Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19.

Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease.

Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients.

Diffuse alveolar damage (DAD) is the histological expression of acute respiratory distress syndrome and characterises lung pathology due to infection with SARS-CoV-2, and other respiratory pathogens of clinical significance. DAD reflects a time-dependent immunopathological process, progressing from an early/exudative stage through to an organising/fibrotic stage, yet within an individual these different stages of DAD may coexist. Understanding the progression of DAD is central to the development of new therapeutics to limit progressive lung damage.

Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19.

T cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T-cells populations, respectively.

The trajectory of COVID-19 cardiopulmonary disease: insights from an autopsy study of community-based, pre-hospital deaths.

Background: examination of lung and heart tissue has been vital to developing an understanding of COVID-19 pathophysiology; however studies to date have almost uniformly used tissue obtained from hospital-based deaths where individuals have been exposed to major medical and pharmacological interventions.

Methods: In this study we investigated patterns of lung and heart injury from 46 community-based, pre-hospital COVID-19-attributable deaths who underwent autopsy.

Results: The cohort comprised 22 females and 24 males, median age 64 years (range 19-91) at time of death with illness duration range 0-23 days.

Immune processes in the pathogenesis of chronic lung allograft dysfunction: identifying the missing pieces of the puzzle.

Lung transplantation is the optimal treatment for selected patients with end-stage chronic lung diseases. However, chronic lung allograft dysfunction remains the leading obstacle to improved long-term outcomes. Traditionally, lung allograft rejection has been considered primarily as a manifestation of cellular immune responses.

Comparing Deceased Organ Donation Performance in Two Countries that Use Different Metrics: Comparing Apples With Apples.

Organ donation networks audit and report on national or regional organ donation performance, however there are inconsistencies in the metrics and definitions used, rendering comparisons difficult or inappropriate. This is despite multiple attempts exploring the possibility for convergently evolving audits so that collectives of donation networks might transparently share data and practice and then target system interventions. This paper represents a collaboration between the United Kingdom and Australian organ donation organisations which aimed to understand the intricacies of our respective auditing systems, compare the metrics and definitions they employ and ultimately assess their level of comparability.

Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19.

The lungs are the main site that is affected in severe COVID-19, and post-mortem lung tissue provides crucial insights into the pathophysiology of severe disease. From basic histology to state-of-the-art multiparameter digital pathology technologies, post-mortem lung tissue provides snapshots of tissue architecture, and resident and inflammatory cell phenotypes and composition at the time of death. Contrary to early assumptions that COVID-19 in the lungs is a uniform disease, post-mortem findings have established a high degree of disease heterogeneity.

Perceptions held by healthcare professionals concerning organ donation after circulatory death in an Australian intensive care unit without a local thoracic transplant service: A descriptive exploratory study.

Background And Objective: Organ donation rates continue to be low in Australia compared with demand. Donation after circulatory death (DCD) has been an important strategy to increase donation rates, facilitated by advances in cardiopulmonary support in intensive care units (ICUs). However, DCD may harbour greater logistical challenges and unfavourable perceptions amongst some ICU healthcare professionals.

Exploring staff perceptions of organ donation after circulatory death.

Background And Objective: Solid organ donation remains low in Australia; however, donation after circulatory death (DCD) bolsters rates and is associated with good short- and long-term clinical outcomes among recipients, especially in lung and kidney recipients. However, its reintroduction is met with resistance within hospitals. The aim of the present study was to develop a greater understanding of DCD perceptions among staff involved.

Lung autoantibodies: Ready for prime time?

Despite advances in our understanding of the immunology of lung allograft tolerance and a reduction in the rate of acute allograft rejection using contemporary immunosuppressive protocols, the rate of chronic lung allograft dysfunction (CLAD), both obstructive and restrictive, remains unacceptably high. CLAD, particularly the restrictive phenotype, is a harbinger of a foreshortened survival. The development of a consensus approach to the diagnosis of antibody-mediated rejection by the International Society for Heart and Lung Transplantation has highlighted the need for a uniform approach toward the investigation, diagnosis, implications and management of both human leukocyte antigen (HLA) and non-HLA-related antibody formation.