Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Impact of the SARS Coronavirus 2 epidemic on tuberculosis treatment outcome, Northern Italy

It is important to recognise the impact of COVID-19 on TB care to mitigate its consequences. TB services have an urgent need to identify novel strategies to ensure the continuum of TB care at the time of the coronavirus pandemic

Consequences of the COVID-19 pandemic on the continuum of care in a cohort of people living with HIV followed in a single center of Northern Italy

During the COVID-19 pandemic, hospitals faced increasing pressure, where people living with HIV risked to either acquire SARS-CoV-2 and to interrupt the HIV continuum of care

Paper microfluidics for nucleic acid amplification testing (NAAT) of infectious diseases

International audienceThe diagnosis of infectious diseases is entering a new and interesting phase. Technologies based on paper microfluidics, coupled to developments in isothermal amplification of Nucleic Acids (NAs) raise opportunities for bringing the methods of molecular biology in the field, in a low setting environment. A lot of work has been performed in the domain over the last few years and the landscape of contributions is rich and diverse. Most often, the level of sample preparation differs, along with the sample nature, the amplification and detection methods, and the design of the device, among other features. In this review, we attempt to offer a structured description of the state of the art. The domain is not mature and there exist bottlenecks that hamper the realization of Nucleic Acid Amplification Tests (NAATs) complying with the constraints of the field in low and middle income countries. In this domain however, the pace of progress is impressively fast. This review is written for a broad Lab on a Chip audience

Reduced Levels of ABCA1 Transporter Are Responsible for the Cholesterol Efflux Impairment in β-Amyloid-Induced Reactive Astrocytes: Potential Rescue from Biomimetic HDLs

The cerebral synthesis of cholesterol is mainly handled by astrocytes, which are also responsible for apoproteins’ synthesis and lipoproteins’ assembly required for the cholesterol transport in the brain parenchyma. In Alzheimer disease (AD), these processes are impaired, likely because of the astrogliosis, a process characterized by morphological and functional changes in astrocytes. Several ATP-binding cassette transporters expressed by brain cells are involved in the formation of nascent discoidal lipoproteins, but the effect of beta-amyloid (Aβ) assemblies on this process is not fully understood. In this study, we investigated how of Aβ1-42-induced astrogliosis affects the metabolism of cholesterol in vitro. We detected an impairment in the cholesterol efflux of reactive astrocytes attributable to reduced levels of ABCA1 transporters that could explain the decreased lipoproteins’ levels detected in AD patients. To approach this issue, we designed biomimetic HDLs and evaluated their performance as cholesterol acceptors. The results demonstrated the ability of apoA-I nanodiscs to cross the blood–brain barrier in vitro and to promote the cholesterol efflux from astrocytes, making them suitable as a potential supportive treatment for AD to compensate the depletion of cerebral HDLs

Screening for Tuberculosis Infection among Migrants: A Cost-Effectiveness Analysis in the Italian Context

Background: Screening of tuberculosis infection (TBI) among migrants from high-incidence countries is a cornerstone of tuberculosis control in low-incidence countries. However, the optimal screening strategy has not been defined yet. Methods: A quasi-experimental study involving migrants residing in the province of Brescia was carried out that aimed at assessing the completion rate, time to completion, preventive treatment initiation rate, and cost-effectiveness of two strategies for TBI screening. They underwent TBI screening with the IGRA-only strategy (arm 1) or with the sequential strategy (tuberculin skin test, TST, followed by IGRA in case of a positive result—arm 2). The two strategies were compared in terms of screening completion, time to complete the screening process, therapy initiation, and cost-effectiveness. Results: Between May 2019 and May 2022, 657 migrants were evaluated, and 599 subjects were included in the study, with 358 assigned to arm 1 and 237 to arm 2. Screening strategy was the only factor associated with screening completion in a multivariable analysis, with the subjects assigned to the IGRA-only strategy more likely to complete the screening cascade (n = 328, 91.6% vs. n = 202, 85.2%, IRR 1.08, 95% CI (1.01–1.14), p = 0.019). The time to complete the screening process was significantly longer for patients assigned to the sequential strategy arm (74 days vs. 46 days, p = 0.002). Therapy initiation did not significantly differ between the two arms, and cost-effectiveness was higher for the sequential strategy. Conclusion: Sequential strategy implementation for TBI screening among migrants may be justified by its higher cost-effectiveness in spite of the lower completion of the screening cascade

The synergistic effect of chlorotoxin-mApoE in boosting drug-loaded liposomes across the BBB

International audienc