Incidence and risk factors for HIV-tuberculosis coinfection in the Cologne-Bonn region: a retrospective cohort study.

PURPOSE: The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. METHODS: We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. RESULTS: During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. CONCLUSION: Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.

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.

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4+ T cell counts <200 µl-1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response.

The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm.

The novel coronavirus pandemic, first reported in December 2019, was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells, which can elicit acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread inflammation, the so-called cytokine storm. In response to viral infections, monocytes are recruited into the lung and subsequently differentiate into dendritic cells (DCs). DCs are critical players in the development of the acute lung inflammation that causes ARDS. Here we focus on the interaction of a specific SARS-CoV-2 open reading frame protein, ORF8, with DCs. We show that ORF8 binds to DCs, causes a pre-maturation of differentiating DCs, and induces the secretion of multiple proinflammatory cytokines by these cells. In addition, we identified DC-SIGN as a possible interaction partner of ORF8 on DCs. Blockade of ORF8 leads to reduced production of IL-1ß, IL-6, IL-12p70, TNF-α, MCP-1 (also named CCL2), and IL-10 by DCs. Therefore, a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutical strategy against severe SARS-CoV-2.

15-month post-COVID syndrome in outpatients: Attributes, risk factors, outcomes, and vaccination status - longitudinal, observational, case-control study.

Background: While the short-term symptoms of post-COVID syndromes (PCS) are well-known, the long-term clinical characteristics, risk factors and outcomes of PCS remain unclear. Moreover, there is ongoing discussion about the effectiveness of post-infection vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) to aid in PCS recovery. Methods: In this longitudinal and observational case-control study we aimed at identifying long-term PCS courses and evaluating the effects of post-infection vaccinations on PCS recovery. Individuals with initial mild COVID-19 were followed for a period of 15 months after primary infection. We assessed PCS outcomes, distinct symptom clusters (SC), and SARS-CoV-2 immunoglobulin G (IgG) levels in patients who received SARS-CoV-2 vaccination, as well as those who did not. To identify potential associating factors with PCS, we used binomial regression models and reported the results as odds ratios (OR) with 95% confidence intervals (95%CI). Results: Out of 958 patients, follow-up data at 15 month after infection was obtained for 222 (23.2%) outpatients. Of those individuals, 36.5% (81/222) and 31.1% (69/222) were identified to have PCS at month 10 and 15, respectively. Fatigue and dyspnea (SC2) rather than anosmia and ageusia (SC1) constituted PCS at month 15. SARS-CoV-2 IgG levels were equally distributed over time among age groups, sex, and absence/presence of PCS. Of the 222 patients, 77.0% (171/222) were vaccinated between 10- and 15-months post-infection, but vaccination did not affect PCS recovery at month 15. 26.3% of unvaccinated and 25.8% of vaccinated outpatients improved from PCS (p= .9646). Baseline headache (SC4) and diarrhoea (SC5) were risk factors for PCS at months 10 and 15 (SC4: OR 1.85 (95%CI 1.04-3.26), p=.0390; SC5: OR 3.27(95%CI 1.54-6.64), p=.0009). Conclusion: Based on the specific symptoms of PCS our findings show a shift in the pattern of recovery. We found no effect of SARS-CoV-2 vaccination on PCS recovery and recommend further studies to identify predicting biomarkers and targeted PCS therapeutics.

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.

Optimizing Antiretroviral Therapy in Heavily ART-Experienced Patients with Multi-Class Resistant HIV-1 Using Proviral DNA Genotypic Resistance Testing.

Resistance to multiple antiretroviral drugs among people living with HIV (PLWH) can result in a high pill burden, causing toxicity and drug interactions. Thus, the goal is to simplify treatment regimens while maintaining effectiveness. However, former resistance analysis data may not be current or complete. The use of proviral DNA genotyping may assist in selecting appropriate treatment options. A retrospective study was carried out on individuals belonging to the Cologne HIV cohort with a resistance history to two or more antiretroviral (ARV) classes and on non-standard antiretroviral therapy (ART). Patients required former viral RNA and a recent proviral DNA resistance test to be available prior to the switch to ART. Potential discrepancies between resistance test results obtained through RNA and proviral DNA methods and the consequent virological and clinical outcomes following ART adjustments were analyzed. Out of 1250 patients, 35 were eligible for inclusion in this study. The median length of known HIV infection was 27 years, and the median duration of ART was 22 years. Of the 35 participants, 16 had received all five ARV classes. Based on proviral DNA genotyping results, ART was simplified in 17 patients. At the last follow-up examination after changing therapy, 15 patients had HIV RNA <50 copies/mL (median 202 days, range 21-636). The mean number of pills per day decreased from eight to three, and the median intake frequency decreased from two to one time/day (ranges 1-2). Our study supports the use of proviral DNA genotyping as a safe strategy for switching to simplified ART regimens. However, the lack of extensive research on the advantages of proviral DNA genotyping makes it challenging to fully assess its benefits in terms of treatment selection.

