Two distinct immunopathological profiles in lungs of lethal COVID-19
bioinformatics clinical imaging immunology/immunity inflammation
Authors: Nienhold et al
Journal/ Pre-Print: medRxiv/bioRxiv
Tags: Bioinformatics, Clinical, Immunology/Immunity, Inflammation
Research Highlights
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Post mortem transcriptional and cellular profiling along with histological analysis of lungs from Covid-19 patients reveal distinct sample clustering driven through high or low expression of interferon stimulated genes (ISGs)
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ISGlow, in comparison to ISGhigh, lungs are characterised by low viral loads, increased CD8+ T cell and macrophage infiltrate and exacerbated pulmonary damage
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ISGlow patients exhibit longer hospitalization periods, thus differences in ISGlow vs ISGhigh immunopathology may be indicative of early vs late stages of lethal SARS-CoV-2 infection
Summary
The authors employ transcriptomic analysis and immunohistochemistry of post mortem lungs to characterise the immunopathology of lethal Covid-19. Clustering of samples based on differential immune gene expression led to the identification of 2 distinct Covid-19 sub-groups, defined by the high or low expression of interferon stimulated genes (ISGhigh or ISGlow). Histological analysis of ISGhigh vs ISGlow lungs revealed, in the latter, increased frequencies of CD8+ T cells and macrophages and exacerbated pulmonary damage. SARS-CoV-2 load correlated positively with ISG expression and inversely with CD8+ T cell activation. Hospitalization periods were notably longer in ISGlow vs ISGhigh patients. This data highlights the potential differences between early vs late stages of lethal Covid-19, which may be used to inform future therapeutic intervention strategies.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Transcriptomic analysis coupled with immunohistochemistry details the immune response that underlies lethal Covid-19
Clinical symptoms and pathogenesis of SARS-Cov2/COVID19
The authors specifically aim to define the immunopathology that underlies lethal Covid-19
Treat of SARS-CoV2/COVID19 positive individuals
Linking immunopathology findings with duration of hospitalization aims to inform strategies taken when treating early vs late lethal Covid-19
Study Type
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Post mortem study
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Clinical
Strengths and limitations of the paper
Novelty: First study to describe 2 distinct lung immunopathological profiles in lethal post mortem Covid-19
Standing in the field: Similar pathology i.e. diffuse alveolar damage with macrophage and lymphocyte infiltrate previously reported in post-mortem lungs of Covid-19 patients. Bacterial co-infection has been linked with severe Covid-19, something which is not found in this study (here, only 3/16 patients had evidence for bacterial superinfection). Sub-populations of individuals who die in early and late stages of hospitalized SARS-CoV-2 infection supported by epidemiological data (https://science.sciencemag.org/content/early/2020/05/12/science.abc3517).
Appropriate statistics: Yes
Viral model used: Human cases of lethal SARS-CoV-2 infection, confirmed in nasopharyngeal swabs taken both when alive and, in 5 cases, post-mortem and in post mortem lung tissues
Translatability:If verified, differences in early vs late stages of lethal Covid-19 could be used to inform therapeutic intervention strategies e.g. the use of antivirals vs immunosuppressants.
Main limitations:
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Relatively small number of cases (n=16 Covid-19 patients)