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Background: All-cause and AIDS-mortality in Europe has been decreasing between 1996 and 2020. However, regional differences as well as their drivers remain unclear. This study investigates mortality differences and their drivers, including usage of and response to antiretroviral therapy (ART) and active tuberculosis (TB), among people with HIV across Europe. Methods: People with HIV enrolled in EuroSIDA were followed from 2001 through 2020. Immunologic-virologic status (IVS) was categorized as poor (CD4-cell count ≤350 cells/mm3 and viral load (VL) > 200 copies/ml), good (CD4 ≥ 500 and VL < 200), or intermediate (remaining combinations). Participants missing either CD4-cell count or VL were categorized as unknown. Regional differences in mortality were analyzed using multivariable Poisson regression with interaction analyses between regions of Europe and IVS, ART, or TB status. Findings: 20,364 people with HIV were included: 13,715/20,346 (67.3%) from Western, 3020/20,364 (14.8%) from Central Eastern, and 3629/20,364 (17.8%) from Eastern Europe. At enrolment, median age was 40 years (inter-quartile range (IQR): 33-48), median CD4-cell count 449 cells/mm3 (IQR: 291-638), and most were male 14,993/20,346 (73.3%). A total of 2639 died during 192,591 person-years of follow-up (crude mortality rate 13.7/1000 person-years, 95% CI: 13.2-14.2), 519/2639 (19.7%) from AIDS (2.7/1000 person-years, 2.5-2.9). All-cause and AIDS-mortality rates decreased over time but remained higher in Eastern Europe after adjusting for confounders. Being off ART (aIRR 2.42; 95% CI 2.14-2.74), poor IVS (aIRR 4.2; 95% CI 3.39-5.20) and prior TB (aIRR 3.33; 95% CI 2.75-4.03) were associated with higher all-cause mortality. For all-cause mortality the effect of ART (test for interaction: p < 0.001) and IVS (p = 0.02), but not TB (p = 0.5) varied across regions. Interpretation: Overall mortality and AIDS-mortality rates decreased over time, but remained higher in Eastern Europe. A poor IVS, being off ART and prior active TB were related to higher mortality. Eastern Europe had the highest proportion of people with poor or unknown IVS, emphasizing the continued need to improve HIV care with a focus on early diagnosis, ART initiation, and adherence. Funding: EuroSIDA has received funding from ViiV Healthcare LLC, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, Gilead Sciences and the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement nË 260694. The study is also supported by a grant from the Danish National Research Foundation and by the International Cohort Consortium of Infectious Disease (RESPOND).
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BACKGROUND AND OBJECTIVES: Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities. METHODS: 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children after the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. RESULTS: 219 885 Pool-PCRs and 352 305 Single-PCRs were performed. 6440 (2.93%) Pool-PCRs tested positive, and 17 208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, confidence interval 0.52-1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. CONCLUSIONS: Our analyses provide evidence that suggest safety of the test-to-stay approach compared with quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.
Subject(s)
COVID-19 , Child Day Care Centers , Humans , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/diagnosis , Child, Preschool , Germany/epidemiology , Infant , Quarantine , Child , SARS-CoV-2 , Male , COVID-19 Nucleic Acid Testing , Female , Mass Screening/methodsABSTRACT
Medicine in Germany is currently facing major structural and economic challenges. Infectious Diseases, with the recent introduction of a new specialty in "Internal Medicine and Infectious Diseases" and with the existing additional training for almost all specializations, will make an important contribution to overcoming these challenges. Expertise in infectious diseases has to be very broad and requires high interdisciplinarity, which makes infectious diseases an attractive and demanding specialty. The complex fundamentals of infectious diseases must now be quickly conveyed to as many physicians as possible in a short period of time, as part of their specialization or as additional training. Until this is achieved, transitional solutions will be necessary for some time. The adaptation of the current billing and reimbursement system for infectious diseases services and improved intersectoral cooperation are of the utmost importance for the further development of the specialty.
Subject(s)
Communicable Diseases , Physicians , Humans , Communicable Diseases/therapy , Germany , Education, Medical, Graduate , Internal Medicine/education , SpecializationABSTRACT
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.