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.

Outpatient care concept and potential inpatient cost savings associated with the administration of dalbavancin - A real-world data and retrospective cost analysis.

BACKGROUND: The treatment of acute bacterial skin and skin structure infections (ABSSSI) usually involves intravenous (i.v.) antibiotics requiring hospitalisation and increasing hospital costs. Since 2014, dalbavancin is approved for ABSSSIs treatment. However, evidence of its health economic impact on the German healthcare system is still limited. METHODS: Diagnosis-related groups (DRG) based cost analysis was used to evaluate real-world data (RWD) from a German tertiary care center. All patients treated with i.v. antibiotics in the Department of Dermatology and Venereology at the University Hospital of Cologne were included to detect potential cost savings from a payer perspective. Thus, for the inpatient care German diagnosis-related groups (G-DRG) tariffs, length of stay (LOS), main- and secondary DRG-diagnoses and for the outpatient setting 'Einheitlicher Bewertungsmaßstab' (EBM) codes were evaluated. RESULTS: This retrospective study identified 480 inpatient cases treated for ABSSSI between January 2016 until December 2020. Complete cost data were available for 433 cases and the detection of long-hospital-stay patients based on surcharges for exceeding the upper limit LOS led to 125 cases (29%) including 67 females (54%) and 58 males (46%) with an overall mean age of 63.6 years; all treated for International Classification of Diseases (ICD -10th revision) code A46 'erysipelas'. A sub-analysis focussed on DRG J64B with a total of 92 cases exceeding the upper limit LOS by a median of 3 days resulted in a median surcharge of €636 (mean value €749; SD €589; IQR €459-€785) per case. In comparison, we calculated outpatient treatment costs of approximately €55 per case. Thus, further treatment of these patients in an outpatient setting before exceeding the upper limit LOS might result in a cost-saving potential of approximately €581 per case. CONCLUSION: Dalbavancin appears a cost-efficient option to reduce inpatient treatment costs by transitioning to an outpatient setting of patients with ABSSSI potentially exceeding the upper limit LOS.

[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.

Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients.

With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients' status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine's potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.

Immune response to mRNA-based COVID-19 booster vaccination in people living with HIV.

OBJECTIVES: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose). METHODS: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID100 ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits. Patients with reported COVID-19 during follow-up were excluded. Predictors of serological immune response were analyzed using multivariate regression models. RESULTS: Of 84 people living with HIV who received an mRNA-based booster vaccination, 76 were eligible for analysis. Participants were on effective antiretroviral therapy (ART) and had a median of 670 CD4+ cells/µL (interquartile range [IQR] 540-850). Following booster vaccination, median anti-spike RBD IgG increased by 705.2 binding antibody units per millilitre (BAU/mL) and median VNA titres increased by 1000 ID100 at the follow-up assessment (median 13 weeks later). Multivariate regression revealed that time since second vaccination was a predictor of stronger serological responses (p < 0.0001). No association was found for other factors, including CD4+ status, choice of mRNA vaccine, or concomitant influenza vaccination. In total, 45 patients (59%) had a reactive baseline IGRA, of whom two lost reactivity during follow-up. Of 31 patients (41%) with non-reactive baseline IGRA, 17 (55%) converted to reactive and seven (23%) remained unchanged following booster vaccination. CONCLUSIONS: People living with HIV with ≥500 CD4+ cells/µL showed favourable immune responses to mRNA-based COVID-19 booster vaccination. A longer time (up to 29 weeks) since second vaccination was associated with higher serological responses, whereas choice of mRNA vaccine or concomitant influenza vaccination had no impact.

Results of the Cologne Corona Surveillance (CoCoS) study - a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection in adults.

