Outpatient parenteral antimicrobial therapy (OPAT) in Germany: insights and clinical outcomes from the K-APAT cohort study.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) offers several key advantages, including enhanced patient quality of life, reduced healthcare costs, and a potential reduction of nosocomial infections. It is acknowledged for its safety and effectiveness. This study provides the first systematic clinical data for Germany, where OPAT has not yet been widely adopted. The aim is to establish a foundational reference point for further research and integration of OPAT into the German healthcare system. METHODS: This prospective observational study descriptively analyses data obtained from a cohort of patients receiving OPAT. Both in- and outpatients from all medical specialties could be recruited. Patients administered the anti-infective medications themselves at home using elastomeric pumps. RESULTS: 77 patients received OPAT, with a median duration of 15 days and saving 1782 inpatient days. The most frequently treated entities were orthopaedic infections (n = 20, 26%), S. aureus bloodstream infection (n = 16, 21%) and infectious endocarditis (n = 11, 14%). The most frequently applied drugs were flucloxacillin (n = 18, 23%), penicillin G (n = 13, 17%) and ceftriaxone (n = 10; 13%). Only 5% of patients (n = 4) reported to have missed more than one outpatient dose (max. 3 per patient). Only one catheter-related adverse event required medical intervention, and there were no catheter-related infections. CONCLUSION: The study demonstrates that OPAT can be safely conducted in Germany. In preparation for its broader implementation, crucial next steps include creating medical guidelines, fostering interdisciplinary and inter-sectoral communication, as well as creating financial and structural regulations that facilitate and encourage the adoption of OPAT. TRIAL REGISTRATION NUMBER: NCT04002453.

Plasma interferon-γ-inducible protein 10 (IP-10) levels correlate with disease severity and paradoxical reactions in extrapulmonary tuberculosis.

BACKGROUND: With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers. METHODS: The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON®-TB Gold Plus (QFT® Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT® Plus and IP-10 levels. RESULTS: Plasma IP-10 levels were found to be significantly increased (p < 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT® Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for Mycobacterium tuberculosis. CONCLUSION: Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT® Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.

[Sex in infectious diseases-How sex differences influence the immune response to infections]. / Das Geschlecht in der Infektiologie ­ wie Geschlechtsunterschiede die Immunantwort auf Infektionen beeinflussen.

The humoral and cellular immune responses to antigen stimulation, vaccinations and infections differ between women and men. Genetic, epigenetic and hormonal factors contribute to the sex-specific immunity. The expression of genes on the X­chromosome and the effect of sex hormones substantially influence the immune defence against infections. Females show stronger cellular and humoral immune responses to infections than males, but the enhanced immune response often leads to aberrant inflammatory reactions and autoimmune diseases. Men are principally more prone to bacterial, viral and fungal infections and more often show severe disease courses. In contrast, a more reactive female immune system results in significantly more adverse reactions to vaccinations. In order to be able to better identify the multiple sex-specific that have an influence on the immune system, sex-specific differences should be investigated in a differentiated way. The better understanding of the sex-specific differences in the immune response will have a long-term influence on the prevention, diagnostics and treatment of infectious diseases, and will ultimately contribute to improving healthcare of both women and men.

Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome.

Background: Symptoms lasting longer than 12 weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs. Methods: Here, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors. Results: Patients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3+) and IL-4 were more abundant in PCS+. Conclusion: This work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments.

CXCR3 Expression Pattern on CD4+ T Cells and IP-10 Levels with Regard to the HIV-1 Reservoir in the Gut-Associated Lymphatic Tissue.

(1) Background: The gut-associated lymphatic tissue (GALT) represents the largest lymphoid organ, and is considered to be the largest HIV reservoir. The exact size of the GALT reservoir remains unclear. Several markers, such as the chemokine receptor CXCR3 and its pro-inflammatory ligand IP-10, have been proposed to define the size of HIV reservoirs in the peripheral blood (PB). However, little is known about the role of CXCR3 and IP-10 within the GALT. (2) Methods: We compared the CXCR3 expression, IP-10 levels, and cell-associated HIV DNA of distinct memory CD4+ T cell subsets from the terminal ileum (TI), PB and rectum (RE) of 18 HIV+ patients with antiretroviral therapy (ART), 6 HIV+ treatment-naive patients and 16 healthy controls. (3) Results: While the relative distributions of CD4+ T cell subsets were similar in PB, TI and RE, HIV DNA and CXCR3 expression were markedly increased and IP-10 levels were decreased in TI when compared to PB. No significant correlation was found between the CXCR3 expression and memory CD4+ T cell subsets, IP-10 levels and the HIV DNA amounts measured in PB, TI or RE. (4) Conclusions: During a chronic HIV-1 infection, neither CXCR3 nor IP-10 are indicative of the size of the viral reservoir in the GALT (TI and RE).

Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study.

BACKGROUND: While the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalisation. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence, we focus on mild COVID-19 in non-hospitalised patients. METHODS: 958 Patients with confirmed SARS-CoV-2 infection were observed from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarised presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model. FINDINGS: We observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8•6% (38/442) of patients presented with shortness of breath, 12•4% (55/442) with anosmia, 11•1% (49/442) with ageusia and 9•7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27•8% (123/442) and 34•8% (123/353) at month 4 and 7 post-infection, respectively. A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhoea during acute COVID-19 were associated with higher risk to develop long-term symptoms. INTERPRETATION: The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalised patients was observed at four and seven months post-infection and summarised as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19. FUNDING: COVIM:"NaFoUniMedCovid19"(FKZ: 01KX2021).

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans.

Understanding antibody-based SARS-CoV-2 immunity is critical for overcoming the COVID-19 pandemic and informing vaccination strategies. We evaluated SARS-CoV-2 antibody dynamics over 10 months in 963 individuals who predominantly experienced mild COVID-19. Investigating 2,146 samples, we initially detected SARS-CoV-2 antibodies in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of individuals demonstrated exceptional SARS-CoV-2 neutralization, with these "elite neutralizers" also possessing SARS-CoV-1 cross-neutralizing IgG. Multivariate statistical modeling revealed age, symptomatic infection, disease severity, and gender as key factors predicting SARS-CoV-2-neutralizing activity. A loss of reactivity to the virus spike protein was observed in 13% of individuals 10 months after infection. Neutralizing activity had half-lives of 14.7 weeks in serum versus 31.4 weeks in purified IgG, indicating a rather long-term IgG antibody response. Our results demonstrate a broad spectrum in the initial SARS-CoV-2-neutralizing antibody response, with sustained antibodies in most individuals for 10 months after mild COVID-19.

Short Communication: Tracking Tregs: Translocation of CD49b/LAG-3+ Type 1 T Regulatory Cells to the Gut-Associated Lymphoid Tissue of HIV+ Patients.

The gastrointestinal mucosa [gut-associated lymphoid tissue (GALT)] represents the largest site of chronic immune activation and HIV replication. Important cellular agents in the immunopathogenesis of an HIV infection are, in particular, CD49b/LAG-3+ type 1 T regulatory cells (Tr1), which secrete large amounts of IL-10 (interleukin-10), and plasmacytoid dendritic cells, the main producers of IFN-α (interferon-alpha). However, the distribution of CD49b/LAG-3+ Tr1 cells along the GALT is unknown.