Organ-specific immune response in lethal SARS-CoV-2 infection by deep spatial phenotyping

Balachander, Akhila, Lee, Bernett, Biswas, Subhra K, Lye, David C, Lin, Raymond TP, Leo, Yee-Sin, Chui, Paul, Ng, Lisa FP ORCID: 0000-0003-4071-5222 and Renia, Laurent (2022) Organ-specific immune response in lethal SARS-CoV-2 infection by deep spatial phenotyping. CLINICAL & TRANSLATIONAL IMMUNOLOGY, 11 (5). e1384-.

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Official URL: http://dx.doi.org/10.1002/cti2.1384

Abstract

<h4>Objectives</h4>Immunopathology of ongoing COVID-19 global pandemic is not limited solely to pulmonary tissue, but is often associated with multi-organ complications, mechanisms of which are intensely being investigated. In this regard, the interplay between immune, stromal cells and cytokines in pulmonary and extrapulmonary infected tissues, especially in young adults (median age 46 years, range 30-53 years) without comorbidities, remains poorly characterised.<h4>Methods</h4>We profiled lung, heart and intestinal autopsy samples from five SARS-CoV-2-infected cases for 18-20 targets to detect immune, cytokine and stromal cell status at subcellular resolution by a novel IHC-based deep-phenotyping technique, iSPOT (immunoSpatial histoPhenOmics using TSA-IHC), to assess spatial and functional patterns of immune response <i>in situ</i>, in lethal COVID-19 infection.<h4>Results</h4>SARS-CoV-2-infected autopsy samples exhibit skewed counts of immune populations in all samples with organ-specific dysfunctions. Lung and ileal tissue reveal altered architecture with marked loss of tissue integrity, while lung and heart tissue show severe hyperinflammation marked by elevated TNF-α in heart tissue and additionally IL-6, IFN-γ and IL-10 cytokines in lung samples.<h4>Conclusion</h4>With resurgence of infection in younger populations, single-cell cytokine localisation in immune and stromal structures provides important mechanistic insights into organ-specific immunopathology of naïve SARS-CoV-2 infection in the absence of other comorbidities.

Item Type:	Article
Uncontrolled Keywords:	COVID-19, immunopathology, in situ spatial multiplexing, SARS-CoV-2 infection
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	18 Oct 2022 09:55
Last Modified:	18 Jan 2023 20:32
DOI:	10.1002/cti2.1384
Open Access URL:	https://doi.org/10.1002/cti2.1384
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3165586