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 geno2phenoresistance, 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.
Purpose
Metabolic disorders have been identified as major risk factors for severe acute courses of COVID-19. With decreasing numbers of infections in many countries, the long COVID syndrome (LCS) ...represents the next major challenge in pandemic management, warranting the precise definition of risk factors for LCS development.
Methods
We identified 50,402 COVID-19 patients in the Disease Analyzer database (IQVIA) featuring data from 1056 general practices in Germany. Multivariate logistic regression analysis was used to identify risk factors for the development of LCS.
Results
Of the 50,402 COVID-19 patients included into this analysis, 1,708 (3.4%) were diagnosed with LCS. In a multivariate regression analysis, we identified lipid metabolism disorders (OR 1.46, 95% CI 1.28–1.65,
p
< 0.001) and obesity (OR 1.25, 95% CI 1.08–1.44,
p
= 0.003) as strong risk factors for the development of LCS. Besides these metabolic factors, patients’ age between 46 and 60 years (compared to age ≤ 30, (OR 1.81 95% CI 1.54–2.13,
p
< 0.001), female sex (OR 1.33, 95% CI 1.20–1.47,
p
< 0.001) as well as pre-existing asthma (OR 1.67, 95% CI 1.39–2.00,
p
< 0.001) and depression (OR 1.27, 95% CI 1.09–1.47,
p
= < 0.002) in women, and cancer (OR 1.4, 95% CI 1.09–1.95,
p
= < 0.012) in men were associated with an increased likelihood of developing LCS.
Conclusion
Lipid metabolism disorders and obesity represent age-independent risk factors for the development of LCS, suggesting that metabolic alterations determine the risk for unfavorable disease courses along all phases of COVID-19.
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.
We retrospectively analyzed data from 6537 predominantly hospitalized COVID‐19 patients registered in the European multinational Lean European Open Survey on SARS‐Infected Patients (LEOSS) registry between January 2020 and February 2021. Common neurological symptoms were 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%). Most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (2.2%) in patients with a complicated or critical disease course. Excessive tiredness (odds ratio OR 1.42) and prior neurodegenerative disease (OR 1.32) were associated with an increased risk of an unfavorable outcome.
Objectives
This study examined the incidence rates and predictive utility of established prognostic factors for the progression to AIDS among people living with HIV under clinical care.
Methods
We ...used data from two observational cohorts of people living with HIV in Germany between 1999 and 2018. The outcome measure was the first AIDS‐defining event that occurred during follow‐up. Incidence rates (IRs) per 1000 person‐years (PY) were calculated by years of follow‐up and calendar periods. We used Cox models in our prediction analyses, including CD4 count, viral load, and age at baseline to estimate the predictive performance. Additionally, we included transmission mode to examine its predictive utility.
Results
A total of 23 299 people living with HIV were included in the analyses. Of these, 1832 developed a first AIDS event during follow‐up, constituting an overall rate of 14.6/1000 PY (95% confidence interval CI 13.9–15.2). IRs were highest in the first year of follow‐up (45.6/1000 PY, 95% CI 42.6–48.8) and then declined continuously. IRs were highest among people living with HIV who enrolled between 1999 and 2003 (36.1/1000 PY, 95% CI 32.6–40.0). A low CD4 count, high viral load, and older age at baseline increased the likelihood of progressing to AIDS. Adding transmission mode to the models did not improve the predictive performance.
Conclusions
The rates of a first AIDS event among people living with HIV have continuously declined in Germany. Health outcomes depend on a person's CD4 count, viral load, and age but not on transmission mode. To further reduce the number of AIDS cases, the focus should be on groups more likely to present in progressed stages of their HIV infection.
Abstract
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.
Assessment of a low skeletal muscle mass (SM) is important for diagnosis of ageing and disease-associated sarcopenia and is hindered by heterogeneous methods and terminologies that lead to ...differences in diagnostic criteria among studies and even among consensus definitions. The aim of this review was to analyze and summarize previously published cut-offs for SM applied in clinical and research settings and to facilitate comparison of results between studies. Multiple published reference values for discrepant parameters of SM were identified from 64 studies and the underlying methodological assumptions and limitations are compared including different concepts for normalization of SM for body size and fat mass (FM). Single computed tomography or magnetic resonance imaging images and appendicular lean soft tissue by dual X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA) are taken as a valid substitute of total SM because they show a high correlation with results from whole body imaging in cross-sectional and longitudinal analyses. However, the random error of these methods limits the applicability of these substitutes in the assessment of individual cases and together with the systematic error limits the accurate detection of changes in SM. Adverse effects of obesity on muscle quality and function may lead to an underestimation of sarcopenia in obesity and may justify normalization of SM for FM. In conclusion, results for SM can only be compared with reference values using the same method, BIA- or DXA-device and an appropriate reference population. Limitations of proxies for total SM as well as normalization of SM for FM are important content-related issues that need to be considered in longitudinal studies, populations with obesity or older subjects.
Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the ...knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.
The history and value of face masks Matuschek, Christiane; Moll, Friedrich; Fangerau, Heiner ...
European journal of medical research,
06/2020, Letnik:
25, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in ...which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.
Background
As a consequence of the improved availability of combined antiretroviral therapy (cART) in resource‐limited countries, an emergence of HIV drug resistance (HIVDR) has been observed. We ...assessed the prevalence and spectrum of HIVDR in patients with failure of second‐line cART at two HIV clinics in central Ethiopia.
Methods
HIV drug resistance was analysed in HIV‐1‐infected patients with virological failure of second‐line cART using the geno2pheno application.
Results
Among 714 patients receiving second‐line cART, 44 (6.2%) fulfilled the criteria for treatment failure and 37 were eligible for study inclusion. Median age was 42 years interquartile range (IQR): 20–45 and 62.2% were male. At initiation of first‐line cART, 23 (62.2%) were WHO stage III, mean CD4 cell count was 170.6 (range: 16–496) cells/µL and median (IQR) HIV‐1 viral load was 30 220 (7963–82 598) copies/mL. Most common second‐line cART regimens at the time of failure were tenofovir disoproxil fumarate (TDF)‐lamivudine (3TC)‐ritonavir‐boosted atazanavir (ATV/r) (19/37, 51.4%) and zidovudine (ZDV)‐3TC‐ATV/r (9/37, 24.3%).
Genotypic HIV‐1 resistance testing was successful in 35 (94.6%) participants. We found at least one resistance mutation in 80% of patients and 40% carried a protease inhibitor (PI)‐associated mutation. Most common mutations were M184V (57.1%), Y188C (25.7%), M46I/L (25.7%) and V82A/M (25.7%). High‐level resistance against the PI ATV (10/35, 28.6%) and lopinavir (LPV) (5/35, 14.3%) was reported. As expected, no resistance mutations conferring integrase inhibitor resistance were detected.
Conclusions
We found a high prevalence of resistance mutations, also against PIs (40%), as the national standard second‐line cART components. Resistance testing before switching to second‐ or third‐line cART is warranted.
The German government has made it mandatory to wear respiratory masks covering mouth and nose (MNC) as an effective strategy to fight SARS-CoV-2 infections. In many countries, this directive has been ...extended on shopping malls or public transportation. The aim of this paper is to critically analyze the statutory regulation to wear protective masks during the COVID-19 crisis from a medical standpoint.
We performed an extensive query of the most recent publications addressing the prevention of viral infections including the use of face masks in the community as a method to prevent the spread of the infection. We addressed the issues of practicability, professional use, and acceptability based on the community and the environment where the user resided.
Upon our critical review of the available literature, we found only weak evidence for wearing a face mask as an efficient hygienic tool to prevent the spread of a viral infection. However, the use of MNC seems to be linked to relevant protection during close contact scenarios by limiting pathogen-containing aerosol and liquid droplet dissemination. Importantly, we found evidence for significant respiratory compromise in patients with severe obstructive pulmonary disease, secondary to the development of hypercapnia. This could also happen in patients with lung infections, with or without SARS-CoV-2.
Epidemiologists currently emphasize that wearing MNC will effectively interrupt airborne infections in the community. The government and the politicians have followed these recommendations and used them to both advise and, in some cases, mandate the general population to wear MNC in public locations. Overall, the results seem to suggest that there are some clinically relevant scenarios where the use of MNC necessitates more defined recommendations. Our critical evaluation of the literature both highlights the protective effects of certain types of face masks in defined risk groups, and emphasizes their potential risks.
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