Subject(s)
Coinfection , HIV Infections , Tuberculosis , Humans , Retrospective Studies , HIV Infections/epidemiology , HIV Infections/complications , Incidence , Risk Factors , Male , Tuberculosis/epidemiology , Tuberculosis/complications , Female , Coinfection/epidemiology , Coinfection/virology , Adult , Germany/epidemiology , Middle Aged , Young Adult , Cohort StudiesABSTRACT
BACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.
Subject(s)
Anti-Bacterial Agents , Staphylococcal Infections , Staphylococcus aureus , Humans , Female , Male , Staphylococcal Infections/drug therapy , Middle Aged , Administration, Oral , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Aged , Bacteremia/drug therapy , Treatment Outcome , Adult , Administration, IntravenousABSTRACT
BACKGROUND: Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH). METHODS: In this analysis, serum samples of PLWH from the RESINA multicenter cohort were reanalyzed for TTV. Investigated clinical and epidemiological parameters included human pegivirus load, patient age and sex, HIV load, CD4+ T-cell count (Centers for Disease Control and Prevention [CDC] stage 1, 2, or 3), and CDC clinical stage (1993 CDC classification system; stage A, B, or C) before initiation of antiretroviral therapy. Regression analysis was used to detect possible associations among parameters. RESULTS: Our analysis confirmed TTV as a strong predictor of CD4+ T-cell count and CDC class 3. This relationship was used to propose a first classification of TTV load with regard to clinical stage. We found no association with clinical CDC stages A-C. The human pegivirus load was inversely correlated with HIV load but not TTV load. CONCLUSIONS: TTV load was associated with immunodeficiency in PLWH. Neither TTV nor HIV load were predictive for the clinical categories of HIV infection.
Subject(s)
DNA Virus Infections , HIV Infections , Torque teno virus , Viral Load , Humans , Torque teno virus/isolation & purification , Male , Female , CD4 Lymphocyte Count , Adult , Middle Aged , HIV Infections/immunology , HIV Infections/virology , HIV Infections/drug therapy , HIV Infections/complications , DNA Virus Infections/virology , DNA Virus Infections/immunology , DNA Virus Infections/epidemiology , United States/epidemiology , Centers for Disease Control and Prevention, U.S. , Flaviviridae/immunology , Cohort Studies , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/virologyABSTRACT
PURPOSE: Antistaphylococcal penicillins and cefazolin have been used as first line therapy in Methicillin-susceptible Staphylococcus aureus bloodstream infection. While efficacy of both regimens seems to be similar, the compounds may differ with regard to tolerability. This study aims to describe the clinical use of cefazolin and flucloxacillin, focussing on discontinuation or change of anti-infective agent due to adverse events. METHODS: This observational prospective study was conducted at two German tertiary care centres with an internal recommendation of flucloxacillin for MSSA-BSI in one, and of cefazolin in the other centre. Adverse events were registered weekly under treatment and at a 90-day follow-up. Descriptive analysis was complemented by a propensity score analysis comparing adverse events (stratified rank-based test applied to the sum of Common Terminology Criteria for adverse events ratings per patient). RESULTS: Of 71 patients included, therapy was initiated with flucloxacillin in 56 (79%), and with cefazolin in 15 (21%). The propensity score analysis indicates a statistically significant difference concerning the severity of adverse events between the treatment groups in favour of cefazolin (p = 0.019). Adverse events led to discontinuation of flucloxacillin in 7 individuals (13% of all patients receiving flucloxacillin). Clinical outcome was not different among treatment groups. CONCLUSION: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data.
