Post-COVID syndrome (PCS) refers to persistent or new-onset symptoms 3 months after SARS-CoV-2 infection lasting for at least 2 months. The characterization of PCS varies across studies, with a substantial heterogeneity regarding different study samples, survey instruments, and follow-up periods. This is particularly the case in hospitalized patients vs. outpatients, as well as regarding different variants of concern (VOCs) and their impact on the frequency and severity of specific symptoms. The study population of Beyond COVID was recruited in six German cities by inviting (1) individuals registered as SARS-CoV-2 PCR positive at the local Public Health Authorities and (2) previously hospitalized patients with infection date after 1st March 2021. Participants were allocated to the predominant VOC of their first infection. Questionnaires to assess pre-existing conditions, symptoms during infection, and persisting symptomswere performed. Follow-up at sixth-month intervals is planned for 3 years. The study is ongoing. This publication describes the parameters at the baseline visit (BV). We included 1257 participants (13

BACKGROUND AND PURPOSE:Immune checkpoint blockade has changed the first-line treatment landscape for advanced esophageal squamous cell carcinoma (ESCC), but the magnitude and consistency of benefit across phase III trials require careful synthesis. METHODS:We conducted a PRISMA 2020-guided systematic review of PubMed, Embase, CENTRAL, and Web of Science (January 1, 2015 to April 30, 2025) for phase III randomized trials comparing first-line PD-1 inhibitor-based therapy with chemotherapy in advanced/metastatic ESCC. The primary endpoint was overall survival (OS). Secondary endpoints were safety and prespecified subgroup outcomes. RoB 2 was used for risk-of-bias assessment; certainty of evidence was judged with GRADE. A fixed-effect inverse-variance model was prespecified for the primary common-effect analysis, with random-effects and sensitivity analyses performed secondarily. RESULTS:Six eligible phase III trials were included in the primary analysis (KEYNOTE-590 ESCC subgroup, CheckMate-648 nivolumab-plus-chemotherapy arm, ESCORT-1st, JUPITER-06, ORIENT-15, and RATIONALE-306). Across the six parent-trial reports, 4137 patients were randomized overall; for pooling, KEYNOTE-590 was restricted to the prespecified ESCC subgroup and CheckMate-648 to the nivolumab-plus-chemotherapy comparison. PD-1 inhibitor-based therapy significantly improved OS versus chemotherapy alone (pooled HR 0.68, 95% CI: 0.63-0.74; I2 = 0%, interpreted as low statistical heterogeneity with caution because only six studies were pooled). Qualitative assessment indicated that the treatment effect was generally larger in PD-L1-high populations; however, biomarker-defined subgroup data were not sufficiently harmonized for formal pooling, and the magnitude of benefit in very low or PD-L1-negative disease remains uncertain. Grade ≥ 3 treatment-related adverse events were common in both arms, whereas immune-related toxicities were more frequent with PD-1 inhibitor-based therapy and required active monitoring. CONCLUSION:First-line PD-1 inhibitor-based therapy confers a robust OS benefit in advanced/metastatic ESCC and supports chemoimmunotherapy as a contemporary standard of care. Remaining uncertainties relate mainly to biomarker-negative disease, assay heterogeneity, and cross-trial differences in chemotherapy backbone and geographic composition.

OBJECTIVE:To assess the impact of COVID-19 vaccination on distinct clinical definitions and phenotypes of post-COVID syndrome (PCS) and to identify risk factors for PCS despite vaccination. METHODS:Data were drawn from the German National Pandemic Cohort Network (NAPKON), including adult COVID-19 patients with known vaccination status recruited between December 2, 2020, and February 13, 2023. The prevalence of PCS was assessed by 3 clinical definitions: the broad World Health Organization definition (any sequelae at 3 months), symptom clusters (fatigue, respiratory, cognitive), and a symptom-based PCS score reflecting clinical severity. Multivariable logistic regression was employed to estimate the protective effect of vaccination. RESULTS:Of 756 patients, 26% were fully vaccinated (≥2 doses) before infection. Vaccination was associated with a significantly reduced risk of PCS according to the World Health Organization definition (odds ratio [OR], 0.555; 95% CI, 0.339 to 0.906), the PCS score (OR, 0.536; 95% CI, 0.335 to 0.856), the respiratory cluster (OR, 0.508; 95% CI, 0.295 to 0.875), and the cognitive cluster (OR, 0.443; 95% CI, 0.213 to 0.923). In contrast, no protective association was observed for the fatigue cluster (OR, 0.917; 95% CI, 0.554 to 1.519). The favorable association with vaccination was particularly observed in patients with mild acute symptoms, regardless of hospitalization. The protective effect of vaccination persisted at 12-month follow-up, although fatigue remained unaffected. CONCLUSION:Findings indicate that broader PCS definitions may mask clinically relevant heterogeneity and support the need for differentiated, phenotype-oriented definitions that reflect clinical presentations of PCS, including differential responses to vaccination. Such refined clinical definitions may facilitate exploration of whether these phenotypes reflect distinct underlying pathophysiologic mechanisms. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04768998.

