Torque Teno Virus Load Is Associated With Centers for Disease Control and Prevention Stage and CD4+ Cell Count in People Living With Human Immunodeficiency Virus but Seems Unrelated to AIDS-Defining Events and Human Pegivirus Load.

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.

Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: 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. METHODS: 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). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

Specialized palliative care for hospitalized patients with SARS-CoV-2 infection: an analysis of the LEOSS registry.

PURPOSE: Symptom control for patients who were severely ill or dying from COVID-19 was paramount while resources were strained and infection control measures were in place. We aimed to describe the characteristics of SARS-CoV-2 infected patients who received specialized palliative care (SPC) and the type of SPC provided in a larger cohort. METHODS: From the multi-centre cohort study Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS), data of patients hospitalized with SARS-CoV-2 infection documented between July 2020 and October 2021 were analysed. RESULTS: 273/7292 patients (3.7%) received SPC. Those receiving SPC were older and suffered more often from comorbidities, but 59% presented with an estimated life expectancy > 1 year. Main symptoms were dyspnoea, delirium, and excessive tiredness. 224/273 patients (82%) died during the hospital stay compared to 789/7019 (11%) without SPC. Symptom control was provided most common (223/273; 95%), followed by family and psychological support (50% resp. 43%). Personal contact with friends or relatives before or during the dying phase was more often documented in patients receiving SPC compared to patients without SPC (52% vs. 30%). CONCLUSION: In 3.7% of SARS-CoV-2 infected hospitalized patients, the burden of the acute infection triggered palliative care involvement. Besides complex symptom management, SPC professionals also focused on psychosocial and family issues and aimed to enable personal contacts of dying patients with their family. The data underpin the need for further involvement of SPC in SARS-CoV-2 infected patients but also in other severe chronic infectious diseases.

Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: Results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS).

BACKGROUND AND PURPOSE: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. METHODS: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. RESULTS: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. CONCLUSION: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.

Quantitative analysis of different respiratory specimens on two automated test systems for detection of SARS-CoV-2 RNA.

Molecular testing of SARS-CoV-2 RNA is essential during the pandemic. Here, we compared the results of different respiratory specimens including anterior nasal swabs, pharyngeal swabs, saliva swabs, and gargle lavage samples to nasopharyngeal swabs on two automated SARS-CoV-2 test systems. Samples were collected and tested simultaneously from a total of 36 hospitalized symptomatic COVID-19 patients. Detection and quantification of SARS-CoV-2 was performed on cobas®6800 (Roche) and NeuMoDx™ (Qiagen) systems. Both assays showed reliable detection and quantification of SARS-CoV-2 RNA, with nasopharyngeal swabs showing the highest sensitivity. SARS-CoV-2 RNA concentrations in other respiratory specimens were lower (mean 2.5 log10 copies/ml) or even undetectable in up to 20%. These data clearly indicate that not all respiratory materials are equally suitable for the management of hospitalized patients, especially, in the late phase of COVID-19, when the viral phase subsides and inflammation becomes the predominant factor, making detection of even lower viral loads increasingly important.

Prevalence and prognostic value of neurological affections in hospitalized patients with moderate to severe COVID-19 based on objective assessments.

Neurological manifestations of coronavirus disease 2019 (COVID-19) have been frequently described. In this prospective study of hospitalized COVID-19 patients without a history of neurological conditions, we aimed to analyze their prevalence and prognostic value based on established, standardized and objective methods. Patients were investigated using a multimodal electrophysiological approach, accompanied by neuropsychological and neurological examinations. Prevalence rates of central (CNS) and peripheral (PNS) nervous system affections were calculated and the relationship between neurological affections and mortality was analyzed using Firth logistic regression models. 184 patients without a history of neurological diseases could be enrolled. High rates of PNS affections were observed (66% of 138 patients receiving electrophysiological PNS examination). CNS affections were less common but still highly prevalent (33% of 139 examined patients). 63% of patients who underwent neuropsychological testing (n = 155) presented cognitive impairment. Logistic regression models revealed pathology in somatosensory evoked potentials as an independent risk factor of mortality (Odds Ratio: 6.10 [1.01-65.13], p = 0.049). We conclude that hospitalized patients with moderate to severe COVID-19 display high rates of PNS and CNS affection, which can be objectively assessed by electrophysiological examination. Electrophysiological assessment may have a prognostic value and could thus be helpful to identify patients at risk for deterioration.

Using drug exposure for predicting drug resistance - A data-driven genotypic interpretation tool.

Antiretroviral treatment history and past HIV-1 genotypes have been shown to be useful predictors for the success of antiretroviral therapy. However, this information may be unavailable or inaccurate, particularly for patients with multiple treatment lines often attending different clinics. We trained statistical models for predicting drug exposure from current HIV-1 genotype. These models were trained on 63,742 HIV-1 nucleotide sequences derived from patients with known therapeutic history, and on 6,836 genotype-phenotype pairs (GPPs). The mean performance regarding prediction of drug exposure on two test sets was 0.78 and 0.76 (ROC-AUC), respectively. The mean correlation to phenotypic resistance in GPPs was 0.51 (PhenoSense) and 0.46 (Antivirogram). Performance on prediction of therapy-success on two test sets based on genetic susceptibility scores was 0.71 and 0.63 (ROC-AUC), respectively. Compared to geno2pheno[resistance], our novel models display a similar or superior performance. Our models are freely available on the internet via www.geno2pheno.org. They can be used for inferring which drug compounds have previously been used by an HIV-1-infected patient, for predicting drug resistance, and for selecting an optimal antiretroviral therapy. Our data-driven models can be periodically retrained without expert intervention as clinical HIV-1 databases are updated and therefore reduce our dependency on hard-to-obtain GPPs.

Running loose or getting lost: how HIV-1 counters and capitalizes on APOBEC3-induced mutagenesis through its Vif protein.

Human immunodeficiency virus-1 (HIV-1) dynamics reflect an intricate balance within the viruses’ host. The virus relies on host replication factors, but must escape or counter its host’s antiviral restriction factors. The interaction between the HIV-1 protein Vif and many cellular restriction factors from the APOBEC3 protein family is a prominent example of this evolutionary arms race. The viral infectivity factor (Vif) protein largely neutralizes APOBEC3 proteins, which can induce in vivo hypermutations in HIV-1 to the extent of lethal mutagenesis, and ensures the production of viable virus particles. HIV-1 also uses the APOBEC3-Vif interaction to modulate its own mutation rate in harsh or variable environments, and it is a model of adaptation in a coevolutionary setting. Both experimental evidence and the substantiation of the underlying dynamics through coevolutionary models are presented as complementary views of a coevolutionary arms race.