬gung vor SARS-CoV-2-Infektionen zu schützen. Die STIKO hat ihre COVID-19-Impfempfehlung seit der Erstpublikation im Dezember 2020 unter der Berücksichtigung neuer Daten und wei¬teren Impfstoffzulassungen fortlaufend angepasst. Beim Übergang von der pandemischen in die ende¬mische Phase des Infektionsgeschehens hat sich die STIKO mit der Überführung der bisherigen Emp¬fehlungen in eine längerfristige COVID-19-Impfempfehlung befasst. Im Epidemiologischen Bulletin 21/2023 wird die dazugehörige wissenschaftliche Begründung der aktualisierten Empfehlung und der Integration in den Impfkalender veröffentlicht. Die neue Empfehlung ersetzt die 25. Aktualisierung der COVID-19-Impfempfehlung von Februar 2023, die nicht mehr länger gültig ist

Wissenschaftliche Begründung der STIKO zur Implementierung der COVID-19-Impfung in die allgemeinen Empfehlungen der STIKO 2023

Die COVID-19-Impfempfehlungen der STIKO ha¬ben seit Beginn der Impfkampagne im Winter 2020/2021 das vordringliche Ziel, schwere Verläufe und Langzeit¬folgen von COVID-19 zu verhindern sowie Beschäf¬tigte in der medizinischen und pflegenden Versor¬gung vor SARS-CoV-2-Infektionen zu schützen. Die STIKO hat ihre COVID-19-Impfempfehlung seit der Erstpublikation im Dezember 2020 unter der Berücksichtigung neuer Daten und wei¬teren Impfstoffzulassungen fortlaufend angepasst. Beim Übergang von der pandemischen in die ende¬mische Phase des Infektionsgeschehens hat sich die STIKO mit der Überführung der bisherigen Emp¬fehlungen in eine längerfristige COVID-19-Impfempfehlung befasst. Im Epidemiologischen Bulletin 21/2023 wird die dazugehörige wissenschaftliche Begründung der aktualisierten Empfehlung und der Integration in den Impfkalender veröffentlicht. Die neue Empfehlung ersetzt die 25. Aktualisierung der COVID-19-Impfempfehlung von Februar 2023, die nicht mehr länger gültig ist

Wissenschaftliche Begründung der STIKO zur Implementierung der COVID-19-Impfung in die allgemeinen Empfehlungen der STIKO 2023

Die COVID-19-Impfempfehlungen der STIKO ha¬ben seit Beginn der Impfkampagne im Winter 2020/2021 das vordringliche Ziel, schwere Verläufe und Langzeit¬folgen von COVID-19 zu verhindern sowie Beschäf¬tigte in der medizinischen und pflegenden Versor¬gung vor SARS-CoV-2-Infektionen zu schützen. Die STIKO hat ihre COVID-19-Impfempfehlung seit der Erstpublikation im Dezember 2020 unter der Berücksichtigung neuer Daten und wei¬teren Impfstoffzulassungen fortlaufend angepasst. Beim Übergang von der pandemischen in die ende¬mische Phase des Infektionsgeschehens hat sich die STIKO mit der Überführung der bisherigen Emp¬fehlungen in eine längerfristige COVID-19-Impfempfehlung befasst. Im Epidemiologischen Bulletin 21/2023 wird die dazugehörige wissenschaftliche Begründung der aktualisierten Empfehlung und der Integration in den Impfkalender veröffentlicht. Die neue Empfehlung ersetzt die 25. Aktualisierung der COVID-19-Impfempfehlung von Februar 2023, die nicht mehr länger gültig ist