BACKGROUND:Although COVID-19 is no longer a public health emergency, it remains the most prevalent circulating infectious-like-illness in Europe. Whether immunocompromising conditions (ICCs) still carry increased mortality risk during the Omicron era is unclear. METHODS:We conducted a cohort study across EuCARE sites in 8 countries among adults admitted to hospital with COVID-19 between 2020-2023. ICCs and COVID-19 pneumonia at hospitalization were defined using clinical information and ICD-10 codes. Logistic regression and counterfactual mediation analysis was used to compare 28-day in-hospital mortality risk associated with ICCs using COVID-19 pneumonia and vaccination at hospital entry as intermediates. Proportion of the total effect of ICCs mediated and the controlled direct effects (CDEs) were calculated. We also formally tested for interaction between SARS CoV-2 variants and ICCs for mortality risk. FINDINGS:42,488 individuals were included, of which 1,675 (3.9%) had an ICC. 55% were male, median (IQR) age was 67 (52, 79) years. Overall, 4,344 (10.2%) individuals died in hospital. ICCs were associated with increased mortality, OR = 1.49 (1.25, 1.79) with no evidence for an attenuation during the Omicron phase (p-interaction=0.60). Mediation analyses showed that the total effect of ICCs was mediated by vaccination but only weakly by pneumonia. With Omicron, the excess mortality associated with ICC was higher under the scenario that everyone in the cohort was to develop COVID-19 pneumonia [CDE =1.22 (0.09, 1.65)]. INTERPRETATION:ICC remains a significant risk factor for in-hospital death, even during the Omicron era, particularly if the infection led to the development of pneumonia.

Immune recovery among people living with HIV (PWHIV) receiving antiretroviral therapy (ART) is determined analysing CD4 cell counts and the CD4/CD8 ratio. Recovery to ≥ 800 CD4 cells/µl and CD4/CD8 ratio ≥ 1 was associated with favourable outcomes. We investigated immune recovery over 10 years among ART-naive PWHIV on ART. Data were obtained from two German HIV cohorts, the HIV-1 Seroconverter study and the ClinSurv-HIV study, between 2003 and 2018. We included ART-naïve PWHIV starting with continuous ART and analysed CD4 cell counts and the CD4/CD8 ratio. The time to reaching immune thresholds was investigated using Kaplan–Meier analyses with inverse probability censoring weights. Overall, 8,927 participants were included. At baseline, PWHIV had a median CD4 cell count of 257 (interquartile range [IQR] 124–393) cells/µl and CD4/CD8 ratio of 0.26 (IQR 0.14–0.43). After ten years, median CD4 counts increased to 630 (IQR 474–811) cells/µl and CD4/CD8 ratio to 0.84 (IQR 0.61–1.11). PWHIV with higher baseline CD4 values and without viral failure had higher median CD4 counts and CD4/CD8 ratios. The cumulative probability of achieving a CD4 count ≥ 800 cells/µl and/or CD4/CD8 ratio ≥ 1 over 10 years of ART were 54

Community-acquired respiratory viruses (CARV), such as influenza-, parainfluenza- or respiratory syncytial virus, pose a significant threat to immunocompromised patients with cancer. Following the COVID-19 pandemic, SARS-CoV-2 has now joined the ranks of endemic respiratory viruses and continues to be a cause of significant morbidity and mortality in patients with cancer. Strategies to protect this vulnerable patient population both by prevention of infection and by early therapeutic intervention in case of infectious disease are therefore of utmost importance. This guideline provides updated evidence-based recommendations on diagnosis, prophylaxis and treatment of CARV infections including COVID-19 in patients with solid tumors or hematologic malignancies to support clinicians in offering optimal care. The guideline is based on a systematic review of currently available data and was developed until the beginning of 2025 by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

Abstract Background Long-acting cabotegravir+rilpivirine (CAB+RPV LA) and dolutegravir+lamivudine (DTG/3TC) are HIV-1 antiretroviral therapy regimens with different administration routes and dosing frequencies, allowing for greater choice. Methods VOLITION is a Phase 3b, multicenter, non-randomized, parallel-group, open-label implementation–effectiveness study (NCT05917509) evaluating viral suppression on DTG/3TC for up to 16 weeks, followed by a participant-determined optional switch to CAB+RPV LA dosed Q2M or continuation of DTG/3TC through Month (M) 11/12. Co-primary endpoints were the time to virologic suppression with DTG/3TC and the proportion of participants with HIV-1 RNA <50 copies/mL per the Snapshot algorithm at M11 with CAB+RPV LA. Safety and participant experience were also assessed. Results 171 participants initiated DTG/3TC. Median time to suppression on DTG/3TC was 4.1 weeks (95% confidence interval: 4.1–4.3), with 98% (n=167/171) achieving virologic suppression and similar rates observed across baseline viral load and CD4+ cell count categories. At Day of Choice (DoC), 85% (n=129/151) of eligible participants chose to switch to CAB+RPV LA. At M11, 113/129 (88%) participants maintained suppression with CAB+RPV LA; one participant had confirmed virologic failure with resistance (INSTI and NNRTI). Both regimens were well tolerated, with no new safety signals observed. Treatment satisfaction improved after DoC and remained high with CAB+RPV LA. Conclusions Providing treatment-naive participants with the option to switch to CAB+RPV LA as soon as virologic suppression was achieved on daily oral therapy allowed them to choose a treatment to meet their individualized needs while maintaining virologic suppression, which is essential for long-term treatment success and optimized quality of life. Clinical Trial Registration NCT05917509

Background Long COVID refers to persistent or new-onset symptoms three months after SARS-CoV-2 infection lasting for at least two months. The prevalence of Long COVID ranges across studies, while the associated risk factors are not well understood. Methods The study population of Beyond COVID was recruited in six German cities by inviting (1) individuals registered as SARS-CoV-2 PCR positive at the local Public Health Authorities and (2) previously hospitalized patients with infection date between 1st March 2021 and 31st May 2022. Participants were allocated to the predominant variant of concern (VOC) of their first infection. Blood exams and questionnaires to assess persisting symptoms, quality of life (QOL), and psychosocial factors were performed. This publication describes the parameters at baseline visit (BV). Results We included 1258 participants (13.4% hospitalized-based; 86.6% population-based). Most participants had BA.2 (34.6%), followed by Delta (26.8%), BA.1 (18.9%), and Alpha (17.3%). The mean age was 47.1, and 59% were female. 68.8% reported at least one persisting symptom. Fatigue was the most frequent ongoing symptom (32.8%), followed by concentration disorders (25.4%) and dyspnoea (22%). Female sex, lower education, and a shorter period between infection and BV were associated with higher rates of persisting symptoms and symptom-severity. BA.1 and BA.2 had lower rates of persisting symptoms and symptom severity. Conclusion Analysis of baseline data from the Beyond-COVID cohort confirms a high percentage of persistent symptoms. Omicron variants had lower rates of persistent symptoms and symptom severity. Long-term follow-up of study participants will contribute to the characterization of Long COVID.