Subject(s)
Anti-Bacterial Agents , Cefazolin , Floxacillin , Staphylococcal Infections , Staphylococcus aureus , Humans , Cefazolin/therapeutic use , Floxacillin/therapeutic use , Male , Female , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Middle Aged , Prospective Studies , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Aged , Staphylococcus aureus/drug effects , Bacteremia/drug therapy , Bacteremia/microbiology , Adult , Aged, 80 and over , GermanyABSTRACT
Drug-resistant Pseudomonas aeruginosa (PA) poses an emerging threat to human health with urgent need for alternative therapeutic approaches. Here, we deciphered the B cell and antibody response to the virulence-associated type III secretion system (T3SS) in a cohort of patients chronically infected with PA. Single-cell analytics revealed a diverse B cell receptor repertoire directed against the T3SS needle-tip protein PcrV, enabling the production of monoclonal antibodies (mAbs) abrogating T3SS-mediated cytotoxicity. Mechanistic studies involving cryoelectron microscopy identified a surface-exposed C-terminal PcrV epitope as the target of highly neutralizing mAbs with broad activity against drug-resistant PA isolates. These anti-PcrV mAbs were as effective as treatment with conventional antibiotics in vivo. Our study reveals that chronically infected patients represent a source of neutralizing antibodies, which can be exploited as therapeutics against PA.
Subject(s)
Antibodies, Bacterial , Antibodies, Neutralizing , Pseudomonas Infections , Pseudomonas aeruginosa , Humans , Antibodies, Bacterial/pharmacology , Cryoelectron Microscopy , Immunoglobulins/metabolism , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Pseudomonas Infections/drug therapyABSTRACT
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.
Subject(s)
AIDS Vaccines , HIV Infections , HIV-1 , Humans , HIV Antibodies , Antibodies, Neutralizing , Virus ReplicationABSTRACT
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.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV Seropositivity , HIV-1 , Humans , HIV Infections/drug therapy , HIV-1/genetics , Proviruses/genetics , Retrospective Studies , Genotype , Anti-Retroviral Agents/pharmacology , Anti-Retroviral Agents/therapeutic use , DNA, Viral/genetics , RNA, Viral/genetics , Viral Load , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/geneticsABSTRACT
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 7â¯months and unexposed donors. Results: Patients with PCS showed as early as 6â¯weeks and 7â¯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.
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BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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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.
Subject(s)
COVID-19 , HIV Infections , Influenza, Human , Humans , Retrospective Studies , COVID-19/prevention & control , Vaccination , RNA, Messenger , Immunity , Immunoglobulin G , Antibodies, ViralABSTRACT
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.
Subject(s)
COVID-19 , Adolescent , Adult , Child , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Risk Factors , SARS-CoV-2ABSTRACT
PURPOSE: School closures have been used as part of lockdown strategies to contain the spread of SARS-CoV-2, adversely affecting children's health and education. To ensure the accessibility of educational institutions without exposing society to the risk of increased transmissions, it is essential to establish SARS-CoV-2 testing strategies that are child-friendly, scalable and implementable in a daily school routine. Self-sampling using non-invasive saliva swabs combined with pooled RT-qPCR testing (Lolli-Method) has been proven to be a sensitive method for the detection of SARS-CoV-2. METHODS: We conducted a pilot project in Cologne, Germany, designed to determine the feasibility of a large-scale rollout of the Lolli-Method for testing without any additional on-site medical staff in schools. Over a period of three weeks, students from 22 schools were sampled using the Lolli-Method. At the end of the project, teachers were asked to evaluate the overall acceptance of the project. RESULTS: We analyzed a total of 757 pooled RT-qPCRs obtained from 8,287 individual swabs and detected 7 SARS-CoV-2 infected individuals. The Lolli-Method was shown to be a feasible and accepted testing strategy whose application is only slightly disruptive to the daily school routine. CONCLUSION: Our observations suggest that the Lolli-Method in combination with pooled RT-qPCR can be implemented for SARS-CoV-2 surveillance in daily school routine, applicable on a large scale.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pilot Projects , SARS-CoV-2/genetics , COVID-19 Testing , COVID-19/diagnosis , COVID-19/epidemiology , Communicable Disease Control , SchoolsABSTRACT
Using concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6 and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28 was associated with lower virological failure (p = 0.012), even after adjusting for baseline CD4 count (p = 0.048), but not when adjusted for baseline HIV-1 viral load (p = 0.082) or both (p = 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir's characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.