The role and uses of antibodies in COVID-19 infections: a living review

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity

T cell phenotypes in COVID-19 - a living review

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation

Autophagy’s roles in the activation and ageing of CD4+ T cells

Autophagy plays an essential role in the differentiation, homeostasis and renewal of various cell types. Though its molecular machinery has been extensively elucidated, what autophagy specifically degrades remains largely unclear. Here, we created the Lc3b-APEX2 transgenic mouse model based on the proximity biotinylation technique, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell. Through inserting APEX2, an engineered ascorbate peroxidase, into the endogenous LC3B allele, proteins residing in the autophagosomes can be specifically labelled with biotin and easily purified. After the systemic validation of the mouse model, next, I utilised it to explore the molecular mechanism of why CD4+ T cells, which orchestrate both humoral and cytotoxic immune responses, rely on autophagy to expand when facing antigen-stimuli. We discovered the interleukin-7 receptor alpha (IL-7Rα) as one of the autophagosomal candidates in proliferating CD4+ T cells. Mechanistically, we confirmed that excessive surface IL-7R sequestrate the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. Moreover, we investigated how CD4+ T cells from aged mice, which mimic some of the phenotypes of autophagy-deficient CD4+ T cells, also show several unique changes related to cellular ageing. This study provides proof of principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy’s contribution to healthy physiology and disease

Turbo Gradient and Spin-Echo BLADE-DWI for Extraocular Muscles in Thyroid-Associated Ophthalmopathy

Purpose: To investigate feasibility and diagnostic performance of turbo gradient and spin-echo BLADE (proprietary name for Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction [PROPELLER] in Siemens MR systems)-diffusion weighted imaging (TGSE-BLADE-DWI) for depicting extraocular muscle (EOM) involvement and activity in thyroid-associated ophthalmopathy (TAO), and to compare TGSE-BLADE-DWI with readout-segmented echo-planar imaging (RESOLVE). Materials and methods: Thirty-five patients with identified TAO underwent the two DWI scans. Two radiologists visually scored the image quality of the two DWIs with respect to the susceptibility artifacts and geometric distortions on a three-point scale. The maximum size (Sizemax) of EOMs and corresponding ADCs (cADCs) of each patient were compared between the active and inactive phases. The clinical activity score (CAS) was used as a reference to assess the diagnostic performance of EOM ADCs for grading TAO activity. ROC analysis, Pearson correlation, and Wilcoxon signed-rank test were used for statistical analyses. Results: For scores of EOMs, the image quality of TGSE-BLADE-DWI was significantly higher than that of RESOLVE. There were no statistically significant differences between the AUCs of the two DWIs, Sizemax, or cADCs between the active and inactive phases. TGSE-BLADE-DWI ADCs were significantly higher than the RESOLVE ADCs in the right superior rectus, right lateral rectus, left superior rectus, and left inferior rectus. There were no statistically significant correlations between the cADC or Sizemax, and CAS. The highest AUC was 0.697 for RESOLVE and 0.657 for TGSE-BLADE-DWI. The best performing ADC threshold was 1.85 × 10−3 mm2/s with 85.7% sensitivity, 58.8% specificity and 66.67% accuracy for RESOLVE and 1.99 × 10−3 mm2/s with 79.0% sensitivity, and 55.6% specificity and 65.27% accuracy for TGSE-BLADE-DWI. Conclusion: Compared to RESOLVE, TGSE-BLADE-DWI provided improved image quality with fewer susceptibility artifacts and geometric distortions for EOM visualization and showed an equivalent performance in detecting active TAO

Catalytic Regio- and Enantioselective Boracarboxylation of Arylalkenes with CO₂ and Diboron

Catalytic asymmetric carboxylation of readily available alkenes with CO2, an abundant and sustainable one-carbon building block, that gives access to value-added α-stereogenic carboxylic acids in an atom- and step-economic manner is highly attractive. However, it has remained a formidable challenge for the synthetic community. Here, the first example of Cu-catalyzed highly regio- and enantioselective boracarboxylation reaction on various arylalkenes with diboron under an atmospheric pressure of CO2 is described, which afforded a variety of chiral β-boron-functionalized α-aryl carboxylic acids with up to 87% yield and 97% ee under mild conditions. Importantly, α-substituted arylalkenes could also be subject to this protocol with excellent enantiopurities, thereby rendering an efficient approach for the generation of enantioenriched carboxylic acids with an α-chiral all-carbon quaternary center. Moreover, high functional group tolerance, scalable synthesis, and facile access to bioactive compounds, like (−)-scopolamine, (−)-anisodamine, and (−)-tropicamide, further demonstrated the synthetic utility of this strategy

Diagnostic Accuracy of Computed Tomography for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Meta-Analysis

<div><p>This study aimed to determine the diagnostic accuracy of computed tomography imaging for the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Additionally, the effect of test and study characteristics was explored. Studies published between 1990 and 2015 identified by PubMed, OVID search and citation tracking were examined. Of the 613 citations, 11 articles (n=712) met the inclusion criteria. The patient-based analysis demonstrated a pooled sensitivity of 76% (95% confidence interval [CI]: 69% to 82%), and a pooled specificity of 96% (95%CI: 93% to 98%). This resulted in a pooled diagnostic odds ratio (DOR) of 191 (95%CI: 75 to 486). The vessel-based analyses were divided into 3 levels: total arteries、main+ lobar arteries and segmental arteries. The pooled sensitivity were 88% (95%CI: 87% to 90%)、95% (95%CI: 92% to 97%) and 88% (95%CI: 87% to 90%), respectively, with a pooled specificity of 90% (95%CI: 88% to 91%)、96% (95%CI: 94% to 97%) and 89% (95% CI: 87% to 91%). This resulted in a pooled diagnostic odds ratio of 76 (95%CI: 23 to 254),751 (95%CI: 57 to 9905) and 189 (95%CI: 21 to 1072), respectively. In conclusion, CT is a favorable method to rule in CTEPH and to rule out pulmonary endarterectomy (PEA) patients for proximal branches. Furthermore, dual-energy and 320-slices CT can increase the sensitivity for subsegmental arterials, which are promising imaging techniques for balloon pulmonary angioplasty (BPA) approach. In the near future, CT could position itself as the key for screening consideration and for surgical and interventional operability.</p></div

Characteristics of included studies¹.

<p>¹mPAP: mean PAP; sPAP: standard PAP.</p><p>Characteristics of included studies<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126985#t001fn001" target="_blank">¹</a>.</p

Flow Diagram of Literature Search.

<div><p>Of 613 potentially relevant citations, 11 articles met our inclusion criteria and were included in the meta-analysis.</p> <p><i>From</i>: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). <i>P</i>referred <i>R</i>eporting <i>I</i>tems for <i>S</i>ystematic Reviews and <i>M</i>eta-<i>A</i>nalyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:<a href="http://dx.doi.org/10.1371/journal.pmed1000097" target="_blank">10.1371/journal.pmed1000097</a></p> <p>For more information, visit <a href="http://www.prisma-statement.org" target="_blank">www.prisma-statement.org</a>.</p></div

Summary ROC curve for CT.

<p>Diagnostic performance of CT in (A) patient basis; (B) total arteries; (C) main + lobar arteries; (D) segmental arteries.</p

Pooled Quality Assessment of Primary Studies.

<p>Pooled Quality Assessment of Primary Studies.</p