Drug-induced liver injury (DILI) is a relevant adverse event of tuberculosis treatment (TBT) especially in sub-Saharan Africa, but data remains limited. Genetic hepatic transport proteins polymorphisms (HTPP) are potential contributors. This study aimed to assess frequency and timing of DILI, identify risk factors, and explore the association of HTPP with DILI risk in Ethiopian TBT-patients. In this prospective study, 424 confirmed tuberculosis patients in Ethiopian were recruited before initiation of TBT. Liver function tests were conducted during the first 8 weeks of treatment. Baseline evaluations included sociodemographic-, lifestyle- and clinical data including testing for viral co-infections, and HTPP as well as liver stiffness measurement by transient elastography (TE). Multivariable logistic regression, Cox proportional hazards models, and Fine and Gray competing risks analyses were employed for statistical analysis. Cumulative DILI incidence was 16.0

To quantify virologic failure (VF), identify predictors, characterize resistance patterns at failure, and evaluate time to resuppression in the RESINA cohort. ART-naïve adults initiating ART in 2001–2024 were followed. VF was defined as at least one HIV-1 RNA > 200 copies/mL after suppression or ≥ 0.5-log₁₀ rebound. Participants were grouped by treatment era (2001–2007, 2008–2013, ≥ 2014), reflecting availability of drug classes. Genotypes at baseline and VF were interpreted using the HIV-GRADE algorithm. Predictors of VF were assessed with logistic regression; time to resuppression (< 50 copies/mL) after first VF with Cox models and Kaplan–Meier plots. Among 5136 participants, 139 (2.7

Viremia defined as detectable SARS-CoV-2 RNA in the blood is a potential marker of disease severity and prognosis in COVID-19 patients. Here, we determined the frequency of viremia in serum of two independent COVID-19 patient cohorts within the German National Pandemic Cohort Network (German: Nationales Pandemie Kohorten Netzwerk, NAPKON) with diagnostic RT-PCR against SARS-CoV-2. A cross-sectional cohort with 1,122 COVID-19 patients (German: Sektorenuebergreifende Platform, SUEP) and 299 patients recruited in a high-resolution platform with patients at high risk to develop severe courses (German: Hochaufloesende Plattform, HAP) were tested for viremia. Our study also involved a comprehensive analysis and association of serological, diagnostic and clinical parameters of the NAPKON medical dataset. Prevalence of viremia at the recruitment visit was 12,8% (SUEP) and 13% (HAP) respectively. Serological analysis revealed that viremic patients had lower levels of SARS-CoV-2 specific antibodies as well as lower neutralizing antibodies compared to aviremic patients. Viremia was associated with severity (<0.0001 SUEP; 0.002 HAP) and mortality of COVID-19 (both cohorts <0.0001) compared to aviremic patients. While rare, viremia was also detected in patients with mild disease (0.7%). In patients of the SUEP cohort with acute kidney disease (p = 0.0099) and hematooncological conditions (p = 0.0091), viremia was detected more frequently. Compared to the aviremic group, treatment with immunomodulating drugs as well as elevated levels of inflammatory markers in the blood was more frequent in the viremic group. In conclusion, our analysis revealed that detectable viremia correlates with hyperinflammatory conditions and higher risk for severe COVID-19 disease.

A total of 2079 healthcare workers (HCWs) responded to an anonymous survey on vaccine hesitancy conducted between December 2022 and October 2023 at centers in Lithuania, Portugal, Poland, Germany, and Brazil. Only 55.7% were confident about the long-term safety of the COVID-19 vaccine; 10% believed the risk of having COVID-19 vaccines was greater than the risk of COVID-19 itself. 54.2% believed that COVID-19 vaccination should be compulsory for all staff working in healthcare settings (unless medically exempt), for all patient-facing HCW (59.0%), and for all medical, nursing, and midwifery students (56.7%); fewer supported compulsory influenza vaccination, i.e., 38.0%, 41.5% and 39.7% for equivalent groups. Under half had been vaccinated for influenza in recent years. Respondents were supportive of childhood vaccinations. Level of education, specific HCW occupation and geography were associated with the degree of vaccination hesitancy. The majority trusted advice from health professionals or scientists/doctors and distrusted statements from politicians. Key factors that HCWs thought would encourage vaccination included: vaccine availability at their workplace, vaccination of professional colleagues, sufficient opportunity to ask about vaccine safety and efficacy, supportive information from international bodies, and HCW plans to visit vulnerable family/friends. Generic vaccine promotion activities, whilst valuable, require nuanced modification for different HCW subgroups, vaccines, education levels, and geography.

