Dataset Information

Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19.

ABSTRACT:

Background

Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19.

Methods

We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed.

Findings

Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production.

Interpretation

Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments.

Funding

CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart & Lung Foundation.

SUBMITTER: Erjefalt JS

PROVIDER: S-EPMC9398470 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19.

Erjefält Jonas S JS de Souza Xavier Costa Natália N Jönsson Jimmie J Cozzolino Olga O Dantas Katia Cristina KC Clausson Carl-Magnus CM Siddhuraj Premkumar P Lindö Caroline C Alyamani Manar M Lombardi Suzete Cleusa Ferreira Spina SCFS Mendroni Júnior Alfredo A Antonangelo Leila L Faria Caroline Silvério CS Duarte-Neto Amaro Nunes AN de Almeida Monteiro Renata Aparecida RA Rebello Pinho João Renato JR Gomes-Gouvêa Michele Soares MS Verciano Pereira Roberta R Monteiro Jhonatas Sirino JS Setubal João Carlos JC de Oliveira Ellen Pierre EP Theodoro Filho Jair J Sanden Caroline C Orengo Jamie M JM Sleeman Matthew A MA da Silva Luiz Fernando Ferraz LFF Saldiva Paulo Hilário Nascimento PHN Dolhnikoff Marisa M Mauad Thais T

EBioMedicine 20220824

<h4>Background</h4>Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19.<h4>Methods</h4>We spatially qu ...[more]

PMID: 36027872

Similar Datasets

Project description:BackgroundLung 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.MethodsLung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns.FindingsForty patients (32M:8F, age: 22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury.InterpretationThe immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established.FundingUK Research and Innovation/Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust.

Dataset Information

Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19.

Background

Methods

Findings

Interpretation

Funding

Publications

Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets