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Dark-field radiography has been proven to be a promising tool for the assessment of various lung diseases. To evaluate the potential of dose reduction in dark-field chest radiography for the detection of the Coronavirus SARS-CoV-2 (COVID-19) pneumonia. Patients aged at least 18 years with a medically indicated chest computed tomography scan (CT scan) were screened for participation in a prospective study between October 2018 and December 2020. Patients were included if they had a CO-RADS (COVID-19 Reporting and Data System) score ≥ 4 (COVID-19 group) or if they had no pathologic lung changes (controls). A total of 89 participants with a median age of 60 years (interquartile range 48 to 68 yrs.) were included in this study. Dark-field and attenuation-based radiographs were simultaneously obtained by using a prototype system for dark-field radiography. By modifying the image reconstruction algorithm, low-dose radiographs were simulated based on real participant images. The simulated radiographs corresponded to 50%, 25%, and 13% of the full dose (41.9 μSv, median value). Four experienced radiologists served as blinded readers assessing both image modalities, displayed side by side in random order. The presence of COVID-19-associated lung changes was rated on a scale from 1 to 6. The readers' diagnostic performance was evaluated by analyzing the area under the receiver operating characteristic curves (AUC) using Obuchowski's method. Also, the dark-field images were analyzed quantitatively by comparing the dark-field coefficients within and between the COVID-19 and the control group. The readers' diagnostic performance in the image evaluation, as described by the AUC value (where a value of 1 corresponds to perfect diagnostic accuracy), did not differ significantly between the full dose images (AUC = 0.86) and the simulated images at 50% (AUC = 0.86) and 25% of the full dose(AUC = 0.84) (p>0.050), but was slightly lower at 13% dose (AUC = 0.82) (p = 0.038). For all four radiation dose levels, the median dark-field coefficients within groups were identical but different significantly by 15% between the controls and the COVID-19 pneumonia group (p<0.001). Dark-field imaging can be used to diagnose the Coronavirus SARS-CoV-2 (COVID-19) pneumonia with a median dose of 10.5 μSv, which corresponds to 25% of the original dose used for dark-field chest imaging.

Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV) infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV) infection with or without thymectomy (Tx) alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV) or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8(+) T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any 'de novo' immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence.

Determination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical for understanding protective immunity. Here we perform a multifactorial analysis of SARS-CoV-2 and HCoV antibody responses in pre-pandemic ( N  = 825) and SARS-CoV-2-infected donors ( N  = 389) using a custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that pre-existing HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, our results suggest that HCoV immunity may promote rapid development of SARS-CoV-2-specific immunity, thereby underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention. How the immune responses induced by SARS-CoV-2 and human coronavirus (hCoV) crosstalk is still unclear. Here the authors profile the humoral responses of prepandemic and SARS-CoV-2-infected donors to find that higher hCoV antibody titers are associated with SARS-CoV-2 negativity, and with reduced hospitalization in SARS-CoV-2 positive patients.

Rapid rebound of plasma viremia in patients after interruption of long-term combination antiretroviral therapy (cART) suggests persistence of low-level replicating cells or rapid reactivation of latently infected cells. To further characterize rebounding virus, we performed extensive longitudinal clonal evolutionary studies of HIV env C2-V3-C3 regions and exploited the temporal relationships of rebounding plasma viruses with regard to pretreatment sequences in 20 chronically HIV-1-infected patients having undergone multiple 2-week structured treatment interruptions (STI). Rebounding virus during the short STI was homogeneous, suggesting mono- or oligoclonal origin during reactivation. No evidence for a temporal structure of rebounding virus in regard to pretreatment sequences was found. Furthermore, expansion of distinct lineages at different STI cycles emerged. Together, these findings imply stochastic reactivation of different clones from long-lived latently infected cells rather than expansion of viral populations replicating at low levels. After treatment was stopped, diversity increased steadily, but pretreatment diversity was, on average, achieved only >2.5 years after the start of STI when marked divergence from preexisting quasispecies also emerged. In summary, our results argue against persistence of ongoing low-level replication in patients on suppressive cART. Furthermore, a prolonged delay in restoration of pretreatment viral diversity after treatment interruption demonstrates a surprisingly sustained evolutionary bottleneck induced by punctuated antiretroviral therapy.

Background. Atherosclerosis has been assessed in human immunodeficiency virus (HIV)-infected persons by using various methods. Peripheral arterial disease (PAD) has not been evaluated, however. We studied the cross-sectional prevalence of lower limb PAD in an HIV-infected population. Methods. PAD was assessed using the Edinburgh Claudication Questionnaire and by measuring the systolic ankle-brachial blood pressure index (ABI) at rest and after exercise. Patients with PAD were further evaluated by duplex scan of lower limb arteries. Results. Ninety-two consecutive HIV-infected patients were evaluated (23.9% women; mean age, 49.5 years; 61.9% current smokers). Claudication was reported by 15.2% of the patients. PAD was found in 20.7% of the patients: 9.8% had an abnormal ABI (<0.90) at rest, and 10.9% had normal ABI at rest but a >25% decrease after exercise. Of the patients with PAD, 84.2% were investigated with duplex scan, all of whom had atherosclerotic occlusions or stenoses of the iliac or femoral arteries. Age, diabetes, smoking, and low CD4+ T lymphocyte counts were identified as independent predictors of PAD. Conclusions. The prevalence of symptomatic and asymptomatic PAD is high in the HIV-infected population and is much higher than expected (prevalence in the general population, ∼3% at 60 years). This study suggests the presence of an epidemic of PAD ∼20 years earlier in the HIV-infected than in the general population. Larger epidemiological studies are needed to better define risk factors and to evaluate whether PAD is associated with increased mortality, as it is in the general population.

The 69 insertion and Q151M mutations are multi-nucleoside/nucleo tide resistance mutations (MNR). The prevalence among 4078 antiretro viral therapy (ART)-experienced individuals was <1.3%. Combined ART fully prevented MNR in subtype infections. Case-control studies were performed to identify risk factors. Control subjects were patients with ≥ 3 thymidine-analogue mutations. The 69 insertion study (27 control subjects, 14 case patients) identified didanosine exposure as a risk (odds ratio, 5.0 per year; P = .019), whereas the Q151M study (which included 44 control subjects and 25 case patients) detected no associations. Following detection, individuals with Q151M tended to have lower suppression rates and higher mortality rates, relative to control subjects. Additional studies are needed to verify these findings in non-subtype B infections.