Human immunodeficiency virus type 2 (HIV-2) is an attenuated retroviral infection characterized by specific natural susceptibility to antiretroviral drugs and acquired resistance profiles. Based on the latest knowledge of phenotypic data and clinical follow-up, HIV-2 resistance interpretation rules have been updated and implemented in a freely available resistance analysis tool.

Abstract Background Population immunity against SARS-CoV-2 has increased, resulting in a decline of COVID-19 mortality. The aim of the study was to analyse the COVID-19-related mortality over the pandemic, stratified by a model of groups at risk of severe COVID-19. Predicted probability of COVID-19-related death in dependence of age and SARS-CoV-2 variant. Methods COVID-19-related patients were included from January 2020 to November 2022 using the international multicentric cohort study Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS). Predicted probability of COVID-19-related death was calculated using a multivariate logistic regression model adjusted to age, gender and vaccination status.Figure 2:Predicted probability of COVID-19-related death in dependence of gender and SARS-CoV-2 variant. Results In total, 12,096 patients were included. The overall mortality was 13% (n=1546), decreasing from 14% during the wildtype (wt) period (01/2020-12/2020), to 13%, 10%, and 6% in the alpha (α) (01/2021-06/2021), delta (δ) (07/2021-12/2021), and omicron (Ω) (01/2022-11/2022) periods, respectively. Patients aged 66-75, 76-85, and >85 years (y) had a 13.3-, 22.5-, and 40.4-fold higher odds of mortality compared to 26-35y old patients (p< 0.001 in all listed comparisons). This increase in mortality between younger (age: 26-35y, mortality: wt 2%, Ω 1%) and older patients (age: >85y, mortality: wt 41%, Ω 23%) decreased with the shift from wt (increase of 39 percentage points) to Ω (increase of 22 percentage points) (Fig. 1). The overall mortality in males (m) (15%) was higher than in females (f) (10%), but this gender-specific difference leveled off with the shift from wt (m: 19%, f: 10%) to Ω (m: 9%, f: 9%) (Fig. 2). Referring to the difference in mortality between patients with zero and four comorbidities, the predicted increase in mortality during the periods wt, α, δ, and Ω was 14, 14, 1, and 0 percentage points, respectively (Fig. 3). Concerning severely immunosuppressed patients, mortality significantly decreased throughout the pandemic (wt: 15%, Ω: 4%, p=0.031) (Fig. 4).Figure 3:Predicted probability of COVID-19-related death in dependence of number of comorbidities and SARS-CoV-2 variant.Comorbidities include cardiovascular diseases, renal diseases, diabetes, pulmonary diseases, liver diseases, rheumatic diseases, haemato-oncological diseases, neurological diseases, autoimmune diseases and HIV/AIDS. Conclusion Overall mortality decreased during the pandemic. This change was observed even among severely immunosuppressed patients. Age, gender, and the number of comorbidities were identified as relevant mortality risk factors, with decreasing importance as the pandemic progressed.Figure 4:Subgroup analysis for severely immunosuppressed patients.Severely immunosuppressed group, including: stem cell transplant, organ transplant, b-cell depletion, autoimmune disease, immunosuppressive therapy (corticosteroids, methotrexate, azathioprine, ciclosporin, calcineurin-inhibitors, mTOR-inhibitors). Disclosures