BACKGROUND: The personal, environmental, and behavioral risk factors that play an important role in the spread of SARS-CoV-2 are still largely unclear. At the same time, there is limited evidence on the effectiveness of specific countermeasures for SARS-CoV-2. As a first approach to these questions, we use data from the Cologne Corona Surveillance (CoCoS) study, a large cross-sectional study conducted in Cologne, Germany, in June 2021. METHODS: This study was conducted in Cologne, Germany. Six thousand randomly selected Cologne residents who were 18 years of age or older were invited to participate in this study. Participant information was obtained via an online survey. Previous SARS-CoV-2 infections were recorded using self-reports. Sociodemographic and environmental information such as age, sex, living situation were collected. Potential SARS-CoV-2 risk behaviors were captured (workplace situation, adherence to hygiene regulations, and regular use of public transportation). Adherence to hygiene regulations was surveyed by determining the compliance with the 'AHA'-rules (German acronym that stands for keeping a distance of 1.5 m from fellow citizens, hand disinfection, and wearing a face mask). Binary logistic regression analysis was used to identify risk factors for SARS-CoV-2 infection. RESULTS: A sample of 2,433 study participants provided information. Comparison of the sample with the general population showed representativeness for most sociodemographic characteristics with a preference for higher level of education in the study sample. Younger age, as well as living with minor children (under 18 years) in the same household were associated with a higher number of self-reported SARS-CoV-2 infections. Adherence to hygiene regulations was associated with fewer self-reported SARS-CoV-2 infections in adults. Gender, size of living space per person, workplace situation (work from home versus working with contact to colleagues/customers), and regular use of public transportation showed no significant association with self-reported SARS-CoV-2 infections in multivariable analysis. CONCLUSION: The presented results provide initial indications of which sociodemographic and behavioral factors may be associated with SARS-CoV-2 infection. However, the fact that these factors were recorded without exact dates and could have changed accordingly during the pandemic or after infection limits the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Post-COVID Syndrome.

BACKGROUND: As defined by the WHO, the term post-COVID syndrome (PCS) embraces a group of symptoms that can occur following the acute phase of a SARS-CoV-2 infection and as a consequence thereof. PCS is found mainly in adults, less frequently in children and adolescents. It can develop both in patients who initially had only mild symptoms or none at all and in those who had a severe course of coronavirus disease 2019 (COVID-19). METHODS: The data presented here were derived from a systematic literature review. RESULTS: PCS occurs in up to 15% of unvaccinated adults infected with SARS-CoV-2. The prevalence has decreased in the most recent phase of the pandemic and is lower after vaccination. The pathogenesis of PCS has not yet been fully elucidated. Virustriggered inflammation, autoimmunity, endothelial damage (to blood vessels), and persistence of virus are thought to be causative. Owing to the broad viral tropism, different organs are involved and the symptoms vary. To date, there are hardly any evidence-based recommendations for definitive diagnosis of PCS or its treatment. CONCLUSION: The gaps in our knowledge mean that better documentation of the prevalence of PCS is necessary to compile the data on which early detection, diagnosis, and treatment can be based. To ensure the best possible care of patients with PCS, regional PCS centers and networks embracing existing structures from all healthcare system sectors and providers should be set up and structured diagnosis and treatment algorithms should be established. Given the sometimes serious consequences of PCS for those affected, it seems advisable to keep the number of SARS-CoV-2 infections low by protective measures tailored to the prevailing pandemic situation.

European Working Group on SARS-CoV-2: Current Understanding, Unknowns, and Recommendations on the Neurological Complications of COVID-19.

Background: The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the etiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Methods: Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Results: In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes, and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against the post-COVID-19 condition. Conclusions: Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Impact statement With our understanding of the neurological complications of the post-COVID-19 condition currently lacking sufficient depth, this review aimed at highlighting the current knowns and unknowns of the post-COVID-19 condition. In this review, we draw upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, as well as explore the current published literature, to evaluate a range of topics associated with the neurological complications of the post-COVID-19 condition. As a result, we have provided a comprehensive review of the topic. The European Working Group on SARS-CoV-2 Many essential questions surrounding COVID-19 remain unanswered, including its neurological complications and associated sequalae. In this review, we aim at identifying the current gaps in our understanding of post-COVID-19 neurological sequalae and suggest how future studies should be undertaken to fill these gaps. This review will draw upon the current biological and mechanistic understanding of COVID-19 and post-COVID-19 complications to discuss the clinically relevant aspects associated with the neurological manifestations of post-COVID-19 syndrome. From our discussions, the following questions were considered highly relevant for contemplation.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel.

Importance: Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice. Objective: Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection. Evidence Review: A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered. Findings: Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential. Conclusions and Relevance: Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.

Outpatient parenteral antimicrobial therapy in Germany: a prospective cohort study protocol.

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) means intravenous administration of antibiotics outside the hospital. The antibiotics are administered at the patient's home. The advantages are the shortening of the inpatient stay, which means that patients can remain in their familiar environment, the reduction of nosocomial infections as well as the reduction of hospital and therapy costs. Nevertheless, OPAT is rarely performed in Germany, despite its international application. Therefore, systematic data on OPAT are not available in Germany. The project objective is to investigate the medical care using OPAT under medical, epidemiological and economic aspects within the framework of the Cologne Network of Infectious Diseases. METHODS AND ANALYSIS: Observational study with mixed-methods approach, qualitative analysis to identify physician-side factors to assess the attitude of general practitioners in Cologne with regard to possible implementation barriers of an OPAT. Longitudinal analysis of an OPAT patient cohort with respect to clinical and patient-relevant outcomes using descriptive and conclusive statistics. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the University of Cologne, Germany (19-1284-1). Written informed consent was obtained from all participants. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: NCT04002453.