The Impact of COVID-19 Pandemic on Medical Doctors' Work-Family Balance at German University Clinics.

The measures taken to cope with the COVID-19 pandemic by governments worldwide have vast consequences on all areas of life. To assess the impact of the COVID-19 pandemic on long-term career development, we evaluated the work-family balance of medical doctors at nine German university clinics. The results indicate a severely disturbed work-family balance, which was mostly due to insufficient childcare, based on restrictions in school operations and childcare. Despite the newly created emergency childcare options, aiming to ensure the functioning of the "systematically important" professional groups, medical doctors feel that they are not sufficiently supported by the measures taken by local governments. Women, in particular, see their professional development at risk. Our results underline that proper and flexible childcare is essential for the career advancement of female medical doctors and is particularly important in times of crises such as the current COVID-19 pandemic. At university medicine clinics, increased work time flexibility and optimized schooling and childcare are needed to promote the career development of female as well as male medical doctors in the early stage of their careers.

Comparison of the Anti-SARS-CoV-2 Surrogate Neutralization Assays by TECOmedical and DiaPROPH-Med with Samples from Vaccinated and Infected Individuals.

Anti-SARS-CoV-2-specific serological responses are a topic of ongoing evaluation studies. In the study presented here, the anti-SARS-CoV-2 surrogate neutralization assays by TECOmedical and DiaPROPH -Med were assessed in a head-to-head comparison with serum samples of individuals after vaccination as well as after previous infection with SARS-CoV-2. In case of discordant results, a cell culture-based neutralization assay was applied as a reference standard. The TECOmedical assay showed sensitivity and specificity of 100% and 61.3%, respectively, the DiaPROPH-Med assay 95.0% and 48.4%, respectively. As a side finding of the study, differences in the likelihood of expressing neutralizing antibodies could be shown for different exposition types. So, 60 of 81 (74.07%) of the samples with only one vaccination showed an expression of neutralizing antibodies in contrast to 85.71% (60 of 70 samples) of the samples with two vaccinations and 100% (40 of 40) of the samples from previously infected individuals. In conclusion, the both assays showed results similar to previous assessments. While the measured diagnostic accuracy of both assays requires further technical improvement of this diagnostic approach, as the calculated specificity values of 61.3% and 48.4%, respectively, appear acceptable for diagnostic use only in populations with a high percentage of positive subjects, but not at expectedly low positivity rates.

Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination.

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.

COVID-19 and immunological regulations - from basic and translational aspects to clinical implications.

The COVID-19 pandemic caused by SARS-CoV-2 has far-reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS-CoV-2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors. Against this background we summarize here the current state of knowledge on the interaction of SARS-CoV-2/COVID-19 with mediators of the acute phase of inflammation (TNF, IL-1, IL-6), type 1 and type 17 immune responses (IL-12, IL-23, IL-17, IL-36), type 2 immune reactions (IL-4, IL-13, IL-5, IL-31, IgE), B-cell immunity, checkpoint regulators (PD-1, PD-L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non-specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte-mediated innate immune mechanisms. From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS-CoV-2/COVID-19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID-19 pandemic; some even appear to alleviate COVID-19.