Jochen Schneider, n/a, AbbVie: Grant/Research Support|AbbVie: Honoraria|AbbVie: non-financial support|Central Innovation Program for small and medium-sized enterprises: Grant/Research Support|Central Innovation Program for small and medium-sized enterprises: Honoraria|Central Innovation Program for small and medium-sized enterprises: Central Innovation Program for small and medium-sized enterprises|Deutsche Forschungsgemeinschaft: Grant/Research Support|Deutsche Forschungsgemeinschaft: Honoraria|Deutsche Forschungsgemeinschaft: non-financial support|Diasorin: Grant/Research Support|Diasorin: Honoraria|Diasorin: non-financial support|Dr. Falk Pharma GmbH: Grant/Research Support|Dr. Falk Pharma GmbH: Honoraria|Dr. Falk Pharma GmbH: non-financial support|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|GSK/ViiV Healthcare: Grant/Research Support|GSK/ViiV Healthcare: Honoraria|GSK/ViiV Healthcare: non-financial support|Janssen-Cilag: Grant/Research Support|Janssen-Cilag: Honoraria|Janssen-Cilag: non-financial support|MSD: Grant/Research Support|MSD: Honoraria|MSD: non-financial support|Takeda Pharmaceutical: Grant/Research Support|Takeda Pharmaceutical: Honoraria|Takeda Pharmaceutical: non-financial support Christoph Spinner, MD, AbbVie: Honoraria|Apeiron: Honoraria|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|BBraun Melsungen: Honoraria|BBraun Melsungen: non-financial support|BioNTech: Honoraria|Cepheid: Grant/Research Support|Eli Lilly: Honoraria|Formycon: Honoraria|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|GSK: Honoraria|Janssen-Cilag: Grant/Research Support|Janssen-Cilag: Honoraria|Molecular partners: Honoraria|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Honoraria|Roche: Honoraria|Shionogi: Honoraria|SOBI: Honoraria|Synairgen: Honoraria|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Maria JGT Vehreschild, Prof. Dr. med., 3M: Honoraria|Ärztekammer Niedersachsen: Honoraria|ADKA: Honoraria|Akademie für Infektionsmedizin: Honoraria|Astellas: Honoraria|Berliner Dialy Seminar: Honoraria|Biontech: Grant/Research Support|CED Service: Honoraria|DiaLog Service: Honoraria|EUMEDICA: Advisor/Consultant|EUMEDICA: Honoraria|Falk Foundation: Honoraria|Ferring: Honoraria|Forum für medizinische Fortbildung Gmbh: Honoraria|GILEAD: Honoraria|Heel: Grant/Research Support|Helios Kliniken: Honoraria|Institute Merieux: Honoraria|Janssen: Honoraria|Kit Kongress: Honoraria|Klinikum Essen: Honoraria|Klinikum Leverkusen: Honoraria|Lahn-Dill-Kliniken: Honoraria|Landesärztekammer Hessen: Honoraria|Limbach Gruppe SE: Honoraria|MaaT: Advisor/Consultant|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support|SD Biosensor: Grant/Research Support|St. Johannes Hospital: Honoraria|St. Josef Hospital: Honoraria|SUMIT OXFORD Ltd.: Honoraria|Tillotts: Advisor/Consultant|Tillotts: Honoraria|Uniklinik Frankfurt: Honoraria|Uniklinik Köln: Honoraria|Uniklinik Karlsruhe: Honoraria|Universitätsklinikum Freiburg: Honoraria|Universitätsklinikum Heidelberg: Honoraria Floran Voit, MD, Gilead Sciences: Honoraria|Gilead Sciences: non-financial support|MSD: Grant/Research Support|Pfizer: non-financial support|ViiV Healthcare: non-financial support Johanna Erber, Dr. med., Gilead Sciences: non-financial support|Pfizer: non-financial support|Tillotts Pharma AG: non-financial support|ViiV Healthcare: non-financial support

