Spatial mapping of SARS-CoV-2 and H1N1 lung injury identifies differential transcriptional signatures

Camilla Margaroli; Paul Benson; Nirmal S Sharma; Matthew C Madison; Sarah W Robison; Nitin Arora; Kathy Ton; Yan Liang; Liang Zhang; Rakesh P Patel; Amit Gaggar

doi:10.1016/j.xcrm.2021.100242

Spatial mapping of SARS-CoV-2 and H1N1 lung injury identifies differential transcriptional signatures

Cell Rep Med. 2021 Apr 20;2(4):100242. doi: 10.1016/j.xcrm.2021.100242. Epub 2021 Mar 23.

Authors

Camilla Margaroli^{1

2}, Paul Benson³, Nirmal S Sharma^{2

4}, Matthew C Madison^{1

2}, Sarah W Robison^{1

2}, Nitin Arora⁵, Kathy Ton⁶, Yan Liang⁶, Liang Zhang⁶, Rakesh P Patel^{2

7

8}, Amit Gaggar^{1

2

8

9}

Affiliations

¹ Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
² Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
³ Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴ Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Department of Pediatrics, Division of Neonatology University of Alabama at Birmingham and Children's Hospital of Alabama, Birmingham, AL, USA.
⁶ Nanostring Technologies Inc., Seattle, WA, USA.
⁷ Department of Pathology, Division of Molecular & Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁸ Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ Birmingham VA Medical Center, Birmingham, AL, USA.

Abstract

Severe SARS-CoV-2 infection often leads to the development of acute respiratory distress syndrome (ARDS), with profound pulmonary patho-histological changes post-mortem. It is not clear whether ARDS from SARS-CoV-2 is similar to that observed in influenza H1N1, another common viral cause of lung injury. Here, we analyze specific ARDS regions of interest utilizing a spatial transcriptomic platform on autopsy-derived lung tissue from patients with SARS-CoV-2 (n = 3), H1N1 (n = 3), and a dual infected individual (n = 1). Enhanced gene signatures in alveolar epithelium, vascular tissue, and lung macrophages identify not only increased regional coagulopathy but also increased extracellular remodeling, alternative macrophage activation, and squamous metaplasia of type II pneumocytes in SARS-CoV-2. Both the H1N1 and dual-infected transcriptome demonstrated an enhanced antiviral response compared to SARS-CoV-2. Our results uncover regional transcriptional changes related to tissue damage/remodeling, altered cellular phenotype, and vascular injury active in SARS-CoV-2 and present therapeutic targets for COVID-19-related ARDS.

Keywords: ARDS; COVID-19; H1N1 influenza; SARS-CoV-2; spatial transcriptomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alveolar Epithelial Cells / metabolism
Alveolar Epithelial Cells / pathology
Autopsy
COVID-19 / complications
COVID-19 / pathology*
COVID-19 / virology
Humans
Influenza A Virus, H1N1 Subtype / isolation & purification
Influenza, Human / complications
Influenza, Human / pathology*
Influenza, Human / virology
Lung / metabolism
Lung / pathology*
Lymphocyte Activation
Macrophages, Alveolar / immunology
Macrophages, Alveolar / metabolism
Metaplasia
Phenotype
Respiratory Distress Syndrome / diagnosis
Respiratory Distress Syndrome / etiology
SARS-CoV-2 / isolation & purification
Spatial Analysis
Transcriptome*

Abstract

Publication types

MeSH terms

Grants and funding