People with HIV (PWH) who have chronic hepatitis B virus (HBV) coinfection are at increased risk of also having hepatitis D virus (HDV) infection given the shared transmission pathways. The current prevalence of HDV in Germany among people with HIV/HBV, however, is unknown. The aim of this study was to determine the percent with HDV screening as well as the current HDV prevalence among German PWH with HBV coinfection and underlying risk factors for HDV infection. 21 German HIV treatment centers (6 university clinics, 15 private practices) recruited all people with a confirmed HIV diagnosis and a positive hepatitis B surface antigen for more than 6 months, aged ≥ 18 years, and actively in care on December 31, 2023. We assessed the percent with anti-HDV antibody testing in the total cohort. In addition, we calculated the prevalence of individuals who ever had an anti-HDV positive serology (i.e., past/current infection) and the prevalence of individuals whose last HDV RNA result was positive (i.e., active infection). Overall, 458 PWH with HBV coinfection were included in the analysis. 17

BACKGROUND:Limited evidence exists on how bacterial and viral coinfections have developed since the SARS-CoV-2 Omicron variant emerged. We investigated whether community-onset coinfections in adult patients hospitalized with COVID-19 differed during the wild type, Alpha, Delta, and Omicron periods and whether such coinfections were associated with an increased risk of mortality. METHODS:We conducted a multinational cohort study including COVID-19 hospitalizations until 30 April 2023 in 5 European countries. The outcome was bacterial and viral coinfections based on 5 test modalities. Variant periods were compared with regard to occurrences of coinfections and risk ratios for coinfections (Omicron vs pre-Omicron), as well as association with in-hospital mortality (Omicron vs pre-Omicron). RESULTS:A total of 29 564 cases were included: 12 601 wild type, 5256 Alpha, 2433 Delta, and 9274 Omicron. The coinfection rate was 2.6% (327/12 601) for wild type, 2.0% (105/5256) for Alpha, 3.2% (77/2433) for Delta, and 7.9% (737/9274) for Omicron. Omicron had a significantly increased risk ratio of coinfection when compared with preceding variants (1.88 [95% CI, 1.53-2.32], P < .001). These results were consistent across several subgroup analyses. An increased occurrence (19% [232/1246] vs 11% [3042/28 318]) and adjusted risk (1.69 [95% CI, 1.49-1.91], P < .001) of in-hospital mortality were observed in patients with a verified coinfection as compared with patients without a coinfection. CONCLUSIONS:Bacterial and viral coinfections were more prevalent during the Omicron period as compared with preceding variants. Such coinfections were associated with an increased risk of in-hospital mortality, calling for sustained monitoring and clinical vigilance.

The benefit of antibiotic treatment (ABT) for patients with moderate COVID-19 is unclear and overtreatment poses the risk of adverse effects such as Clostridioides difficile infection and antibiotic resistance. This multi-center study compares health status improvement between patients with and without ABT at hospital admission. Between March 2020 and May 2023, hospitalized adults with confirmed SARS-CoV-2 infection were recruited from the German National Pandemic Cohort Network (NAPKON), which includes patients from various hospitals across Germany. The study population included patients with moderate or severe COVID-19 at baseline. The primary objective was to compare health improvement or decline after two weeks between patients who received ABT at baseline and those who did not in the moderate COVID-19 population. The statistical analysis adjusted for confounders such as gender, age, vaccination status, clinical condition, and comorbidities. The severe COVID-19 population was investigated as a secondary objective. A total of 1,317 patients (median age 59 years; 38

Time-stamped genomic sequences from rapidly evolving pathogens can be used to estimate the rates of evolution through molecular tip-dating. The validity of this approach, however, depends on whether detectable levels of genetic variation have accumulated over the given sampling interval, generating a temporal signal. Moreover, molecular dating methods have demonstrated varying degrees of systematic biases under different biologically realistic scenarios, such as the presence of phylo-temporal clustering. Persistent SARS-CoV-2 infections in immunocompromised individuals have been linked to accelerated intrahost molecular rates compared to those of global lineages, facilitating the emergence of novel viral lineages. Yet, studies reporting elevated rates lack assessment of data properties, such as evaluation of temporal signal and comparison of multiple methods of inference, both crucial for robust rate estimation. In this study, we applied a range of molecular dating approaches to reassess the rate of SARS-CoV-2 intrahost evolution in immunocompromised individuals using publicly available datasets. Our findings suggest that even during long-term infections, the limited number of genetic changes accumulating may pose a challenge for robust inference of within-host evolutionary rates, particularly when relying on consensus sequences and when datasets are small or unevenly sampled. Moreover, our results highlight that when certain methodological limitations are overlooked, evolutionary rates can be significantly overestimated. In general, our findings demonstrate that estimating within-host evolutionary rates is a challenging question necessitating thorough assessment of data quality, careful selection of appropriate methods, and cautious interpretation of the resulting estimates. Whereas our phylogenetic analyses of viral consensus sequences provide no evidence of elevated evolutionary rates across the complete genome during chronic SARS-CoV-2 infection, prolonged viral shedding may nevertheless promote the emergence of new viral variants in immunocompromised individuals.

The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). Six hundred three patients (mean 54.0 years, 60.6 www.clinicaltrials.gov under NCT04768998.